PHN patients differ concerning their cutaneous nociceptor function: In the group I pain is caused by pathologically sensitised nociceptors. In subset II there is a loss of function of cutaneous C-nociceptors within the allodynic skin. Patients responded well to topical lidocaine even if the skin was completely deprived of nociceptors. Different underlying mechanisms of lidocaine action in nociceptor-deprived skin are discussed.

Physiologically, itch and pain are transmitted in separate specific peripheral C-units and central afferent pathways. Some neuropathic pain patients with intact but sensitized (irritable) primary C-nociceptors have spontaneous pain, heat hyperalgesia, static and dynamic mechanical hyperalgesia. The question was whether cutaneous histamine application induces pain in these patients. For comparison histamine was applied into normal skin experimentally sensitized by capsaicin. Histamine application in the capsaicin-induced primary or secondary hyperalgesic skin did not change the intensity and quality of capsaicin pain. Itch was profoundly inhibited. Conversely, histamine application in neuropathic skin induced severe increase in spontaneous burning pain but no itch. In neuropathies irritable nociceptors may express histamine receptors or induce central sensitization to histaminergic stimuli so that itch converts into pain.