Anitch (also known aspruritus) is asensation that causes a strong desire orreflex to scratch.[1] Itches have many similarities topain, and while both are unpleasant sensory experiences, their behavioral response patterns are different. Pain creates awithdrawal reflex, whereas itches lead to ascratch reflex.[2]
Unmyelinatednerve fibers for itches and pain both originate in theskin. Information for them is conveyed centrally in two distinct systems that both use the samenerve bundle andspinothalamic tract.[3]
Most commonly, an itch is felt in one place. If it is felt all over the body, then it is calledgeneralized itch orgeneralized pruritus.[4] Generalized itch is infrequently a symptom of a serious underlying condition, such ascholestatic liver disease.
If the sensation of itching persists for six weeks or longer, then it is calledchronic itch orchronic pruritus.[4][5]Chronic idiopathic pruritus orchronic pruritus of unknown origin is a form of itch that persists for longer than six weeks, and for whichno clear cause can be identified.[6][7]
Pain and itch have different mechanisms of onset and different behavioral responses. Pain elicits a withdrawal reflex, which leads to retraction, and therefore a reaction trying to protect an endangered part of the body. By contrast, an itch creates ascratch reflex, which draws one to the affected skin site. Itch generates stimulus of a foreign object underneath or upon the skin, and also the urge to remove it. For example, responding to a local itch sensation is an effective way to remove insects from one's skin.
Scratching has traditionally been regarded as a way to relieve oneself by reducing the annoying itch sensation. However, there arehedonic aspects to scratching, as one would find noxious scratching highly pleasurable.[2] This can be problematic withchronic itch patients, such as ones withatopic dermatitis, who may scratch affected spots until they no longer produce a pleasant or painful sensation, instead of when the itch sensation disappears.[8] These aspects might contribute to the compulsive nature of itch and scratching.[2]
Studies done in the last decade have shown that itch can be inhibited by many other forms of painful stimuli, such asnoxious heat,[9] physical rubbing or scratching, noxious chemicals, andelectric shock.[10]
Xerosis, dry skin, frequently seen in the winter and also associated with older age, frequent bathing in hot showers or baths, and high-temperature and low-humidity environments.
Polycythemia, which can cause generalized itching due to increased histamines. Inpolycythemia vera itching is particularly caused by skin contact with warm water, such as in bath or shower.
Itch originating in the skin is known aspruritoceptive, and can be induced by a variety of stimuli, including mechanical, chemical, thermal, and electrical stimulation, or infection. The primaryafferent neurons responsible forhistamine-induced itch areunmyelinatedC-fibres.[1]
Nociceptors. Two major classes of humanC-fibrenociceptors exist: mechano-responsivenociceptors 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 itch produced without aflare reaction that involves no histamine.[1] Therefore, it is possible that pruritoceptivenerve fibres have different classes of fibres, which is unclear in current research.[2]
Histology and skin layers. Sensitivity to pruritic stimuli is evenly distributed across the skin and has a clear spot distribution with similar density to that of pain.[medical citation needed] The different substances that elicit itch upon intracutaneous injection (injection within the skin) elicit only pain when injectedsubcutaneously (beneath the skin).[citation needed]
Itch is often classified as that which is histamine mediated (histaminergic) and nonhistaminergic.
Itch is readily abolished in skin areas treated with nociceptorexcitotoxincapsaicin but remains unchanged in skin areas rendered touch insensitive by pretreatment withanti-inflammatorysaponins. Although experimentally induced itch can still be perceived under a complete A-fiberconduction block, it is significantly diminished. Overall, itch sensation is mediated by A-delta and C nociceptors located in the uppermost layer of the skin.[26]
Gene expression. Using single-cell mRNA sequencing, clusters of genes expressed in itch-related tissues were identified, e.g. NP1-3, transmitting itch information; where NP3 expresses neuropeptidesNppb andSst as well as genes involved in inflammatory itch (Il31ra,Osmr andCrystrl2). The histamine receptor geneHrh1 was found in NP2 and NP3, suggesting that histaminergic itch is transmitted by both these pruriceptive sub clusters.[27]
Infection.Staphylococcus aureus, a bacterial pathogen associated with itchy skin diseases, directly activates pruriceptor sensory neurons to drive itch. Skin exposure toS. aureus causes robust itch and scratch-induced damage.[28]
After the pruriceptive primary afferent has been activated, the signal is transmitted from the skin into the spinal dorsal horn. In this area, a number of interneurons will either be inhibited or activated to promote activation of projection neurons, mediating the pruriceptive signal to the brain. The GRP-GRPR interneuron system has been found to be important for mediating both histaminergic and non-histaminergic itch, where the GRP neurons activate GRPR neurons to promote itch.[29][30]
Neurogenic itch, which is itch induced centrally but with no neural damage, is mostly associated with increased accumulation of exogenousopioids and possiblysynthetic opioids.[24]
Inflammatory mediators—such asbradykinin,serotonin (5-HT) andprostaglandins—released during a painful or pruritic inflammatory condition not only activate pruriceptors but also causeacute sensitization of the nociceptors. In addition, expression of neuro growth factors (NGF) can cause structural changes innociceptors, such as sprouting. NGF is high in injured or inflamed tissue. Increased NGF is also found inatopic dermatitis, ahereditary and non-contagious skin disease withchronicinflammation.[32] NGF is known to up-regulate neuropeptides, especiallysubstance 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 increasingneuronal sensitization and may affect release ofmast cells, which contain many granules rich in histamine, during long-term interaction.[2]
Noxious input to thespinal cord is known to produce central sensitization, which consists ofallodynia, exaggeration of pain, and punctuatehyperalgesia, 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 punctuatehyperalgesia does not require continuous firing which means it can persist for hours after atrauma and can be stronger than normally experienced. In addition, it was found that patients withneuropathic pain, histamineionophoresis 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 toC-fiber input inchronic pain.[2]
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.
Crotamiton (trade name Eurax) is an antipruritic agent available as a cream or lotion, often used to treatscabies. Its mechanism of action remains unknown.
Sometimes scratching relieves isolated itches, hence the existence of devices such as theback scratcher. Often, however, scratching only offers temporary relief and can intensify itching, even causing further damage to the skin, dubbed the "itch-scratch cycle".[36]
The mainstay of therapy for dry skin is maintaining adequate skin moisture and topicalemollients.
No studies have been conducted to investigate the effectiveness of emollient creams, cooling lotions, topical corticosteroids, topical antidepressants, systemic antihistamines, systemic antidepressants, systemic anticonvulsants, and phototherapy on chronic pruritus of unknown origin.[33] However, there are clinical trials currently underway withdupilumab which is thought to alleviate itch by acting on the IL-4 receptor on sensory neurons.[37][38] The effectiveness of therapeutic options for people who are terminally ill with malignant cancer is not known.[22]
Approximately 280 million people globally, 4% of the population, have difficulty with itchiness.[39] This is comparable to the 2–3% of the population who havepsoriasis.
^Ward L, Wright E, McMahon SB (January 1996). "A comparison of the effects of noxious and innocuous counterstimuli on experimentally induced itch and pain".Pain.64 (1):129–138.doi:10.1016/0304-3959(95)00080-1.PMID8867255.S2CID25772165.
^Karaosmanoğlu, N.; Cetinkaya, P. O.; Mülkoğlu, C. (2024). "Investigating the relationship between chronic pruritus and fibromyalgia: An evaluation of 200 patients".Archives of Dermatological Research.316 (8): 545.doi:10.1007/s00403-024-03291-8.PMID39162842.
^Usoskin D, Furlan A, Islam S, et al. (January 2015). "Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing".Nature Neuroscience.18 (1):145–153.doi:10.1038/nn.3881.PMID25420068.S2CID205437148.
^Rukwied R, Lischetzki G, McGlone F, et al. (June 2000). "Mast cell mediators other than histamine induce pruritus in atopic dermatitis patients: a dermal microdialysis study".The British Journal of Dermatology.142 (6):1114–1120.doi:10.1046/j.1365-2133.2000.03535.x.PMID10848733.S2CID23996950.
Andrew D, Craig AD (January 2001). "Spinothalamic lamina I neurons selectively sensitive to histamine: a central neural pathway for itch".Nature Neuroscience.4 (1):72–77.doi:10.1038/82924.PMID11135647.S2CID28727869.
"Pruritus". National Cancer Institute. 2003. Archived fromthe original on 25 December 2005. Retrieved22 August 2005.
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