Three-Day Continuous Oxytocin Infusion Attenuates Thermal and Mechanical Nociception by Rescuing Neuronal Chloride Homeostasis via Upregulation KCC2 Expression and Function.
Three-Day Continuous Oxytocin Infusion Attenuates Thermal and Mechanical Nociception by Rescuing Neuronal Chloride Homeostasis via Upregulation KCC2 Expression and Function.
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三天连续输注催产素通过上调 KCC2 表达和功能来挽救神经元氯稳态，从而减轻热和机械伤害感受
DOI：
10.3389/fphar.2022.845018
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发表时间：
2022
影响因子：
5.6
通讯作者：
Hao Y
中科院分区：
文献类型：
--
作者：
Ba X;Ran C;Guo W;Guo J;Zeng Q;Liu T;Sun W;Xiao L;Xiong D;Huang Y;Jiang C;Hao Y
催产素及其受体是治疗和预防神经性疼痛的重要靶点。在本研究中，我们比较了单次和连续鞘内输注OT对小鼠神经损伤性神经性疼痛行为的影响，并进一步探讨其镇痛特性的机制。我们发现，连续3天的鞘内OT输注可以缓解随后14天的疼痛行为，而单次OT注射则会导致30分钟的短暂镇痛，这表明只有连续的鞘内OT才能减轻神经性疼痛行为的建立和发展。支持这一行为发现的是，持续鞘内输注，而不是短期的OT孵育，通过恢复脊髓K+-Cl-共转运蛋白2 （KCC2）的功能和表达，逆转了神经损伤诱导的Cl-逆转电位的去极化移动，这可能是由OT诱导的GABA抑制性传递增强引起的。这一结果提示，只有持续使用OT才能逆转神经损伤引起的病理改变，从而机械性地阻断疼痛的建立和发展。这些发现提供了新的证据，有助于进一步了解连续OT治疗对疼痛病理生理的影响。
Oxytocin (OT) and its receptor are promising targets for the treatment and prevention of the neuropathic pain. In the present study, we compared the effects of a single and continuous intrathecal infusion of OT on nerve injury-induced neuropathic pain behaviours in mice and further explore the mechanisms underlying their analgesic properties. We found that three days of continuous intrathecal OT infusion alleviated subsequent pain behaviours for 14 days, whereas a single OT injection induced a transient analgesia for 30 min, suggesting that only continuous intrathecal OT attenuated the establishment and development of neuropathic pain behaviours. Supporting this behavioural finding, continuous intrathecal infusion, but not short-term incubation of OT, reversed the nerve injury-induced depolarizing shift in Cl− reversal potential via restoring the function and expression of spinal K+-Cl- cotransporter 2 (KCC2), which may be caused by OT-induced enhancement of GABA inhibitory transmission. This result suggests that only continuous use of OT may reverse the pathological changes caused by nerve injury, thereby mechanistically blocking the establishment and development of pain. These findings provide novel evidence relevant for advancing understanding of the effects of continuous OT administration on the pathophysiology of pain.
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影响因子：
3.5
作者：
Koshimizu, Taka-aki;Tsujimoto, Gozoh
通讯作者：
Tsujimoto, Gozoh
影响因子：
82.9
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影响因子：
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作者：
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通讯作者：
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作者：
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通讯作者：
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作者：
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