Rahman Wahida, Suzuki Rie, Webber Mark, Hunt Stephen P, Dickenson Anthony H
Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
Pain. 2006 Aug;123(3):264-274. doi: 10.1016/j.pain.2006.02.033. Epub 2006 Apr 27.
There is compelling evidence for a strong facilitatory drive modulating spinal nociceptive transmission. This is in part via serotonergic pathways and originates from the rostroventral medulla. We previously demonstrated that neuropathic pain is associated with an enhanced descending facilitatory drive onto the mechanical evoked responses of dorsal horn neurones, mediated by 5-HT acting at spinal 5-HT3 receptors. Furthermore, depletion of spinal 5-HT has been shown to reduce the at-level mechanical allodynia that follows spinal cord injury. To further clarify the role and direction of effect of endogenous 5-HT, we investigated the effects of depleting spinal 5-HT, via intrathecal injection of 5,7di-hydroxytryptamine (5,7DHT), on pain behaviours after spinal nerve ligation (SNL). Depletion of spinal 5-HT in normal animals leads to reductions in mechanical and thermal evoked responses of deep dorsal horn neurones implying that spinal 5-HT has a predominant facilitatory function. After nerve injury, the frequency of paw withdrawals to low intensity mechanical and cooling stimulation of the ipsilateral hindpaw in the SNL-5,7DHT group was significantly attenuated when compared with the SNL-saline group from day seven post-nerve injury. Sham-5,7DHT and sham-saline animals showed very little response sensitivity on either hindpaw. This 5-HT-mediated difference in behaviour was independent of both the up-regulation of the NK1 receptor and spinal microglial activation produced by nerve injury. These data suggest that supraspinal serotonergic influences under these conditions are facilitatory and are implicated in the maintenance of spinal cord neuronal events leading to the behavioural hypersensitivity manifested after peripheral nerve damage.
有确凿证据表明存在一种强大的易化驱动调节脊髓伤害性信息传递。这部分是通过血清素能通路实现的，且起源于延髓头端腹内侧。我们之前证明，神经性疼痛与下行易化驱动增强有关，该驱动作用于背角神经元的机械诱发反应，由作用于脊髓5-HT3受体的5-羟色胺介导。此外，已表明脊髓5-羟色胺耗竭可减轻脊髓损伤后出现的损伤平面机械性异常性疼痛。为进一步阐明内源性5-羟色胺的作用和效应方向，我们通过鞘内注射5,7-二羟基色胺（5,7DHT）来研究脊髓5-羟色胺耗竭对脊髓神经结扎（SNL）后疼痛行为的影响。正常动物脊髓5-羟色胺耗竭会导致深部背角神经元的机械和热诱发反应降低，这意味着脊髓5-羟色胺具有主要的易化功能。神经损伤后，与神经损伤后第7天的SNL-生理盐水组相比，SNL-5,7DHT组同侧后爪对低强度机械和冷刺激的爪退缩频率显著降低。假手术-5,7DHT组和假手术-生理盐水组动物的任一后爪反应敏感性都很低。这种由5-羟色胺介导的行为差异与神经损伤引起的NK1受体上调和脊髓小胶质细胞激活均无关。这些数据表明，在这些条件下，脊髓上的血清素能影响具有易化作用，并参与维持脊髓神经元活动，导致外周神经损伤后出现行为超敏反应。
