Su X, Gebhart G F
The University of Iowa, College of Medicine, Department of Pharmacology, Iowa City 52242, USA.
Pain. 1998 May;76(1-2):105-14. doi: 10.1016/s0304-3959(98)00031-1.
The aim of this study was to examine the effects of tricyclic antidepressants on responses of mechanosensitive afferent fibers innervating the rat colon. A total of 53 fibers in the decentralized S1 dorsal root were studied. The effects of the non-specific monoamine reuptake inhibitor imipramine (IMI), the noradrenaline reuptake inhibitor desipramine (DES), and the serotonin reuptake inhibitor clomipramine (CLO) were tested on responses of 22 mechanosensitive afferent fibers to noxious colorectal distension (CRD; 80 mmHg). Cumulative doses of 16 mg/kg of IMI, DES and of CLO reduced responses to noxious CRD to a mean 20%, 22% and 46% of control, respectively. The mean inhibitory doses of the three antidepressants did not differ significantly. Inhibitory effects were independent of potential effects on neurotransmitter reuptake: the effects of IMI and DES were not blocked by the adrenoreceptor antagonist phentolamine, and the effects of IMI and CLO were not affected by the serotonin receptor antagonist metergoline. Attenuation of afferent nerve activity was not mimicked by the anticholinergic glycopyrrolate; the cholinesterase inhibitor neostigmine did not attenuate the effect of IMI on responses to noxious CRD. Interestingly, the opioid receptor antagonist naloxone partially reversed the effects of IMI, and the NMDA receptor channel blocker MK-801 enhanced the inhibitory effects of DES and CLO. These results document that responses of mechanosensitive pelvic nerve afferent fibers to noxious CRD are significantly attenuated by tricyclic antidepressants, a peripheral action that may contribute to the beneficial effects of tricyclic antidepressants in treatment of irritable bowel syndrome.
本研究旨在考察三环类抗抑郁药对支配大鼠结肠的机械敏感传入纤维反应的影响。共研究了去传入神经支配的S1背根中的53根纤维。测试了非特异性单胺再摄取抑制剂丙咪嗪（IMI）、去甲肾上腺素再摄取抑制剂地昔帕明（DES）和5-羟色胺再摄取抑制剂氯米帕明（CLO）对22根机械敏感传入纤维对有害性结直肠扩张（CRD；80 mmHg）反应的影响。累积剂量为16 mg/kg的IMI、DES和CLO分别将对有害性CRD的反应降低至对照值的平均20%、22%和46%。这三种抗抑郁药的平均抑制剂量无显著差异。抑制作用与对神经递质再摄取的潜在影响无关：IMI和DES的作用未被肾上腺素能受体拮抗剂酚妥拉明阻断，IMI和CLO的作用未受5-羟色胺受体拮抗剂麦角新碱影响。抗胆碱能药物格隆溴铵未模拟传入神经活动的减弱；胆碱酯酶抑制剂新斯的明未减弱IMI对有害性CRD反应的作用。有趣的是，阿片受体拮抗剂纳洛酮部分逆转了IMI的作用，NMDA受体通道阻滞剂MK-801增强了DES和CLO的抑制作用。这些结果证明，三环类抗抑郁药可显著减弱机械敏感盆神经传入纤维对有害性CRD的反应这一外周作用，可能有助于三环类抗抑郁药治疗肠易激综合征的有益效果。
