CENTRAL RELEASE OF TRACER AFTER NOXIOUS-STIMULATION OF THE SKIN SUGGESTS NONSYNAPTIC SIGNALING BY UNMYELINATED FIBERS

Injury to a peripheral nerve causes central changes of various nature and complexity reflecting activation of multiple signaling mechanisms. (8,24) In a previous study we reported that nerve lesion triggers cent ral release of a tracer, wheatgerm-agglutinin conjugated to horseradis h peroxidase, by unmyelinated fibers in the spinal cord.(20) The relea sed tracer occupies the space between nerve terminals and dendrites wi thout extending into the synaptic cleft.(22) We interpreted this to su ggest release of unidentified endogenous factor(s) at nonsynaptic site s, which may contribute to the signaling of peripheral injury to the c entral nervous system.(10) For such signaling to occur, a message must first be communicated along the axon. This message may depend on axon al transport and/or altered electrical activity. In pilot experiments we observed that application of tetrodotoxin (to block impulse conduct ion) to the intact nerve did not result in tracer release. We hypothes ized that the message might be the sustained discharge of C fibers tha t occurs after injury.(1,7) We show here that selective activation of C fibers (by applying mustard oil to the hindlimb of anesthetized rats ) causes central release of tracer previously transported from the sci atic nerve to superficial laminae of the dorsal horn,