Cutaneous afferent C-fibers regenerating along the distal nerve stump after crush lesion show two types of cold sensitivity

Cutaneous C-fiber afferents show two distinct types of cold sensitivity corresponding to non-noxious and noxious cold sensations. Here, responses to cold stimulation of afferent fibers regenerating in the rat sural nerve were studied in vivo 7-14 days after nerve crush and compared with responses to mechanical and heat stimulation. The physiological stimuli were applied to the sural nerve at or distal to the lesion site. Ectopic activity was evoked in 43% of 98 A-fibers (all mechanosensitive; a few additionally weakly thermosensitive). Ectopic activity was evoked in 127 (49.2%) of 258 electrically identified C-fibers by the physiological stimuli. Eight C-fibers were spontaneously active only. Of the 127 C-fibers, 46% had one of two distinct response patterns to cooling: (1) type 1 cold-sensitive C-fibers (n = 29) had a high rate of activity at 28 °C on the nerve surface and showed graded responses to cooling with maximal discharge rates of 11.5 ± 1.1 imp/s. This activity was completely inhibited by heating, while 12/29 fibers were also excited at high threshold (median 48 °C) by heating. Only one type 1 cold-sensitive C-fiber was mechanosensitive. (2) Type 2 cold-sensitive C-fibers (n = 29) were silent or showed a low rate of activity at 28 °C, had a high threshold (median 5 °C) and low maximal discharge rates (2.4 ± 0.4 imp/s) to cooling. They were also heat-sensitive (n = 25) and/or mechanosensitive (n = 20). These C-fibers were, apart from their cold sensitivity, functionally indistinguishable from C-fibers with mechano- and/or heat sensitivity only. Thus regenerating cutaneous C-fibers show two types of cold sensitivity similar to those observed in intact skin: fibers of one group are predominantly sensitive to cooling, whereas the others are polymodal.