The Effect of Postoperative Analgesics on Sleep of Rats

描述（由申请人提供）：疼痛和睡眠障碍是重大的公共卫生问题。术后疼痛和睡眠障碍是相互关联的后遗症，如果不能有效控制，会对康复产生不利影响。一些研究表明，术后疼痛程度和急性睡眠中断预示着不良的健康和功能结果，包括持续疼痛的发展。术后阿片类药物虽然能有效减轻疼痛，但可能对睡眠产生不良影响。非甾体抗炎药（NSAIDs）在侵入性手术后单独使用时可能无法提供足够的疼痛缓解；然而，数据表明它们对睡眠的不利影响可能很小。迄今为止，研究尚未直接比较阿片类药物与非甾体抗炎药（单独或联合使用）对急性睡眠改变、恢复基线睡眠时间或随后的疼痛感知的影响。一个合理的推测是，服用阿片类药物和非甾体抗炎药的患者会经历更好的急性疼痛管理，对睡眠的不良影响更少，更快地恢复到基线睡眠，并且随后的疼痛水平更低。本转化研究的目的是探讨术后接受阿片类药物或非甾体抗炎药镇痛方案或两者兼有的大鼠，相对于术后镇痛方案，在睡眠结构、睡眠连续性、恢复基线睡眠时间或机械敏感性方面是否存在差异，以及这些结果是否存在性别差异。14-16周龄的雄性和雌性Sprague Dawley大鼠将被植入遥测发射器，记录基线和术后睡眠的脑电图/肌电图生物电位，恢复后将接受坐骨炎性神经炎（SIN）手术，然后接受三种术后镇痛方案中的一种：1)阿片类药物，2)非甾体抗炎药，或3)阿片类药物加非甾体抗炎药。恢复后，将使用von Frey纤维测试动物的机械敏感性。这项拟议的研究涉及由国家卫生研究院、国家护理研究所和医学研究所确定的需要研究的领域。通过探索特定的术后镇痛方案是否对睡眠的干扰更小，本研究有可能提高目前使用处方镇痛药治疗疼痛的患者的护理质量。

DESCRIPTION (provided by applicant): Pain and sleep disturbance are significant public health problems. Postoperative pain and sleep disturbance are inter-related sequelae that can adversely affect recovery if not effectively managed. Several studies have shown that the degree of postoperative pain and acute sleep disruption predict adverse health and functional outcomes, including the development of persistent pain. Postoperative opioids, while effective in attenuating pain, may exert adverse effects on sleep. Non-steroidal anti-inflammatory drugs (NSAIDs) may not provide adequate pain relief when administered as stand-alone analgesic following more invasive surgeries; however, data suggest that their adverse effects on sleep may be minimal. To-date, research has not directly compared the effects of opioid versus NSAID, alone or in combination, on acute sleep changes, time to return to baseline sleep, or subsequent pain perception. A reasonable speculation is that patients who are administered opioid plus NSAID will experience better acute pain management, fewer adverse effects on their sleep, more rapid return to baseline sleep, and lower levels of subsequent pain. The purposes of this translational research are to explore in rats who receive a postoperative analgesic regimen of opioid or NSAID or both, whether there are differences in sleep architecture, sleep continuity, time to return to baseline sleep, or mechanical sensitivity, relative to the postoperative analgesic regimen, and whether there are sex differences in these outcomes. Male and female Sprague Dawley rats who are 14-16 weeks old will be implanted with telemetric transmitters to record electroencephalogram/electromyogram biopotentials for baseline and postoperative sleep, and following recovery, will undergo the Sciatic Inflammatory Neuritis (SIN) surgery and then receive one of three postoperative analgesic regimens: 1) opioid, 2) NSAID, or 3) opioid plus NSAID. Following recovery, animals will be tested for mechanical sensitivity using von Frey filaments. This proposed research addresses areas of needed research as identified by the National Institutes of Health, the National Institute of Nursing Research, and the Institute of Medicine. Through exploring whether particular postoperative analgesic regimens are less disruptive of sleep, this proposed research has the potential to improve the quality of care to persons currently taking prescribed analgesics for pain.