Formalin-induced nociception activates a monoaminergic descending inhibitory system

Neural plasticity of afferent pain pathways that is induced by prolonged or repeated noxious stimuli may contribute to activate intrinsic inhibitory m echanisms in CNS. In order to clarify the role of the monoaminergic descend ing inhibitory system in acute nociception and inflammatory pain, we examin ed if this inhibitory system would modulate the tonic response to formalin- induced nociception. Yohimbine, alpha 2 adrenergic antagonist, or methyserg ide, serotonin antagonist was administered intrathecally before or after su bcutaneous 2% formalin injection into the plantar of the hind paw in rats. In another series of the experiment, the tissue of the spinal dorsal half o f the untreated rats and post-formalin-treated rats were sampled and analys es of monoamine levels were carried out by HPLC. The subcutaneous formalin evoked biphasic flinching behavior of the injected paw. Intrathecal pretrea tment with yohimbine and methysergide produced a significantly greater incr ease in the number of flinches than in the control in phase 1, intermediate period and phase 2. Posttreatment with yohimbine and methysergide showed a significantly greater increase in the number of flinches in phase 2. Furth ermore, formalin injection induced significant increases in noradrenaline, MHPG, serotonin (5-hydroxytryptamine; 5-HT) and 5-HIAA concentrations in bo th the ipsi- and contralateral dorsal halves. These results suggest that th e pain state produced by formalin-induced chemical and/or inflammatory noci ception is under the modulation of the monoaminergic (noradrenergic and ser otonergic) descending inhibitory system. (C) 1998 Elsevier Science B.V. All rights reserved.