反复注射吗啡可延长雄性大鼠的术后疼痛时程
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Repeated Morphine Prolongs Postoperative Pain in Male Rats
背景与目的
阿片类药物是有效的术后镇痛药。但我们之前曾报道过吗啡等阿片类药物会加重炎性疼痛以及周围和中枢神经病理性疼痛。这些影响由促进脊髓背角神经元兴奋性的免疫介质介导所引起。因此，本研究探讨了围术期吗啡使用是否能同样延长雄性大鼠的术后疼痛时程。
方 法
在开腹手术前给予吗啡治疗7天，大鼠在开腹后立即开始接受吗啡治疗7天，而第二组吗啡逐用量渐减少。检测脊髓背角炎症介质基因的表达量。在开腹手术前给予吗啡治疗7天。
结 果
剖腹手术后吗啡治疗延长术后疼痛3周以上(时间:P < .001;;治疗:P <0 .05)。术后疼痛的延长与吗啡戒断无关，剂量逐渐减少也不能预防此效应(时间:P =0 .8;时间:P < .001;治疗:P =0.0 9)。长时间手术后的疼痛与炎症介质的表达增加有关,包括TLR4受体, NLRP3蛋白, NFκB，半胱氨酸蛋白酶-1（caspase-1）, 白细胞介素1β（interleukin-1β）和肿瘤坏死因子(P <0 .05)；我们发现术前应用吗啡，在剖腹手术结束前立即停用，同样延长了术后疼痛（时间治疗：P<0.001；时间治疗：P<0.001；治疗：P<0.001）。吗啡增强疼痛有一个关键的窗口，因为在开腹前一周结束的7天吗啡疗程并没有延长术后疼痛。
结 论
研究表明吗啡对术后疼痛时程产生不利影响。
原始文献摘要
Peter M. Grace,et al；Repeated Morphine Prolongs Postoperative Pain in Male Rats.[J] Anesth
Analg.2019;00:1–9.
BACKGROUND:
Opioids are effective postoperative analgesics. Disturbingly, we have previously reported that opioids such as morphine can worsen inflammatory pain and peripheral and central neuropathic pain. These deleterious effects are mediated by immune mediators that promote neuronal hyperexcitability in the spinal dorsal horn. Herein, we tested whether perioperative morphine could similarly prolong postoperative pain in male rats.
Methed:
Rats were treated with morphine for 7 days, beginning immediately after laparotomy, while the morphine was tapered in a second group. Expression of genes for inflammatory mediators was quantified in the spinal dorsal horn. In the final experiment, morphine was administered before laparotomy for 7 days.
Results：
We found that morphine treatment after laparotomy extended postoperative pain by more than 3 weeks (time × treatment: P < .001; time: P < .001; treatment: P < .05). Extension of postoperative pain was not related to morphine withdrawal, as it was not prevented by dose tapering (time × treatment: P = .8; time: P < .001; treatment: P = .9). Prolonged postsurgical pain was associated with increased expression of inflammatory genes, including those encoding Toll-like receptor 4, NOD like receptor protein 3 (NLRP3), nuclear factor kappa B (NFκB), caspase-1, interleukin-1β, and tumor necrosis factor (P < .05). Finally, we showed that of preoperative morphine, concluding immediately before laparotomy, similarly prolonged postoperative pain (time × treatment: P < .001; time: P < .001; treatment: P < .001). There is a critical window for morphine potentiation of pain, as a 7-day course of morphine that concluded 1 week before laparotomy did not prolong postsurgical pain.
Conclusion:
These studies indicate the morphine can have a deleterious effect on postoperative pain. These studies further suggest that longitudinal studies could be performed to test whether opioids similarly prolong postoperative pain in the clinic.
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贵州医科大学高鸿教授课题组
翻译：唐剑 编辑：何幼芹 审校：王贵龙