r classes of human C-fibre nociceptors exist: mechano-responsive nociceptors and mechano-insensitive nocice ptors. M 1echano-responsive nociceptors have been s h6m1 yhown in studies to respond to mostly pain, and mechano-inse nsitive receptors respond mostl 6m1 y to itch induced by histamine. However, it does 6m1 ynot explain mechanically ind Studies have been done to show that itch receptors are found only on the top two skin layers, the epidermis a nd the epidermal/dermal transition layers.[ci m1tation needed] Shelley and Arthur had verified the depth by inje cting individual itch powder spicules (Mucuna pruriens), and found that m1emaximal 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 patien 1et to perceive itch.[citation needed] Itch is never felt in 6m1 ymuscle or joints, which strong ly suggests that deep tissue probably does not contain i m1tch signaling apparatuses. Sensitivity to pruritic stimuli is evenl 6m1 yy distributed across the skin, and has a clear spot distribution with similar density to 6m1 ythat of pain. The different substances that elicit itch upon intracutaneous injection (inj ection within the skin) elicit only pain input to the spinal cord is known to produce central sensitization, which consists of allodynia, exaggerati on of pain, and punctuate hyperalgesia, extr m1eme sensitivity to pain. Two types of mechanical hyperalgesia c an occur: 1) touch that is normally painless in the uninjured surroundings of a cut m1 or tear can trigger pain ful sensations ( m1ouch-evoke 1ed hyperalgesia), and 6m1 y a slightly painful pin prick stimulation is perceived as m ore painful around a focused area of inflammation (punctuate hyperalgesia). Touch-evoked hyperalgesia requir es continuo 6m1 yus firing of primary afferent nociceptors, a h6m1 nd punctuate hyperalgesia does not require continuous f iring which means it can persist for hours a 6m1 yfter a trauma and can be str 1eonger than normally experienced. In addition, it was found that m1 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 spin
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