Influence of the descending pain-inhibiting serotonergic pathway on the antihyperalgesic effect of gabapentin in neuropathic pain model rats

IF 2.4 4区医学 Q3 NEUROSCIENCES

Neuroscience Research Pub Date : 2024-05-01 DOI:10.1016/j.neures.2023.11.003

Harue Yanagimura , Mika Sasaki , Hiroshi Baba , Yoshinori Kamiya

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Abstract

Gabapentinoids are used worldwide as first-line agents for the treatment of neuropathic pain. Accumulating evidence indicates that one of the antihyperalgesic mechanisms of gabapentinoids is through activation of the noradrenergic pathway of the descending pain inhibition system. However, the involvement of the serotonin pathway is unclear. We investigated the effects of gabapentin (GBP) on the serotonergic pathway of the descending inhibitory system using the spinal nerve ligation (SNL) rat model. As in previous reports, administration of GBP to SNL rats improved paw withdrawal thresholds (PWT). Intrathecally administered serotonin receptor antagonists abolished GBP's amelioration in PWT. GBP did not ameliorate PWT in noradrenaline-depleted SNL rats by DSP-4. However, GBP ameliorated PWT in serotonin-depleted SNL rats by para-chlorophenylalanine, which was not inhibited by intrathecal administration of a serotonin receptor antagonist. Immunohistochemical analysis of serotonin in the spinal dorsal horn revealed a slight, albeit statistically insignificant, increase in 5-HT levels in SNL rats compared to naive rats. However, no apparent changes were observed before or after GBP administration in naive and SNL rats. In conclusion, the involvement of the serotonergic pathway in the antihyperalgesic effects of GBP on the spinal cord is secondary, although it cooperates with the noradrenergic system to produce analgesia.

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下行疼痛抑制5-羟色胺能通路对加巴喷丁在神经病理性疼痛模型大鼠中抗镇痛作用的影响。

Gabapentinoids在世界范围内被用作治疗神经性疼痛的一线药物。越来越多的证据表明，加巴喷丁类药物的抗镇痛机制之一是通过激活下行疼痛抑制系统的去甲肾上腺素能通路。然而，血清素途径的参与尚不清楚。我们使用脊神经结扎（SNL）大鼠模型研究了加巴喷丁（GBP）对下行抑制系统5-羟色胺能通路的影响。与之前的报道一样，对SNL大鼠施用GBP改善了爪退缩阈值（PWT）。鞘内给药5-羟色胺受体拮抗剂消除了GBP对PWT的改善作用。GBP不能通过DSP-4改善去甲肾上腺素耗竭的SNL大鼠的PWT。然而，GBP通过对氯苯丙氨酸改善了血清素缺乏的SNL大鼠的PWT，而鞘内给药血清素受体拮抗剂并没有抑制这一作用。脊髓背角5-羟色胺的免疫组织化学分析显示，与未成年大鼠相比，SNL大鼠的5-HT水平略有增加，尽管在统计学上不显著。然而，在幼稚大鼠和SNL大鼠中，在GBP给药前后没有观察到明显的变化。总之，5-羟色胺能通路参与GBP对脊髓的抗高镇痛作用是次要的，尽管它与去甲肾上腺素能系统协同产生镇痛作用。（200字）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuroscience Research 医学-神经科学

CiteScore

5.60

自引率

3.40%

发文量

136

审稿时长

28 days

期刊介绍： The international journal publishing original full-length research articles, short communications, technical notes, and reviews on all aspects of neuroscience Neuroscience Research is an international journal for high quality articles in all branches of neuroscience, from the molecular to the behavioral levels. The journal is published in collaboration with the Japan Neuroscience Society and is open to all contributors in the world.