Altered skin sensitivity in chronic itch: role of peripheral and central mechanisms

Nodular prurigo (NP) is a chronic skin disease causing severe itch of unknown origin in restricted skin areas surrounded by healthy skin areas. In the present investigation we studied cutaneous sensibility in five NP-patients and in five control subjects. Pain thresholds were determined with short argon laser pulses using two different sizes of stimulus surface (diameters 2 and 4 mm), tactile threshold with calibrated monofilaments and skin blood flow with a laser Doppler flowmeter. We also studied the effect of prolonged capsaicin treatment which should predominantly impair the function of nociceptive C-fibers. In both the itching and healthy skin areas the pain thresholds were lower in NP-patients than in healthy control subjects. Before capsaicin, an increase in stimulus area produced an equal decrease in pain threshold in all subjects. Following prolonged capsaicin treatment the pain threshold obtained with a large but not a small stimulus surface was elevated to control levels in NP-patients. Tactile thresholds in NP-patients were lower than in control subjects, and this abnormality was reversed by capsaicin. The basal skin blood flow level was more labile (fluctuating) in itching skin areas than in healthy skin areas of NP-patients. Capsaicin reduced blood flow fluctuation in the itching area. A lowered pain threshold not only in the itching area but also in the healthy skin area of NP-patients suggests that central convergence of itch and pain may contribute to increased pain sensitivity in chronic itch. Capsaicin-reversible abnormal fluctuation of the blood flow in the itching skin area might be explained by abnormal spontaneous activity of nociceptive peripheral nerve fibers and a consequent release of vasoactive agents from their terminals (axon reflex). The decreased tactile threshold and the elevation of it by capsaicin indicates that also the mechanisms underlying tactile sensibility are changed in chronic itch patients.