Hong Y, Abbott F V
Department of Psychiatry, McGill University, Montreal, Canada.
Eur J Pharmacol. 1996 Apr 22;301(1-3):41-8. doi: 10.1016/0014-2999(96)00009-x.
We examined the peripheral adrenergic mechanisms involved in pain induced by alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT) plus (+/-)-noradrenaline or prostaglandin E2 and by intraplantar formalin. Agents were injected s.c. into the plantar surface of rats' paws, and the paw lifting and licking response scored. Pain produced by alpha-methyl-5-HT (10 micrograms) plus noradrenaline (10 micrograms) was blocked by pretreatment with the alpha-adrenoceptor antagonists, phentolamine (10 micrograms) and prazocin HCl (alpha 1; 40 micrograms), but not by timolol (beta; 10 micrograms) or idazoxan (alpha 2; 40 micrograms). Phenylepherine, but not clonidine, substituted for noradrenaline to induce pain when combined with alpha-methyl-5-HT. The alpha 1A-adrenoceptor antagonist, WB-4101 (2-(2,6-dimethoxyphenoxyethyl) aminomethyl-1,4-benzodioxane HCl), but not the alpha 1B- adrenoceptor antagonist, chloroethylclonidine, also blocked the pain response produced by alpha-methyl-5-HT plus noradrenaline. Neither of these agents altered pain produced by alpha-methyl-5-HT plus prostaglandin E2 (0.1 microgram). Formalin-induced pain (1%, 50 microliters) was biphasic, and timolol increased the first phase response. The second phase was attenuated by 40% by phentolamine (10 micrograms) injected 10 min before formalin or at the beginning of the second phase; 30 micrograms did not produce a larger effect. Prazosin and WP-4101, but not idazoxan or chloroethylclonidine, also attenuated the second phase. Thus, activation of alpha 1A-adrenoceptors can contribute to pain, but pain induced by alpha-methyl-5-HT plus prostaglandin E2 is independent of adrenergic function, indicating that adrenergic function is not necessary for induction of pain by inflammatory mediators. alpha 1A-Adrenoceptor blockade attenuates pain when administered after development of pain, implying that peripheral adrenergic mechanisms contribute to ongoing maintenance of pain.
我们研究了参与由α-甲基-5-羟色胺（α-甲基-5-羟色胺）加（±）-去甲肾上腺素或前列腺素E2以及足底注射福尔马林诱导的疼痛的外周肾上腺素能机制。将药物皮下注射到大鼠爪的足底表面，并对爪抬起和舔舐反应进行评分。由α-甲基-5-羟色胺（10微克）加去甲肾上腺素（10微克）产生的疼痛可被α-肾上腺素能受体拮抗剂酚妥拉明（10微克）和盐酸哌唑嗪（α1；40微克）预处理阻断，但不能被噻吗洛尔（β；10微克）或咪唑克生（α2；40微克）阻断。苯肾上腺素而非可乐定，在与α-甲基-5-羟色胺联合使用时可替代去甲肾上腺素诱导疼痛。α1A-肾上腺素能受体拮抗剂WB-4101（2-（2,6-二甲氧基苯氧基乙基）氨基甲基-1,4-苯并二恶烷盐酸盐）而非α1B-肾上腺素能受体拮抗剂氯乙可乐定，也可阻断α-甲基-5-羟色胺加去甲肾上腺素产生的疼痛反应。这些药物均未改变α-甲基-5-羟色胺加前列腺素E2（0.1微克）产生的疼痛。福尔马林诱导的疼痛（1%，50微升）是双相的，噻吗洛尔增加了第一相反应。在福尔马林注射前10分钟或第二相开始时注射酚妥拉明（10微克）可使第二相减弱40%；30微克并未产生更大的效果。哌唑嗪和WP-4101而非咪唑克生或氯乙可乐定也可减弱第二相。因此，α1A-肾上腺素能受体的激活可导致疼痛，但由α-甲基-5-羟色胺加前列腺素E2诱导的疼痛与肾上腺素能功能无关，这表明肾上腺素能功能对于炎症介质诱导疼痛并非必需。α1A-肾上腺素能受体阻断在疼痛发生后给药时可减轻疼痛，这意味着外周肾上腺素能机制有助于疼痛的持续维持。
