Itch

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For other uses, see Itch (disambiguation).
Pruritus
Classification and external resources
Itch.jpg
A man scratching his back
ICD-10 L29
ICD-9 698
DiseasesDB 25363
MedlinePlus 003217
eMedicine derm/946
MeSH D011537

Itch (Latin: pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to classify it as any one type of sensory experience. Modern science has shown that itch has many similarities to pain, and while both are unpleasant sensory experiences, their behavioral response patterns are different. Pain creates a withdrawal reflex, while itch leads to a scratch reflex.[1]

Unmyelinated nerve fibers for itch and pain both originate in the skin; however, information for them is conveyed centrally in two distinct systems that both use the same nerve bundle and spinothalamic tract.[2]

Signs and symptoms[edit]

Pain and itch have very different behavioral response patterns. Pain evokes a withdrawal reflex, which leads to retraction and therefore a reaction trying to protect an endangered part of the body. Itch in contrast creates a scratch reflex, which draws one to the affected skin site. For example, responding to a local itch sensation is an effective way to remove insects on one's skin.

Scratching has traditionally been regarded as a way to relieve oneself by reducing the annoying itch sensation. However there are hedonic aspects of scratching, as one would find noxious scratching highly pleasurable.[1] This can be problematic with chronic itch patients, such as ones with atopic dermatitis, who may scratch affected spots until they no longer produce a pleasant or painful sensation, instead of when the itch sensation disappears.[3] It has been hypothesized that motivational aspects of scratching include the frontal brain areas of reward and decision making. These aspects might therefore contribute to the compulsive nature of itch and scratching.[1]

Contagious itch[edit]

Events of "contagious itch" are very common occurrences. Even a discussion on the topic of itch can give one the desire to scratch. Itch is likely to be more than a localized phenomenon in the place we scratch. Results from a study showed that itching and scratching were induced purely by visual stimuli in a public lecture on itching.

There is little detailed data on central activation for contagious itching, but it is hypothesized that a human mirror neuron system exists in which we imitate certain motor actions when we view others performing the same action. A similar phenomenon in which mirror neurons are used to explain the cause is contagious yawning.[1]

Causes[edit]

Scabies is one cause of itching.

Infections and infestations:

Environmental and allergic:

Dermatological disorders:

Medical disorders:

Medication:

  • Drugs (such as opioids) that activate histamine (H1) receptors or trigger histamine release
  • Chloroquine, a drug

Related to pregnancy:

Mechanism[edit]

Itch can originate in the peripheral nervous system (dermal or neuropathic) or in the central nervous system (neuropathic, neurogenic, or psychogenic).[10][11]

Dermal/pruritoceptive[edit]

A squirrel scratching itself.

Itch originating in the skin is known as pruritoceptive, and can be induced by a variety of stimuli, including mechanical, chemical, thermal, and electrical stimulation. The primary afferent neurons responsible for histamine-induced itch are unmyelinated C-fibres.

Two major classes of human C-fibre nociceptors exist: mechano-responsive nociceptors and mechano-insensitive nociceptors. Mechano-responsive nociceptors have been shown in studies to respond to mostly pain, and mechano-insensitive receptors respond mostly to itch induced by histamine. However, it does not explain mechanically induced itch or when itch is produced without a flare reaction which involves no histamine. Therefore, it is possible that pruritoceptive nerve fibres have different classes of fibres, which is unclear in current research.[1]

Studies have been done to show that itch receptors are found only on the top two skin layers, the epidermis and the epidermal/dermal transition layers.[citation needed] Shelley and Arthur had verified the depth by injecting individual itch powder spicules (Mucuna pruriens), and found that maximal sensitivity was found at the basal cell layer or the innermost layer of the epidermis. Surgical removal of those skin layers removed the ability for a patient to perceive itch.[citation needed] Itch is never felt in muscle or joints, which strongly suggests that deep tissue probably does not contain itch signaling apparatuses.

Sensitivity to pruritic stimuli is evenly distributed across the skin, and has a clear spot distribution with similar density to that of pain. The different substances that elicit itch upon intracutaneous injection (injection within the skin) elicit only pain when injected subcutaneously (beneath the skin).

Itch is readily abolished in skin areas treated with nociceptor excitotoxin capsaicin, but remains unchanged in skin areas which were rendered touch-insensitive by pretreatment with saponins, an anti-inflammatory agent. Although experimentally induced itch can still be perceived under a complete A-fiber conduction block, it is significantly diminished. Overall, itch sensation is mediated by A-delta and C nociceptors located in the uppermost layer of the skin.[12]

Neuropathic[edit]

Neuropathic itch can originate at any point along the afferent pathway as a result of damage of the nervous system. They could include diseases or disorders in the central nervous system or peripheral nervous system.[11] Examples of neuropathic itch in origin are notalgia paresthetica, brachioradial pruritus, brain tumors, multiple sclerosis, peripheral neuropathy, and nerve irritation.[13]

Neurogenic[edit]

Neurogenic itch, which is itch induced centrally but with no neural damage, is mostly associated with increased accumulation of exogenous opioids and possibly synthetic opioids.[11]

Psychogenic[edit]

Itch is also associated with some symptoms of psychiatric disorders such as tactile hallucinations, delusions of parasitosis, or obsessive-compulsive disorders (as in OCD-related neurotic scratching).[11]

Interactions between itch and pain[edit]

Pain inhibits itch[edit]

The sensation of itch can be reduced by many painful sensations. Numerous studies done in the last decade have shown that itch can be inhibited by many other forms of painful stimuli, such as noxious heat, physical rubbing/scratching, noxious chemicals, and electric shock.[citation needed]

The inhibition of itch by painful stimuli, including heat, physical stimulus, and chemical stimulus, has been shown experimentally. In an article written by Louise Ward and others, the effects of noxious and non-noxious counterstimuli, such as heat, physical vibration, or chemical stimulation on skin, were studied in healthy adults after they had experimentally induced itch (transdermal iontophoresis of histamine) and pain (with topical mustard oil) in their skin. They found that when they induced non-noxious counterstimuli, the reduction of pain and itch only lasted for up to 20 seconds. However when they induced noxious counterstimuli, there was a significant inhibition of itch for an extended period of time but no inhibition of pain. In addition, it was found that brief noxious stimuli created an anti-itch state for more than 30 minutes. These findings show that itch is not a subliminal form of pain and that noxious counterstimulus is likely to act through a central mechanism, instead of a peripheral one.[14]

Chloroquine has been used in animal studies and in humans as a tool to study the itch mechanisms. In studies in rats, an inverted U-shaped dose response curve to chloroquine pruritogenicity was first described by Onigbogi et al.,[15] and has been subsequently confirmed by others.[16] This may suggest the involvement of several receptor types centrally. Indeed, naltrexone and Mu opiate down-regulation with chronic morphine attenuated the frequency of chloroquine pruritus in rats[15] and in mice.[16] Further, a kappa-opioid antagonist, nalfurafine further attenuated the chloroquine-induced itching frequency in mice.[16] These results further suggested that multiple opiate receptors (mu and kappa) interact to modulate itching behavior to chloroquine. Chloroquine exhibits a pharmacogenetic variation in its itch sensitivity, being common in Africans but rare in other races. It also shows an age-related difference in prevalence. Chloroquine itching is uncommon in children but increases in age with a peak in the fourth decade of life and with increased familial concurrence in families and concordance among twins.[17] Whether the pain sensation exhibits such distribution in Africans is yet to be studied.

Painful electrical stimulation reduced histamine-induced itch for several hours at a maximum distance of 10 cm from the stimulated site, which suggests a central mode of action.[citation needed] A new method has been recently found, by Hans-Jorgen Nilsson and others,[vague] that is able to relieve itch without damaging the skin: cutaneous field stimulation (CFS). CFS consists of a flexible rubber plate with 16 needle-like electrodes placed regularly at 2-centimeter intervals in a 4 by 4 matrix used to electrically stimulate nerve fibers in the surface of the skin. The electrodes were stimulated continuously at 4 hertz per electrode, with a pulse duration of 1 millisecond, and an intensity of 0.4–0.8 milliampere lasting for 25 minutes. CFS resulted in a pricking and burning sensation that usually faded away very quickly. The burning sensation was still present during a selective block of impulse conduction of A-fibres in myelinated fibers, which indicates that nociceptive C-fibres are activated by CFS. In addition, a flare reaction was noted to develop around the CFS electrodes, suggesting activation of axon reflexes in nociceptive C-fibres. Itch, which was induced by transdermal iontophoresis of histamine, was inhibited within the skin area treated with CFS and was also significantly reduced at 10 cm from the treatment area. CFS proves to offer a new method of combating itch by using painful electrical stimulation as it creates a long-lasting inhibitory effect, does not create any significant skin injuries, and is simple to apply. It is able to activate powerful itch-inhibitory mechanisms possibly routed through central mechanisms, which could normally be activated by scratching the skin.[18]

A study done by Gil Yosipovitch, Katharine Fast, and Jeffrey Bernhard showed that noxious heat and scratching were able to inhibit or decrease itch induced by transdermal iontophoresis of histamine and, most interestingly, decrease skin blood flow. Twenty-one healthy volunteers participated in the study. Baseline measurements of skin blood flow were obtained on the flexor part of the forearm and then compared with skin blood flow after various stimuli. Then transdermal iontophoresis of histamine was performed and tested with various stimuli. It is well known that skin blood flow is significantly increased during mechanical scratching, warming, and noxious heat. This study is the first to examine the changes of blood flow by stimuli during iontophoresis of histamine and how itch is perceived in those conditions. Its examination provided an unexpected result that noxious heat and scratching have an inhibitory effect.[19]

A negative correlation was found between pain sensitivity and itch sensitivity. In a study done by Amanda Green and others, they aimed to determine itch-related genetic factors and establish a more useful animal model for itch. They looked at 11 inbred mouse strains and compared their scratching behavior in response to two itch-inducing agents, histamine and chloroquine. Every strain revealed an inverted-U-shaped dose response relationship from chloroquine, indicating that moderate dosages produced more scratching than at higher dosages. An explanation is that higher dosage produces more pain and the presence of pain inhibits itch thereby lowering the amount of overall scratching. Another notable result was that histamine-induced scratching occurred in female mice on average 23% more than in males. Finally, it was found that mice having strains sensitive to pain were resistant to itch and vice versa.[20]

Peripheral sensitization[edit]

Inflammatory mediators—such as bradykinin, serotonin (5-HT) and prostaglandins—released during a painful or pruritic inflammatory condition not only activate pruriceptors but also cause acute sensitization of the nociceptors. In addition, expression of neuro growth factors (NGF) can cause structural changes in nociceptors, such as sprouting. NGF is high in injured or inflamed tissue. Increased NGF is also found in atopic dermatitis, a hereditary and non-contagious skin disease with chronic inflammation.[21] NGF is known to up-regulate neuropeptides, especially substance P. Substance P has been found to have an important role in inducing pain; however, there is no confirmation that substance P directly causes acute sensitization. Instead, substance P may contribute to itch by increasing neuronal sensitization and may affect release of mast cells, which contain many granules rich in histamine, during long-term interaction.[1]

Central sensitization[edit]

Noxious input to the spinal cord is known to produce central sensitization, which consists of allodynia, exaggeration of pain, and punctuate hyperalgesia, extreme sensitivity to pain. Two types of mechanical hyperalgesia can occur: 1) touch that is normally painless in the uninjured surroundings of a cut or tear can trigger painful sensations (touch-evoked hyperalgesia), and 2) a slightly painful pin prick stimulation is perceived as more painful around a focused area of inflammation (punctuate hyperalgesia). Touch-evoked hyperalgesia requires continuous firing of primary afferent nociceptors, and punctuate hyperalgesia does not require continuous firing which means it can persist for hours after a trauma and can be stronger than normally experienced. In addition, it was found that patients with neuropathic pain, histamine ionophoresis resulted in a sensation of burning pain rather than itch, which would be induced in normal healthy patients. This shows that there is spinal hypersensitivity to C-fiber input in chronic pain.[1]

Treatment[edit]

Main article: Antipruritic

A variety of over-the-counter and prescription anti-itch drugs are available. Some plant products have been found to be effective anti-pruritics, others not. Non-chemical remedies include cooling, warming, soft stimulation.

Topical antipruritics in the form of creams and sprays are often available over-the-counter. Oral anti-itch drugs also exist and are usually prescription drugs. The active ingredients usually belong to the following classes:

Phototherapy is helpful for severe itching, especially if caused by renal failure. The common type of light used is UVB.[9]

Sometimes scratching relieves isolated itches, hence the existence of devices such as the back scratcher. Often, however, scratching can intensify itching and even cause further damage to the skin, dubbed the "itch-scratch-itch cycle."[citation needed]

The mainstay of therapy for dry skin is maintaining adequate skin moisture and topical emollients.

Epidemiology[edit]

Approximately 280 million people globally (4% of the population) have difficulty with itchiness.[23]

See also[edit]

  • Formication, a sensation that resembles that of small insects crawling on or under the skin
  • Pruritus ani (also known as anusitis), irritation of skin at the exit of the rectum (anus), causing the desire to scratch
  • Referred itch, phenomenon in which a stimulus applied in one region of the body is felt as an itch or irritation in a different part of the body

Notes[edit]

  1. ^ a b c d e f g Ikoma A, Steinhoff M, Ständer S, Yosipovitch G, Schmelz M (2006). "The neurobiology of itch". Nat. Rev. Neurosci. 7 (7): 535–47. doi:10.1038/nrn1950. PMID 16791143. 
  2. ^ Greaves MW, Khalifa N (2004). "Itch: more than skin deep". Int. Arch. Allergy Immunol. 135 (2): 166–72. doi:10.1159/000080898. PMID 15375326. 
  3. ^ Karsak, M.; Gaffal, E.; Date, R.; Wang-Eckhardt, L.; Rehnelt, J.; Petrosino, S.; Starowicz, K.; Steuder, R. et al. (2007). "Attenuation of allergic contact dermatitis through the endocannabinoid system". Science 316 (5830): 1494–7. doi:10.1126/science.1142265. PMID 17556587. 
  4. ^ "Systemic Contact Dermatitis Elicited by Oral Intake of Balsam of Peru". 2003-02-20. Retrieved 2014-04-09. 
  5. ^ "Diagnosis and Management of Contact Dermatitis". Aafp.org. Retrieved 2014-04-09. 
  6. ^ Metalworking Fluids, Second Edition. 2006. Retrieved 2014-04-23. 
  7. ^ Ben F. Feingold. Introduction to clinical allergy. Retrieved 2014-04-23. 
  8. ^ James LaBagnara eMedicine –Hyperparathyroidism. emedicine.com
  9. ^ a b Botero F. (1978). "Pruritus as a manifestation of systemic disorders". Cutis; cutaneous medicine for the practitioner 21 (6): 873–80. PMID 657843. 
  10. ^ Yosipovitch G, Greaves MW, Schmelz M (2003). "Itch". Lancet 361 (9358): 690–4. doi:10.1016/S0140-6736(03)12570-6. PMID 12606187. 
  11. ^ a b c d Twycross, R.; Greaves, MW; Handwerker, H; Jones, EA; Libretto, SE; Szepietowski, JC; Zylicz, Z (2003). "Itch: scratching more than the surface". QJM 96 (1): 7–26. doi:10.1093/qjmed/hcg002. PMID 12509645. 
  12. ^ Schmelz M, Schmidt R, Bickel A, Handwerker HO, Torebjörk HE (1997). "Specific C-receptors for itch in human skin". J. Neurosci. 17 (20): 8003–8. PMID 9315918. 
  13. ^ Bernhard JD (2005). "Itch and pruritus: what are they, and how should itches be classified?". Dermatol Ther 18 (4): 288–91. doi:10.1111/j.1529-8019.2005.00040.x. PMID 16296999. 
  14. ^ Ward L, Wright E, McMahon SB (1996). "A comparison of the effects of noxious and innocuous counterstimuli on experimentally induced itch and pain". Pain 64 (1): 129–38. doi:10.1016/0304-3959(95)00080-1. PMID 8867255. 
  15. ^ a b Onigbogi O, Ajayi AA, Ukponmwan OE, (2000). "Mechanisms of Chloroquine-Induced Body-Scratching Behavior in Rats". Pharmacol Biochem Behavior 65 (2): 333. doi:10.1016/S0091-3057(99)00221-X. 
  16. ^ a b c Inan, Saadet; Cowan, Alan (2004). "Kappa opioid agonists suppress chloroquine-induced scratching in mice". European Journal of Pharmacology 502 (3): 233–7. doi:10.1016/j.ejphar.2004.09.010. PMID 15476749. 
  17. ^ Ajayi, A. A.; Oluokun, A.; Sofowora, O.; Akinleye, A.; Ajayi, A. T. (1989). "Epidemiology of antimalarial-induced pruritus in Africans". European Journal of Clinical Pharmacology 37 (5): 539–40. doi:10.1007/BF00558141. PMID 2598998. 
  18. ^ Nilsson HJ, Levinsson A, Schouenborg J (1997). "Cutaneous field stimulation (CFS): a new powerful method to combat itch". Pain 71 (1): 49–55. doi:10.1016/S0304-3959(97)03339-3. PMID 9200173. 
  19. ^ Yosipovitch G, Fast K, Bernhard JD (2005). "Noxious heat and scratching decrease histamine-induced itch and skin blood flow". J. Invest. Dermatol. 125 (6): 1268–72. doi:10.1111/j.0022-202X.2005.23942.x. PMID 16354198. 
  20. ^ Green AD, Young KK, Lehto SG, Smith SB, Mogil JS (2006). "Influence of genotype, dose and sex on pruritogen-induced scratching behavior in the mouse". Pain 124 (1–2): 50–8. doi:10.1016/j.pain.2006.03.023. PMID 16697529. 
  21. ^ Rukwied R, Lischetzki G, McGlone F, Heyer G, Schmelz M (2000). "Mast cell mediators other than histamine induce pruritus in atopic dermatitis patients: a dermal microdialysis study". Br. J. Dermatol. 142 (6): 1114–20. doi:10.1046/j.1365-2133.2000.03535.x. PMID 10848733. 
  22. ^ Hercogová J (2005). "Topical anti-itch therapy". Dermatologic therapy 18 (4): 341–3. doi:10.1111/j.1529-8019.2005.00033.x. PMID 16297007. 
  23. ^ Vos, T; Flaxman, Abraham D; Naghavi, Mohsen; Lozano, Rafael; Michaud, Catherine; Ezzati, Majid; Shibuya, Kenji; Salomon, Joshua A; Abdalla, Safa; Aboyans, Victor; Abraham, Jerry; Ackerman, Ilana; Aggarwal, Rakesh; Ahn, Stephanie Y; Ali, Mohammed K; Almazroa, Mohammad A; Alvarado, Miriam; Anderson, H Ross; Anderson, Laurie M; Andrews, Kathryn G; Atkinson, Charles; Baddour, Larry M; Bahalim, Adil N; Barker-Collo, Suzanne; Barrero, Lope H; Bartels, David H; Basáñez, Maria-Gloria; Baxter, Amanda; Bell, Michelle L et al. (Dec 15, 2012). "Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet 380 (9859): 2163–96. doi:10.1016/S0140-6736(12)61729-2. PMID 23245607. 

References[edit]

External links[edit]