Rojas-Corrales Olga M, Ortega-Alvaro Antonio, Gibert-Rahola Juan, Roca-Vinardell Aranzazu, Micó Juan A
Department of Neuroscience, Neuropsycopharmacology Unit, University of Cádiz, Plz. Fragela 9, 11003 Cádiz, Spain.
Pain. 2000 Nov;88(2):119-124. doi: 10.1016/S0304-3959(00)00299-2.
The ability of pindolol, a beta-adrenoceptor blocker/5-hydroxytryptamine(1A/1B) antagonist, to enhance the clinical antidepressant response to selective serotonin re-uptake inhibitors is generally attributed to a blocking of the feedback that inhibits the serotoninergic neuronal activity mediated by somatodendritic 5-hydroxytryptamine (5-HT)(1A) autoreceptors. The current study examined the ability of pindolol to enhance the analgesic effect of tramadol, an atypical centrally-acting analgesic agent with relatively weak opioid receptor affinity and which, like some antidepressants, is able to inhibit the re-uptake of 5-HT in the raphe nuclei. Racemic pindolol (2 mg/kg, s.c.), rendered analgesic a non-effective acute dose of tramadol (10-40 mg/kg, i.p.) in two nociceptive tests: a hot plate test in mice and a plantar test in rats. Moreover, (+/-)8-OH-DPAT (0.125-1 mg/kg, s.c.), a selective 5-HT(1A) agonist, reduces the analgesic effect of tramadol in the same tests. These results suggest an implication of the somatodendritic 5-HT(1A) receptors in the analgesic effect of tramadol and open a new adjuvant analgesic strategy for the use of this compound.
吲哚洛尔是一种β-肾上腺素能受体阻滞剂/5-羟色胺（1A/1B）拮抗剂，其增强对选择性5-羟色胺再摄取抑制剂临床抗抑郁反应的能力通常归因于对由树突体5-羟色胺（5-HT）（1A）自身受体介导的抑制5-羟色胺能神经元活动的反馈的阻断。本研究考察了吲哚洛尔增强曲马多镇痛作用的能力，曲马多是一种非典型的中枢性镇痛药，对阿片受体亲和力相对较弱，并且像一些抗抑郁药一样，能够抑制中缝核中5-羟色胺的再摄取。消旋吲哚洛尔（2mg/kg，皮下注射）在两种伤害性感受试验中使无效的急性剂量曲马多（10-40mg/kg，腹腔注射）产生镇痛作用：小鼠热板试验和大鼠足底试验。此外，选择性5-HT（1A）激动剂（+/-）8-OH-DPAT（0.125-1mg/kg，皮下注射）在相同试验中降低了曲马多的镇痛作用。这些结果表明树突体5-HT（1A）受体参与了曲马多的镇痛作用，并为该化合物的使用开辟了一种新的辅助镇痛策略。
