病理性疼痛的分子机制

Molecular and cellular mechanisms of pain

持续性或慢性疼痛是很多患者的主要描述症状。然而,现在的治疗手段还不能充分解决某些疼痛或会引起不能忍受的副作用。近来疼痛生物学者阐明了大量的参与疼痛发生和维持的细胞和分子活动。如何更好的理解这些分子活动的机制将有助于发展高效的,特异性的治疗手段。背根神经节中小细胞神经元向脊髓传递温觉和伤害性信息的感觉传递。这些神经元的外周突感受生理性和化学性刺激后,可以在脊髓背角的中枢突通过突触囊泡和大致密性囊泡释放兴奋性的神经递质和神经肽。这种兴奋性突触传递可以被一些抑制因子调控如脊髓中间神经元和下行系统中分泌的阿片肽、GABA、甘氨酸、5-羟色胺。本文将回顾脊髓抑制性系统所取得的一些研究进展,将重点介绍在阿片受体转运,阿片镇痛以及吗啡耐受研究中的进展,这些发现可能的治疗前景也会一并讨论。

Persistent or chronic pain is the primary reason people seek medical care. However, current therapies are inadequate for certain types of pain or cause intolerable side effects. Pain neurobiologists have recently identified a number of cellular and molecular processes that lead to the initiation and maintenance of pain. Understanding these underlying mechanisms has given significant promise for the development of more effective and specific pain therapies in the future. Small-diameter neurons in the dorsal root ganglion （DRG） convey thermal and nociceptive sensory signals to the spinal cord. In response to physical and chemical stimulation of their peripheral terminals, these neurons release excitatory neurotransmitter glutamate and neuropeptides via exocytosis of synaptic vesicles and large dense-core vesicles （LDCVs） at their afferent terminals in the dorsal spinal cord, respectively.This excitatory afferent transmission can be negatively regulated by inhibitory factors, including opioid peptides, T-aminobutyric acid （GABA）, glycine and serotonin, which are secreted by spinal interneurons and descending fibers. In the present lecture, I will review our recent progress in understanding of the regulation of spinal inhibitory system. I will focus on the recent findings of mechanisms for regulating opioid receptor trafficking, opioid analgesia and morphine analgesic tolerance. The therapeutic potential of these findings in pain treatment will be discussed.