Cutaneous nerve terminal degeneration in painful mononeuropathy

Nociceptive nerves innervate the skin and play an important role in the gen eration of neuropathic pain. However, it remains elusive whether and how no ciceptive nerve terminals degenerate in neuropathic pain conditions. To add ress this issue, we investigated cutaneous innervation in a model of painfu l mononeuropathy, the chronic constriction injury (CCI). The hind paws of r ats were immunocytochemically stained with a pan-axonal marker, protein gen e product 9.5 (PGP 9.5). Within 2 days after CCI, rats exhibited thermal hy peralgesia, and there was a partial depletion of epidermal nerves. The exte nt of reduction in epidermal nerves after CCI was variable with an epiderma l nerve density of 3.65 +/- 1.97 fibers/mm (compared to 15.39 +/- 1.58 fibe rs/mm on the control side, P < 0.02). There was a mild but concomitant incr ease in PGP 9.5 (+) Langerhans cells in the epidermis of the skin with CCI (10.19 +/- 1.99 vs 7.75 +/- 1.36 cells/mm, P < 0.05). In the skin denervate d by tight ligation of the sciatic nerve, epidermal nerves were completely depleted (0 fibers/mm. vs 12.26 +/- 1.44 fibers/mm on the control side, P < 0.001). Animals with tight ligation of the sciatic nerve exhibited thermal anesthesia. These findings suggest that the epidermis is partially denerva ted in CCI, and that a partial injury of nerves is correlated with the deve lopment of neuropathic pain. (C) 2001 Academic Press.