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The role of CGRP receptor antagonist (CGRP8-37) and Endomorphin-1 combination therapy on neuropathic pain alleviation and expression of Sigma-1 receptors and antioxidants in rats
Journal of Chemical Neuroanatomy ( IF 2.8 ) Pub Date : 2020-07-01 , DOI: 10.1016/j.jchemneu.2020.101771
Atousa Janzadeh 1 , Zohreh Karami 2 , Marjan Hosseini 2 , Leila Zarepour 2 , Mahmoud Yousefifard 2 , Farinaz Nasirinezhad 3
Affiliation  

BACKGROUND Spinal cord injury is one of the most common causes of neuropathic pain which is not responsive to common treatments. Owing to the adverse effects of drugs, it seems that the use of calcitonin Gene-Related Protein (CGRP) receptor antagonist or Morphine and their combination could be an appropriate strategy for pain alleviation. METHOD To achieve the objective, fifty six male Wistar rats were divided into seven groups. CGRP8-37 and Endomorphin-1 alone, and in combinated administration, as bolus and continues dose. Both mechanical and cold allodynia, and mechanical hyperalgesia were evaluated before and also15 and 60 min after injection to indicate the efficacy of the therapies in the acute and chronic circumstances on pain induced by spinal cord compression injury. Sigma-1 receptor experssion, oxidant and antioxidant activity after the seven days of the drug adminestration were evaluated. RESULT The results showed that Endomorphin-1and CGRP8-37 injections were able to reduce neuropathic pain after spinal cord compression injury. Compared to Endomorphin-1, or CGRP8-37 monotherapy, combination therapy did not show more attenuating effects on the pain threshold. Compared to the continous administration of Endomorphin-1 alone, and CGRP8-37 alone, the continous combination therapy did not reduce the pain further. Molecular studies disclosed the increased expression of the Sigma1 receptor, in the spinal cord after administration of Endomorphin-1, and CGRP8-37 alone, as well as combination therapy. Although, an increase in GPx and SOD activity, and decrease in MDA activity was observed in the combination therapy. CONCLUSION Our results demonstrate that either Endomorphin-1 or CGRP receptor antagonist is able to decrease the neuropathic pain after SCI but combination therapy by a CGRP receptor antagonist and Endomorphin-1 did not make any further reduction in pain sensation.

中文翻译:

CGRP受体拮抗剂(CGRP8-37)与Endomorphin-1联合治疗对大鼠神经病理性疼痛缓解及Sigma-1受体和抗氧化剂表达的作用

背景脊髓损伤是对普通治疗无反应的神经性疼痛的最常见原因之一。由于药物的不良反应,降钙素基因相关蛋白(CGRP)受体拮抗剂或吗啡及其组合的使用似乎是缓解疼痛的合适策略。方法为达到目的,将56只雄性Wistar大鼠分为7组。CGRP8-37 和 Endomorphin-1 单独和联合给药,作为推注和连续给药。在注射前和注射后 15 和 60 分钟评估机械性和冷性异常性疼痛以及机械痛觉过敏,以表明治疗在急性和慢性情况下对脊髓压迫损伤引起的疼痛的疗效。Sigma-1 受体表达,评价给药7天后的氧化和抗氧化活性。结果 结果表明,内吗啡肽-1和CGRP8-37注射液能够减轻脊髓压迫损伤后的神经性疼痛。与 Endomorphin-1 或 CGRP8-37 单一疗法相比,联合疗法对痛阈没有显示出更多的减弱作用。与单独连续给药 Endomorphin-1 和单独 CGRP8-37 相比,连续联合治疗并未进一步减轻疼痛。分子研究表明,在单独使用 Endomorphin-1 和 CGRP8-37 以及联合治疗后,脊髓中 Sigma1 受体的表达增加。尽管如此,在联合治疗中观察到 GPx 和 SOD 活性增加,MDA 活性降低。
更新日期:2020-07-01
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