Neurogenic inflammation

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Neurogenic inflammation is inflammation arising from the local release from afferent neurons of inflammatory mediators such as Substance P, Calcitonin Gene-Related Peptide (CGRP), neurokinin A (NKA), and endothelin-3 (ET-3).[1][2][3]

This process appears to play an important role in the pathogenesis of numerous diseases including migraine,[4][5][6] psoriasis,[7][8][9] asthma,[10] fibromyalgia, eczema, rosacea, dystonia, and multiple chemical sensitivity.[11][12]

In migraine, stimulation of the trigeminal nerve causes neurogenic inflammation via release of neuropeptides including Substance P, nitric oxide, vasoactive intestinal polypeptide, 5-HT, Neurokinin A and CGRP.[13][14] leading to a "sterile neurogenic inflammation."[15]


Anticipating later botox therapy for migraine, early work by Jancsó et al. found some success in treatment using denervation or pretreatment with capsaicin to prevent uncomfortable symptoms of neurogenic inflammation.[16]

Current study of the treatment of migraine with CGRP blockers show promise.[17] In early trials, the first oral nonpeptide CGRP antagonist, MK-0974 (Telcagepant), was shown effective in the treatment of migraine attacks,[18] but elevated liver enzymes in two participants were found. Other therapies and other links in the neurogenic inflammatory pathway for interruption of disease are under study, including migraine therapies.[19]

Noting that botulinum toxin has been shown to have an effect on inhibiting neurogenic inflammation, and evidence suggesting the role of neurogenic inflammation in the pathogenesis of psoriasis,[20] the University of Minnesota has begun a clinical trial to follow up on the observation that patients treated with botulinum toxin for dystonia had dramatic improvement in psoriasis.[21]

Astelin (Azelastine) "is indicated for symptomatic treatment of vasomotor rhinitis including rhinorrhea, nasal congestion, and post nasal drip in adults and children 12 years of age and older."[22]

Statins may be useful for treating diseases presenting with predominant neurogenic inflammation [23]


Magnesium deficiency causes neurogenic inflammation in a rat model. Researchers have theorized that since substance P which appears at day five of induced magnesium deficiency, is known to stimulate in turn the production of other inflammatory cytokines including IL-1, Interleukin 6 (IL-6), and TNF-alpha (TNFα), which begin a sharp rise at day 12, substance P is a key in the path from magnesium deficiency to the subsequent cascade of neuro-inflammation.[24] In a later study, researchers provided rats dietary levels of magnesium that were reduced but still within the range of dietary intake found in the human population, and observed an increase in substance P, TNF alpha (TNFα) and Interleukin-1 beta (IL-1β), followed by exacerbated bone loss. These and other data suggest that deficient dietary magnesium intake, even at levels not uncommon in humans, may trigger neurogenic inflammation and lead to an increased risk of osteoporosis.[25]


  1. ^ Peroutka, Stephen J. (October 2005). "Neurogenic inflammation and migraine: implications for the therapeutics". Molecular Interventions (Mol Interv.) 5 (5): 304–311. doi:10.1124/mi.5.5.10. PMID 16249526. Retrieved 21 September 2014. 
  2. ^ Chen, Ying; Lyga, John (Jun 2014). "Brain-Skin Connection: Stress, Inflammation and Skin Aging". Inflamm Allergy Drug Targets. 13(3) (Jun 2014): 177–190. doi:10.2174/1871528113666140522104422. PMID 24853682. Retrieved 7 August 2014. 
  3. ^ "The concept of neurogenic inflammation". BJU Int. 101 Suppl 3: 2–6. March 2008. doi:10.1111/j.1464-410X.2008.07493.x. PMID 18307678. 
  4. ^ Frediani, F; Villani, V; Casucci, G (2008). "Peripheral mechanism of action of antimigraine prophylactic drugs". Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 29 Suppl 1: S127–30. doi:10.1007/s10072-008-0903-8. PMID 18545913. 
  5. ^ Peroutka, SJ (2005). "Neurogenic inflammation and migraine: implications for the therapeutics". Molecular interventions 5 (5): 304–11. doi:10.1124/mi.5.5.10. PMID 16249526. 
  6. ^ Geppetti, P; Capone, JG; Trevisani, M; Nicoletti, P; Zagli, G; Tola, MR (2005). "CGRP and migraine: neurogenic inflammation revisited". The journal of headache and pain 6 (2): 61–70. doi:10.1007/s10194-005-0153-6. PMC 3452316. PMID 16362644. 
  7. ^ Chen, Ying; Lyga, John (Jun 2014). "Brain-Skin Connection: Stress, Inflammation and Skin Aging". Inflamm Allergy Drug Targets. 13(3) (Jun 2014): 177–190. doi:10.2174/1871528113666140522104422. PMID 24853682. Retrieved 7 August 2014. 
  8. ^ Schön and Boehncke, Psoriasis: Neurogenic inflammation and other mechanisms NEJM 352:1899-1912, Number 18, 2005
  9. ^ Saraceno, R; Kleyn, CE; Terenghi, G; Griffiths, CE (2006). "The role of neuropeptides in psoriasis". The British journal of dermatology 155 (5): 876–82. doi:10.1111/j.1365-2133.2006.07518.x. PMID 17034513. 
  10. ^ Verones, B; Oortgiesen, M (December 2001). "Neurogenic inflammation and particulate matter (PM) air pollutants". Neurotoxicology 22 (6): 795–810. doi:10.1016/S0161-813X(01)00062-6. PMID 11829413. 
  11. ^ Orriols, Ramon; Costa, Roser; Cuberas, Gemma; Jacas, Carlos; Castell, Joan; Sunyer, Jordi (December 2009). "Brain dysfunction in multiple chemical sensitivity". J. Neurol. Sci. 287 (1–2): 72–8. doi:10.1016/j.jns.2009.09.003. PMID 19801154. 
  12. ^ Bascom, R; Meggs, WJ; Frampton, M; Hudnell, K; Killburn, K; Kobal, G; Medinsky, M; Rea, W (1997). "Neurogenic inflammation: with additional discussion of central and perceptual integration of nonneurogenic inflammation". Environmental health perspectives. 105 Suppl 2: 531–7. doi:10.2307/3433365. PMC 1469802. PMID 9167992. 
  13. ^ Arun A Kalra, AA; Debra Elliott, D (June 2007). "Acute migraine: Current treatment and emerging therapies". Ther Clin Risk Manag (Dove Medical Press Limited) 3 (3): 449–459. PMC 2386351. PMID 18488069. 
  14. ^ Andrea Stephanie Link, AS; Anikó Kuris et. al, A; Edvinsson, L (23 January 2008). "Treatment of migraine attacks based on the interaction with the trigemino-cerebrovascular system". J Headache Pain (Biomedical Center Lund) 9 (1): 5–12. doi:10.1007/s10194-008-0011-4. PMC 2245994. PMID 18217201. 
  15. ^ Werner Grossmann, MD, and Hanns Schmidramsl, MD An Extract of Petasites hybridus is Effective in the Prophylaxis of Migraine Alternative Medicine Review, Volume 6, Number3 2001, Page303
  16. ^ "Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin". Br J Pharmacol Chemother 31 (1): 138–51. September 1967. doi:10.1111/j.1476-5381.1967.tb01984.x. PMC 1557289. PMID 6055248. 
  17. ^ Durham, PL; Vause, CV (2010). "Calcitonin gene-related peptide (CGRP) receptor antagonists in the treatment of migraine". CNS Drugs 24 (7): 539–48. doi:10.2165/11534920-000000000-00000. PMC 3138175. PMID 20433208. 
  18. ^ Farinelli, I; Missori, S; Martelletti, P (2008). "Proinflammatory mediators and migraine pathogenesis: moving towards CGRP as a target for a novel therapeutic class". Expert Review of Neurotherapeutics 8 (9): 1347–54. doi:10.1586/14737175.8.9.1347. PMID 18759547. 
  19. ^ Farinelli, I; De Filippis, S; Coloprisco, G; Missori, S; Martelletti, P (2009). "Future drugs for migraine". Internal and emergency medicine 4 (5): 367–73. doi:10.1007/s11739-009-0273-0. PMID 19551474. 
  20. ^ Saraceno, R; Kleyn, CE; Terenghi, G; Griffiths, CE (2006). "The role of neuropeptides in psoriasis". The British Journal of Dermatology 155 (5): 876–82. doi:10.1111/j.1365-2133.2006.07518.x. PMID 17034513. 
  21. ^ Clinical trial number NCT00816517 for "Use of Botulinum Toxin to Treat Psoriasis" at
  22. ^ Product Information: Astelin, azelastine. Wallace Laboratories, Cranbury, NJ. (PI Revised 08/2000) PI Reviewed 01/2001
  23. ^ Bucelli, RC; Gonsiorek, EA; Kim, WY; Bruun, D; Rabin, RA; Higgins, D; Lein, PJ (2008). "Statins decrease expression of the proinflammatory neuropeptides calcitonin gene-related peptide and substance P in sensory neurons". The Journal of Pharmacology and Experimental Therapeutics 324 (3): 1172–80. doi:10.1124/jpet.107.132795. PMID 18079356. 
  24. ^ Weglicki WB, Phillips TM. Pathobiology of magnesium deficiency: a cytokine/neurogenic inflammation hypothesis PMID 1384353 Am J Physiol. 1992 Sep;263(3 Pt 2):R734-7
  25. ^ Rude, RK; Singer, FR; Gruber, HE (April 2009). "Skeletal and hormonal effects of magnesium deficiency". J Am Coll Nutr 28 (2): 131–41. PMID 19828898. 

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