Reorganization of muscle afferent projections accompanies peripheral nerve regeneration

Dorsal horn projections from muscle innervated by the common peroneal branch of the rat sciatic nerve were studied in three experimental situations: after either epineurial or individual fascicular suture of the sciatic nerve, or after isolated severance and repair of the peroneal sciatic fascicle. Four months after surgery, the peroneal-innervated muscles were injected with a conjugate of horseradish peroxidase and wheatgerm agglutinin. Projections from these muscles, as well as from peroneal-innervated skin and the entire sciatic nerve, were also studied in normal controls. Rats were perfused forty-eight hours after enzyme exposure, and the presence of horseradish peroxidase demonstrated by reaction of spinal cord sections with H₂O₂ and tetramethylbenzidine. Injection of normal peroneal-innervated muscle labeled a sharply-defined area within the substantia gelatinosa of the ipsilateral dorsal horn. After regeneration from individual fascicular sciatic repair, or suture of the isolated peroneal fascicle, this projection was more widespread, resembling that from normal peroneal-innervated skin. The muscle projection was even wider and more variable following epineurial repair, yet always confined within the normal sciatic projection. The width and variability of muscle projections after epineurial suture probably reflect inter-fascicular misdirection of regenerating axons. The finding of expanded projections even after partial (individual fascicular) and total (isolated peroneal repair) elimination of this misdirection, and the similarity of these projections to those of peroneal-innervated skin, suggest confusion at the intra-fascicular level as well. Muscle could be reinnervated by peroneal nerve axons which previously served non-muscular structures, and which project to a wider area of the dorsal horn not originally labeled by muscle injection. These experiments demonstrate a substantial projection from muscle to the substantia gelatinosa, an area strongly implicated in the processing of nociceptive information. Reorganization of these projections might provide an anatomical substrate for abnormal pain perception after peripheral nerve injury, including confusion as to its tissue of origin. Furthermore, this reorganization is not eliminated by individual fascicular suture. This technique, which decreases the frequency with which regenerating axons cross from one fascicle to another, does not, therefore, prevent axon disorganization within the fascicle itself.