CONTRIBUTION OF PERIPHERAL ALPHA(1A)-ADRENOCEPTORS TO PAIN INDUCED BYFORMALIN OR BY ALPHA-METHYL-5-HYDROXYTRYPTAMINE PLUS NORADRENALINE

We examined the peripheral adrenergic mechanisms involved in pain indu ced by alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT) plus (+/-) -noradrenaline or prostaglandin E(2) and by intraplantar formalin. Age nts were injected s.c. into the plantar surface of rats' paws, and the paw lifting and licking response scored. Pain produced by alpha-methy l-5-HT (10 mu g) plus noradrenaline (10 mu g) was blocked by pretreatm ent with the alpha-adrenoceptor antagonists, phentolamine (10 mu g) an d prazocin HCl (alpha(1) 40 mu g), but not by timolol(beta; 10 mu g) o r idazoxan (alpha(2); 40 mu g). Phenylepherine, but not clonidine, sub stituted for noradrenaline to induce pain when combined with alpha-met hyl-5-HT. The alpha(1A)-adrenoceptor antagonist, WB-4101 dimethoxyphen oxyethyl)aminomethyl-1,4-benzodioxane HCl), but not the alpha(1B)- adr enoceptor antagonist, chloroethylclonidine, also blocked the pain resp onse produced by alpha-methyl-5-HT plus noradrenaline. Neither of thes e agents altered pain produced by alpha-methyl-5-HT plus prostaglandin E(2) (0.1 mu g). Formalin-induced pain (1%, 50 mu l) was biphasic, an d timolol increased the first phase response. The second phase was att enuated by 40% by phentolamine (10 mu g) injected 10 min before formal in or at the beginning of the second phase; 30 mu g did not produce a larger effect. Prazosin and WP-4101, but not idazoxan or chloroethylcl onidine, also attenuated the second phase. Thus, activation of alpha(1 A)-adrenoceptors can contribute to pain, but pain induced by alpha-met hyl-5-HT plus prostaglandin E(2) is independent of adrenergic function , indicating that adrenergic function is not necessary for induction o f pain by inflammatory mediators. alpha(1A)-Adrenoceptor blockade atte nuates pain when administered after development of pain, implying that peripheral adrenergic mechanisms contribute to ongoing maintenance of pain.