Department of Anesthesiology, University of Toyama, Toyama, Japan.
PLoS One. 2020 Dec 3;15(12):e0243325. doi: 10.1371/journal.pone.0243325. eCollection 2020.
Chronic pain and sleep have a bidirectional relationship that promotes a vicious circle making chronic pain more difficult to treat. Therefore, pain and sleep should be treated simultaneously. In our previous study, we suggested that hyperactivation of ascending serotonergic neurons could cause secondary sleep disturbance in chronic pain. This study aimed to demonstrate the effects of a tricyclic antidepressant (amitriptyline) and a selective 5-hydroxy-tryptamine 2A (5-HT2A) antagonist (MDL 100907) that adjust serotonergic transmission, on secondary sleep disturbance induced in a preclinical chronic pain model. We produced a chronic neuropathic pain model by partial sciatic nerve ligation in mice, analyzed their electroencephalogram (EEG) and electromyogram (EMG) using the SleepSign software, and evaluated the sleep condition of the pain model mice after administration of amitriptyline or MDL 100907. Amitriptyline improved thermal hyperalgesia and the amount of sleep, especially non-REM sleep. Time change of normalized power density of δ wave in the nerve ligation group with amitriptyline administration showed a normal pattern that was similar to sham mice. In addition, MDL 100907 normalized sleep condition similar to amitriptyline, without improvement in pain threshold. In conclusion, amitriptyline could improve sleep quantity and quality impaired by chronic pain. 5-HT2A receptor antagonism could partially contribute to this sleep improvement, but is not associated with pain relief.
慢性疼痛和睡眠之间存在双向关系，会形成恶性循环，使慢性疼痛的治疗更加困难。因此，疼痛和睡眠应该同时治疗。在我们之前的研究中，我们提出，上行 5-羟色胺能神经元的过度激活可能导致慢性疼痛中的继发性睡眠障碍。本研究旨在证明调节 5-羟色胺能传递的三环类抗抑郁药（阿米替林）和选择性 5-羟色胺 2A（5-HT2A）拮抗剂（MDL 100907）对临床前慢性疼痛模型中诱导的继发性睡眠障碍的影响。我们通过部分坐骨神经结扎在小鼠中产生慢性神经病理性疼痛模型，使用 SleepSign 软件分析其脑电图（EEG）和肌电图（EMG），并评估疼痛模型小鼠在给予阿米替林或 MDL 100907 后的睡眠状况。阿米替林改善了热痛觉过敏和睡眠量，特别是非快速眼动睡眠。给予阿米替林后神经结扎组δ波归一化功率密度的时间变化呈现出与假手术小鼠相似的正常模式。此外，MDL 100907 使睡眠状况正常化，类似于阿米替林，但对疼痛阈值没有改善。总之，阿米替林可以改善慢性疼痛引起的睡眠数量和质量下降。5-HT2A 受体拮抗作用可能部分有助于这种睡眠改善，但与缓解疼痛无关。
