INFLAMMATORY MEDIATORS SENSITIZE ACUTELY AXOTOMIZED NERVE-FIBERS TO MECHANICAL STIMULATION IN THE RAT

Many axotomized myelinated as well as unmyelinated cutaneous nerve fib ers are sensitive to mechanical stimuli applied to the cut nerve end w ithin a few hours after nerve lesion. Here we investigated the influen ce of inflammatory mediators on this ectopic mechanosensitivity after cutting and ligating the sural nerve in anesthetized rats. Neural acti vity was recorded from single axons in filaments teased from the sural or sciatic nerve proximally to the lesion site 2-33 hr after axotomy. Using calibrated von Frey hairs (1.0-128.5 mN), 30 sec trains of phas ic stimuli were applied to the cut nerve end immediately before and af ter local application of a mixture of inflammatory mediators [inflamma tory soup (IS), consisting of bradykinin, 5-HT, prostaglandin E-2, his tamine (all 10 mu M), and K+ 7 mM, pH 7.0] for 2 min. Before as well a s after IS application, von Frey thresholds were significantly lower i n myelinated (A) fibers than in unmyelinated (C) fibers. IS applicatio n enhanced the ectopic mechanical excitability, as expressed in reduce d von Frey thresholds and increased response magnitudes, of most sever ed mechanosensitive C fibers (77%) and some mechanosensitive A fibers (46%). The sensitization lasted for 10-40 min after a 2 min IS applica tion. Additionally, among axotomized nerve fibers unresponsive to prob ing of the nerve lesion site before IS application, 1 of 63 (1.6%) A a nd 3 of 106 (2.8%) C fibers became mechanosensitive immediately after IS application. The results indicate that after axotomy, inflammatory processes augment touch-evoked ectopic activity in lesioned sensory ne rve fibers. Because many affected afferents are presumably of nocicept ive function, their enhanced neural barrage may contribute to neuropat hic pain states.