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.

[8] It has been hypothesized that motivational aspects of scratching include the frontal brain areas of reward and decision making.

[19][20][21] 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.

[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.

Although experimentally induced itch can still be perceived under a complete A-fiber conduction block, it is significantly diminished.

The histamine receptor gene Hrh1 was found in NP2 and NP3, suggesting that histaminergic itch is transmitted by both these pruriceptive sub clusters.

Staphylococcus aureus, a bacterial pathogen associated with itchy skin diseases, directly activates pruriceptor sensory neurons to drive itch.

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.

[24] After the pruriceptive primary afferent has been activated, the signal is transmitted from the skin into the spinal dorsal horn.

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

In addition, expression of neuro growth factors (NGF) can cause structural changes in nociceptors, such as sprouting.

Increased NGF is also found in atopic dermatitis, a hereditary and non-contagious skin disease with chronic inflammation.

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.

The active ingredients usually belong to the following classes: Phototherapy is helpful for severe itching, especially if caused by chronic kidney disease.

Often, however, scratching only offers temporary relief and can intensify itching, even causing further damage to the skin, dubbed the "itch-scratch cycle".

[29] 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.