Afferent A- and C-fibers regenerating into a nerve following peripheral nerve injury are exposed to inflammatory mediators released by Schwann cells, resident and invading macrophages, and other inflammatory cells. Here we tested the hypothesis that ongoing and evoked activity in these afferent fibers are enhanced by a mixture of inflammatory mediators [inflammatory soup (IS)] applied to the injured nerve. Using in vivo electrophysiology, regenerating afferent nerve fibers were studied 7-14 days after sural nerve crush lesion. ⋯ Some initially nonresponsive C- and A-fibers developed new ectopic properties, i.e., were recruited, and exhibited ongoing activity and/or could be activated by physiological stimuli after application of IS. The results suggest that inflammatory mediators may be critical to enhance ectopic excitability of regenerating afferent nerve fibers. These peripheral mechanisms may be important triggering and maintaining neuropathic pain.

keep reading… or not…