Itch

For other uses, see Itch (disambiguation).

Pruritus
Classification and external resources
File:Itch 01.JPG A man trying to reach for an itch
ICD-10	L29.
ICD-9	698
DiseasesDB	25363
MedlinePlus	003217
eMedicine	derm/946
MeSH	D011537

Itch (Latin: pruritus) is an unpleasant 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. 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 peripheral nerve bundle and spinothalamic tract.

Mechanism

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

Dermal/pruritoceptive

File:Squirrel Scratching the Armpit with its Hindlimb.jpg

A chipmunk scratching itself, presumably in a response to an itch

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-fibers. Two major classes of human C-fiber 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 fibers have different classes of fibers, which is unclear in current research.

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. 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. Itch is never felt in muscle, joints, or inner organs, which show that deep tissue does not contain itch signaling apparatuses.

Sensitivity to pruritic stimuli is not evenly distributed across the skin and has a random spot distribution with similar density to that of pain. The same 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.

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. Examples of neuropathic itch in origin are notalgia paresthetica, brachioradial pruritis, brain tumors, multiple sclerosis, peripheral neuropathy, and nerve irritation.

Neurogenic

Neurogenic itch, which is itch induced centrally but with no neural damage, is often associated with increased accumulation of endogenous opioids and possibly synthetic opioids.

Psychogenic

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).

Interactions between itch and pain

Pain inhibits itch

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.

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.

Chloroquine has been used in animal studies and in humans as a tool to study the itch mechanisms. In animal studies in rats, an inverted U shaped dose response curve to chloroquine pruritogenicity was first described by Onigbogi et al. (Onigbogi O, Ajayi AA, Ukponmwan OE,Pharmacol, Biochem Behavior 2000, 65: 333-7), this has been subsequently confirmed by others ( Inan & Conan 2004, Eur J pharmacol; 502 , 233-7 ). This may suggest the involvement of several receptor types centrally . Indeed, nalrexone and Mu opiate down -regulation with chronic morphine attenuated the frequency of chloroquine pruritus in both rats (Onigbogi etal 2000) and in mice (Inan and Cowan 2004). Further, a kappa-opioid antagonist, nalfurafine also further attenuated the chloroquine -induced itching frequency in mice (inan and cowan). 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 4th decade of life, and with increased familial concurrence in families and concordance among twins( Ajayi AA et al. Eur J Clin Pharmacol 1989, 39, 539-40). 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. A new method has been recently found, by Hans-Jorgen Nilsson and others, that is able to relieve itch without damaging the skin by the name of 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-fibers in myelinated fibers, which indicates that nociceptive C-fibers 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-fibers. 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 of the skin.

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. However it is quite interesting that 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.

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 different 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.

Peripheral sensitization

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. 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.

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 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.

Causes

File:Scabies-burrow.jpg

Scabies is one cause of itching.

Infections and infestations:

• Head lice, if limited to the neck and scalp.
• Pubic lice, if limited to the genital area.
• Body louse. Body lice can be seen in substandard living conditions.
• Scabies especially when several other persons in close contact also itch.
• Cutaneous larva migrans
• Varicella (Chickenpox) Most common in young children. Highly contagious.

Environmental and allergic:

• Insect bites, such as those from mosquitos or chiggers.
• Urticaria (also called hives) usually causes itching.
• Allergic reaction to contact with specific chemicals, such as Urushiol, derived from Poison Ivy or Poison Oak.
• Photodermatitis – (sun)light reacts with chemicals in the skin, leading to the formation of irritant metabolites
• Shaving, which may irritate the skin.

Dermatological disorders:

• Xerosis (dry skin). This is the most common cause,, 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.
• Skin conditions (such as psoriasis, eczema, sunburn, athlete's foot, hidradenitis suppurativa and many others). Most are of an inflammatory nature.
• Scab healing; scar growth; and the development or emergence of moles, pimples and ingrown hairs from below the epidermis.
• Punctate palmoplantar keratoderma.
• Dandruff. (An unusually large amount of flaking is associated with this sensation.)

Medical disorders:

• Malignancy or internal cancer such as lymphoma, Hodgkin's disease.
• Jaundice and Cholestasis. (Bilirubin is a skin irritant at high concentrations.)
• Polycythemia, which can cause generalized itching due to increased histamine.
• Thyroid illness.
• Hyperparathyroidism.
• Uraemia.
• Diabetes Mellitus.
• Iron deficiency anemia.
• Menopause or changes in hormonal balances associated with aging

Medication:

• Directly (e.g. morphine and other opiates)
• Chloroquine.

Related to pregnancy:

• Intrahepatic cholestasis of pregnancy
• Pruritic urticarial papules and plaques of pregnancy (PUPPP)
• Gestational pemphigoid

Psychiatric disease.

Treatment

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:

• Antihistamines such as diphenhydramine (Benadryl)
• Corticosteroids such as hydrocortisone topical cream, see topical steroid
• Local anesthetics such as benzocaine topical cream (Lanacane)
• Counterirritants, such as mint oil, menthol, or camphor
• 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.

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

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".

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

Sensations associated with scratching

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 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 the 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. This can be problematic with chronic itch patients, such as ones with atopic dermatitis, who may scratch affected spots until it no longer produces a pleasant or painful sensation instead of when the itch sensation disappears. 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.

Contagious itch

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 recent study showed that itching and scratching were induced purely by visual stimuli in a public lecture on itching. There is currently 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.

See also

• Referred itch
• Formication
• Personal grooming
• Pruritus ani

References

• Andrew D, Craig AD (2001). "Spinothalamic lamina I neurons selectively sensitive to histamine: a central neural pathway for itch". Nat. Neurosci. 4 (1): 72–7. doi:10.1038/82924. PMID 11135647. 
• National Cancer Institute (2003) "Pruritus" Retrieved Aug. 22, 2005.

External links

• 168165389 at GPnotebook

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