Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
Brain Res. 2011 Mar 25;1382:29-36. doi: 10.1016/j.brainres.2011.01.057. Epub 2011 Jan 26.
Serotonin (5-HT) plays a major yet complex role in modulating spinal nociceptive transmission as a consequence of the number of 5-HT receptor subtypes. These include the 5-HT2 receptor, which is further sub classified into 5-HT2A, B and C. Studies have described both a pro- and antinociceptive action following 5-HT2A-receptor activation; therefore, to shed light on the directional nature of spinal 5-HT2A receptor activity, we investigated the effects of spinal administration of the 5-HT2A receptor antagonist, ketanserin, on the evoked responses of dorsal horn neurones to electrical, mechanical and thermal stimulation. We also assessed the effects of systemic administration of ritanserin, a 5-HT2A/2C receptor antagonist and spinal application of (±)-2,5-Dimethoxy-4-iodoamphetamine hydrochloride (DOI) (3.6 and 17.8μg/50μl), a 5-HT2A/2C agonist, on the same evoked neuronal responses. Ketanserin (1, 10 and 100μg/50μl) produced a dose related inhibition of the evoked responses to noxious mechanical punctate and thermal stimuli only. Ritanserin (2mg/kg) replicated the inhibitory effects seen with ketanserin on the natural evoked neuronal responses and also potently inhibited the C-fibre, post discharge, input and wind-up evoked responses. DOI increased the mechanical and thermal evoked responses, an effect reversed by ketanserin. Thus, our findings show that spinal ketanserin (1-100μg/50μl) and systemic ritanserin (2mg/kg), at these doses, have similar antinociceptive effects, whereas the agonist, DOI, produced excitatory effects, on spinal neuronal activity. Our data, therefore, supports a pronociceptive role for 5-HT2 receptors, most likely through modulation of 5-HT2A receptor activity, on spinal nociceptive transmission under normal conditions.
血清素（5-HT）在调节脊髓伤害性传递中发挥着主要但复杂的作用，这是由于 5-HT 受体亚型的数量众多。这些受体包括 5-HT2 受体，它进一步细分为 5-HT2A、B 和 C。研究描述了 5-HT2A 受体激活后的促伤害和抗伤害作用；因此，为了阐明脊髓 5-HT2A 受体活性的方向性，我们研究了脊髓给予 5-HT2A 受体拮抗剂酮色林对背角神经元对电、机械和热刺激的诱发反应的影响。我们还评估了系统给予利坦色林（一种 5-HT2A/2C 受体拮抗剂）和脊髓给予（±）-2,5-二甲氧基-4-碘苯丙胺盐酸盐（DOI）（3.6 和 17.8μg/50μl），一种 5-HT2A/2C 激动剂，对相同诱发神经元反应的影响。酮色林（1、10 和 100μg/50μl）对伤害性机械点状和热刺激的诱发反应呈剂量相关抑制。利坦色林（2mg/kg）复制了酮色林对自然诱发神经元反应的抑制作用，并且强烈抑制 C 纤维后放电、输入和wind-up 诱发反应。DOI 增加了机械和热诱发反应，这种作用被酮色林逆转。因此，我们的发现表明，脊髓酮色林（1-100μg/50μl）和系统利坦色林（2mg/kg）在这些剂量下具有相似的抗伤害作用，而激动剂 DOI 对脊髓神经元活动产生兴奋作用。因此，我们的数据支持 5-HT2 受体在正常情况下对脊髓伤害性传递具有促伤害作用，这很可能是通过调节 5-HT2A 受体活性。
