Curcumin exerts antinociceptive effects in a mouse model of neuropathic pain: Descending monoamine system and opioid receptors are differentially involved
Curcumin exerts antinociceptive effects in a mouse model of neuropathic pain: Descending monoamine system and opioid receptors are differentially involved
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姜黄素在神经性疼痛小鼠模型中发挥抗伤害作用：降序单胺系统和阿片受体有不同程度的参与
DOI：
10.1016/j.neuropharm.2011.08.050
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发表时间：
2012-02-01
影响因子：
4.7
通讯作者：
Huang, Zhi-Li
中科院分区：
文献类型：
--
作者：
Zhao, Xin;Xu, Ying;Huang, Zhi-Li
姜黄素是姜黄中含有的一种酚类化合物，据报道在一些动物模型中具有抗伤害感受作用，但其作用机制尚不清楚。本研究旨在探讨姜黄素对神经性疼痛的抗感知作用及其机制。慢性收缩性损伤（CCI）是一种典型的神经性疼痛动物模型，通过松散结扎小鼠坐骨神经，分别采用von Frey毛发或热板试验评估机械异常性痛或热痛感过敏（对热）。慢性（非急性）姜黄素治疗（5、15或45 mg/kg， p.o，每天两次，持续三周）减轻了CCI小鼠的机械异常性痛和热痛觉过敏，并伴有脊柱单胺（或代谢物）含量的增加。6-羟基多巴胺（6-OHDA）化学消融降去甲肾上腺素（NA），或对氯苯丙氨酸（PCPA）消耗降血清素，分别消除姜黄素对机械异常性痛或热痛觉过敏的抗伤害作用。姜黄素对机械刺激的抗异动作用被与β(2)-肾上腺素受体拮抗剂ICI 118,551慢性联合治疗或与δ -阿片受体拮抗剂纳曲多急性联合治疗完全阻断。同时，长期与5-HT1A受体拮抗剂WAY-100635或急性与不可逆的mu-阿片受体拮抗剂β -funaltrexamine联合治疗，姜黄素对热刺激的抗痛觉作用完全消失。总的来说，这些发现表明，下降单胺系统（与脊髓β(2)-肾上腺素能受体和5-HT1A受体结合）对姜黄素在神经性疼痛中的模式特异性抗感觉作用至关重要。因此，δ -和μ -阿片受体可能是下游的靶标。这篇文章是《创伤后应激障碍》特刊的一部分。(C) 2011 Elsevier Ltd.版权所有。
Curcumin, a phenolic compound present in Curcuma longa, has been reported to exert antinociceptive effects in some animal models, but the mechanisms remain to be elucidated. This work aimed to investigate the antinociceptive action of curcumin on neuropathic pain and the underlying mechanism(s). Chronic constriction injury (CCI), a canonical animal model of neuropathic pain, was produced by loosely ligating the sciatic nerve in mice and von Frey hair or hot plate test was used to assess mechanical allodynia or thermal hyperalgesia (to heat), respectively. Chronic, but not acute, curcumin treatment (5, 15 or 45 mg/kg, p.o., twice per day for three weeks) alleviated mechanical allodynia and thermal hyperalgesia in CCI mice, accompanied by increasing spinal monoamine (or metabolite) contents. Chemical ablation of descending noradrenaline (NA) by 6-hydroxydopamine (6-OHDA), or depletion of descending serotonin by p-chlorophenylalanine (PCPA), abolished curcumin's antinociceptive effect on mechanical allodynia or thermal hyperalgesia, respectively. The anti-allodynic action of curcumin on mechanical stimuli was totally blocked by chronic co-treatment with the beta(2)-adrenoceptor antagonist ICI 118,551, or by acute co-treatment with the delta-opioid receptor antagonist naltrindole. Meanwhile, co-treatment with the 5-HT1A receptor antagonist WAY-100635 chronically, or with the irreversible mu-opioid receptor antangonist beta-funaltrexamine acutely, completely abrogated the anti-hyperalgesic action of curcumin on thermal stimuli. Collectively, these findings indicate that the descending monoamine system (coupled with spinal beta(2)-adrenoceptor and 5-HT1A receptor) is critical for the modality-specific antinociceptive effect of curcumin in neuropathic pain. Delta- and mu-opioid receptors are likely rendered as downstream targets, accordingly.This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. (C) 2011 Elsevier Ltd. All rights reserved.