Editing Itch

{{Short description|Uncomfortable skin sensation}}
{{Other uses}}
{{Infobox medical condition
| name          = Itch
| synonyms      = 
| image         = Itch 01.JPG
| caption       = A man scratching his back
| pronounce     = 
| field         = [[Dermatology]]
| symptoms      = [[Scratch reflex|Compulsion to scratch]] an irritated area of skin
| complications = 
| onset         = 
| duration      = 
| types         = 
| causes        = Certain infections, allergies, blood derangements and environmental factors
| risks         = [[Dry skin]]
| diagnosis     = Often based on the causes of itching
| differential  = [[Pain]]
| prevention    = 
| treatment     = [[Antipruritic]]s, [[phototherapy]]
| medication    = 
| prognosis     = 
| frequency     = 
| deaths        = 
}}

An '''itch''' (also known as '''pruritus''') is a [[Wikt:sensation|sensation]] that causes a strong desire or [[reflex to scratch]].<ref name=andersen>{{cite journal |vauthors=Andersen HH, Elberling J, Arendt-Nielsen L |title=Human surrogate models of histaminergic and non-histaminergic itch |journal=Acta Dermato-Venereologica |volume=95 |issue=7 |pages=771–777 |date=September 2015 |pmid=26015312 |doi=10.2340/00015555-2146 |doi-access=free}}</ref> Itches have resisted many attempts to be classified as any one type of [[sense|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]].<ref name=ikoma>{{cite journal |vauthors=Ikoma A, Steinhoff M, Ständer S, Yosipovitch G, Schmelz M |display-authors=3 |title=The neurobiology of itch |journal=Nature Reviews. Neuroscience |volume=7 |issue=7 |pages=535–547 |date=July 2006 |pmid=16791143 |doi=10.1038/nrn1950 |s2cid=9373105}}</ref>

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]].<ref>{{cite journal |vauthors=Greaves MW, Khalifa N |title=Itch: more than skin deep |journal=International Archives of Allergy and Immunology |volume=135 |issue=2 |pages=166–172 |date=October 2004 |pmid=15375326 |doi=10.1159/000080898 |s2cid=13376216}}</ref>

== Classification ==
Most commonly, an itch is felt in one place. If it is felt all over the body, then it is called ''generalized itch'' or ''generalized pruritus''.<ref name=":0">{{cite journal |vauthors=Molkara S, Sabourirad S, Molooghi K |title=Infectious differential diagnosis of chronic generalized pruritus without primary cutaneous lesions: a review of the literature |journal=International Journal of Dermatology |volume=59 |pages=30–36 |date=July 2019 |issue=1 |pmid=31364165 |doi=10.1111/ijd.14587 |s2cid=198998956 |doi-access=free}}</ref> 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 itch'' or ''chronic pruritus''.<ref name=":0" /><ref>{{cite journal |vauthors=Harrison IP, Spada F |title=Breaking the Itch-Scratch Cycle: Topical Options for the Management of Chronic Cutaneous Itch in Atopic Dermatitis |journal=Medicines |volume=6 |issue=3 |page=76 |date=July 2019 |pmid=31323753 |pmc=6789602 |doi=10.3390/medicines6030076 |doi-access=free}}</ref> ''Chronic idiopathic pruritus'' or ''Chronic Pruritus of Unknown Origin'' is a form of itch that persists for longer than six weeks, and for which [[idiopathic disease|no clear cause can be identified]].<ref>{{cite journal |vauthors=Erickson S, Nahmias Z, Rosman IS, Kim BS |title=Immunomodulating Agents as Antipruritics |journal=Dermatologic Clinics |volume=36 |issue=3 |pages=325–334 |date=July 2018 |pmid=29929604 |doi=10.1016/j.det.2018.02.014 |s2cid=49336771}}</ref><ref>{{Cite book |vauthors=Hinkle JL, Cheever KH |url=https://books.google.com/books?id=yS7vDwAAQBAJ&pg=PA1269 |title=Brunner and Suddarth's Textbook of Medical-Surgical Nursing |date=2018-08-30 |publisher=Wolters kluwer india Pvt Ltd |isbn=978-93-87963-72-6 |pages=1269 |language=en |access-date=2022-07-02 |archive-date=2023-09-23 |archive-url=https://web.archive.org/web/20230923133951/https://books.google.com/books?id=yS7vDwAAQBAJ&pg=PA1269 |url-status=live }}</ref>

== Signs and symptoms ==
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.<ref name=ikoma/> This can be problematic with [[chronic (medicine)|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.<ref>{{cite journal |vauthors=Karsak M, Gaffal E, Date R, Wang-Eckhardt L, Rehnelt J, Petrosino S, Starowicz K, Steuder R, Schlicker E, Cravatt B, Mechoulam R, Buettner R, Werner S, Di Marzo V, Tüting T, Zimmer A |display-authors=3 |title=Attenuation of allergic contact dermatitis through the endocannabinoid system |journal=Science |volume=316 |issue=5830 |pages=1494–1497 |date=June 2007 |pmid=17556587 |doi=10.1126/science.1142265 |s2cid=37611370 |bibcode=2007Sci...316.1494K}}</ref> 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.<ref name=ikoma/>

=== Contagious itch ===
Events of "[[Contagious disease|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 [[Stimulus (physiology)|stimuli]] in a public lecture on itching.<ref>[citation needed]</ref> 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]].<ref name=ikoma/>

=== Itch inhibition due to pain ===
Studies done in the last decade have shown that itch can be inhibited by many other forms of painful stimuli, such as [[Noxious stimulus|noxious]] heat,<ref>{{cite journal |vauthors=Yosipovitch G, Fast K, Bernhard JD |title=Noxious heat and scratching decrease histamine-induced itch and skin blood flow |journal=The Journal of Investigative Dermatology |volume=125 |issue=6 |pages=1268–1272 |date=December 2005 |pmid=16354198 |doi=10.1111/j.0022-202X.2005.23942.x |doi-access=free}}</ref> physical rubbing/scratching, noxious chemicals, and [[electric shock]].<ref>{{cite journal |vauthors=Ward L, Wright E, McMahon SB |title=A comparison of the effects of noxious and innocuous counterstimuli on experimentally induced itch and pain |journal=Pain |volume=64 |issue=1 |pages=129–138 |date=January 1996 |pmid=8867255 |doi=10.1016/0304-3959(95)00080-1 |s2cid=25772165}}</ref>

== Causes ==
[[File:Scabies-burrow.jpg|thumb|[[Scabies]] is one cause of itching]]
[[File:CercariaDermatitis.JPG|thumb|[[Swimmer's itch]]]]
[[File:Tinea pedis interdigitalis.jpg|thumb|[[Athlete's foot]] (showing the toes from below plus the front part of the sole)]]

=== Infectious ===
*[[Body louse]], found in substandard living conditions
*[[Cutaneous larva migrans]], a skin disease caused by [[hookworm]] infection
*[[Head lice]], if limited to the neck and scalp
*[[Herpes]], a viral disease
*[[Insect bite]]s, such as those from [[mosquitos]] or [[chiggers]]
*[[Pubic lice]], if limited to the [[genital area]]
*[[Scabies]], especially when several other persons in close contact also itch
*[[Shaving#Razor burn|Shaving]], which may irritate the skin
*[[Swimmer's itch]], a short-term immune reaction
*[[Chickenpox|Varicella]]&nbsp;– i.e. chickenpox, prevalent among young children and highly contagious
*[[Tungiasis]], ectoparasite of skin

=== Environmental and allergic ===
*[[Allergic reaction]] to contact with specific chemicals, such as [[urushiol]], derived from [[poison ivy]] or [[poison oak]], or [[Balsam of Peru]], found in many foods and fragrances.<ref>{{cite journal |vauthors=Pfützner W, Thomas P, Niedermeier A, Pfeiffer C, Sander C, Przybilla B |display-authors=3 |title=Systemic contact dermatitis elicited by oral intake of Balsam of Peru |journal=Acta Dermato-Venereologica |volume=83 |issue=4 |pages=294–295 |date=2003-02-20 |pmid=12926805 |doi=10.1080/00015550310016599 |doi-access=free}}</ref><ref>{{cite journal |vauthors=Usatine RP, Riojas M |title=Diagnosis and management of contact dermatitis |journal=American Family Physician |volume=82 |issue=3 |pages=249–255 |date=August 2010 |pmid=20672788 |url=http://www.aafp.org/afp/2010/0801/p249.html |access-date=2014-04-09 |publisher=Aafp.org |archive-date=2014-04-09 |archive-url=https://web.archive.org/web/20140409161328/http://www.aafp.org/afp/2010/0801/p249.html |url-status=live }}</ref> Certain allergens may be diagnosed in a [[patch test]].<ref>{{cite book |url=https://books.google.com/books?id=QhWgKgiT6FoC&pg=PA329 |title=Metalworking Fluids |edition=Second |publisher=CRC Press |isbn=142001773X |date=2006 |vauthors=Byers JP |access-date=2016-03-05 |archive-date=2023-01-12 |archive-url=https://web.archive.org/web/20230112213927/https://books.google.com/books?id=QhWgKgiT6FoC&pg=PA329 |url-status=live }}</ref><ref>{{cite book |url=https://books.google.com/books?id=Me5rAAAAMAAJ&q=pruritus+%22patch+test%22 |title=Introduction to clinical allergy |vauthors=Feingold BF |veditors=Byers JP |publisher=the University of Michigan |date=1973 |isbn=0398027978 |access-date=2020-06-24 |archive-date=2023-01-12 |archive-url=https://web.archive.org/web/20230112223856/https://books.google.com/books?id=Me5rAAAAMAAJ&q=pruritus+%22patch+test%22 |url-status=live }}</ref>
*[[Foreign body|Foreign object]]s on the skin are the most common cause of non-pathological itching. 
*[[Photodermatitis]]&nbsp;– [[sunlight]] reacts with chemicals in the skin, leading to the formation of irritant metabolites.
*[[Urticaria]] (also called [[hives]]) usually causes itching.

=== Dermatologic ===
* [[Dandruff]], an unusually large amount of flaking is associated with this sensation.
* [[Punctate palmoplantar keratoderma]], a group of disorders characterized by abnormal thickening of the palms and soles.
* [[Skin condition]]s (such as [[psoriasis]], [[eczema]], [[seborrhoeic dermatitis]], [[sunburn]], [[athlete's foot]], and [[hidradenitis suppurativa]]). Most are of an inflammatory nature.
* [[Wound healing|Scab]] healing, [[scar]] growth, and the development or emergence of [[Melanocytic nevus|moles]], [[pimple]]s, and [[ingrown hair]]s from below the epidermis.
* [[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.

=== Other diseases ===
* [[Diabetes mellitus]], a group of metabolic diseases in which a person has high blood sugar
* [[Hyperparathyroidism]], overactivity of the parathyroid glands resulting in excess production of parathyroid hormone (PTH)<ref>LaBagnara, James. [http://www.emedicine.com/ent/TOPIC299.HTM eMedicine&nbsp;–Hyperparathyroidism] {{Webarchive|url=https://web.archive.org/web/20081202153050/http://www.emedicine.com/ent/topic299.htm |date=2008-12-02 }}. emedicine.com</ref>
* [[Iron deficiency anemia]], a common anemia (low red blood cell or hemoglobin levels)
* [[Cholestasis]], where bile acids leaking into the serum activate peripheral opioid receptors, resulting in the characteristic generalized, severe itching
* [[Malignancy]] or internal cancer, such as [[lymphoma]] or [[Hodgkin's disease]]<ref>{{Cite journal |last1=Jovičić |first1=Sanja |last2=Balaban |first2=Jagoda |last3=Gajanin |first3=Vesna |date=2023-06-24 |title=Association of systemic diseases with chronic pruritus |journal=Scripta Medica |volume=54 |issue=2 |pages=163–167 |doi=10.5937/scriptamed54-43882 |issn=2490-3329|doi-access=free }}</ref>
* [[Polycythemia]], which can cause generalized itching due to increased histamines
* [[Psychiatric]] disease ("[[psychogenic disease|psychogenic itch]]", as may be seen in [[delusional parasitosis]])
* [[Thyroid]] illness
* [[Uraemia]]&nbsp;– the itching sensation this causes is known as [[uremic pruritus]]

=== Medication ===
* Drugs (such as [[opioids]]) that activate histamine (H1) receptors or trigger histamine release
* [[Chloroquine]], a drug used in the treatment and prevention of [[malaria]]
* [[Bile acid]] congeners such as obeticholic acid

=== Related to pregnancy ===
* [[Gestational pemphigoid]], a dermatosis of pregnancy
* [[Intrahepatic cholestasis of pregnancy]], a medical condition in which cholestasis occurs
* [[Pruritic urticarial papules and plaques of pregnancy]] (PUPPP), a chronic hives-like rash

=== Other ===
* [[Menopause]], or changes in hormonal balances associated with aging
*[[Terminal illness]]<ref name=":1">{{Cite journal |last1=Boehlke |first1=Christopher |last2=Joos |first2=Lisa |last3=Coune |first3=Bettina |last4=Becker |first4=Carola |last5=Meerpohl |first5=Joerg J. |last6=Buroh |first6=Sabine |last7=Hercz |first7=Daniel |last8=Schwarzer |first8=Guido |last9=Becker |first9=Gerhild |date=2023-04-14 |title=Pharmacological interventions for pruritus in adult palliative care patients |url=https://pubmed.ncbi.nlm.nih.gov/37314034 |journal=The Cochrane Database of Systematic Reviews |volume=4 |issue=2023 |pages=CD008320 |doi=10.1002/14651858.CD008320.pub4 |issn=1469-493X |pmid=37314034 |pmc=11339634 |pmc-embargo-date=August 22, 2025 |access-date=2023-07-27 |archive-date=2023-07-27 |archive-url=https://web.archive.org/web/20230727181335/https://pubmed.ncbi.nlm.nih.gov/37314034/ |url-status=live }}</ref>

== Mechanism ==
Itch can originate in the [[peripheral nervous system]] ([[dermal]] or [[neuropathic]]) or in the [[central nervous system]] (neuropathic, [[neurogenic]], or [[psychogenic pain|psychogenic]]).<ref>{{cite journal |vauthors=Yosipovitch G, Greaves MW, Schmelz M |title=Itch |journal=Lancet |volume=361 |issue=9358 |pages=690–694 |date=February 2003 |pmid=12606187 |doi=10.1016/S0140-6736(03)12570-6 |s2cid=208793207}}</ref><ref name=twycross>{{cite journal |vauthors=Twycross R, Greaves MW, Handwerker H, Jones EA, Libretto SE, Szepietowski JC, Zylicz Z |display-authors=3 |title=Itch: scratching more than the surface |journal=QJM |volume=96 |issue=1 |pages=7–26 |date=January 2003 |pmid=12509645 |doi=10.1093/qjmed/hcg002 |doi-access=free}}</ref><ref>{{Cite web |url=https://medical-dictionary.thefreedictionary.com/essential+pruritus |title=Essential pruritus |access-date=25 July 2019 |archive-date=6 August 2020 |archive-url=https://web.archive.org/web/20200806141524/https://medical-dictionary.thefreedictionary.com/essential+pruritus |url-status=live }}</ref>

=== Pruritoceptive ===
{{multiple image
| width             = 220
| image1            = Squirrel Scratching the Armpit with its Hindlimb.jpg
| direction         = vertical
| caption1          = A [[ground squirrel]] scratching itself
| image2            = Canis lupus scratching.jpg
| caption2          = A [[wolf]] scratching itself
| image3            = Lioness (Panthera leo) scratching ... (52016987141).jpg
| caption3          = A [[lion]]ess scratching herself
}}

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 neuron]]s responsible for [[histamine]]-induced itch are [[unmyelinated]] [[group C nerve fiber|C-fibres]].<ref name=andersen/>

'''Nociceptors'''. Two major classes of human [[Group C nerve fiber|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 itch produced without a [[flare]] reaction that involves no histamine.<ref name=andersen/> Therefore, it is possible that pruritoceptive [[nerve fibre]]s have different classes of fibres, which is unclear in current research.<ref name=ikoma/>

'''Histology and skin layers'''. Studies have been done to show that itch receptors are found only on the top two [[skin]] layers, the [[Epidermis (skin)|epidermis]] and the epidermal/[[dermal]] transition layers.{{Citation needed|date=August 2008}} Shelley and Arthur verified the depth by injecting individual itch powder (''[[Mucuna pruriens]]'') [[wikt:spicule|spicule]]s 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|date=August 2008}} Itch is never felt in [[muscle]] or joints, which strongly suggests that deep tissue probably does not contain itch signaling apparatuses.{{citation needed|date=October 2021}}

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|date=October 2021}}

=== Molecular basis ===
Itch is often classified as that which is histamine mediated (histaminergic) and nonhistaminergic.

Itch is readily abolished in skin areas treated with nociceptor [[Excitotoxicity|excitotoxin]] [[capsaicin]] but remains unchanged in skin areas rendered touch insensitive by pretreatment with [[anti-inflammatory]] [[saponin]]s. Although experimentally induced itch can still be perceived under a complete A-fiber [[nerve block|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.<ref>{{cite journal |vauthors=Schmelz M, Schmidt R, Bickel A, Handwerker HO, Torebjörk HE |display-authors=3 |title=Specific C-receptors for itch in human skin |journal=The Journal of Neuroscience |volume=17 |issue=20 |pages=8003–8008 |date=October 1997 |pmid=9315918 |pmc=6793906 |doi=10.1523/JNEUROSCI.17-20-08003.1997}}</ref>

'''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 and'' ''Crystrl2''). The histamine receptor gene ''Hrh1'' was found in NP2 and NP3, suggesting that histaminergic itch is transmitted by both these pruriceptive sub clusters.<ref>{{cite journal |vauthors=Usoskin D, Furlan A, Islam S, Abdo H, Lönnerberg P, Lou D, Hjerling-Leffler J, Haeggström J, Kharchenko O, Kharchenko PV, Linnarsson S, Ernfors P |display-authors=3 |title=Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing |journal=Nature Neuroscience |volume=18 |issue=1 |pages=145–153 |date=January 2015 |pmid=25420068 |doi=10.1038/nn.3881 |s2cid=205437148}}</ref>

'''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 (gene)|PAR1]]) on mouse and human sensory neurons. Targeting PAR1 through genetic deficiency, small interfering RNA ([[Small interfering RNA|siRNA]]) knockdown, or pharmacological blockade decreases itch and skin damage caused by V8 and ''S. aureus'' exposure.<ref>{{Cite journal |title=S. aureus drives itch and scratch-induced skin damage through a V8 protease-PAR1 axis |url=https://doi.org/10.1016/j.cell.2023.10.019 |journal=[[Cell (journal)|Cell]] |date=2023 |doi=10.1016/j.cell.2023.10.019 |last1=Deng |first1=Liwen |last2=Costa |first2=Flavia |last3=Blake |first3=Kimbria J. |last4=Choi |first4=Samantha |last5=Chandrabalan |first5=Arundhasa |last6=Yousuf |first6=Muhammad Saad |last7=Shiers |first7=Stephanie |last8=Dubreuil |first8=Daniel |last9=Vega-Mendoza |first9=Daniela |last10=Rolland |first10=Corinne |last11=Deraison |first11=Celine |last12=Voisin |first12=Tiphaine |last13=Bagood |first13=Michelle D. |last14=Wesemann |first14=Lucia |last15=Frey |first15=Abigail M. |last16=Palumbo |first16=Joseph S. |last17=Wainger |first17=Brian J. |last18=Gallo |first18=Richard L. |last19=Leyva-Castillo |first19=Juan-Manuel |last20=Vergnolle |first20=Nathalie |last21=Price |first21=Theodore J. |last22=Ramachandran |first22=Rithwik |last23=Horswill |first23=Alexander R. |last24=Chiu |first24=Isaac M. |volume=186 |issue=24 |pages=5375–5393.e25 |pmid=37995657 |pmc=10669764 }}</ref>

=== Spinal itch pathway ===
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 <ref>{{cite journal |vauthors=Han L, Ma C, Liu Q, Weng HJ, Cui Y, Tang Z, Kim Y, Nie H, Qu L, Patel KN, Li Z, McNeil B, He S, Guan Y, Xiao B, Lamotte RH, Dong X |display-authors=3 |title=A subpopulation of nociceptors specifically linked to itch |journal=Nature Neuroscience |volume=16 |issue=2 |pages=174–182 |date=February 2013 |pmid=23263443 |pmc=3557753 |doi=10.1038/nn.3289}}</ref><ref>{{cite journal |vauthors=Sun YG, Chen ZF |title=A gastrin-releasing peptide receptor mediates the itch sensation in the spinal cord |journal=Nature |volume=448 |issue=7154 |pages=700–703 |date=August 2007 |pmid=17653196 |doi=10.1038/nature06029 |bibcode=2007Natur.448..700S |s2cid=4407979}}</ref>

=== Neuropathic ===
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]].<ref name=twycross/> Examples of neuropathic itch in origin are notalgia paresthetica, [[brachioradial pruritus]], [[brain tumors]], [[multiple sclerosis]], [[peripheral neuropathy]], and [[nerve injury|nerve irritation]].<ref>{{cite journal |vauthors=Bernhard JD |title=Itch and pruritus: what are they, and how should itches be classified? |journal=Dermatologic Therapy |volume=18 |issue=4 |pages=288–291 |year=2005 |pmid=16296999 |doi=10.1111/j.1529-8019.2005.00040.x |s2cid=7107271 |doi-access=free}}</ref>

=== Neurogenic ===
Neurogenic itch, which is itch induced centrally but with no neural damage, is mostly associated with increased accumulation of exogenous [[opioids]] and possibly [[Organic compound#Synthetic compounds|synthetic]] opioids.<ref name=twycross/>

=== Psychogenic ===
Itch is also associated with some symptoms of [[psychiatric]] disorders such as tactile [[hallucinations]], [[delusions]] of [[parasitosis]], or [[obsessive-compulsive disorder]]s (as in [[Obsessive–compulsive disorder|OCD]]-related [[neurosis|neurotic]] scratching).<ref name=twycross/>

=== Peripheral sensitization ===
[[Inflammation|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 (medicine)|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 (medicine)|chronic]] [[inflammation]].<ref>{{cite journal |vauthors=Rukwied R, Lischetzki G, McGlone F, Heyer G, Schmelz M |display-authors=3 |title=Mast cell mediators other than histamine induce pruritus in atopic dermatitis patients: a dermal microdialysis study |journal=The British Journal of Dermatology |volume=142 |issue=6 |pages=1114–1120 |date=June 2000 |pmid=10848733 |doi=10.1046/j.1365-2133.2000.03535.x |s2cid=23996950}}</ref> 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.<ref name=ikoma/>

=== Central sensitization ===
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 [[Physical trauma|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 (medicine)|chronic]] pain.<ref name=ikoma/>

== Treatment ==
{{Main|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 [[cream (pharmaceutical)|cream]]s and [[spray (liquid drop)|spray]]s are often available [[Over-the-counter drugs|over-the-counter]]. [[Mouth|Oral]] anti-itch drugs also exist and are usually [[prescription drug]]s. The [[active ingredient]]s usually belong to the following classes:

* [[Antihistamine]]s, such as [[diphenhydramine]] (Benadryl)<ref name=":2" />
* [[Corticosteroid]]s, such as [[hydrocortisone]] topical cream {{xref|(see: [[Topical steroid]])}}
* [[Counterirritant]]s, such as [[Mentha|mint oil]], [[menthol]], or [[camphor]]<ref>{{cite journal |vauthors=Hercogová J |title=Topical anti-itch therapy |journal=Dermatologic Therapy |volume=18 |issue=4 |pages=341–343 |year=2005 |pmid=16297007 |doi=10.1111/j.1529-8019.2005.00033.x |s2cid=31573591 |doi-access=free}}</ref>
* [[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.
* [[JAK inhibitor]]s, such as [[ruxolitinib]] topical cream; ''see'' [[topical JAK inhibitor]]
* [[Local anesthetic]]s, such as [[benzocaine]] topical cream (Lanacane)

[[Phototherapy]] is helpful for severe itching, especially if caused by [[chronic kidney disease]]. The common type of light used is [[UVB]].<ref>{{Cite journal |vauthors=El Mulla KF, Khalifa DE, Gawish RI, Eldeeb ME |date=2023 |title=Phototherapy versus pregabalin in treatment of chronic kidney disease associated pruritus: randomized controlled study |journal=Journal of the Egyptian Women's Dermatologic Society |language=en |volume=20 |issue=2 |pages=81 |doi=10.4103/jewd.jewd_50_22 |doi-access=free |issn=1687-1537}}</ref>

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".<ref>{{cite journal |vauthors=Rinaldi G |title=The Itch-Scratch Cycle: A Review of the Mechanisms |journal=Dermatology Practical & Conceptual |volume=9 |issue=2 |pages=90–97 |date=April 2019 |pmid=31106010 |pmc=6502296 |doi=10.5826/dpc.0902a03}}</ref>

The mainstay of therapy for dry skin is maintaining adequate skin moisture and topical [[emollient]]s.

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.<ref name=":2">{{cite journal |vauthors=Andrade A, Kuah CY, Martin-Lopez JE, Chua S, Shpadaruk V, Sanclemente G, Franco JV |display-authors=3 |title=Interventions for chronic pruritus of unknown origin |journal=The Cochrane Database of Systematic Reviews |volume=1 |pages=CD013128 |date=January 2020 |issue=1 |pmid=31981369 |pmc=6984650 |doi=10.1002/14651858.CD013128.pub2 |collaboration=Cochrane Skin Group}}</ref> 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.<ref>{{cite journal |pmid=28890086 |date=2017 |vauthors=Oetjen LK, Mack MR, Feng J, Whelan TM, Niu H, Guo CJ, Chen S, Trier AM, Xu AZ, Tripathi SV, Luo J, Gao X, Yang L, Hamilton SL, Wang PL, Brestoff JR, Council ML, Brasington R, Schaffer A, Brombacher F, Hsieh CS, Gereau RW IV, Miller MJ, Chen ZF, Hu H, Davidson S, Liu Q, Kim BS |display-authors=3 |title=Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch |journal=Cell |volume=171 |issue=1 |pages=217–228.e13 |pmc=5658016 |doi=10.1016/j.cell.2017.08.006 |doi-access=free}}</ref><ref>{{cite web |title=Efficacy and Safety of Subcutaneous Dupilumab for the Treatment of Adult Participants With Chronic Pruritus of Unknown Origin (CPUO) (LIBERTY-CPUO-CHIC) |website=ClinicalTrials.gov |url=https://clinicaltrials.gov/ct2/show/NCT05263206|access-date=2023-01-14 |id=NCT05263206 |archive-date=2023-01-14 |archive-url=https://web.archive.org/web/20230114212251/https://clinicaltrials.gov/ct2/show/NCT05263206 |url-status=live}}</ref> The effectiveness of therapeutic options for people who are terminally ill with malignant cancer is not known.<ref name=":1" />

== Epidemiology ==
Approximately 280&nbsp;million people globally, 4% of the population, have difficulty with itchiness.<ref>{{cite journal |vauthors=Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, etal |display-authors=3 |title=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 |collaboration=Global Burden of Disease Study Collaborators |journal=Lancet |volume=380 |issue=9859 |pages=2163–2196 |date=December 2012 |pmid=23245607 |pmc=6350784 |doi=10.1016/S0140-6736(12)61729-2}}</ref> This is comparable to the 2–3% of the population who have [[psoriasis]].

== History ==
In 1660, German physician [[Samuel Hafenreffer]] introduced the definition of pruritus (itch).<ref>{{Cite book |title=Dermatology |date=2008 |publisher=Mosby/Elsevier |author1=Jean Bolognia |author2=Joseph L. Jorizzo |author3=Ronald P. Rapini |isbn=978-1-4160-2999-1 |edition=2nd |location=St. Louis, Mo. |oclc=212399895}}</ref>

== See also ==
* [[Feeling]], a perceptual state of conscious experience.
* [[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]], a 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
* [[Itching powder]], a powder or powder-like substance that induces itching when applied onto human skin.

== References ==
{{Reflist}}

== Further reading ==
{{refbegin}}
* {{cite journal |vauthors=Han L, Dong X |title=Itch mechanisms and circuits |journal=Annual Review of Biophysics |volume=43 |issue=1 |pages=331–355 |date=6 May 2014 |pmid=24819620 |pmc=4081479 |doi=10.1146/annurev-biophys-051013-022826}}
* {{cite journal |vauthors=Andrew D, Craig AD |title=Spinothalamic lamina I neurons selectively sensitive to histamine: a central neural pathway for itch |journal=Nature Neuroscience |volume=4 |issue=1 |pages=72–77 |date=January 2001 |pmid=11135647 |doi=10.1038/82924 |s2cid=28727869}}
* {{cite web |publisher=National Cancer Institute |date=2003 |url=http://www.nci.nih.gov/cancertopics/pdq/supportivecare/pruritus/ |archive-url=https://web.archive.org/web/20051225074936/http://www.nci.nih.gov/cancertopics/pdq/supportivecare/pruritus/ |archive-date=25 December 2005 |title=Pruritus |access-date=22 August 2005}}
{{refend}}

{{Medical resources
|  DiseasesDB     = 25363 
|  ICD10          = {{ICD10|L|29||l|20}} 
|  ICD9           = {{ICD9|698}} 
|  ICDO           = 
|  OMIM           = 
|  MedlinePlus    = 003217 
|  eMedicineSubj  = derm 
|  eMedicineTopic = 946 
|  MeshID         = D011537
}}
{{Diseases of the skin and subcutaneous tissue}}
{{Authority control}}

[[Category:Pruritic skin conditions]]