Talk:Neurogenic inflammation

Substance P (Substance p key cause of neurogenic inflammation, implicated in many inflammatory diseases) PMID 11378438

Harrison S, Geppetti P.

Substance p.

Int J Biochem Cell Biol. 2001 Jun;33(6):555-76.

Abstract

This article provides a brief overview of the history of substance P from its discovery in the 1930s to the present day. The development of substance P receptor agonists and antagonists, and more recently the employment of transgenic mice, provide a framework to explore the functional role of substance P. Chronic inflammation and pain are associated with a number of diseases, and it has been proposed that substance P, released from primary afferent nerve endings play a role in these conditions. Recent developments with substance P antagonists have demonstrated the importance of substance P in several models of disease that span from asthma to chronic bronchitis; from cystitis, inflammatory bowel disease to migraine; emesis, depression, pain and seizures. Advancements in the knowledge of the role of substance P, its agonists and antagonists could provide clinical solutions for a variety of chronic inflammatory conditions.

PMID 11378438

Neurogenic inflammation is also a cause of vasomotor rhinitis / sinusitis

Also a cause of vasomotor rhinitis / sinusitis

Ocdcntx

Pathobiology of magnesium deficiency: a cytokine/neurogenic inflammation hypothesis. (Magnesium deficiency in rats caused neurogenic inflammation) PMID 1384353

PMID 1384353

Weglicki WB, Phillips TM.

Pathobiology of magnesium deficiency: a cytokine/neurogenic inflammation hypothesis.

Am J Physiol. 1992 Sep;263(3 Pt 2):R734-7. Department of Medicine, George Washington University Medical Center, Washington, DC 20037.

During the progression of Mg deficiency in a rodent model, we have observed dramatic increases in serum levels of inflammatory cytokines [interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)] after 3 wk on a Mg-deficient diet. Sequential analyses of these cytokine changes in the serum of rats revealed an initial rise at day 12, followed by a major elevation in all three cytokine levels by day 21. Of greater interest was an early peak in the serum level of the neuropeptide substance P after only 5 days on the diet. This "neuronal" tachykinin is thought to be released from neural tissues, and it is known to stimulate production of certain cytokines, including IL-1, IL-6, and TNF-alpha. In addition, there was a concomitant increase in histamine levels, which may have resulted from stimulation and degranulation of mast cells by substance P. Thus we hypothesize that the release of substance P may be the earliest pathophysiological event leading to stimulation of the inflammatory cytokines, which may then stimulate the free radical mechanisms of injury previously confirmed by our work. —Preceding unsigned comment added by Ocdcntx (talk • contribs) 01:54, 2 March 2010 (UTC)

Neurogenic inflammation and particulate matter (PM) air pollutants. (N.I. as cause of airway inflammation, bronchoconstriction, vasodilation, histamine release, mucous secretion) PMID 11829413

PMID 11829413

Verones B, Oortgiesen M.

Neurogenic inflammation and particulate matter (PM) air pollutants.

Neurotoxicology Division, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.

Exposure to a class of airborne pollutants known as particulate matter (PM) is an environmental health risk of global proportions. PM is thought to initiate and/or exacerbate respiratory disorders, such as asthma and airway hyper-responsiveness and is epidemiologically associated with causing death in the elderly and those with pre-existing respiratory, or cardiopulmonary disease. Plausible mechanisms of action to explain PM inflammation and its susceptible sub-population component are lacking. This review describes a series of published studies which indicate that PM initiates airway inflammation through sensory neural pathways, specifically by activation of capsaicin-sensitive vanilloid (e.g. VRI) irritant receptors. These acid-sensitive receptors are located on the sensory C nerve fibers that innervate the airways as well as on various immune and non-immune airway target cells. The activation of these receptors results in the release of neuropeptides from the sensory terminals that innervate the airways. Their interactions with airway target cells, result in signs of inflammation (e.g. bronchoconstriction, vasodilation, histamine release, mucous secretion etc.). Our data have linked the activation of the VR1 receptors to the surface charge carried on the colloidal particulates which constitute PM pollution. Related studies have examined how genetic and non-genetic factors modify the sensitivity of these irritant receptors and enhance the inflammatory responsiveness to PM. In summary, this review proposes a mechanism by which neurogenic elements initiate and sustain PM-mediated airway inflammation. Although neurogenic influences have been appreciated in normal airway homeostasis, they have not, until now, been associated with PM toxicity. The sensitivity of the sensory nervous system to irritants and its interactions with pulmonary target tissues, should encourage neuroscientists to explore the relevance of neurogenic influences to toxic disorders involving other peripheral target systems.

—Preceding unsigned comment added by Ocdcntx (talk • contribs) 02:16, 2 March 2010 (UTC)

Peripheral mechanism of action of antimigraine prophylactic drugs. (Migraine caused by neurogenic inflammation, alleviated by drugs inhibiting it) PMID 18545913

PMID 18545913

Frediani F, Villani V, Casucci G.

Peripheral mechanism of action of antimigraine prophylactic drugs.

Neurol Sci. 2008 May;29 Suppl 1:S127-30.

Neurological Department and Headache Center, Policlinico S. Pietro, via Forlanini 15, 24036 Ponte San Pietro (BG), Italy. fabio_frediani@yahoo.it

Migraine is a visceral pain. According to current theories, activation of trigeminocervical nerve endings releases calcitonin gene-related peptide and substance P, inducing vasodilation and plasma protein extravasation, leading to 'neurogenic' inflammation. Activation of the trigeminovascular system is followed by sensitisation of trigeminocervical fibres, maintaining a condition of hypersensitivity to non-noxious stimuli that support persistent pain during migraine attack. Other neurotransmitters (nitric oxide, bradykinins, 5-HT, etc.) play a role in regulating this complex mechanism. In this brief review, we consider the effect of drugs that, acting on the different transmitters involving in pain perception, can stop or inhibit these pathogenetic mechanisms. —Preceding unsigned comment added by Ocdcntx (talk • contribs) 02:20, 2 March 2010 (UTC)

Neurogenic inflammation induced by capsaicin in patients with psoriasis. (Neurogenic inflammation induced in skin of psoriasis patients only at capsaicin doses 10-20X as high as normals) PMID 1711752.

Neurogenic inflammation and flare could be induced in patients with late-onset psoriasis only at doses of capsaicin sharply higher than those required with normal controls. PMID 1711752.

Glinski W, Glinska-Ferenz M, Pierozynska-Dubowska M.

Neurogenic inflammation induced by capsaicin in patients with psoriasis. Acta Derm Venereol. 1991;71(1):51-4. Comment in:

• Acta Derm Venereol. 1992;72(3):234-5.

Abstract

Increasing doses of capsaicin were applied topically to the forearm skin of 30 patients with psoriasis, 16 patients with systemic scleroderma and 16 healthy volunteers. Only one-third of the patients with psoriasis responded with neurogenic inflammation to capsaicin doses of 0.125 and 0.25 microgram/cm2 in contrast to 81% of scleroderma patients and all the normal controls, who showed a positive cutaneous reaction. Higher doses of capsaicin (0.5-4 micrograms/cm2) were required to induce erythema and flare in patients with late-onset psoriasis (after 21 years of age) as well as in patients with more than 40% of skin surface involved with psoriatic lesion.

PMID: 1711752 —Preceding unsigned comment added by 68.165.11.29 (talk) 13:57, 19 April 2010 (UTC)

Neurogenic inflammation from capsaicin effective in treating psoriasis symptoms -- text and two journal cites -- Please tweak if needed and add to article.

The neurogenic inflammation induced by capsaicin is an effective means to ameliorate the itching and inflammation of psoriasis. PMID 1711752 ; ( http://www.ncbi.nlm.nih.gov/pubmed/1711752 )

pmid 8021363 ( http://www.ncbi.nlm.nih.gov/pubmed/8021363 )

TRPV1 capsaicin receptor is a central actor in neurogenic inflammation (wikipedia TRPV1 article excerpts).

From Wikipedia, the free encyclopedia (Redirected from Vanilloid receptors)

TRPV1

The transient receptor potential cation channel, subfamily V, member 1 (TRPV1), also known as the capsaicin receptor is a protein that, in humans, is encoded by the TRPV1 gene.[2][3] This protein is a member of the TRPV group of transient receptor potential family of ion channels.[4]

... Sensitization

The sensitivity of TRPV1 to noxious stimuli, such as high temperatures or low pH, is not static. Upon tissue damage and the consequent inflammation, a number of inflammatory mediators, such as various prostaglandins and bradykinin, are released. These agents increase the sensitivity of TRPV1 to noxious stimuli. This manifests as an increased sensitivity to painful stimuli (hyperalgesia) or pain sensation in response to non-painful stimuli allodynia. Most sensitizing pro-inflammatory agents activate the phospholipase C pathway. Phopshorylation of TRPV1 by protein kinase C have been shown to play a role in sensitzation of TRPV1.

[edit] Desensitization

Upon prolonged exposure to capsaicin, TRPV1 activity decreases, a phenomenon called desensitization. Extracellular calcium ions are required for this phenomenon, thus influx of calcium and the consequentual increase of intracellular calcium mediate this effect. Various signaling pathways such as calmodulin and calcineurin, and the decrease of PIP2, have been implicated in desensitization of TRPV1. Desensitization of TRPV1 is thought to underlie the paradoxical analgesic effect of capsaicin.

... In humans, drugs acting at TRPV1 receptors could be used to treat neuropathic pain associated with multiple sclerosis, chemotherapy, or amputation, as well as pain associated with the inflammatory response of damaged tissue, such as in osteoarthritis.[10]

...

Agonists

Agonists such as capsaicin and resiniferatoxin activate TRPV1, and, upon prolonged application TRPV1 activity, would decrease (desensitization), leading to alleviation of pain. Agonists can be applied locally to the painful area as through a patch or an ointment. Numerous capsaicin-containing creams are available over the counter, containing low concentrations of capsaicin (0.025 - 0.075 %). It is debated whether these preparations actually lead to TRPV1 desensitization, it is possible that they act via counter-irritation. Novel preparations containing higher capsaicin concentration (up to 10%) are under clinical trials [17]

[edit] Central nervous system

TRPV1 is also expressed at high levels in the central nervous system and has been proposed as a target for treatment not only of pain but also for other conditions such as anxiety.[18] Furthermore TRPV1 appears to mediate long term depression (LTD) in the hippocampus.[19] LTD has been linked to a decrease in the ability to make new memories, unlike its opposite long term potentiation (LTP), which aids in memory formation. A dynamic pattern of LTD and LTP occurring at many synapses provides a code for memory formation. Long-term depression and subsequent pruning of synapses with reduced activity is an important aspect of memory formation. In rat brain slices, activation of TRV1 with heat or capsaicin induced LTD while capsazepine blocked capsaicin's ability to induce LTD.[19] Hence there may be therapeutic potential in antagonizing TRPV1 in the central nervous system, perhaps as a treatment for epilepsy (TRPV1 is already a target in the peripheral nervous system for pain relief).

—Preceding unsigned comment added by 68.165.11.29 (talk) 14:40, 19 April 2010 (UTC)

Role of NGF and neurogenic inflammation in the pathogenesis of psoriasis (Neurogenic inflammation accompanied by high levels of Nerve growth factor) PMID 14699978

PMID 14699978

Raychaudhuri and Raychaudhuri

Role of NGF and neurogenic inflammation in the pathogenesis of psoriasis. Prog Brain Res. 2004;146:433-7.

Psoriasis Research Institute, Stanford University School of Medicine, 510 Ashton Avenue, Palo Alto, CA 94306, USA. raysiba@aol.com

Abstract

A contributing role of neurogenic inflammation has provided a new dimension in understanding the pathogenesis of various cutaneous and systemic inflammatory diseases such as atopic dermatitis, urticaria, rheumatoid arthritis, ulcerative colitis and bronchial asthma. Several critical observations, such as (i) psoriasis resolves at sites of anaesthesia, (ii) neuropeptides are upregulated, and (iii) there is a marked proliferation of terminal cutaneous nerves in psoriatic plaques, encouraged us to search for a mechanism of neural influence in inflammation and inflammatory diseases. In immunohistochemical studies, we found that keratinocytes in lesional and nonlesional psoriatic tissue express high levels of nerve growth factor (NGF) and that there is a marked upregulation of NGF receptors, p75 neurotrophin receptor (p75NTR) and tyrosine kinase A (TrkA), in the terminal cutaneous nerves of psoriatic lesions. As keratinocytes of psoriatic plaques express increased levels of NGF, it is likely that murine nerves will promptly proliferate into the transplanted plaques on a severe combined immunodeficient mouse. Indeed, we have noted marked proliferation of nerve fibers in transplanted psoriatic plaques compared with the few nerves in transplanted normal human skin. By double label immunofluorescence staining, we have further demonstrated that in these terminal cutaneous nerves there is a marked upregulation of neuropeptides, such as substance P and calcitonin gene-related protein. These observations, as well as recent findings about NGF-induced chemokine expression in keratinocytes, further substantiate a role of the NGF-p75NTR-TrkA system in the inflammatory process of psoriasis. Currently, we are evaluating antagonists to selected neuropeptides and NGF/receptors, with the expectation of identifying pharmacological agents to counter neurogenic inflammation in psoriasis.

PMID: 14699978 —Preceding unsigned comment added by 68.165.11.33 (talk) 23:09, 16 May 2010 (UTC)

Bronchial asthma as neurogenic inflammatory paroxysmal disease: mechanisms and therapy (reprint of link cut from external links)

• Bronchial Asthma as Neurogenic Inflammatory Paroxysmal Disease Common neurogenic inflammatory mechanisms of asthma with migraine and trigeminal neuralgia. —Preceding unsigned comment added by 68.165.11.33 (talk) 23:16, 16 May 2010 (UTC)

3 studies -- chemokines / cutaneous neurogenic inflammation / psoriasis

• Homey B. Chemokines and chemokine receptors as targets in the therapy of psoriasis. Curr Drug Targets Inflamm Allergy 2004;3:169-74 PMID 15180470
• Steinhoff M, Ständer S, Seeliger S, Ansel JC, Schmelz M, Luger TA. Modern aspects of cutaneous neurogenic inflammation. Arch Dermatol 2003;139:1479-1488. http://archderm.ama-assn.org/cgi/content/abstract/139/11/1479?ijkey=42e2e5f8d61d8d5c2df4f243b0d4bf6263d3cc99&keytype2=tf_ipsecsha
• Raychaudhuri SP, Raychaudhuri SK. Role of NGF and neurogenic inflammation in the pathogenesis of psoriasis. Prog Brain Res 2004;146:433-437. PMID 14699978 —Preceding unsigned comment added by 66.167.95.160 (talk) 01:57, 17 May 2010 (UTC)

Neurogenic inflammation in rats exposed to diesel exhaust or cigarette smoke -- PMID 15916011

Witten, Mark L, Simon S Wong, Nina N Sun, Ingegerd Keith, Chol-Bum Kweon, David E Foster, James J Schauer, and Duane L Sherrill,

Neurogenic Responses in Rat Lungs After Nose-Only Exposure to Diesel Exhaust

"Involvement of neurogenic inflammation in the response to DE or CS was assessed via comparison of plasma extravasation, a sensitive endpoint of neurogenic inflammation ..."

PMID 15916011

PubMed U.S. National Library of Medicine National Institutes of Health

Res Rep Health Eff Inst. 2005 Jan;(128):1-37; discussion 39-47.

Neurogenic responses in rat lungs after nose-only exposure to diesel exhaust.

Witten ML, Wong SS, Sun NN, Keith I, Kweon CB, Foster DE, Schauer JJ, Sherrill DL.

Department of Pediatrics, College of Medicine, Arizona Health Sciences Center, University of Arizona, 1501 N Campbell Ave, 3352 A, Tucson, AZ 85724, USA. Abstract

Using an in-line, real-time, in vivo exposure system, we investigated whether acute adverse effects of diesel exhaust (DE*) exposure involve neurogenic inflammation in the lungs via sensory nerve C fibers. A total of 168 female F344 rats (175 g, 8 weeks old) were randomly assigned to pretreatment with capsaicin or saline to deplete C-fiber neurotransmitters. In a 2 x 3 factorial design, groups of animals were then exposed nose-only to a low level of DE (LDE, 35.3 microg/m3), a high level of DE (HDE, 632.9 microg/m3), or side-stream cigarette smoke (CS, 0.4 mg/m3). Two control groups were exposed whole body to filtered air in the animal room (fRA) or unfiltered air in the diesel engine room (eRA), respectively. DE was taken directly from a heavy-duty Cummins N14 research engine operated at 75% throttle (California Air Resources Board [CARB] 8, mode 6). Exposure to DE or air was 4 hours/day, 5 days/week, for 3 weeks. Exposure to CS was for 4 hours/day for 7 days. Involvement of neurogenic inflammation in the response to DE or CS was assessed via comparison of plasma extravasation, a sensitive endpoint of neurogenic inflammation, between rats with and without capsaicin pretreatment. Lung injury was assessed via analysis of proinflammatory cytokines, respiratory permeability, and histopathology. Moreover, whether DE exposure affected the molecular mechanisms of neurogenic inflammation was analyzed through quantification of substance P (SP) and its primary neurokinin-1 (NK1) receptor at the gene and protein levels and through neutral endopeptidase (NEP) activity. DE and CS exposure induced dose-dependent plasma extravasation, which may play an important role in initiating the associated lung inflammation and injury. Exposure of rats to DE affected the SP signaling pathway as indicated by overexpression of the NK1 receptor or reduction of SP in the lung tissue. DE exposure consistently inactivated tissue NEP, a key factor that switches neurogenic inflammation from its physiological and protective functions to a role that increases and perpetuates lung injury. The roles of these overlapping neurokininergic mechanisms in the initiation of DE-associated lung injury are plausible, and these changes may contribute to DE-associated respiratory disorders. Capsaicin rats followed the same trends as those of saline animals when exposed to DE or CS: capsaicin rats did not have significantly different plasma extravasation in the airways or lung parenchyma compared to their corresponding controls. Histopathology evaluation likewise demonstrated the same degree of tissue changes, such as edema and alveolar macrophage collection, in capsaicin and saline rats after the same level of DE exposure. In summary, our data suggest that neurokininergic mechanisms may have been involved in DE-induced inflammatory conditions in rat lung but that C fibers did not appear to be involved under these exposure conditions. We believe that time-course or protein knockdown/knockout animal studies are required to characterize further the role of neurokininergic mechanisms in DE-induced lung injury.

PMID 15916011

FULL TEXT: http://pubs.healtheffects.org/getfile.php?u=123 http://pubs.healtheffects.org/view.php?id=93

Report #: 128, Publication Type: Research Reports

2005-01-01

About This Publication

Dr. Witten and colleagues investigated the inflammatory effects of diesel exhaust exposure on rat airways. The investigators focused on the role of neurogenic inflammation, an inflammatory response defined by the release of neuropeptides, such as substance P (SP), from sensory nerve fibers known as C fibers located within the lung tissue. Neurogenic inflammation has been implicated in responses to inhaled irritants such as ozone and cigarette smoke and has been implied to play a role in asthma.

"The investigators exposed female rats (8 weeks old) to two concentrations of whole diesel exhaust emissions (35 and 630 µg/m3 particulate matter) from a heavy-duty 1990s Cummins research engine. Exposures were conducted over 3 weeks (4 hr/day, 5 days/week); neurogenic and other inflammatory markers were measured immediately after the end of exposure. Half of the rats in each exposure group were pretreated with capsaicin, a neurotoxin that depletes sensory C fibers of neuropeptides and thereby inhibits the neurogenic inflammatory pathway.

...

"Neurogenic inflammation has been convincingly demonstrated after exposure to ozone, SO2, hydrogen sulfide, cigarette smoke, and wood smoke."

Free Downloads: Title Description Size PDF File

Investigators' Report 02/25/05, Final. Includes a Critique by the HEI Health Review Committee. 2590 kb PDF (FULL TEXT) File http://pubs.healtheffects.org/getfile.php?u=123 http://pubs.healtheffects.org/getfile.php?u=123

Statement http://pubs.healtheffects.org/getfile.php?u=124 53 kb pdf Unknown File Type

Statement http://www.healtheffects.org/Pubs/st128.htm

STATEMENT Synopsis of Research Report 128 http://www.healtheffects.org/Pubs/st128.htm

Neurogenic Responses of Rat Lung to Diesel Exhaust

This Statement, prepared by the Health Effects Institute, summarizes a research project funded by HEI and conducted by Dr Mark L Witten at the University of Arizona, Tucson AZ. The complete report, Neurogenic Responses in Rat Lungs After Nose-Only Exposure to Diesel Exhaust, can be obtained from HEI. WITTEN 128

Air pollution, including gases and particulate matter emitted from motor vehicles, has been associated with increases in both morbidity and mortality, but the underlying mechanisms responsible for these effects are not well understood. Insight into such mechanisms will aid in the understanding of human risk associated with air pollution. In 1998, HEI issued Request for Preliminary Applications 98-6, entitled “Health Effects of Air Pollution”. In response, Dr Witten and colleagues proposed to investigate the inflammatory effects of diesel exhaust exposure on rat airways. The investigators focused on the role of neurogenic inflammation, an inflammatory response defined by the release of neuropeptides, such as substance P (SP), from sensory nerve fibers known as C fibers located within the lung tissue. Neurogenic inflammation has been implicated in responses to inhaled irritants such as ozone and cigarette smoke and has been implied to play a role in asthma. HEI funded Dr Witten’s study because they thought it would provide valuable information on the pathogenic mechanisms involved in respiratory responses to diesel exhaust.

APPROACH

The investigators exposed female rats (8 weeks old) to two concentrations of whole diesel exhaust emissions (35 and 630 µg/m3 particulate matter) from a heavy-duty 1990s Cummins research engine. Exposures were conducted over 3 weeks (4 hr/day, 5 days/week); neurogenic and other inflammatory markers were measured immediately after the end of exposure. Half of the rats in each exposure group were pretreated with capsaicin, a neurotoxin that depletes sensory C fibers of neuropeptides and thereby inhibits the neurogenic inflammatory pathway. Control groups were exposed to air. Cigarette smoke exposure (~400 µg/m3, 4 hr/day for 7 days) provided a positive control. The investigators measured endpoints of neurogenic inflammation: SP protein and gene expression, density of the SP receptor neurokinin-1 (NK1), and activity of neutral endopeptidase (NEP), the enzyme that breaks down SP. They also assessed leakage of blood plasma into lung tissue and other inflammatory markers, such as levels of the cytokines interleukin (IL)-1ß, IL-6, IL-10, IL-12, and tumor necrosis factor α, numbers of inflammatory cells in lung tissue, and cellular lung pathology.

Witten collaborated with researchers from the University of Wisconsin to develop the diesel exhaust exposure system. Before animal exposures started, they evaluated a number of engine operation modes using the California Air Resources Board 8-mode test system for gaseous, particulate, and metal emissions. The investigators selected California Air Resources Board mode 6 for the animal experiments.

RESULTS AND INTERPRETATION

The authors are among the first to investigate neurogenic inflammation in the lungs of rats exposed to whole diesel exhaust. After exposure to both concentrations of diesel exhaust, consistently higher levels of plasma leakage and lower activity of the enzyme NEP were observed. Changes in levels of SP and its receptor NK1 were less consistent, however, and few changes were observed in cytokine levels. These results confirm previous findings of mild inflammatory responses after exposure to diesel exhaust.

The role of neurogenic inflammation remains unclear, however. Neurogenic inflammation has been convincingly demonstrated after exposure to ozone, sulfur dioxide, hydrogen sulfide, cigarette smoke, and wood smoke. In those studies, inflammatory responses were eliminated after animals had been treated neonatally with capsaicin. In the Witten study, rats were treated with capsaicin as young adults. Witten and colleagues showed that capsaicin treatment caused a complete absence of SP in lung tissue, but it had little effect on the inflammatory response to diesel exhaust. Thus, the results do not support a role for C fibers in the airway inflammatory response to diesel exhaust. The results of the current study may also have been complicated by neuropeptide release from sources other than C fibers (such as the airway ganglia, mast cells, and eosinophils). The investigators did find evidence for neurogenic inflammation after exposure to cigarette smoke, which was in part reversed by capsaicin treatment. —Preceding unsigned comment added by 68.165.11.67 (talk) 21:16, 29 May 2010 (UTC)

The neuropeptide calcitonin gene-related peptide (CGRP) may play a role in neurogenic inflammation PMID 11836000

Pokabla MJ, Dickerson IM, Papka RE.

Calcitonin gene-related peptide-receptor component protein expression in the uterine cervix, lumbosacral spinal cord, and dorsal root ganglia.

Peptides. 2002 Mar;23(3):507-14. PMID 11836000

Department of Neurobiology and Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown, OH 44272, USA. Abstract

The neuropeptide calcitonin gene-related peptide (CGRP) may play a role in neurogenic inflammation, tissue remodeling of the uterine cervix, promoting vasodilation, parturition, and processing of sensory information in the spinal cord. CGRP-immunoreactive nerves of the cervix and spinal cord have been studied but cellular identification of the CGRP receptor has received little attention. CGRP-receptor component protein (CGRP-RCP) is a small protein associated with the CGRP receptor; thus, immunostaining for the CGRP-RCP can be used to identify sites of the CGRP receptor. We determined sites of CGRP-RCP immunoreactivity relative to the presence of CGRP-ir nerve fibers in the female rat uterine cervix, spinal cord, and dorsal root ganglia. CGRP-RCP immunoreactivity was expressed in the dorsal horn of the spinal cord, venules of the uterine cervix, and perikarya of sensory neurons in dorsal root ganglia. CGRP-immunoreactive fibers were adjacent to CGRP-RCP-immunoreactive vessels in the cervix and among CGRP-RCP-immunoreactive structures in the dorsal horn of the spinal cord. This suggests CGRP-RCP is associated with structures innervated by CGRP nerves and these interactions may be changed in tissues in response to an appropriate stimulus.

PMID: 11836000 —Preceding unsigned comment added by 68.165.11.67 (talk) 23:32, 29 May 2010 (UTC)

Neurogenic Inflammation and Sensitivity to Environmental Chemicals -- William J. Meggs -- PMID 8404760

Neurogenic Inflammation and Sensitivity to Environmental Chemicals William J. Meggs Environmental Health Perspectives, Volume 101, Number 3, August 1993

Department of Emergency Medicine, East Carolina University School of Medicine, Greenville, NC 27858 USA

Abstract Neurogenic inflammation as a pathway distinct from antigen-driven, immune-mediated inflammation may play a pivotal role in understanding a broad class of environmental health problems resulting from chemical exposures. Recent progress in understanding the mediators, triggers, and regulation of neurogenic inflammation is reviewed. Evidence for and speculations about a role for neurogenic inflammation in established disorders such as asthma, rhinitis, contact dermatitis, migraine headache, and rheumatoid arthritis are presented. The sick building syndrome and multiple chemical sensitivity syndrome have been defined as clinical entities in which exposure to chemical inhalants gives rise to disease. Current data on the existence of chemical irritant receptors in the airway and skin are discussed; neurogenic inflammation arising from stimulation of chemical irritant receptors is a possible model to explain many of the aspects of chemical sensitivities. Key words: asthma, indoor air pollution, multiple chemical sensitivity syndrome, neurogenic inflammation, neutral endopeptidase, reactive airways dysfunction syndrome, reactive upper airways dysfunction syndrome, rhinitis, substance P, sick building syndrome. Environ Health Perspect 101: 234-238(1993)

http://ehpnet1.niehs.nih.gov/docs/1993/101-3/meggs.html

---

SAME, from pubmed

Meggs WJ.

Neurogenic inflammation and sensitivity to environmental chemicals. PMID 8404760

Environ Health Perspect. 1993 Aug;101(3):234-8.

Department of Emergency Medicine, East Carolina University School of Medicine, Greenville, NC 27858.

Comment in:

• Environ Health Perspect. 1994 Jan;102(1):12-3; author reply 13.

• Environ Health Perspect. 1994 Jan;102(1):12; author reply 13.

Abstract

Neurogenic inflammation as a pathway distinct from antigen-driven, immune-mediated inflammation may play a pivotal role in understanding a broad class of environmental health problems resulting from chemical exposures. Recent progress in understanding the mediators, triggers, and regulation of neurogenic inflammation is reviewed. Evidence for and speculations about a role for neurogenic inflammation in established disorders such as asthma, rhinitis, contact dermatitis, migraine headache, and rheumatoid arthritis are presented. The sick building syndrome and multiple chemical sensitivity syndrome have been defined as clinical entities in which exposure to chemical inhalants gives rise to disease. Current data on the existence of chemical irritant receptors in the airway and skin are discussed; neurogenic inflammation arising from stimulation of chemical irritant receptors is a possible model to explain many of the aspects of chemical sensitivities.

PMID: 8404760 [PubMed - indexed for MEDLINE]PMCID: PMC1519776Free PMC Article —Preceding unsigned comment added by 68.165.11.72 (talk) 16:52, 9 June 2010 (UTC)

Pathogenesis of Stress-Associated Skin Disorders: Exploring the Brain-Skin Axis

Lev Pavlovsky, Alon Friedman

Skin and the Nervous System: Stress, Itch and More'

Tur E (ed): Environmental Factors in Skin Diseases.

Curr Probl Dermatol. Basel, Karger,

2007,

vol 35, pp 136–145

Pathogenesis of Stress-Associated Skin Disorders: Exploring the Brain-Skin Axis

Abstract

The association between psychological stress and skin diseases is well known from clinical practice and the literature. Stress – a complex adaptive response – acts on different levels of the nervous system and affects many organ systems. We review here the available knowledge regarding the possible mechanisms underlying stress actions in the pathogenesis and course of skin diseases.

... Increased plasma levels of SP and nerve growth factor, which modu- lates the synthesis of SP, were also found in AD patients [36]. These findings suggest that specific neurogenic factors modulate the systemic allergic response in AD. The mechanisms of SP action in these diseases are most probably related to the activation of mast cells to secrete specific cytokines, chemokines and tumor necrosis factor-􏰀 [37].

32 Singh LK, Pang X, Alexacos N, Letourneau R, Theoharides TC: Acute immobilization stress triggers skin mast cell degranulation via corticotropin releasing hormone, neurotensin, and substance P: a link to neurogenic skin disorders. Brain Behav Immun 1999;13:225–239.

37 Theoharides TC, Donelan JM, Papadopoulou N, Cao J, Kempuraj D, Conti P: Mast cells as targets of corticotropin-releasing factor and related peptides. Trends Pharmacol Sci 2004;25:563–568. —Preceding unsigned comment added by 68.165.11.148 (talk) 15:06, 7 August 2010 (UTC)

... stress triggers skin mast cell degranulation via corticotropin releasing hormone, neurotensin, and substance P: a link to neurogenic skin disorders

Singh LK, Pang X, Alexacos N, Letourneau R, Theoharides TC:

Acute immobilization stress triggers skin mast cell degranulation via corticotropin releasing hormone, neurotensin, and substance P: a link to neurogenic skin disorders.

Brain Behav Immun

1999;

13:225–239.

Mast cells as targets of corticotropin-releasing factor and related peptides

Theoharides TC, Donelan JM, Papadopoulou N, Cao J, Kempuraj D, Conti P:

Mast cells as targets of corticotropin-releasing factor and related peptides.

Trends Pharmacol Sci

2004;

25:563–568 —Preceding unsigned comment added by 68.165.11.148 (talk) 15:09, 7 August 2010 (UTC)

Use of Botulinum Toxin to Treat Psoriasis -- patients treated with botulinum toxin for dystonia had dramatic improvement in psoriasis -- neurogenic

Evidence suggests the role of neurogenic inflammation in the pathogenesis of psoriasis. Botulinum toxin has been shown to have an effect on inhibiting neurogenic inflammation.

http://clinicaltrials.gov/ct2/show/NCT00816517?term=psoriasis+neurogenic&rank=1

Use of Botulinum Toxin to Treat Psoriasis This study is currently recruiting participants. Verified by University of Minnesota - Clinical and Translational Science Institute, March 2010 First Received: December 31, 2008 Last Updated: March 23, 2010 History of Changes Sponsor: University of Minnesota - Clinical and Translational Science Institute Information provided by: University of Minnesota - Clinical and Translational Science Institute ClinicalTrials.gov Identifier: NCT00816517

 Purpose

Psoriasis vulgaris is a chronic disease in which psoriatic plaques may appear on the knees, elbows, scalp and trunk. Evidence suggests the role of neurogenic inflammation in the pathogenesis of psoriasis. Botulinum toxin has been shown to have an effect on inhibiting neurogenic inflammation.

Recently, it was reported that patients who suffered from dystonia and had concomitant psoriasis, when treated with botulinum toxin for dystonia noted a dramatic improvement of their psoriatic lesions.

This pilot study will determine the safety and efficacy of botulinum toxin in the management of psoriasis vulgaris.

Condition Intervention Phase Psoriasis Vulgaris Procedure: injection of botulinum toxin type A. Procedure: normal saline Phase I

Study Type: Interventional Study Design: Allocation: Randomized Control: Placebo Control Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment Official Title: Pilot Study on the Safety and Efficacy of Botulinum Toxin Injections in the Treatment of Psoriasis Vulgaris.

Resource links provided by NLM:

MedlinePlus related topics: Botox Psoriasis Drug Information available for: Clostridium botulinum toxin U.S. FDA Resources

Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:

   * psoriasis scoring scale [ Time Frame: baseline and 3months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

   * 3mm skin biopsy. [ Time Frame: baseline and at 3 months. ] [ Designated as safety issue: No ]

Estimated Enrollment: 10 Study Start Date: January 2009 Estimated Study Completion Date: March 2010 Estimated Primary Completion Date: January 2010 (Final data collection date for primary outcome measure) Arms Assigned Interventions placebo: Placebo Comparator Procedure: normal saline injection around skin lesion (plaque) one time. botulinum toxin: Active Comparator Procedure: injection of botulinum toxin type A. 35 to 100 units injected around a skin lesion (plaque) one time.

 Eligibility

Ages Eligible for Study: 18 Years to 65 Years Genders Eligible for Study: Both Accepts Healthy Volunteers: Yes Criteria

Inclusion Criteria:

   * Healthy subjects. Psoriasis vulgaris diagnosis made by a board certified dermatologist involving at least one area that has been intolerant or recalcitrant to at least two forms of recognized topical or systemic treatments in the past. In addition, the subject should have at least a score of 2 for keratoderma and erythema. Signed informed consent. Willing to adhere to protocol.

Exclusion Criteria:

   * Immunosuppressed patients, pregnant, secondary skin infections, phototherapy within 4 weeks of the botulinum toxin injection, exposure to any topical or systemic retinoid treatment with the last 12 months, volunteers taking chloroquine and hydroxychloroquine, volunteers on warfarin.

 Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00816517

Contacts Contact: Ioanna Panoutsopoulou, MD 612-625-8625 panou001@umn.edu

Locations United States, Minnesota Univerisity of Minnesota Recruiting Minneapolis, Minnesota, United States, 55444 Principal Investigator: Dennis D Dykstra, MD,PhD Sponsors and Collaborators University of Minnesota - Clinical and Translational Science Institute Investigators Principal Investigator: Dennis D Dykstra, MD, PhD University of Minnesota - Clinical and Translational Science Institute —Preceding unsigned comment added by 68.165.11.177 (talk) 14:10, 26 August 2010 (UTC)

Neuropeptides and Receptors possibly Involved in Neurogenic Inflammation and Migraine Pain -- 5-HT1-D, SEROTONIN, GABA-A, CB-1, VR-1, PAR-2

Salvatore Salomone, Filippo Caraci and Anna Capasso* Migraine: An Overview The Open Neurology Journal, 2009, 3, 64-71 —Preceding unsigned comment added by 68.165.11.146 (talk) 19:34, 3 October 2010 (UTC) www.ncbi.nlm.nih.gov/pmc/articles/PMC2771268/pdf/TONEUJ-3-64.pdf

Table 1. Receptors Present at the Level of Sensory Primary Neurons and Possible Effects on the Release of Neuropeptides Involved in Neurogenic Inflammation and Migraine Pain

• At nanomolar concentrations. **At micromolar concentrations.

((SUMMARY: DECREASED RELEASE OF CGRP AND SUBSTANCE P IS CAUSED BY: 5-HT1-D, SEROTONIN, GABA-A, CB-1. INCREASED RELEASE OF CGRP AND SUBSTANCE P IS CAUSED BY: VR-1, PAR-20))

BELOW TABLE CAN BE SEEN AS A TABLE ON THE URL AT www.ncbi.nlm.nih.gov/pmc/articles/PMC2771268/pdf/TONEUJ-3-64.pdf

RECEPTORS LIGANDS ACTIVITY ON THE SENSORY PRIMARY NEURON

5-HT1-D SEROTONIN DECREASED RELEASE OF CGRP AND SUBSTANCE P

GABA-A GABA DECREASED RELEASE OF CGRP AND SUBSTANCE P

CB-1 ANANDAMIDE* DECREASED RELEASE OF CGRP AND SUBSTANCE P

VR-1 CAPSAICIN OR ANANDAMIDE** INCREASED RELEASE OF CGRP AND SUBSTANCE P

PAR-2 PEPTIDIC CHAINS SLIGRL AND SLIGKV INCREASED RELEASE OF CGRP AND SUBSTANCE P —Preceding unsigned comment added by 68.165.11.146 (talk) 19:24, 3 October 2010 (UTC)

During migraine CGRP is released from peripheral terminals of trigeminal perivascular neurons and dilates cranial arterial vessels

Benemei S, Nicoletti P, Capone JG, De Cesaris F, Geppetti P. Handb Exp Pharmacol. 2009;(194):75-89. Migraine

Abstract

Migraine is a neurovascular disorder which affects one fifth of the general population. Disability due to migraine is severe and involves patients from infancy through senescence and it is aggravated by the fact there is no complete cure. However, various drugs for the symptomatic or prophylactic treatment of the disease are available. Recently, better knowledge of the neurobiological and pharmacological aspects of a subset of trigeminal primary sensory neurons has provided key information for the development of effective molecules that specifically target the activation of the trigeminovascular system and may represent a significant advancement in the treatment of the disease. These novel antagonists block the receptor for the sensory neuropeptide calcitonin gene-related peptide (CGRP), which upon release from peripheral terminals of trigeminal perivascular neurons dilates cranial arterial vessels. Whether neurogenic vasodilatation is the major contributing factor to generate the pain and the associated symptoms of the migraine attack or whether other sites of action of CGRP receptor antagonists are responsible for the antimigraine effect of these compounds is the subject of current and intense research.

PMID: 19655105 [PubMed - indexed for MEDLINE] —Preceding unsigned comment added by 68.165.11.146 (talk) 19:39, 3 October 2010 (UTC)

Inhibition of neurogenic inflammation by the Amazonian herbal medicine sangre de grado. PMID 11564183

J Invest Dermatol. 2001 Sep;117(3):725-30. Miller MJ, Vergnolle N, McKnight W, Musah RA, Davison CA, Trentacosti AM, Thompson JH, Sandoval M, Wallace JL. Department of Pediatrics, Albany Medical College, Albany, New York, New York 12208, USA. millermj@mail.amc.edu

Inhibition of neurogenic inflammation by the Amazonian herbal medicine sangre de grado.

PMID 11564183 [PubMed - indexed for MEDLINE] Free Article

http://www.nature.com/jid/journal/v117/n3/full/5601201a.html

Abstract

This study was designed to determine if the Amazonian medicinal sangre de grado, confers benefit by suppressing the activation of sensory afferent nerves. METHODS: (i) vasorelaxation of rat mesenteric arteries in response to calcitonin gene-related peptide; (ii) rat paw edema in response to protease- activating peptide receptor 2-activating peptide; (iii) rat paw hyperalgesia in response to low-dose protease-activating peptide receptor 2-activating peptide or prostaglandin E2; (iv) gastric hyperemia in response luminal capsaicin; (v) a clinical trial of a sangre de grado balm in pest control workers. The parent botanical was fractionated for evaluation of potential active components. In preconstricted rat mesenteric arteries, highly diluted sangre de grado (1:10,000) caused a shift to the right of the calcitonin gene-related peptide dose-response curve (p < 0.01). Paw edema in response to protease-activating peptide receptor 2-activating peptide (500 microg) was reduced by as single topical administration sangre de grado balm (1% concentration, p < 0.01) for at least 6 h. Hyperalgesia induced by either low-dose protease-activating peptide receptor 2-activating peptide (50 microg) or prostaglandin E2 was prevented by sangre de grado balm. A fraction possessing analgesic and capsaicin antagonistic properties was isolated and high-performance liquid chromatography and gas chromatography-mass spectrometry analysis indicated that it was a proanthocyandin oligomer. In pest control workers, sangre de grado balm (Zangrado) was preferred over placebo, for the relief of itching, pain, discomfort, edema, and redness in response to wasps, fire ants, mosquitoes, bees, cuts, abrasions, and plant reactions. Subjects reported relief within minutes. We conclude that sangre de grado is a potent inhibitor of sensory afferent nerve mechanisms and supports its ethnomedical use for disorders characterized by neurogenic inflammation.

PMID: 11564183 [PubMed - indexed for MEDLINE] Free Article http://www.nature.com/jid/journal/v117/n3/full/5601201a.html —Preceding unsigned comment added by 68.165.11.38 (talk) 21:53, 14 October 2010 (UTC)

Effects of sangre de drago in an in vitro model of cutaneous neurogenic inflammation; PMID 20698880

Pereira U, Garcia-Le Gal C, Le Gal G, Boulais N, Lebonvallet N, Dorange G, Lefeuvre L, Gougerot A, Misery L.

Effects of sangre de drago in an in vitro model of cutaneous neurogenic inflammation.

Exp Dermatol. 2010 Sep;19(9):796-9.

University of Western Brittany, Laboratory of Nervous Factors and Tissular Struturation (EA 4326), Brest, France.

Abstract

Sangre de drago (SD) is a viscous bright red resin collected from Croton lechleri trees that grow in the South American jungle. This sap is used extensively in the native pharmacopoeia to treat skin disorders. Its effectiveness as an inhibitor of neurogenic inflammation has been recently demonstrated. To understand the underlying mechanisms of these effects, we examined the ability of SD to reduce substance P (SP) release in an in vitro model of cutaneous neurogenic inflammation (CNI). This model is based on an enzyme immunoassay of SP (an inducer of CNI) in a porcine co-culture of dorsal root ganglion neurons and keratinocytes. After incubation with different concentrations of SD, we noted an immediate and significant dose-dependent decrease in basal SP release, with average values of 32% at 1% SD (v/v) and 26% at 0.1% (v/v). On the other hand, pretreatment (72 or 1 h) of the co-culture with 1% SD (v/v) was sufficient to induce a 111% (72 h) or 65% (1 h) inhibition of capsaicin-induced SP release, while 0.1% SD (v/v) triggered a 109% (72 h) or 30% (1 h) inhibition. We conclude that sangre de drago is a potent inhibitor of CNI through direct inhibition of neuropeptide release by sensory afferent nerves.

PMID 20698880

Wiktionary definition of neurogenic -- "Originating in, or caused by, the nervous system"

http://en.wiktionary.org/wiki/neurogenic

neurogenic Definition from Wiktionary, the free dictionary

Contents

   * 1 English
         o 1.1 Etymology
         o 1.2 Adjective
               + 1.2.1 Derived terms
         o 1.3 Anagrams

[edit] Etymology

neuro- + -genic [edit] Adjective

neurogenic (not comparable)

  1. Originating in, or caused by, the nervous system

[edit] Derived terms

   * neurogenically
   * neurogenicity
   * neurogenic shock

Bruxism as mediated by neurogenic inflammation

Magnesium, shown to dampen neurogenic inflammation, is helpful or curative in many cases of Bruxism.

Ocdncntx (talk) 20:51, 16 November 2010 (UTC)

Further exploring the brain-skin connection: stress worsens dermatitis via substance P-dependent neurogenic inflammation in mice. PMID 17914449 Free Article

Pavlovic S, Daniltchenko M, Tobin DJ, Hagen E, Hunt SP, Klapp BF, Arck PC, Peters EM.

Further exploring the brain-skin connection: stress worsens dermatitis via substance P-dependent neurogenic inflammation in mice.

Psycho-Neuro-Immunology, Center for Internal Medicine and Dermatology, Neuroscience Research Center, Charité-University Medicine, Campus Mitte, Berlin, Germany.

J Invest Dermatol. 2008 Feb;128(2):434-46. Epub 2007 Oct 4.

Comment in:

• J Invest Dermatol. 2008 Feb;128(2):260-1.

Abstract

A neurogenic component in atopy and allergy is evident and potentially of great pathogenic relevance. Stress was recently shown to activate elements of this component and is vividly discussed as a cause of exacerbation. However, to date, scientific proof of stress-induced neuronal plasticity and neuro-immune interaction in atopy or allergy remains lacking. Here we show early evidence that exposure to sound stress and atopic dermatitis-like allergic dermatitis (AD) equipotently raise the number of cutaneous nerve fibers containing the prototypic stress neuropeptide substance P (SP) in mice. Stress increases AD readout parameters by at least 30% (eosinophil infiltration, vascular cell adhesion molecule-positive blood vessels, epidermal thickness). This dramatic pathologic exacerbation is associated with increased neurogenic inflammation (degranulated mast cells; interstitial neuropeptidergic dense core granules, mast cell apoptosis, endothelial gaping). Key features of AD exacerbation could not be induced in mice lacking the neurokinin-1 SP receptor (NK1). Interestingly, stress had no significant additional effect on CD4+ cell number, but shifted the cytokine profile toward TH2 in skin. Thus, we conclude that stress primarily exacerbates AD via SP-dependent cutaneous neurogenic inflammation and subsequent local cytokine shifting and should be considered as a therapeutic target, while it offers a convincing pathogenic explanation to affected patients and their frustrated physicians alike.

PMID: 17914449 Free Article —Preceding unsigned comment added by Ocdncntx (talk • contribs) 01:18, 17 November 2010 (UTC)

Warm SPA-induced hyperthermia confers protection to rats against airway inflammation evoked by capsaicin and substance P. PMID 20138590

Warm SPA-induced hyperthermia confers protection to rats against airway inflammation evoked by capsaicin and substance P.

Fu YS, Wang PH, Liu SP, Huang WH, Huang HT.

Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan. Abstract

Auton Neurosci. 2010 Jun 24;155(1-2):49-58.

Solus par aqua (SPA) is a traditional health care therapy. Warm SPA may enhance immunity and cellular defense to protect body against diseases. The present study investigated whether the warm SPA could confer protection to neurogenic inflammation in rats. The rats were immersed in water where the body core temperatures were maintained at hyperthermia (41.5 degrees C) or normothermia (37 degrees C) for a period of 15min. After SPA for 1 or 6 days, neurogenic inflammation was induced by intravenous injection of capsaicin (90microg/kg) or substance P (SP; 3microg/kg). The plasma leakage and arterial pressures in rats after neurogenic inflammation were monitored. The extent of capsaicin- or SP-induced plasma leakage and hypotension was significantly attenuated in rats on day 1 after SPA hyperthermia. However, such resistance to neurogenic inflammation was not found on day 6 after hyperthermia. Western blotting analysis showed that the expression of heat shock protein 72 (HSP 72) in the trachea on days 1 and 2 after hyperthermia was 9.61-fold and 6.66-fold, respectively, of that in normothermia. Afterwards, the hyperthermia-induced HSP 72 upregulation gradually declined in a time-dependent manner. Thus, SPA hyperthermia may protect rats against neurogenic inflammation through modulation of HSP expression.

PMID: 20138590

Ocdncntx (talk) 02:36, 17 November 2010 (UTC)

Re-sensitization of neuropeptide receptors: should we stop the recycling? PMID 19338573 PMCID PMC2697749 Free PMC Article

Re-sensitization of neuropeptide receptors: should we stop the recycling?

Keeble JE.

Centre for Integrative Biomedicine, Pharmaceutical Science Research Division, King's College London, London, UK. julie.keeble@kcl.ac.uk

Br J Pharmacol. 2009 Mar;156(5):728-9.

Comment on:

• Br J Pharmacol. 2009 Mar;156(5):730-9.

Abstract

Neurogenic inflammation, an important component of many disease states, is mediated by the release of neuropeptides from sensory nerves. To date, it has been possible to inhibit neurogenic inflammation using neuropeptide receptor blockers or by prevention of neuropeptide release. In the current edition of the British Journal of Pharmacology, Cattaruzza and co-workers discuss a novel way of blocking the action of neuropeptides. They have shown that the re-sensitization of the substance P neurokinin-1 receptor and the substance P-induced pro-inflammatory effects are mediated by the enzyme, endothelin-converting enzyme 1 (ECE-1). Therein, they showed that ECE-1 inhibition could prevent the re-sensitization process. This is exciting progress in our understanding of neurogenic inflammation, but it remains to be seen how inhibition of receptor recycling via ECE-1 blockade will affect other inflammatory pathways.

PMID: 19338573 PMCID: PMC2697749 Free PMC Article —Preceding unsigned comment added by Ocdncntx (talk • contribs) 02:40, 17 November 2010 (UTC)

Nasal hyperreactivity in rhinitis rhinitis correlated with strong innervation pattern with sensory nerve fibers containing SP and CGRP demonstrated neurogenic inflammation PMID 18651116

Nasal hyperreactivity in allergic rhinitis and idiopathic rhinitis correlated with strong innervation pattern with sensory nerve fibers containing SP and CGRP demonstrated neurogenic inflammation, when compared to normal controls.

HNO. 2008 Aug;56(8):799-807. [Ultrastructural changes in allergic rhinitis vs. idiopathic rhinitis]

[Article in German]

Knipping S, Holzhausen HJ, Riederer A, Schrom T.

Universitätsklinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde, Kopf - und Halschirurgie, Martin-Luther-Universität Halle-Wittenberg, Magdeburger Strasse 12, 06097 Halle/Saale. stephan.knipping@medizin.uni-halle.de Abstract

BACKGROUND: Nasal hyperreactivity is one of the most important underlying mechanisms in allergic rhinitis (AR) as well as idiopathic rhinitis (IR). The aim of the present study was to examine pathomorphological changes in nasal mucosa in these subgroups of rhinitis.

PATIENTS AND METHODS: Tissue samples of human inferior turbinates from 20 patients with AR and 16 patients with IR were taken during nasal surgery and preserved in glutaraldehyde or paraformaldehyde. Ultrathin sections of specimens from 15 patients without chronic inflammation of nasal mucosa were used as controls. Primary antibodies against substance P (SP), calcitonin-gene-related peptide (CGRP), and endothelial nitric oxide synthase (NOS III) were applied, and the immunocomplexes were visualized by an immunocytochemical staining technique using gold-labeled antibodies. Immunostained structures were photodocumented using light and transmission electron microscopy.

RESULTS: The nasal mucosa of patients with AR and IR showed similarities on the ultrastructural level. A strong innervation pattern with sensory nerve fibers containing SP and CGRP demonstrated neurogenic inflammation. Extensive edema and cellular infiltrations were found in AR. A decreased presence of eosinophils and nitric oxide was observed in IR.

CONCLUSIONS: On the ultrastructural level, AR and IR showed many similarities but also some differences. Based on these findings, anti-inflammatory therapy could be recommended for both types of rhinitis.

PMID 18651116

Migraine: current theories, activation of trigeminocervical nerve endings releases calcitonin gene-related peptide and substance P, leading to 'neurogenic' inflammation PMID 18545913

current theories, activation of trigeminocervical nerve endings releases calcitonin gene-related peptide and substance P, inducing vasodilation and plasma protein extravasation, leading to 'neurogenic' inflammation

PMID 18545913

Peripheral mechanism of action of antimigraine prophylactic drugs.

Frediani F, Villani V, Casucci G.

Neurological Department and Headache Center, Policlinico S. Pietro, via Forlanini 15, 24036 Ponte San Pietro (BG), Italy. fabio_frediani@yahoo.it

Neurol Sci. 2008 May;29 Suppl 1:S127-30.

Abstract

Migraine is a visceral pain. According to current theories, activation of trigeminocervical nerve endings releases calcitonin gene-related peptide and substance P, inducing vasodilation and plasma protein extravasation, leading to 'neurogenic' inflammation. Activation of the trigeminovascular system is followed by sensitisation of trigeminocervical fibres, maintaining a condition of hypersensitivity to non-noxious stimuli that support persistent pain during migraine attack. Other neurotransmitters (nitric oxide, bradykinins, 5-HT, etc.) play a role in regulating this complex mechanism. In this brief review, we consider the effect of drugs that, acting on the different transmitters involving in pain perception, can stop or inhibit these pathogenetic mechanisms.

PMID 18545913

Statins may be useful for treating diseases presenting with predominant neurogenic inflammation. PMID 18079356

J Pharmacol Exp Ther. 2008 Mar;324(3):1172-80. Epub 2007 Dec 13. Statins decrease expression of the proinflammatory neuropeptides calcitonin gene-related peptide and substance P in sensory neurons.

Bucelli RC, Gonsiorek EA, Kim WY, Bruun D, Rabin RA, Higgins D, Lein PJ.

Oregon Health Science University, CROET/L606, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. Abstract

Clinical and experimental observations suggest that statins may be useful for treating diseases presenting with predominant neurogenic inflammation, but the mechanism(s) mediating this potential therapeutic effect are poorly understood. In this study, we tested the hypothesis that statins act directly on sensory neurons to decrease expression of proinflammatory neuropeptides that trigger neurogenic inflammation, specifically calcitonin gene-related peptide (CGRP) and substance P. Reverse transcriptase-polymerase chain reaction, radioimmunoassay, and immunocytochemistry were used to quantify CGRP and substance P expression in dorsal root ganglia (DRG) harvested from adult male rats and in primary cultures of sensory neurons derived from embryonic rat DRG. Systemic administration of statins at pharmacologically relevant doses significantly reduced CGRP and substance P levels in DRG in vivo. In cultured sensory neurons, statins blocked bone morphogenetic protein (BMP)-induced CGRP and substance P expression and decreased expression of these neuropeptides in sensory neurons pretreated with BMPs. These effects were concentration-dependent and occurred independent of effects on cell survival or axon growth. Statin inhibition of neuropeptide expression was reversed by supplementation with mevalonate and cholesterol, but not isoprenoid precursors. BMPs signal via Smad activation, and cholesterol depletion by statins inhibited Smad1 phosphorylation and nuclear translocation. These findings identify a novel action of statins involving down-regulation of proinflammatory neuropeptide expression in sensory ganglia via cholesterol depletion and decreased Smad1 activation and suggest that statins may be effective in attenuating neurogenic inflammation.

PMID 18079356 Free Article —Preceding unsigned comment added by Ocdncntx (talk • contribs) 14:38, 17 November 2010 (UTC)

"... cutaneous neurogenic inflammation ... [is probably involved in the] pathogenesis of psoriasis". PMID 17034513

Saraceno R, Kleyn CE, Terenghi G, Griffiths CE.

The role of neuropeptides in psoriasis. PMID 17034513

Dermatology Centre, Hope Hospital, The University of Manchester, Salford, Manchester M6 8HD, UK.

Abstract

The pathogenesis of psoriasis is incompletely understood but cutaneous neurogenic inflammation is probably involved. This involvement is suggested by a number of clinical and histological observations. Reports about the distribution of cutaneous nerves and the quantification of nerve growth factor and neuropeptides, including calcitonin gene-related peptide and vasoactive intestinal peptide, in lesional and nonlesional psoriatic skin suggest that sensory neuropeptides contribute to the development of psoriasis. This review summarizes what is known about the role of neurogenic markers in psoriasis.

PMID 17034513 —Preceding unsigned comment added by Ocdncntx (talk • contribs) 14:58, 17 November 2010 (UTC)

Heart disease arising from neurogenic inflammation caused by Mg. deficiency PMID 16819576

Tejero-Taldo MI, Kramer JH, Mak IuT, Komarov AM, Weglicki WB.

The nerve-heart connection in the pro-oxidant response to Mg-deficiency.

Dept. of Biochemistry & Molecular Biology, Div. of Experimental Medicine, The George Washington University Medical Center, Washington, DC 20037, USA. phymit@gwumc.edu

Heart Fail Rev. 2006 Mar;11(1):35-44.

Abstract

Magnesium is a micronutrient essential for the normal functioning of the cardiovascular system, and Mg deficiency (MgD) is frequently associated in the clinical setting with chronic pathologies such as CHF, diabetes, hypertension, and other pathologies. Animal models of MgD have demonstrated a systemic pro-inflammatory/pro-oxidant state, involving multiple tissues/organs including neuronal, hematopoietic, cardiovascular, and gastrointestinal systems; during later stages of MgD, a cardiomyopathy develops which may result from a cascade of inflammatory events. In rodent models of dietary MgD, a significant rise in circulating levels of proinflammatory neuropeptides such as substance P (SP) and calcitonin gene-related peptide among others, was observed within days (1-7) of initiating the Mg-restricted diet, and implicated a neurogenic trigger for the subsequent inflammatory events; this early "neurogenic inflammation" phase may be mediated in part, by the Mg-gated N: -methyl-D-aspartate (NMDA) receptor/channel complex. Deregulation of the NMDA receptor may trigger the abrupt release of neuronal SP from the sensory-motor C-fibers to promote the subsequent pro-inflammatory changes: elevations in circulating inflammatory cells, inflammatory cytokines, histamine, and PGE(2) levels, as well as formation of nitric oxide, reactive oxygen species, lipid peroxidation products, and depletion of key endogenous antioxidants. Concurrent elevations of tissue CD14, a high affinity receptor for lipopolyssacharide, suggest that intestinal permeability may be compromised leading to endotoxemia. If exposure to these early (1-3 weeks MgD) inflammatory/pro-oxidant events becomes prolonged, this might lead to impaired cardiac function, and when co-existing with other pathologies, may enhance the risk of developing chronic heart failure.

PMID 16819576

Ocdncntx (talk • contribs) 15:21, 17 November 2010 (UTC)

Neurogenic inflammation from Ultrafine particles like those found in diesel exhaust impair mental functioning

Ultrafine particles like those found in diesel exhaust are small enough to pass through the air-blood barriers of the lung, enter the circulation, and travel to various tissues in the body, including the brain. They are also able to get to the brain via the olfactory nerve. Once in the brain, the particles cause neuroinflammation and oxidative stress. —Preceding unsigned comment added by 66.167.61.163 (talk) 20:06, 29 December 2010 (UTC)

Neurogenic Inflammation in Chronic Pain Conditions

Neurogenic Inflammation in Chronic Pain Conditions Thomas Janicki, M.D. Director of Pelvic Pain Center MacDonald Womens' Hospital, University Hospitals of Cleveland

Bibliography

1. Black, P.H., Stress and the inflammatory response: a review of neurogenic inflammation. Brain Behav Immun, 2002. 16(6): p. 622-53.

2. Jasmin, L. and G. Janni, Experimental neurogenic cystitis. Adv Exp Med Biol, 2003. 539(Pt A): p. 319-35.

3. Aubock, L. and M. Ratzenhofer, "Extraepithelial enterochromaffin cell-- nerve-fibre complexes" in the normal human appendix, and in neurogenic appendicopathy. J Pathol, 1982. 136(3): p. 217-26.

4. Franke, C., et al., Neurogenic appendicopathy: a clinical disease entity? Int J Colorectal Dis, 2002. 17(3): p. 185-91.

5. Naik, R., P. Baliga, and M.R. Pai, Neurogenic appendicopathy--role of enterochromaffin cells in its pathogenesis. Indian J Pathol Microbiol, 1999. 42(3): p. 279-81.

6. O'Sullivan, M., et al., Increased mast cells in the irritable bowel syndrome. Neurogastroenterol Motil, 2000. 12(5): p. 449-57.

7. Park, C.H., et al., Activated mast cells infiltrate in close proximity to enteric nerves in diarrhea-predominant irritable bowel syndrome. J Korean Med Sci, 2003. 18(2): p. 204-10.

8. Pontari, M.A. and M.R. Ruggieri, Mechanisms in prostatitis/chronic pelvic pain syndrome. J Urol, 2004. 172(3): p. 839-45.

9. Theoharides, T.C., et al., Interstitial cystitis: a neuroimmunoendocrine disorder. Ann N Y Acad Sci, 1998. 840: p. 619-34.

10. Wesselmann, U., Neurogenic inflammation and chronic pelvic pain. World J Urol, 2001. 19(3): p. 180-5.

11. Maier, S.F., Bi-directional immune-brain communication: Implications for understanding stress, pain, and cognition. Brain Behav Immun, 2003. 17(2): p. 69-85.

12. Dines, K.C. and H.C. Powell, Mast cell interactions with the nervous system: relationship to mechanisms of disease. J Neuropathol Exp Neurol, 1997. 56(6): p. 627-40.

13. Gupta, V., D. Sheffield, and G.N. Verne, Evidence for autonomic dysregulation in the irritable bowel syndrome. Dig Dis Sci, 2002. 47(8): p. 1716-22. 14. Irwin, P.P., et al., Abnormal pedal thermoregulation in interstitial cystitis.

Neurourol Urodyn, 1993. 12(2): p. 139-44. 15. Lutgendorf, S.K., et al., Autonomic response to stress in interstitial cystitis.

J Urol, 2004. 172(1): p. 227-31. 16. Spanos, C., et al., Stress-induced bladder mast cell activation: implications for interstitial cystitis. J Urol, 1997. 157(2): p. 669-72.

17. Bjorling, D.E. and Z.Y. Wang, Estrogen and neuroinflammation. Urology, 2001. 57(6 Suppl 1): p. 40-6.

18. Alexacos, N., et al., Neurotensin mediates rat bladder mast cell degranulation triggered by acute psychological stress. Urology, 1999. 53(5): p. 1035-40.

19. Anaf, V., et al., Hyperalgesia, nerve infiltration and nerve growth factor expression in deep adenomyotic nodules, peritoneal and ovarian endometriosis. Hum Reprod, 2002. 17(7): p. 1895-900.

20. Tamburro, S., et al., Expression of transforming growth factor beta1 in nerve fibers is related to dysmenorrhea and laparoscopic appearance of endometriotic implants. Fertil Steril, 2003. 80(5): p. 1131-6.

21. Fujiwara, H., et al., Localization of mast cells in endometrial cysts. Am J Reprod Immunol, 2004. 51(5): p. 341-4.

22. Kempuraj, D., et al., Increased numbers of activated mast cells in endometriosis lesions positive for corticotropin-releasing hormone and urocortin. Am J Reprod Immunol, 2004. 52(4): p. 267-75.

23. Konno, R., et al., Role of immunoreactions and mast cells in pathogenesis of human endometriosis--morphologic study and gene expression analysis. Hum Cell, 2003. 16(3): p. 141-9.

24. Matsuzaki, S., et al., Increased mast cell density in peritoneal endometriosis compared with eutopic endometrium with endometriosis. Am J Reprod Immunol, 1998. 40(4): p. 291-4.

full article http://www.pelvicpain.org/pdf/Neurogenic_Inflammation.pdf —Preceding unsigned comment added by 66.167.95.10 (talk) 13:48, 31 December 2010 (UTC)

Neurogenic Inflammation and Sensitivity to Environmental Chemicals PMID 8404760

William J. Meggs

Neurogenic Inflammation and Sensitivity to Environmental Chemicals

Environmental Health Perspectives, Volume 101, Number 3, August 1993

PMID 8404760 PMC1519776

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1519776/

http://www.herc.org/news/mcsarticles/meggs-full.html

Department of Emergency Medicine, East Carolina University School of Medicine, Greenville, NC 27858 USA

Abstract http://ehpnet1.niehs.nih.gov/docs/1993/101-3/meggs.html

Neurogenic inflammation as a pathway distinct from antigen-driven, immune-mediated inflammation may play a pivotal role in understanding a broad class of environmental health problems resulting from chemical exposures. Recent progress in understanding the mediators, triggers, and regulation of neurogenic inflammation is reviewed. Evidence for and speculations about a role for neurogenic inflammation in established disorders such as asthma, rhinitis, contact dermatitis, migraine headache, and rheumatoid arthritis are presented. The sick building syndrome and multiple chemical sensitivity syndrome have been defined as clinical entities in which exposure to chemical inhalants gives rise to disease. Current data on the existence of chemical irritant receptors in the airway and skin are discussed; neurogenic inflammation arising from stimulation of chemical irritant receptors is a possible model to explain many of the aspects of chemical sensitivities.

Key words: asthma, indoor air pollution, multiple chemical sensitivity syndrome, neurogenic inflammation, neutral endopeptidase, reactive airways dysfunction syndrome, reactive upper airways dysfunction syndrome, rhinitis, substance P, sick building syndrome.

Environ Health Perspect 101: 234-238(1993)

http://ehpnet1.niehs.nih.gov/docs/1993/101-3/meggs.html (broken link?)

FULL FREE ARTICLE: http://ehpnet1.niehs.nih.gov/members/1993/101-3/meggs-full.html (broken link?)

Ocdnctx (talk) 21:26, 1 May 2011 (UTC)

Neurogenic inflammation as a cause of chemical sensitivity - 4 studies

Meggs WJ (1993)

Neurogenic inflammation and sensitivity to environmental chemicals.

Environ Health Perspect 101,234-238.

PMID 8404760

PMCID: PMC1519776

Free PMC Article

Comment in

Environ Health Perspect. 1994 Jan;102(1):12-3; author reply 13.

Environ Health Perspect. 1994 Jan;102(1):12; author reply 13.

Meggs WJ (1994)

RADS and RUDS--the toxic induction of asthma and rhinitis.

J Toxicol Clin Toxicol. 1994;32(5):487-501. PMID 7932908

Abstract

Inhalation exposures can produce asthma and rhinitis by several mechanisms. Sensitization with the production of IgE specific for a substance can lead to symptoms on reexposure via mast cell degranulation and the release of inflammatory mediators. Some substances, known as environmental adjuvants, enhance the immune response to concomitant exposures with the environmental adjuvant. Respiratory irritants can lead to asthma and rhinitis through interaction with chemical irritant receptors in the airway, leading to release of substance P from sensory nerves and neurogenic inflammation. The reactive airways dysfunction syndrome is a chronic asthma-like syndrome resulting from a single acute exposure to a respiratory irritant, while the reactive upper-airways dysfunction syndrome is chronic rhinitis stemming from an irritant exposure. The dysregulation of neurogenic inflammation by chemical exposures may be an important mechanism in the toxic induction of reactive airways dysfunction syndrome and reactive upper-airways dysfunction syndrome and may play a role in understanding the sick building syndrome and the multiple chemical sensitivity syndrome.

PMID 7932908

Meggs WJ (1997)

Hypothesis for induction and propagation of chemical sensitivity based on biopsy studies.

Environ Health Perspect 105 Suppl 2,473-478.

Meggs WJ, Elsheik T, Metzger WJ, Albernaz M, Bloch RM (1996)

Nasal pathology and ultrastructure in patients with chronic airway inflammation (RADS and RUDS) following an irritant exposure.

J Toxicol Clin Toxicol 34,383-396.

Ocdncntx (talk • contribs) 18:38, 28 February 2011 (UTC)

Neurogenic inflammation: with additional discussion of central and perceptual integration of nonneurogenic inflammation - PMID 9167992

PMID 9167992

Bascom, Meggs, Frampton, Hudnell, Kilburn, Kobal, Medinsky, Rea (1997)

Neurogenic inflammation: with additional discussion of central and perceptual integration of nonneurogenic inflammation.

Environ Health Perspect 105 Suppl 2:531-537.

PMCID: PMC1469802

Free PMC Article

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1469802/?tool=pubmed

Abstract

The Working Group on Neurogenic Inflammation proposed 11 testable hypotheses in the three domains of neurogenic inflammation, perceptual and central integration, and nonneurogenic inflammation. The working group selected the term people reporting chemical sensitivity (PRCS) to identify the primary subject group. In the domain of neurogenic inflammation, testable hypotheses included: PRCS have an increased density of c-fiber neurons in symptomatic tissues; PRCS produce greater quantities of neuropeptides and prostanoids than nonsensitive subjects in response to exposure to low-level capsaicin or irritant chemicals; PRCS have an increased and prolonged response to exogenously administered c-fiber activators such as capsaicin; PRCS demonstrate augmentation of central autonomic reflexes following exposure to agents that produce c-fiber stimulation; PRCS have decreased quantities of neutral endopeptidase in their mucosa; exogenous neuropeptide challenge reproduces symptoms of PRCS. In the domain of perceptual and central integration, testable hypotheses included: PRCS have alterations in adaptation, habituation, cortical representation, perception, cognition, and hedonics compared to controls; the qualitative and quantitative interactions between trigeminal and olfactory systems are altered in PRCS; higher integration of sensory inputs is altered in PRCS. In the domain of nonneurogenic inflammation, testable hypotheses included: increased inflammation is present in PRCS in symptomatic tissues and is associated with a heightened neurosensory response; PRCS show an augmented inflammatory response to chemical exposure. The working group recommended that studies be initiated in these areas.

PMID 9167992

PMCID: PMC1469802

Free PMC Article

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1469802/?tool=pubmed

Ocdnctx (talk)

"Neurogenic inflammation in the airways" - 2001 PMID 11240158

PMID 11240158

Barnes PJ

Neurogenic inflammation in the airways.

Respir Physiol. 2001 Mar;125(1-2):145-54.

Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, SW3 6LY, London, UK. p.j.barnes@ic.ac.uk

Abstract

Release of neuropeptides, including tachykinins and calcitonin gene-related peptide, from sensory nerves via an axon or local reflex may have inflammatory effects in the airways. This neurogenic inflammation may be initiated by activation of sensory nerves by inflammatory mediators and irritants. Neurogenic inflammation is well developed in rodents and may contribute to the inflammatory response to allergens, infections and irritants in animal models. However, the role of neurogenic inflammation in airway inflammatory diseases, such as asthma and COPD is still uncertain as there is little direct evidence for the involvement of sensory neuropeptides in human airways. Initial clinical studies using strategies to block neurogenic inflammation have not been encouraging, but it is important to study more severe forms of airway disease in more prolonged studies in the future to explore the role of neurogenic inflammation.

PMID 11240158 —Preceding unsigned comment added by Ocdnctx (talk • contribs) 20:19, 1 May 2011 (UTC)

[Airway sensory nerve and tachykinins in asthma and COPD]. - PMID 16463247

Comment: Conditions identified to cause neurogenic inflammation are well-recognized migraine triggers.

PMID 16463247

Dinh QT, Klapp BF, Fischer A.

[Airway sensory nerve and tachykinins in asthma and COPD].

Pneumologie. 2006 Feb;60(2):80-5.

[Article in German]

Medizinische Klinik mit Schwerpunkt Psychosomatik, Charité-Universitätsmedizin Berlin, Germany. q-thai.dinh@charite.de

Abstract

The airway nerve has gained importance in the field of respiratory research as it is known to have the capacity to release numerous mediators which can cause pulmonary effects in the airways. Meanwhile, a broad range of stimuli including capsaicin, bradykinin, hyperosmolar saline, tobacco smoke, allergens, ozone, inflammatory mediators and cold dry air have been shown to activate sensory nerve fibres to release neuropeptides such as the tachykinins substance P (SP) and neurokinin A (NKA) to mediate neurogenic inflammation. SP is synthesized in cell bodies of airway neurons of the trigeminal, jugulare and nodose ganglia. Following their release, tachykinins are degraded by neutral endopeptidase (NEP) and an angiotensin-converting enzyme. Tachykinins have been proposed to play an important role in human respiratory diseases such as bronchial asthma und chronic obstructive diseases (COPD) as they have been shown to have potent effects on the tone of airway smooth muscle, airway secretions, bronchial circulation and on inflammatory and immune cells by activation of the neurokinin-1 (NK-1) and neurokinin-2 (NK-2) receptors. Recently, new tachykinins such as virokinin and hemokinin were identified and characterised. Different aspects of the neurogenic inflammation have been well studied in animal models of allergic airway inflammation, but only little is known about the role of neurogenic airway inflammation in human diseases. To address the precise role of tachykinins and airway sensory nerves in human asthma und COPD, experiments on sensory nerve sensitisation and neuro-immune interaction have to be carried out in future studies.

PMID 16463247

Neurogenic switching: A hypothesis for a mechanism for shifting the site of inflammation in allergy and chemical sensitivity.

PMID 7628426

Meggs WJ.

Neurogenic switching: A hypothesis for a mechanism for shifting the site of inflammation in allergy and chemical sensitivity.

Environm Health Perspectives 1995; 103:54-55.

Environ Health Perspect. 1995 Jan;103(1):54-6. Neurogenic switching: a hypothesis for a mechanism for shifting the site of inflammation in allergy and chemical sensitivity. Meggs WJ. Source

Department of Emergency Medicine, East Carolina University School of Medicine, Greenville, NC 27858, USA. Abstract

Neurogenic switching is proposed as a hypothesis for a mechanism by which a stimulus at one site can lead to inflammation at a distant site. Neurogenic inflammation occurs when substance P and other neuropeptides released from sensory neurons produce an inflammatory response, whereas immunogenic inflammation results from the binding of antigen to antibody or leukocyte receptors. There is a crossover mechanism between these two forms of inflammation. Neurogenic switching is proposed to result when a sensory impulse from a site of activation is rerouted via the central nervous system to a distant location to produce neurogenic inflammation at the second location. Neurogenic switching is a possible explanation for systemic anaphylaxis, in which inoculation of the skin or gut with antigen produces systemic symptoms involving the respiratory and circulatory systems, and an experimental model of anaphylaxis is consistent with this hypothesis. Food-allergy-iducing asthma, urticaria, arthritis, and fibromyalgia are other possible examples of neurogenic switching. Neurogenic switching provides a mechanism to explain how allergens, infectious agents, irritants, and possibly emotional stress can exacerbate conditions such as migraine, asthma, and arthritis. Because neurogenic inflammation is known to be triggered by chemical exposures, it may play a role in the sick building syndrome and the multiple chemical sensitivity syndrome. Thus neurogenic switching would explain how the respiratory irritants lead to symptoms at other sites in these disorders.

PMID 7628426

PMCID: PMC1519059

Free PMC Article

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1519059/?tool=pubmed

Ocdnctx (talk) 20:58, 1 May 2011 (UTC)

Essential role for nitric oxide in neurogenic inflammation in rat cutaneous microcirculation. Evidence for an endothelium-independent mechanism

Kajekar, Moore, Brain (1995)

Essential role for nitric oxide in neurogenic inflammation in rat cutaneous microcirculation. Evidence for an endothelium-independent mechanism.

Circ Res. 1995 Mar;76(3):441-7. PMID 7532119

Abstract

The possible modulatory role of nitric oxide (NO) in neurogenic edema formation in rat paw skin, induced by electrical stimulation of the saphenous nerve, was investigated by using two NO synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI). Both L-NAME (100 mg/kg IV, P < .05) and 7-NI (10 mg/kg IV, P < .05) caused an L-arginine (100 mg/kg IV, P < .01)-reversible inhibition of neurogenic edema as measured by 125I-albumin accumulation, whereas D-NAME (inactive enantiomer of L-NAME) and 6-aminoindazole (structurally similar to 7-NI) were without inhibitory effect. L-NAME produced the predicted vasopressor effect (before, 115 +/- 18 mm Hg; 5 minutes after, 174 +/- 18 mm Hg; n = 6; P < .05), whereas 7-NI showed no significant increase in blood pressure (before, 96 +/- 9 mm Hg; 5 minutes after, 102 +/- 10 mm Hg; n = 6), and neither L-NAME nor 7-NI had any effect on basal or vasodilator calcitonin gene-related peptide (CGRP, 10 pmol per site)-stimulated local blood flow in rat skin, as measured by laser Doppler flowmetry. Furthermore, systemic and local 7-NI had no effect on edema formation induced by local administration of substance P (with or without CGRP) and histamine (with or without CGRP) in rat skin. Since 7-NI blocks edema produced by stimulation of the saphenous nerve, it is suggested that release of NO is involved in neurogenic edema formation, but the vasodilator action of NO is unimportant in this context.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID 7532119

Ocdnctx (talk) 21:43, 1 May 2011 (UTC)

"[N]eurogenic inflammation, which occurs very early during hypomagnesemia, predisposes the myocardium to reperfusion injury - PMID 7518201

PMID 7518201 Weglicki WB, Phillips TM, Mak IT, Cassidy MM, Dickens BF, Stafford R, Kramer JH. Cytokines, neuropeptides, and reperfusion injury during magnesium deficiency. Ann N Y Acad Sci. 1994 Jun 17;723:246-57.

In summary, hypomagnesemia enhances reperfusion injury. We postulate that neurogenic inflammation, which occurs very early during hypomagnesemia, predisposes the myocardium to reperfusion injury by depleting endogenous antioxidants and recruiting inflammatory cells, which can participate in enhanced free radical production during postischemic reperfusion. Vitamin E supplements can prevent the occurrence of this enhanced injury possibly through the restoration of endogenous antioxidant defenses.

PMID 7518201 —Preceding unsigned comment added by Ocdnctx (talk • contribs) 21:48, 9 May 2011 (UTC)

Aphthous ulcers were found to contain nerve fibers with synaptic vesicles and shown to contain substance P and CGRP. PMID 7478757

Recurrent aphthous ulcers were found to contain nerve fibers with synaptic vesicles and shown to contain substance P and CGRP, which can exert potent paracrine, e.g. on local inflammatory cells nearby.

PMID 7478757

Konttinen YT, Hayrinen-Immonen RH, Nordstrom D, Malmstrom MJ, Hukkanen M, Sorsa T, Polak J.

Innervation of recurrent aphthous ulcers.

Source

Oral Microbiol Immunol. 1994 Feb;9(1):60-4.

Department of Anatomy, University of Helsinki, Finland. Abstract

Specimens from nonkeratinized oral mucosa were obtained from diseased and clinically healthy mucosa from 7 patients with minor recurrent aphthous ulcers. The innervation of the specimens was visualized using antibodies to neuron-specific intermediate cytoskeletal neurofilament fiber, the cytoplasmic protein gene product 9.5 and a 38 kDa integral membrane protein of synaptic vesicles applied in avidin-biotin-peroxidase staining. Mapping with these 3 antibodies revealed dense and basically similar pattern of innervation in the specimens of the clinically healthy oral mucosa. In recurrent aphthous ulcers, all 3 general markers disclosed peripheral nerve fibers also in the lesions, apart from the necrotic area, among the inflammatory cells without signs of retraction from the diseased area. Synaptophysin staining suggested that these peripheral nerve fibers in the inflammatory areas still contained synaptic vesicles. Accordingly, they were shown to contain substance P and calcitonin gene-related peptide, which are known to be released upon stimulation of the nerve and can exert potent paracrine actions, possibly on the local inflammatory cells as suggested by a close spatial relationship between neuropeptide-containing nerves and inflammatory cells.

PMID 7478757

3 studies on neurotransmitters, neuropeptides, and vascular factors in migraine

Limmroth V, Cuter FM. Moskowitz MA. Neurotransmitters and neuropeptides in headache. Curr Opin Neurol 1996;9:206-210.

Paratainen J, Vapaatalo H, Hokkanen E. Clinical aspects of prostaglandines and leucotrienes in migraine. Cephalagia 1986;4(Suppl):S95.

Moskowitz MA, MacFarlane R. Neurovascular and molecular mechanism in migraine headaches. Cerebrovasc Brain Metab Rev 1993;5:159-177. — Preceding unsigned comment added by Ocdncntx (talk • contribs) 17:59, 22 September 2011 (UTC)

Substance P triggered by moderate dietary restriction of magnesium leading release of other inflammatory and to osteopenia in the rat PMID 19828898

PMID 19828898

J Am Coll Nutr. 2009 Apr;28(2):131-41. Skeletal and hormonal effects of magnesium deficiency. Rude RK, Singer FR, Gruber HE. Source

USC Keck School of Medicine, Los Angeles, CA, USA. rrude60075@aol.com Abstract

Magnesium (Mg) is the second most abundant intracellular cation where it plays an important role in enzyme function and trans-membrane ion transport. Mg deficiency has been associated with a number of clinical disorders including osteoporosis. Osteoporosis is common problem accounting for 2 million fractures per year in the United States at a cost of over $17 billion dollars. The average dietary Mg intake in women is 68% of the RDA, indicating that a large proportion of our population has substantial dietary Mg deficits. The objective of this paper is to review the evidence for Mg deficiency-induced osteoporosis and potential reasons why this occurs, including a cumulative review of work in our laboratories and well as a review of other published studies linking Mg deficiency to osteoporosis. Epidemiological studies have linked dietary Mg deficiency to osteoporosis. As diets deficient in Mg are also deficient in other nutrients that may affect bone, studies have been carried out with select dietary Mg depletion in animal models. Severe Mg deficiency in the rat (Mg at <0.0002% of total diet; normal = 0.05%) causes impaired bone growth, osteopenia and skeletal fragility. This degree of Mg deficiency probably does not commonly exist in the human population. We have therefore induced dietary Mg deprivation in the rat at 10%, 25% and 50% of recommended nutrient requirement. We observed bone loss, decrease in osteoblasts, and an increase in osteoclasts by histomorphometry. Such reduced Mg intake levels are present in our population. We also investigated potential mechanisms for bone loss in Mg deficiency. Studies in humans and and our rat model demonstrated low serum parathyroid hormone (PTH) and 1,25(OH)(2)-vitamin D levels, which may contribute to reduced bone formation. It is known that cytokines can increase osteoclastic bone resorption. Mg deficiency in the rat and/or mouse results in increased skeletal substance P, which in turn stimulates production of cytokines. With the use of immunohistocytochemistry, we found that Mg deficiency resulted in an increase in substance P, TNFalpha and IL1beta. Additional studies assessing the relative presence of receptor activator of nuclear factor kB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG), found a decrease in OPG and an increase in RANKL favoring an increase in bone resorption. These data support the notion at dietary Mg intake at levels not uncommon in humans may perturb bone and mineral metabolism and be a risk factor for osteoporosis.

Free full text http://www.jacn.org/cgi/pmidlookup?view=long&pmid=19828898 (not able to access Oct. 2011) — Preceding unsigned comment added by 99.190.133.143 (talk) 01:59, 27 October 2011 (UTC)

SPECT and psychometric scale changes after a chemical challenge suggest neurogenic origin of MCS - PMID 19801154

Orriols R, Costa R, Cuberas G, Jacas C, Castell J, Sunyer J.

Brain dysfunction in multiple chemical sensitivity.

J Neurol Sci. 2009 Dec 15;287(1-2):72-8. Epub 2009 Oct 3

PMID 19801154

Abstract

Multiple Chemical Sensitivity (MCS) is a chronic acquired disorder of unknown pathogenesis. The aim of this study was to ascertain whether MCS patients present brain single photon emission computed tomography (SPECT) and psychometric scale changes after a chemical challenge. This procedure was performed with chemical products at non-toxic concentrations in 8 patients diagnosed with MCS and in their healthy controls. In comparison to controls, cases presented basal brain SPECT hypoperfusion in small cortical areas of the right parietal and both temporal and fronto-orbital lobes. After chemical challenge, cases showed hypoperfusion in the olfactory, right and left hippocampus, right parahippocampus, right amygdala, right thalamus, right and left Rolandic and right temporal cortex regions(p<or=0.01). By contrast, controls showed hyperperfusion in the cingulus, right parahippocampus, left thalamus and some cortex regions (p<or=0.01). The clustered deactivation pattern in cases was stronger than in controls (p=0.012) and the clustered activation pattern in controls was higher than in cases (p=0.012). In comparison to controls, cases presented poorer quality of life and neurocognitive function at baseline, and neurocognitive worsening after chemical exposure. Chemical exposure caused neurocognitive impairment, and SPECT brain dysfunction particularly in odor-processing areas, thereby suggesting a neurogenic origin of MCS.

PMID 19801154 — Preceding unsigned comment added by 99.190.133.143 (talk) 23:34, 8 November 2011 (UTC)

The role of sensory nerve endings in neurogenic inflammation induced in human skin and in the eye and paw of the rat. PMCID PMC1570273

N Jancsó, A Jancsó-Gábor, and J Szolcsányi

The role of sensory nerve endings in neurogenic inflammation induced in human skin and in the eye and paw of the rat.

Br J Pharmacol Chemother. 1968 May; 33(1): 32–41.

PMCID PMC1570273

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1570273/?tool=pubmed

The vanilloid receptor as a putative target of diverse chemicals in multiple chemical sensitivity. -- PMID 16241041

Pall ML, Anderson JH.

The vanilloid receptor as a putative target of diverse chemicals in multiple chemical sensitivity.

Arch Environ Health. 2004 Jul;59(7):363-75.

Abstract

The vanilloid receptor (TRPV1 or VR1), widely distributed in the central and peripheral nervous system, is activated by a broad range of chemicals similar to those implicated in Multiple Chemical Sensitivity (MCS) Syndrome. The vanilloid receptor is reportedly hyperresponsive in MCS and can increase nitric oxide levels and stimulate N-methyl-D-aspartate (NMDA) receptor activity, both of which are important features in the previously proposed central role of nitric oxide and NMDA receptors in MCS. Vanilloid receptor activity is markedly altered by multiple mechanisms, possibly providing an explanation for the increased activity in MCS and symptom masking by previous chemical exposure. Activation of this receptor by certain mycotoxins may account for some cases of sick building syndrome, a frequent precursor of MCS. Twelve types of evidence implicate the vanilloid receptor as the major target of chemicals, including volatile organic solvents (but not pesticides) in MCS.

PMID 16241041 — Preceding unsigned comment added by Ocdnctx (talk • contribs) 15:54, 16 August 2012 (UTC)

A google search for images of "Neurogenic inflammation" may yield open-source diagrams of value

A google search for images of "Neurogenic inflammation" may yield open-source diagrams of value

Superb survey of state of the art by Chen and Lyga, June 2014

Ying Chen* and John Lyga Brain-Skin Connection: Stress, Inflammation and Skin Aging Published online Jun 2014. doi: 10.2174/1871528113666140522104422 Inflamm Allergy Drug Targets. Jun 2014; 13(3): 177–190. PMCID: PMC4082169 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082169/

Neurovascular Aspects of Skin Neurogenic Inflammation ... "...both TRPV1 and TRPA1 receptors may be promising therapeutic targets for the treatment of the inflammatory symptoms of rosacea."

Aisah A Aubdool and Susan D Brain

Review

Neurovascular Aspects of Skin Neurogenic Inflammation

Journal of Investigative Dermatology Symposium Proceedings (2011) 15, 33–39; doi:10.1038/jidsymp.2011.8

http://www.nature.com/jidsp/journal/v15/n1/full/jidsymp20118a.html

Received 8 June 2011; Revised 13 August 2011; Accepted 16 August 2011

Neurogenic inflammation is involved in skin inflammation. ... Here we describe the potential for TRPV1 and TRPA1 receptors to be involved in the pathophysiology of rosacea due to their polymodal activation, including cold and hot temperature, pungent products from vegetable and spices, reactive oxygen species, and mechanical stimuli. We discuss the role of both receptors and the sensory neuropeptides that they release in inflammation and pain sensation and evidence suggesting that both TRPV1 and TRPA1 receptors may be promising therapeutic targets for the treatment of the inflammatory symptoms of rosaceaboth TRPV1 and TRPA1 receptors may be promising therapeutic targets for the treatment of the inflammatory symptoms of rosacea.

Speculative marketing message cut from article and moved here

Given the pathogenesis of neurogenic inflammation the anti-inflammatory and analgesic compound palmitoylethanolamide seems a logical inroad into the treatment of a number of neurogenic inflammation-states and neuropathic pain.

Anti-migraine effects a new CGRP receptor antagonist - response rates similar to those reported for triptans - PMID 16802852

Trocóniz IF1, Wolters JM, Tillmann C, Schaefer HG, Roth W.

Modelling the anti-migraine effects of BIBN 4096 BS: a new calcitonin gene-related peptide receptor antagonist.

Clin Pharmacokinet. 2006;45(7):715-28.

PMID 16802852

Migraine attacks are associated with release of the calcitonin gene-related peptide (CGRP) from trigeminal nerves. BIBN 4096 BS is the first CGRP receptor antagonist tested in humans showing response rates similar to those reported for triptans, together with very good safety and tolerability profiles.

CGRP antagonist BIBN 4096 BS was effective in treating acute attacks of migraine - NEJM - PMID 15014183

Jes Olesen, M.D., Hans-Christoph Diener, M.D., Ingo W. Husstedt, M.D., Peter J. Goadsby, M.D., David Hall, Ph.D., Ulrich Meier, Ph.D., Stephane Pollentier, M.D., and Lynna M. Lesko, M.D. for the BIBN 4096 BS Clinical Proof of Concept Study Group

Calcitonin Gene–Related Peptide Receptor Antagonist BIBN 4096 BS for the Acute Treatment of Migraine

N Engl J Med 2004; 350:1104-1110

March 11, 2004

DOI: 10.1056/NEJMoa030505

PMID 15014183

Free full text http://www.nejm.org/doi/full/10.1056/NEJMoa030505

CGRP receptor antagonists terminate migraine with efficacy similar to triptans. - Headache

Stewart J. Tepper, MD, Mark J. Stillman, MD

Clinical and Preclinical Rationale for CGRP-Receptor Antagonists in the Treatment of Migraine

Headache. 2008;48(8):1259-1268.

http://www.medscape.com/viewarticle/580996

CGRP receptor antagonists terminate migraine with efficacy similar to triptans. Both intravenous olcegepant (BIBN 4096 BS) and oral telcagepant (MK-0974) have been effective, safe, and well tolerated in phase I and II studies. Telcagepant is currently in phase III trials, and preliminary results are favorable. The potential for a migraine-specific medication without vasoconstrictive or vascular side effects is enormous. CGRP receptor blockade may also have applications in other pathologic and pain syndromes.

(Caveat Telcagepant may have been abandoned due to reversible changes on metabolic workup)

Seminal article by Jancsó, cited by 1039+, Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin

N Jancsó, A Jancsó-Gábor, and J Szolcsányi

Br J Pharmacol Chemother. Sep 1967; 31(1): 138–151.

Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin.

PMCID: PMC1557289

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1557289/

Good history of neurogenic inflammation science & application to migraine

Stephen J. Peroutka

Neurogenic inflammation and migraine: implications for the therapeutics.

Mol Interv. 2005 Oct;5(5):304-11.

http://triggered.stanford.clockss.org/ServeContent?rft_id=info:doi/10.1124/mi.5.5.10

http://triggered.stanford.clockss.org/ServeContent?url=http%3A%2F%2Fmolinterv.aspetjournals.org%2Fcontent%2F5%2F5%2F304.full.pdf%2Bhtml

PMID 16249526

Begins

" Migraine is a clinical syndrome of self-limited neurogenic inflammation (1). "

In 1910, Bruce observed that the application of mustard oil to the conjunctival sac in experimental animal models produced inflammation that could be blocked by sensory nerve ablation ...

Substance P a possible cause of pruritic psoriasis? Topically applied capsaicin effectively treats. PMID 7688774

Ellis CN1, Berberian B, Sulica VI, Dodd WA, Jarratt MT, Katz HI, Prawer S, Krueger G, Rex IH Jr, Wolf JE.

A double-blind evaluation of topical capsaicin in pruritic psoriasis.

J Am Acad Dermatol. 1993 Sep;29(3):438-42.

PMID 7688774

Abstract

BACKGROUND:

Substance P, an undecapeptide neurotransmitter, has been implicated in the pathophysiology of psoriasis and pruritus.

...

METHODS:

Patients applied capsaicin 0.025% cream (n = 98) or vehicle (n = 99) four times a day for 6 weeks in this double-blind study. Efficacy was based on a physician's global evaluation and a combined psoriasis severity score including scaling, thickness, erythema, and pruritus.

RESULTS:

Capsaicin-treated patients demonstrated significantly greater improvement in global evaluation (p = 0.024 after 4 weeks and p = 0.030 after 6 weeks) and in pruritus relief (p = 0.002 and p = 0.060, respectively), as well as a significantly greater reduction in combined psoriasis severity scores (p = 0.030 and p = 0.036, respectively). The most frequently reported side effect in both treatment groups was a transient burning sensation at application sites.

CONCLUSION:

Topically applied capsaicin effectively treats pruritic psoriasis, a finding that supports a role for substance P in this disorder.

Comment in

Topical capsaicin in pruritic psoriasis. [J Am Acad Dermatol. 1994]

Ocdcntx (talk) 21:58, 9 April 2015 (UTC)

Neurogenic inflammation and cardiac dysfunction due to hypomagnesemia. PMID 19593099. PMCID PMC3753099

Kramer JH1, Spurney C, Iantorno M, Tziros C, Mak IT, Tejero-Taldo MI, Chmielinska JJ, Komarov AM, Weglicki WB.

Neurogenic inflammation and cardiac dysfunction due to hypomagnesemia.

Am J Med Sci. 2009 Jul;338(1):22-7.

doi: 10.1097/MAJ.0b013e3181aaee4d.

PMID 19593099

Free PMC Article. PMCID PMC3753099

Abstract

Hypomagnesemia continues to be a significant clinical disorder that is present in patients with diabetes mellitus, alcoholism, and treatment with magnesuric drugs (diuretics, cancer chemotherapy agents, etc.). To determine the role of magnesium in cardiovascular pathophysiology, we have used dietary restriction of this cation in animal models. This review highlights some key observations that helped formulate the hypothesis that release of substance P (SP) during experimental dietary Mg deficiency (MgD) may initiate a cascade of deleterious inflammatory, oxidative, and nitrosative events, which ultimately promote cardiomyopathy, in situ cardiac dysfunction, and myocardial intolerance to secondary stresses. SP acts primarily through neurokinin-1 receptors of inflammatory and endothelial cells, and may induce production of reactive oxygen and nitrogen species (superoxide anion, NO*, peroxynitrite, hydroxyl radical), leading to enhanced consumption of tissue antioxidants; stimulate release of inflammatory mediators; promote tissue adhesion molecule expression; and enhance inflammatory cell tissue infiltration and cardiovascular lesion formation. These SP-mediated events may predispose the heart to injury if faced with subsequent oxidative stressors (ischemia/reperfusion, certain drugs) or facilitate development of in situ cardiac dysfunction, especially with prolonged dietary Mg restriction. Significant protection against most of these MgD-mediated events has been observed with interventions that modulate neuronal SP release or its bioactivity, and with several antioxidants (vitamin E, probucol, epicaptopril, d-propranolol). In view of the clinical prevalence of hypomagnesemia, new treatments, beyond magnesium repletion, may be needed to diminish deleterious neurogenic and prooxidative components described in this article. — Preceding unsigned comment added by 99.190.133.143 (talk) 22:11, 21 June 2015 (UTC)

The role of magnesium deficiency in cardiovascular and intestinal inflammation. PMID 20971697. PMC 3800093.

Weglicki WB1, Mak IuT, Chmielinska JJ, Tejero-Taldo MI, Komarov AM, Kramer JH.

The role of magnesium deficiency in cardiovascular and intestinal inflammation.

Magnes Res. 2010 Dec;23(4):S199-206.

Epub 2010 Oct 25.

PMID 20971697

Free PMC Article. PMCID: PMC 3800093

doi: 10.1684/mrh.2010.0218.

http://www.ncbi.nlm.nih.gov/pubmed/20971697

Abstract

Hypomagnesemia continues to cause difficult clinical problems, such as significant cardiac arrhythmias where intravenous magnesium therapy can be lifesaving. Nutritional deficiency of magnesium may present with some subtle symptoms such as leg cramps and occasional palpitation. We have investigated dietary-induced magnesium deficiency in rodent models to assess the pathobiology associated with prolonged hypomagnesemia. We found that neuronal sources of the neuropeptide, substance P (SP), contributed to very early prooxidant/proinflammatory changes during Mg deficiency. This neurogenic inflammation is systemic in nature, affecting blood cells, cardiovascular, intestinal, and other tissues, leading to impaired cardiac contractility similar to that seen in patients with heart failure. We have used drugs that block the release of SP from neurons and SP-receptor blockers to prevent some of these pathobiological changes; whereas, blocking SP catabolism enhances inflammation. Our findings emphasize the essential role of this cation in preventing cardiomyopathic changes and intestinal inflammation in a well-studied animal model, and also implicate the need for more appreciation of the potential clinical relevance of optimal magnesium nutrition and therapy.