Morphine amplifies mechanical allodynia via TLR4 in a rat model of spinal cord injury.
Morphine amplifies mechanical allodynia via TLR4 in a rat model of spinal cord injury.
复制标题
吗啡通过TLR4在大鼠脊髓损伤模型中通过TLR4扩增机械性异常。
DOI：
10.1016/j.bbi.2016.08.004
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发表时间：
2016-11
影响因子：
15.1
通讯作者：
Watkins, Linda R.
中科院分区：
文献类型：
--
作者：
Ellis, Amanda;Grace, Peter M.;Wieseler, Julie;Favret, Jacob;Springer, Kendra;Skarda, Bryce;Ayala, Monica;Hutchinson, Mark R.;Falci, Scott;Rice, Kenner C.;Maier, Steven F.;Watkins, Linda R.
关键词：
中枢神经性疼痛（CNP）是一种普遍的、使人衰弱的问题，影响着成千上万的中枢神经系统疾病患者，包括脊髓损伤（SCI）。目前治疗这类疼痛的疗法是无效的，而且往往有剂量限制的副作用。虽然阿片类药物是最常用的CNP治疗方法之一，但最近的动物文献表明，在创伤后不久施用阿片类药物实际上会对长期健康和恢复产生有害影响。为了研究创伤后不久给予吗啡的有害影响，我们采用了低胸（T13）背根撕脱伤模型（脊柱神经性撕脱痛，SNAP）。SNAP后24小时开始给予为期一周的10mg /kg/天吗啡治疗，导致机械性异常性疼痛加剧。在整个吗啡治疗方案中，联合使用非阿片类toll样受体4 （TLR4）拮抗剂(+)-纳曲酮可防止吗啡诱导的SNAP扩增。对创伤后早期吗啡诱导的变化的探索发现，脊髓损伤部位TLR4、TNF、IL-1β、NLRP3以及IL-1β蛋白的基因表达升高。这些数据表明，脊髓外伤后早期给予短期吗啡可长期加重CNP。TLR4引发了这一现象，因此，可能是预防创伤性损伤后使用阿片类药物的有害作用的潜在治疗靶点。
Central neuropathic pain (CNP) is a pervasive, debilitating problem that impacts thousands of people living with central nervous system disorders, including spinal cord injury (SCI). Current therapies for treating this type of pain are ineffective and often have dose-limiting side effects. Although opioids are one of the most commonly used CNP treatments, recent animal literature has indicated that administering opioids shortly after a traumatic injury can actually have deleterious effects on long-term health and recovery. In order to study the deleterious effects of administering morphine shortly after trauma, we employed our low thoracic (T13) dorsal root avulsion model (Spinal Neuropathic Avulsion Pain, SNAP). Administering a weeklong course of 10 mg/kg/day morphine beginning 24 hr after SNAP resulted in amplified mechanical allodynia. Co-administering the non-opioid toll-like receptor 4 (TLR4) antagonist (+)-naltrexone throughout the morphine regimen prevented morphine-induced amplification of SNAP. Exploration of changes induced by early post-trauma morphine revealed that this elevated gene expression of TLR4, TNF, IL-1β, and NLRP3, as well as IL-1β protein at the site of spinal cord injury. These data suggest that a short course of morphine administered early after spinal trauma can exacerbate CNP in the long term. TLR4 initiates this phenomenon and, as such, may be potential therapeutic targets for preventing the deleterious effects of administering opioids after traumatic injury.
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影响因子：
9.8
作者：
van Gulik, L.;Ahlers, S. J. G. M.;Knibbe, C. A. J.
通讯作者：
Knibbe, C. A. J.
影响因子：
5.3
作者：
Milligan, ED;O'Connor, KA;Watkins, LR
通讯作者：
Watkins, LR
影响因子：
2.7
作者：
Hook, Michelle A.;Liu, Grace T.;Grau, James W.
通讯作者：
Grau, James W.
影响因子：
5
作者：
Grace PM;Maier SF;Watkins LR
通讯作者：
Watkins LR
影响因子：
4
作者：
Ellis, Amanda;Wieseler, Julie;Watkins, Linda R.
通讯作者：
Watkins, Linda R.