Direct influence of systemic desensitization by resiniferatoxin on the activities of Aδ- and C-fibers in the rat primary bladder mechanosensitive afferent nerves.

Abstract

To examine whether systemic resiniferatoxin treatment can desensitize the single-unit afferent activities of Aδ- and C-fibers in rat primary bladder mechanosensitive afferent nerves. Female Sprague-Dawley rats were divided into two groups (resiniferatoxin-treated: n = 9, vehicle-treated: n = 9). Resiniferatoxin (0.3 mg/kg) or its vehicle (10% ethanol) was injected subcutaneously after the first eye-wipe behavior test with capsaicin. The second eye-wipe behavior test was carried out 48 h after the injection under urethane (1.2 g/kg intraperitoneally) anesthesia. The bladder mechanosensitive single-unit afferent activities originating from the left L6 dorsal roots were identified by electrical stimulation of the left pelvic nerve and bladder distension, and classified by conduction velocity as either Aδ-fibers or C-fibers. The single-unit afferent activity measurements were carried out with constant bladder filling with saline (0.1 mL/min, <30 cmH2 O). After resiniferatoxin treatment, but not vehicle treatment, eye-wipe behavior with capsaicin was completely abolished. A total of 104 single afferent fibers were isolated (Aδ-fibers: n = 41, C-fibers: n = 63). Single-unit afferent activities of both Aδ-fibers and C-fibers in response to bladder filling in the resiniferatoxin-treated group were significantly lower than those in the vehicle-treated group. These differences were observed throughout the filling phase in Aδ-fibers and during the initial half of the filling phase in C-fibers. The present results show the existence of resiniferatoxin desensitization-resistant mechanosensitive Aδ- and C-fibers in rat primary bladder afferent nerves, suggesting that systemic resiniferatoxin treatment might induce non-specific partial desensitization or denervation of mechanosensitive capsaicin-insensitive Aδ- and C-fibers of the rat bladder.