Ito Hisakatsu, Kawakami Masaaki, Yoshida Masashi, Sugimoto Sadamu, Takazawa Tomonori
Department of Anesthesiology, Toyama University Hospital, Toyama, Toyama, Japan.
Department of Anesthesiology and Intensive Care Unit, Gunma University Hospital, Maebashi, Gunma, Japan.
Front Pain Res (Lausanne). 2025 Jul 4;6:1516935. doi: 10.3389/fpain.2025.1516935. eCollection 2025.
Sleep disturbances have been shown to exacerbate pain sensitivity and prolong recovery from pain. However, conventional animal models of sleep disturbance, which involve physical disruptions, such as water or forced movement, might not fully represent modern human sleep disorders.
We utilized a novel sleep disorder model, the perpetual avoidance of water on a wheel (PAWW) model, which induces spontaneous activity, chronic stress, and abnormal sleep-wake cycles in mice. We investigated the effects of a kappa opioid receptor (KOR) antagonist, nor-binaltorphimine (nor-BNI), on pain recovery in a postoperative pain model in mice in a state of disordered sleep. After 1 week of acclimation, the mice were housed in PAWW or regular cages for 2 weeks. Sleep conditions were evaluated using electroencephalogram and electromyogram recordings, and postoperative pain recovery following plantar incision was assessed using von Frey tests. We also examined the effects of nor-BNI on pain recovery.
The evaluation showed that PAWW housing significantly increased activity during the light phase, disrupted sleep patterns, and delayed postoperative pain recovery. The administration of nor-BNI alleviated the delayed pain recovery.
These findings suggest that sleep disorders, such as those modeled by PAWW, could delay postoperative pain recovery, and that KOR antagonists might provide therapeutic benefits in the management of delayed recovery of postoperative pain induced by sleep disorders.
睡眠障碍已被证明会加剧疼痛敏感性并延长疼痛恢复时间。然而，传统的睡眠障碍动物模型涉及身体干扰，如水或强制运动，可能无法完全代表现代人类睡眠障碍。
我们采用了一种新型睡眠障碍模型，即轮上持续避水（PAWW）模型，该模型可诱导小鼠自发活动、慢性应激和异常的睡眠-觉醒周期。我们研究了κ阿片受体（KOR）拮抗剂诺-纳洛酮啡（nor-BNI）对处于睡眠紊乱状态的小鼠术后疼痛模型中疼痛恢复的影响。适应1周后，将小鼠置于PAWW或常规笼中饲养2周。使用脑电图和肌电图记录评估睡眠状况，并使用von Frey测试评估足底切口后的术后疼痛恢复情况。我们还研究了nor-BNI对疼痛恢复的影响。
评估显示，置于PAWW环境中显著增加了小鼠在光照期的活动，扰乱了睡眠模式，并延迟了术后疼痛恢复。给予nor-BNI可缓解延迟的疼痛恢复。
这些发现表明，如PAWW模型所模拟的睡眠障碍可能会延迟术后疼痛恢复，并且KOR拮抗剂可能在治疗由睡眠障碍引起的术后疼痛延迟恢复方面具有治疗益处。
