Center for Pain Management and Department of Anesthesiology, Fukushima Medical University, 1 Hikarigaoka, Fukushima-City, Fukushima 960-1295, Japan.
Int J Mol Sci. 2017 Nov 21;18(11):2483. doi: 10.3390/ijms18112483.
Tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors are used to treat chronic pain, such as neuropathic pain. Why antidepressants are effective for treatment of neuropathic pain and the precise mechanisms underlying their effects, however, remain unclear. The inhibitory effects of these antidepressants for neuropathic pain manifest more quickly than their antidepressive effects, suggesting different modes of action. Recent studies of animal models of neuropathic pain revealed that noradrenaline is extremely important for the inhibition of neuropathic pain. First, increasing noradrenaline in the spinal cord by reuptake inhibition directly inhibits neuropathic pain through α₂-adrenergic receptors. Second, increasing noradrenaline acts on the locus coeruleus and improves the function of an impaired descending noradrenergic inhibitory system. Serotonin and dopamine may reinforce the noradrenergic effects to inhibit neuropathic pain. The mechanisms of neuropathic pain inhibition by antidepressants based mainly on experimental findings from animal models of neuropathic pain are discussed in this review.
三环类抗抑郁药和 5-羟色胺去甲肾上腺素再摄取抑制剂用于治疗慢性疼痛，如神经病理性疼痛。然而，为什么抗抑郁药对治疗神经病理性疼痛有效，以及它们作用的确切机制仍不清楚。这些抗抑郁药对神经病理性疼痛的抑制作用比抗抑郁作用更快，这表明它们的作用模式不同。最近对神经病理性疼痛动物模型的研究表明，去甲肾上腺素对抑制神经病理性疼痛非常重要。首先，通过再摄取抑制增加脊髓中的去甲肾上腺素可直接通过 α₂-肾上腺素能受体抑制神经病理性疼痛。其次，增加去甲肾上腺素作用于蓝斑核，改善受损的下行去甲肾上腺素抑制系统的功能。5-羟色胺和多巴胺可能增强去甲肾上腺素的作用以抑制神经病理性疼痛。本文综述了主要基于神经病理性疼痛动物模型的实验结果的抗抑郁药抑制神经病理性疼痛的机制。
