Department of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, KY, USA.
Department of Physiology, University of Louisville, Louisville, KY, USA.
Spinal Cord. 2022 Apr;60(4):312-319. doi: 10.1038/s41393-021-00705-6. Epub 2021 Sep 24.
Preclinical pilot study.
To test the hypothesis that spinal opioidergic circuitry contributes to muscle stretch-induced locomotor deficits.
Kentucky Spinal Cord Injury Research Center, Louisville, KY, USA.
A pilot study with eight female Sprague-Dawley rats that received 25 g-cm T10 contusion injuries and recovered for 5 weeks. Rats were divided into two groups with one group receiving subcutaneous injections of naltrexone dissolved in saline (15 mg/kg) or an equal volume of saline. Each group received a daily 24-minute stretching protocol during weeks 6, 8, and 11 post-injury. Locomotor function was assessed throughout using the BBB Open Field Locomotor Scale.
Consistent with previous findings, stretching reduced locomotor function in both naltrexone and saline groups. However, the loss of locomotor function appeared earlier in the naltrexone group. Animals in both groups had a similar rate of recovery following the termination of stretching. Interestingly, the administration of naltrexone did not influence acute thermal cutaneous nociceptive responses as measured by a tail-flick assay but caused a significant increase in spasticity following stretch.
The results of this study suggest that the endogenous opioid system plays a role in modulating the negative impact of muscle stretch on spinal cord motor circuitry that is vulnerable due to loss of descending input. The observed actions of the broad-spectrum opioid antagonist naltrexone imply that pharmaceuticals targeting the endogenous opioid system post-SCI may have unintended consequences.
临床前初步研究。
检验假说，即脊髓阿片能回路有助于肌肉拉伸引起的运动功能障碍。
美国肯塔基州脊髓损伤研究中心，路易斯维尔，肯塔基州。
一项初步研究，纳入 8 只接受 25g-cm T10 挤压伤并恢复 5 周的雌性 Sprague-Dawley 大鼠。大鼠分为两组，一组接受皮下注射纳曲酮溶于生理盐水（15mg/kg）或等量生理盐水。每组在损伤后第 6、8 和 11 周接受每日 24 分钟的拉伸方案。使用 BBB 开放式场运动评分量表全程评估运动功能。
与先前的发现一致，拉伸降低了纳曲酮组和生理盐水组的运动功能。然而，纳曲酮组的运动功能丧失更早出现。两组动物在拉伸结束后都有相似的恢复速度。有趣的是，纳曲酮的给药并未影响急性热皮肤痛觉反应，如尾巴摆动试验所示，但拉伸后会导致痉挛显著增加。
这项研究的结果表明，内源性阿片系统在调节肌肉拉伸对脊髓运动回路的负面影响方面发挥作用，而脊髓运动回路由于失去下行输入而变得脆弱。广泛作用的阿片受体拮抗剂纳曲酮的观察作用表明，针对 SCI 后内源性阿片系统的药物可能会产生意想不到的后果。
