Itch (also known as pruritus) is a sensation that causes a strong desire or reflex to scratch.[1] Itches have resisted many attempts to be classified as any one type of sensory experience. Itches have many similarities to pain, and while both are unpleasant sensory experiences, their behavioral response patterns are different. Pain creates a withdrawal reflex, whereas itches leads to a scratch reflex.[2]
Unmyelinated nerve fibers for itches and pain both originate in the skin. Information for them is conveyed centrally in two distinct systems that both use the same nerve bundle and spinothalamic tract.[3]
Most commonly, an itch is felt in one place. If it is felt all over the body, then it is called generalized itchorgeneralized pruritus.[4] Generalized itch is infrequently a symptom of a serious underlying condition, such as cholestatic liver disease.
If the sensation of itching persists for six weeks or longer, then it is called chronic itchorchronic pruritus.[4][5]Chronic idiopathic pruritusorChronic Pruritus of Unknown Origin is a form of itch that persists for longer than six weeks, and for which no clear cause can be identified.[6][7]
Pain and itch have very different behavioral response patterns. Pain elicits 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. 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 are hedonic aspects to scratching, as one would find noxious scratching highly pleasurable.[2] 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.[8] 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.[2]
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 one scratches. Results from a study showed that itching and scratching were induced purely by visual stimuli in a public lecture on itching. The sensation of pain can also be induced in a similar fashion, often by listening to a description of an injury, or viewing an injury itself.
There is little detailed data on central activation for contagious itching, but it is hypothesized that a human mirror neuron system exists in which one imitates certain motor actions when they view others performing the same action. A similar hypothesis has been used to explain the cause of contagious yawning.[2]
Studies done in the last decade have shown that itch can be inhibited by many other forms of painful stimuli, such as noxious heat,[9] physical rubbing/scratching, noxious chemicals, and electric 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.
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, or infection. The primary afferent neurons responsible for histamine-induced itch are unmyelinatedC-fibres.[1]
Nociceptors. Two major classes of human C-fibrenociceptors 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 itch produced without a flare reaction that involves no histamine.[1] Therefore, it is possible that pruritoceptive nerve fibres have different classes of fibres, which is unclear in current research.[2]
Histology and skin layers. 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 verified the depth by injecting individual itch powder (Mucuna pruriens) spicules and noting that maximal sensitivity occurred 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.[citation needed]
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).[citation needed]
Itch is often classified as that which is histamine mediated (histaminergic) and nonhistaminergic.
Itch is readily abolished in skin areas treated with nociceptor excitotoxincapsaicin but remains unchanged in skin areas rendered touch insensitive by pretreatment with anti-inflammatorysaponins. 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.[21]
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 neuropeptides Nppb and Sst as well as genes involved in inflammatory itch (Il31ra, Osmr andCrystrl2). The histamine receptor gene Hrh1 was found in NP2 and NP3, suggesting that histaminergic itch is transmitted by both these pruriceptive sub clusters.[22]
Infection. Staphylococcus aureus, a bacterial pathogen associated with itchy skin diseases, directly activates pruriceptor sensory neurons to drive itch. Skin exposure to S. aureus causes robust itch and scratch-induced damage. This reaction is mediated by S. aureus serine protease V8 which cleaves proteinase-activated receptor 1 (PAR1) on mouse and human sensory neurons. Targeting PAR1 through genetic deficiency, small interfering RNA (siRNA) knockdown, or pharmacological blockade decreases itch and skin damage caused by V8 and S. aureus exposure.[23]
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 [24][25]
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.[19]
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 chronicinflammation.[27] 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.[2]
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.[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 treat scabies. Its mechanism of action remains unknown.
Sometimes scratching relieves isolated itches, hence the existence of devices such as the back scratcher. Often, however, scratching only offers temporary relief and can intensify itching, even causing further damage to the skin, dubbed the "itch-scratch cycle".[31]
The mainstay of therapy for dry skin is maintaining adequate skin moisture and topical emollients.
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.[28] However, there are clinical trials currently underway with dupilumab which is thought to alleviate itch by acting on the IL-4 receptor on sensory neurons.[32][33] The effectiveness of therapeutic options for people who are terminally ill with malignant cancer is not known.[17]
Approximately 280 million people globally, 4% of the population, have difficulty with itchiness.[34] This is comparable to the 2–3% of the population who have psoriasis.
^Greaves MW, Khalifa N (October 2004). "Itch: more than skin deep". International Archives of Allergy and Immunology. 135 (2): 166–172. doi:10.1159/000080898. PMID15375326. S2CID13376216.
^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.
^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.
^Jean Bolognia; Joseph L. Jorizzo; Ronald P. Rapini (2008). Dermatology (2nd ed.). St. Louis, Mo.: Mosby/Elsevier. ISBN978-1-4160-2999-1. OCLC212399895.
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 from the original on 25 December 2005. Retrieved 22 August 2005.
