Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Brain Behav. 2020 May;10(5):e01576. doi: 10.1002/brb3.1576. Epub 2020 Mar 18.
Due to side effects of medications used for chronic pain, combination therapy seems to be an appropriate solution for alleviation of chronic pain and reducing the side effects. The role of inhibitory GABA system is well proven in reducing neuropathic pain. Also, special attention has been focused on endogenous morphine (endomorphins) in reducing chronic pain originates from damage to the nervous system. The purpose of this study is to investigate the analgesic effect of simultaneous administration of GABA agonist and endomorphin-1 on neuropathic pain in rat model of spinal cord injury (SCI). The role of oxidative stress, NR1 subunits of NMDA receptors, and α subunits of GABA receptors in the spinal cord has also been investigated.
Spinal cord at level of T6-T8 was compressed. Three weeks after spinal cord injury, muscimol and endomorphin-1 were injected (intrathecally once a day for 7 days) individually or in combination. Mechanical and cold allodynia, thermal and mechanical hyperalgesia were evaluated before injection and 15 and 60 min after injection. At the end of behavioral experiments, histological and biochemical evaluations were done on prepared spinal cord samples.
Isobologram results showed that combination therapy significantly increased the pain threshold comparing to injection of endomorphin-1 (EM) or muscimol alone. Histological studies indicated the increased expression of α2 subunits of GABA receptors, and NR1 subunits of NMDA receptors in the spinal cord. The combination therapy also increased the glutathione (GSH) and superoxide dismutase (SOD) level and decreased the malondialdehyde (MDA) levels in the spinal cord.
Simultaneous administration of muscimol and endomorphine-1 could be a new candidate for alleviation of pain resulting from spinal cord injury.
由于用于慢性疼痛的药物的副作用，联合治疗似乎是缓解慢性疼痛和减少副作用的一种合适的解决方案。抑制性 GABA 系统在减轻神经病理性疼痛方面的作用已得到充分证明。此外，人们特别关注内源性吗啡（内吗啡肽）在减轻源自神经系统损伤的慢性疼痛方面的作用。本研究旨在研究 GABA 激动剂和内吗啡肽-1 同时给药对脊髓损伤（SCI）大鼠模型中神经性疼痛的镇痛作用。还研究了氧化应激、NMDA 受体的 NR1 亚单位和 GABA 受体的 α 亚单位在脊髓中的作用。
T6-T8 水平的脊髓受压。脊髓损伤 3 周后，单独或联合（鞘内每天注射一次，共 7 天）注射 muscimol 和内吗啡肽-1。在注射前、注射后 15 和 60 分钟评估机械性和冷感觉过敏、热痛觉过敏和机械性痛觉过敏。行为实验结束后，对准备好的脊髓样本进行组织学和生化评估。
等辐射图结果表明，与单独注射内吗啡肽-1（EM）相比，联合治疗显著提高了疼痛阈值。组织学研究表明，脊髓中 GABA 受体的 α2 亚单位和 NMDA 受体的 NR1 亚单位表达增加。联合治疗还增加了脊髓中的谷胱甘肽（GSH）和超氧化物歧化酶（SOD）水平，并降低了丙二醛（MDA）水平。
同时给予 muscimol 和内吗啡肽-1 可能是缓解脊髓损伤引起的疼痛的一种新的候选药物。
