Uninjured C-fiber nociceptors develop spontaneous activity and alpha-adrenergic sensitivity following L-6 spinal nerve ligation in monkey

We investigated whether uninjured cutaneous C-fiber nociceptors in primates develop abnormal responses after partial denervation of the skin. Partial denervation was induced by tightly ligating spinal nerve L-6 that innervate s the dorsum of the foot. Using an in vitro skin-nerve preparation, we reco rded from uninjured single afferent nerve fibers in the superficial peronea l nerve. Recordings were made from 32 C-fiber nociceptors 2-3 wk after liga tion and from 29 C-fiber nociceptors in control animals. Phenylephrine, a s elective alpha(1)-adrenergic agonist, and UK14304 (UK), a selective alpha(2 )-adrenergic agonist, were applied to the receptive field for 5 min in incr easing concentrations from 0.1 to 100 mu M. Nociceptors from in vitro contr ol experiments were not significantly different from nociceptors recorded b y us previously in in vivo experiments. In comparison to in vitro control a nimals, the afferents found in lesioned animals had 1) a significantly high er incidence of spontaneous activity, 2) a significantly higher incidence o f response to phenylephrine, and 3) a higher incidence of response to UK. I n lesioned animals, the peak response to phenylephrine was significantly gr eater than to UK, and the mechanical threshold of phenylephrine-sensitive a fferents was significantly lower than for phenylephrine-insensitive afferen ts. Staining with protein gene product 9.5 revealed an similar to 55% reduc tion in the number of unmyelinated terminals in the epidermis of the lesion ed limb compared with the contralateral limb. Thus uninjured cutaneous C-fi ber nociceptors that innervate skin partially denervated by ligation of a s pinal nerve acquire two abnormal properties: spontaneous activity and alpha -adrenergic sensitivity. These abnormalities in nociceptor function may con tribute to neuropathic pain.