Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain.
Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain.
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DOI：
10.1186/1744-8069-5-35
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发表时间：
2009-07-01
期刊：
影响因子：
3.3
通讯作者：
Chapman V
中科院分区：
文献类型：
--
作者：
Guasti L;Richardson D;Jhaveri M;Eldeeb K;Barrett D;Elphick MR;Alexander SP;Kendall D;Michael GJ;Chapman V
脊髓小胶质细胞的激活有助于与神经病理性疼痛状态相关的异常疼痛反应。内源性大麻素（EC）存在于脊髓中，并抑制伤害性处理; EC的水平可以通过调节内源性大麻素在体外的周转的小胶质细胞而改变。在这里，我们研究了米诺环素（一种活化小胶质细胞的抑制剂）对神经病性脊髓中内源性大麻素大麻素anandamine和2-花生四烯酰甘油（2-AG）以及相关化合物N-棕榈酰乙醇胺（PEA）水平的影响。大鼠选择性脊神经结扎（SNL）导致机械性异常性疼痛和同侧脊髓中存在活化的小胶质细胞。与赋形剂治疗的SNL大鼠相比，用米诺环素（30 mg/kg，ip持续14天）长期每日治疗显著减少了SNL手术后第5、10和14天的机械性异常性疼痛的发展（P < 0.001）。与溶剂对照组相比，米诺环素治疗还显著减弱了SNL大鼠同侧（P < 0.001）和对侧（P <0.01）脊髓中OX-42免疫反应性，OX-42是活化小胶质细胞的标志物。与对侧脊髓相比，米诺环素治疗显着（P < 0.01）降低SNL大鼠同侧脊髓中2-AG的水平，显着（P < 0.01）增加PEA的水平。因此，小胶质细胞的活化影响神经性疼痛状态中内源性大麻素和相关化合物的脊髓水平。
Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic pain states. Endocannabinoids (ECs) are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro. Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG), and the related compound N-palmitoylethanolamine (PEA), in neuropathic spinal cord. Selective spinal nerve ligation (SNL) in rats resulted in mechanical allodynia and the presence of activated microglia in the ipsilateral spinal cord. Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days) significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-SNL surgery, compared to vehicle-treated SNL rats (P < 0.001). Minocycline treatment also significantly attenuated OX-42 immunoreactivity, a marker of activated microglia, in the ipsilateral (P < 0.001) and contralateral (P < 0.01) spinal cord of SNL rats, compared to vehicle controls. Minocycline treatment significantly (P < 0.01) decreased levels of 2-AG and significantly (P < 0.01) increased levels of PEA in the ipsilateral spinal cord of SNL rats, compared to the contralateral spinal cord. Thus, activation of microglia affects spinal levels of endocannabinoids and related compounds in neuropathic pain states.
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影响因子：
3.6
作者：
Carrier, EJ;Kearn, CS;Hillard, CJ
通讯作者：
Hillard, CJ
影响因子：
7.4
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Piao, ZG;Cho, IH;Oh, SB
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Oh, SB
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2.9
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Leung, D;Saghatelian, A;Cravatt, BF
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Cravatt, BF
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3.6
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7.4
作者：
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通讯作者：
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