Responses of C-fiber low threshold mechanoreceptors and nociceptors to cold were facilitated in rats persistently inflamed and hypersensitive to cold

Cold allodynia is an annoying symptom in conditions of chronic inflammation such as rheumatoid arthritis. To examine whether primary afferent nerve activities are changed in association with hypersensitivity to cold, we recorded single nerve activities from the sural nerve in persistently inflamed rats in vivo. Inflammation was induced by an injection of complete Freund's adjuvant (CFA) solution into the tibio-tarsal joint. Inflamed rats showed an increased number of paw shakes to paw immersion in 25°C water (pre-inflammation: 1.15±0.58, 2-week inflammation: 4.70±1.15). We also recorded cutaneous C-fiber activities under pentobarbital anesthesia and studied their responses to thermal and mechanical stimuli. The response of C-low threshold mechanoreceptors to cooling (total discharges between 27 and 23°C) increased 1.8-fold (control group: 5.17±1.04 impulses, inflamed group: 9.38±1.47 impulses). In addition, the proportion of C-nociceptor units responding to cold down to 2°C was significantly greater in the inflamed group (9 out of 18units; threshold: 10.0±2.6°C) than in the intact group (1 out of 14units; threshold: 4.0°C). These results suggest that the facilitated responses of these primary afferents are associated with cold hypersensitivity in chronically inflamed conditions.