Novel analgesic effects of melanin-concentrating hormone on persistent neuropathic and inflammatory pain in mice.
Novel analgesic effects of melanin-concentrating hormone on persistent neuropathic and inflammatory pain in mice.
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DOI：
10.1038/s41598-018-19145-z
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发表时间：
2018-01-15
影响因子：
4.6
通讯作者：
Park HJ
中科院分区：
文献类型：
--
作者：
Jang JH;Park JY;Oh JY;Bae SJ;Jang H;Jeon S;Kim J;Park HJ
黑色素浓缩激素（melanin- concentrerghormone， MCH）是一种多肽神经调节剂，由下丘脑外侧和中间带的神经元合成。mcchergic神经元分布在整个中枢神经系统，表明其参与了许多生理功能，但在疼痛中的作用尚未确定。在这项研究中，我们发现pMCH - / -小鼠对机械和热刺激的基线疼痛阈值低于pMCH+/+小鼠，并且在炎症和神经性疼痛中达到最大痛觉反应的时间也明显提前。为了检验其药理学性质，我们给小鼠鼻内注射MCH，结果表明MCH治疗显著增加了两种疼痛模型的机械和热痛阈值。在两种疼痛模型中，纳曲酮（阿片受体拮抗剂）和AM251（大麻素1受体拮抗剂）的拮抗剂挑战逆转了MCH的镇痛作用，表明阿片和大麻素系统参与其中。MCH处理还增加了内侧前额叶皮层和背外侧和腹外侧导水管周围灰质中CB1R的表达和激活。MCH1R拮抗剂消除了MCH诱导的作用。本研究首次提出了MCH的新型镇痛作用，为MCH在疼痛相关疾病治疗中的应用提供了广阔的前景。
The melanin-concentrating hormone (MCH) is a peptidergic neuromodulator synthesized by neurons in the lateral hypothalamus and zona incerta. MCHergic neurons project throughout the central nervous system, indicating the involvements of many physiological functions, but the role in pain has yet to be determined. In this study, we found that pMCH−/− mice showed lower baseline pain thresholds to mechanical and thermal stimuli than did pMCH+/+ mice, and the time to reach the maximum hyperalgesic response was also significantly earlier in both inflammatory and neuropathic pain. To examine its pharmacological properties, MCH was administered intranasally into mice, and results indicated that MCH treatment significantly increased mechanical and thermal pain thresholds in both pain models. Antagonist challenges with naltrexone (opioid receptor antagonist) and AM251 (cannabinoid 1 receptor antagonist) reversed the analgesic effects of MCH in both pain models, suggesting the involvement of opioid and cannabinoid systems. MCH treatment also increased the expression and activation of CB1R in the medial prefrontal cortex and dorsolateral- and ventrolateral periaqueductal grey. The MCH1R antagonist abolished the effects induced by MCH. This is the first study to suggest novel analgesic actions of MCH, which holds great promise for the application of MCH in the therapy of pain-related diseases.
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影响因子：
7.4
作者：
Bushnell MC;Case LK;Ceko M;Cotton VA;Gracely JL;Low LA;Pitcher MH;Villemure C
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作者：
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