Characterization of Adelta- and C-fibers innervating the plantar rat hindpaw one day after an incision

Abstract

Primary hyperalgesia after tissue injury is suggested to result from sensitization of primary afferent fibers, but sensitization to mechanical stimuli has been difficult to demonstrate. In the companion study, sensitization of mechano-responsive Adelta- and C-fibers did not explain pain behaviors 45 min after an incision in the rat hindpaw. In the present study, we examined mechanical response properties of Adelta- and C-fibers innervating the glabrous skin of the plantar hindpaw in rats 1 day after an incision or sham procedure. In behavioral experiments, median withdrawal thresholds to von Frey filaments were reduced from 522 mN before to 61 mN 2 and 20 h after incision; median withdrawal thresholds after sham procedure were stable (522 mN). Responses to a nonpunctate mechanical stimulus were increased after incision. In neurophysiological experiments in these same rats, 67 single afferent fibers were characterized from the left tibial nerve 1 day after sham procedure (n = 39) or incision (n = 28); electrical stimulation was used as the search stimulus to identify a representative population of Adelta- and C-fibers. In the incision group, 11 fibers (39%) had spontaneous activity with frequencies ranging from 0.03 to 39.3 imp/s; none were present in the sham group. The median response threshold of Adelta-fibers was less in the incision (56 mN, n = 13) compared with sham (251 mN, n = 26) group, mainly because the proportion of mechanically insensitive afferents (MIAs) was less (8 vs. 54% after sham procedure). Median C-fiber response thresholds were similar in incised (28 mN, n = 15) and sham rats (56 mN, n = 13). Responsiveness to monofilaments was significantly enhanced in Adelta-fibers 1 day after incision; stimulus response functions of C-fibers after incision and after sham procedure did not differ significantly. Only Adelta-fibers but not C-fibers sensitized to the nonpunctate mechanical stimulus. The size of receptive fields was increased in Adelta- and C-fibers 1 day after incision. The results indicate that sensitization of Adelta- and C-fibers is apparent 1 day after incision. Because sensitization of afferent fibers to mechanical stimuli correlated with behavioral results, sensitization may contribute to the reduced withdrawal threshold after incision. Spontaneous activity in Adelta- and C-fibers may account for nonevoked pain behavior and may also contribute to mechanical hyperalgesia by amplifying responses centrally.