Su X, Sengupta J N, Gebhart G F
University of Iowa, College of Medicine, Department of Pharmacology, Iowa City 52242, USA.
J Neurophysiol. 1997 Mar;77(3):1566-80. doi: 10.1152/jn.1997.77.3.1566.
A total of 443 pelvic nerve afferent fibers in the L6 dorsal root of the rat were identified by electrical stimulation of the pelvic nerve; 319 (72%) were myelinated A delta fibers with a mean conduction velocity (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 noxious urinary bladder distension (UBD; 80 mmHg); 108 were C fibers (mean CV; 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 increases in firing to increasing distending pressures. Thirty-six fibers (73%) had a low-threshold (LT) for response (mean: 6 mmHg) and 13 fibers (27%) had high-thresholds (HT) for response (mean: 32 mmHg). Responses of 15 fibers to graded UBD (11 LT and 4 HT) were tested before and after instillation of 0.5 ml 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 responses to graded UBD 30 min after xylenes or mustard oil instillation. All 4 HT fibers were sensitized; 3 of the 11 LT fibers were sensitized (i.e., gave increased responses to UBD). The effects of opioid receptor agonists were tested on responses to noxious UBD (80 mmHg). Cumulative intraarterial doses of mu-opioid receptor agonists (morphine, 8 mg/kg, and fentanyl, 300 micrograms/kg) and of delta-opioid receptor agonists (DPDPE, 300 micrograms/kg, and SNC-80, 300 micrograms/kg) did not affect responses to 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 differences in the dose-response relationships of these drugs on afferent fibers from untreated and xylenes- or mustard oil-treated urinary bladder. These results reveal that there is a greater proportion of UBD-sensitive 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 potential use for peripherally acting kappa opioid receptor agonists in the control of urinary bladder pain.
通过对大鼠盆神经进行电刺激，在L6背根中总共鉴定出443条盆神经传入纤维；其中319条（72%）是有髓鞘的Aδ纤维，平均传导速度（CV）为11.8米/秒，124条（28%）是无髓鞘的C纤维，平均CV为1.9米/秒。252条纤维（57%）对有害膀胱扩张（UBD；80毫米汞柱）有反应；108条是C纤维（平均CV；1.9米/秒），144条是Aδ纤维（平均CV；8.2米/秒）。对49条对UBD敏感的纤维进行了进一步表征；所有纤维对逐渐增加的扩张压力的放电均呈单调增加。36条纤维（73%）反应阈值低（LT）（平均：6毫米汞柱），13条纤维（27%）反应阈值高（HT）（平均：32毫米汞柱）。在向膀胱内注入0.5毫升30%二甲苯（n = 11）或5%芥子油（n = 4）之前和之后，测试了15条纤维对分级UBD（11条LT和4条HT）的反应。13条纤维的平均静息活动显著增加，7条纤维在注入二甲苯或芥子油30分钟后对分级UBD的反应出现敏感化。所有4条HT纤维均出现敏感化；11条LT纤维中有3条出现敏感化（即对UBD的反应增强）。测试了阿片受体激动剂对有害UBD（80毫米汞柱）反应的影响。μ阿片受体激动剂（吗啡，8毫克/千克，和芬太尼，300微克/千克）以及δ阿片受体激动剂（DPDPE，300微克/千克，和SNC - 80，300微克/千克）的累积动脉内给药剂量均不影响对有害UBD的反应。相比之下，κ阿片受体激动剂U50,488H、U69,593和U62,066的累积动脉内给药剂量为16毫克/千克时，对有害UBD反应呈剂量依赖性减弱。这些药物对未处理膀胱以及二甲苯或芥子油处理膀胱的传入纤维的剂量 - 反应关系没有差异。这些结果表明，大鼠L6背根中对UBD敏感的纤维比例（57%）高于S1背根（38%；先前的一项研究）。κ阿片受体激动剂而非μ或δ阿片受体激动剂对UBD反应的减弱表明，外周作用的κ阿片受体激动剂在控制膀胱疼痛方面具有潜在用途。
