Comparison of immunohistochemical and functional reinnervation of skin and muscle after peripheral nerve injury.

In order to investigate the usefulness of immunohistochemical detection of regenerating axons as a correlate of functional recovery, reinnervation of mouse foot pads, hairy skin, and muscle were studied at several intervals along 3 months after sciatic nerve crush using immunohistochemical markers PGP 9.5 and CGRP. These histological results were compared with functional recovery of sweat glands (SGs), plantar muscles, and pain sensibility. One week after nerve injury all neural functions were abolished in the operated hindpaw of all mice, no CGRP-immunoreactive (-ir) fibers were seen in the samples studied, while PGP 9.5 immunofluorescence remained at dim levels within nerve trunks, but disappeared from terminal innervation. The first PGP 9.5- and CGRP-ir regenerating fibers were seen at 15-16 days postoperation (dpo) in dermal nerve trunks of dorsal hairy skin and some days later in dermal trunks of foot pads. Regenerating nerve fibers progressed along the periphery of the dermis reinnervating the different dermal appendages. At 25 dpo all target organs were reinnervated. The first SGs activated by pilocarpine reappeared by 16 dpo and increased in number to 88% of control counts. Nociceptive responses reappeared at 17 dpo and reached 100% of control values. The first PGP immunofluorescence in neuromuscular junctions was seen at 16 dpo, while the first muscle action potentials were recorded at 19 dpo, and the potentials amplitude increased to 66% of controls. Good correlations were found between morphological and functional results of reinnervation. However, the density and distribution of nerve profiles in the tissues studied did not reach normal levels, while neural functions conveyed by small fibers reached levels similar to controls.