Department of Anatomy, School of Medicine, Chung Shan Medical University, Taichung, 40201, Taiwan.
Department of Medical Education, Chung Shan Medical University Hospital, Taichung, 40201, Taiwan.
Neurotox Res. 2018 Feb;33(2):362-376. doi: 10.1007/s12640-017-9799-5. Epub 2017 Aug 23.
Nerve decompression is an essential therapeutic strategy for pain relief clinically; however, its potential mechanism remains poorly understood. Opioid analgesics acting on opioid receptors (OR) within the various regions of the nervous system have been used widely for pain management. We therefore hypothesized that nerve decompression in a neuropathic pain model of chronic constriction injury (CCI) improves the synaptic OR plasticity in the dorsal horn, which is in response to alleviate pain hypersensitivity. After CCI, the Sprague-Dawley rats were assigned into Decompression group, in which the ligatures around the sciatic nerve were removed at post-operative week 4 (POW 4), and a CCI group, in which the ligatures remained. Pain hypersensitivity, including thermal hyperalgesia and mechanical allodynia, was entirely normalized in Decompression group within the following 4 weeks. Substantial reversal of mu- and delta-OR immunoreactive (IR) expressions in Decompression group was detected in primary afferent terminals in the dorsal horn. In Decompression group, mu-OR antagonist (CTOP, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 [Disulfide Bridge: 2-7]) and delta-OR antagonist (NTI, 17-(cyclopropylmethyl)-6,7-dehydro-4,5α-epoxy-3,14-dihydroxy-6,7-2',3'-indolomorphinan hydrochloride) re-induced pain hypersensitivity by intrathecal administration in a dose-responsive manner. Additionally, mu-OR agonist (DAMGO, [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin) and delta-OR agonist (SNC80, ((+)-4-[(αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethyl-benzamide) were administrated intrathecally to attenuating CCI-induced chronic and acute pain hypersensitivity dose-dependently. Our current results strongly suggested that nerve decompression provides the opportunity for improving the synaptic OR plasticity in the dorsal horn and pharmacological blockade presents a novel insight into the therapeutic strategy for pain hypersensitivity.
神经减压是临床上缓解疼痛的一种重要治疗策略；然而，其潜在机制仍知之甚少。作用于神经系统各个区域阿片受体 (OR) 的阿片类镇痛药已广泛用于疼痛管理。因此，我们假设神经减压可改善慢性缩窄性损伤 (CCI) 神经病理性疼痛模型中的背角突触 OR 可塑性，从而缓解痛觉过敏。CCI 后，将 Sprague-Dawley 大鼠分为减压组和 CCI 组。减压组在术后第 4 周（POW 4）去除坐骨神经周围的结扎线，CCI 组则保留结扎线。减压组在接下来的 4 周内完全缓解了热痛觉过敏和机械性痛觉过敏。在减压组中，背角初级传入末端检测到 μ 和 δ-OR 免疫反应性 (IR) 表达的显著逆转。在减压组中，μ-OR 拮抗剂 (CTOP，D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 [二硫键：2-7]) 和 δ-OR 拮抗剂 (NTI，17-(环丙基甲基)-6,7-去氢-4,5α-环氧-3,14-二羟基-6,7-2',3'-吲哚吗啡喃盐酸盐) 以剂量反应方式鞘内给药重新引起痛觉过敏。此外，μ-OR 激动剂 (DAMGO，[D-Ala2，NMe-Phe4，Gly-ol5]-脑啡肽) 和 δ-OR 激动剂 (SNC80，((+)-4-[(αR)-α-((2S,5R)-4-烯丙基-2,5-二甲基-1-哌嗪基)-3-甲氧基苄基]-N,N-二乙基-苯甲酰胺) 鞘内给药可减轻 CCI 诱导的慢性和急性痛觉过敏，具有剂量依赖性。我们的研究结果强烈表明，神经减压为改善背角突触 OR 可塑性提供了机会，而药理学阻断为痛觉过敏的治疗策略提供了新的见解。
