EFFECTS OF OPIOIDS ON MECHANOSENSITIVE PELVIC NERVE AFFERENT-FIBERS INNERVATING THE URINARY-BLADDER OF THE RAT

A total of 443 pelvic nerve afferent fibers in the L6 dorsal root of t he rat were identified by electrical stimulation of the pelvic nerve; 319 (72%) were myelinated A delta fibers with a mean conduction veloci ty (CV) of 11.8 m/s and 124 (28%) were unmyelinated C fibers with mean CV of 1.9 m/s. Two hundred fifty-two fibers (57%) responded to noxiou s urinary bladder distension (UBD; 80 mmHg); 108 were C fibers (mean C V: 1.9 m/s) and 144 were A delta fibers (mean CV: 8.2 m/s). Forty-nine UBD-sensitive fibers were further characterized; all gave monotonic i ncreases in firing to increasing distending pressures. Thirty-six fibe rs (73%) had a low-threshold (LT) for response (mean: 6 mmHg) and 13 f ibers (27%) had high-thresholds (HT) for response (mean: 32 mmHg). Res ponses of 15 fibers to graded UBD (11 LT and 4 HT) were tested before and after instillation of 0.5 mi of 30% xylenes (n = 11) or 5% mustard oil (n = 4) into the bladder. The mean resting activity of 13 fibers significantly increased, and 7 fibers exhibited sensitization of respo nses to graded UBD 30 min after xylenes or mustard oil instillation. A ll 4 HT fibers were sensitized; 3 of the 11 LT fibers were sensitized (i.e., gave increased responses to UBD). The effects of opioid recepto r agonists were tested on responses to noxious UBD (80 mmHg). Cumulati ve intraaterial doses of mu-opioid receptor agonists (morphine, 8 mg/k g, and fentanyl, 300 mu g/kg) and of delta-opioid receptor agonists (D PDPE, 300 mu g/kg, and SNC-80, 300 mu g/kg) did not affect responses t o noxious UBD. In contrast, cumulative 16 mg/kg intraarterial doses of the kappa-opioid receptor agonists U50,488H, U69,593 and U62,066 dose -dependently attenuated responses to noxious UBD. There were no differ ences in the dose-response relationships of these drugs on afferent fi bers from untreated and xylenes- or mustard oil-treated urinary bladde r. These results reveal that there is a greater proportion of UBD-sens itive fibers in the L6 dorsal root (57%) than in the S1 dorsal root of the rat (38%; a previous study). The attenuation of responses to UBD by kappa, but not mu or delta opioid receptor agonists suggests a pote ntial use for peripherally acting kappa opioid receptor agonists in th e control of urinary bladder pain.