Analgesic and Opioid Sparing Brain Mechanisms of Mindfulness-Oriented Recovery Enhancement for Chronic Low Back Pain

摘要 慢性下腰痛(CLBP)是全世界最常见的临床疼痛状况，也是最常见的 开阿片类药物的慢性非癌症疾病。美国目前的阿片类药物危机 美国在很大程度上是由于慢性下腰痛患者过度使用和滥用阿片类药物。然而，在那里 几乎没有循证干预措施来减少阿片类药物的使用和误用 CLBP。面对缺乏有效的治疗选择，一些慢性下腰痛患者陷入困境。 在阿片类药物剂量上升的螺旋式下降中。以正念为基础的干预减少慢性 疼痛和阿片类药物的剂量。然而，缺乏机械数据限制了这些设备的部署 具有成本效益的非药物治疗方法。多项临床试验表明 以正念为导向的恢复增强(更多)，一种新的身心疗法， 将正念与其他情绪调节技术相结合，缓解慢性疼痛症状 以及慢性腰痛患者中阿片类药物的使用。然而，活跃的大脑作用机制 More的止痛和阿片类药物节制作用仍不清楚。此外，目前尚不清楚 安慰剂对照研究解开了MORE或其他疾病的特定神经机制 基于正念的cLBP干预来自非特定的治疗因素，如信念， 期望和社会支持。因此，拟议的研究将采用最多的 到目前为止，正念文献中的严格控制条件--一种经过验证的虚假正念 冥想技巧结合支持性心理治疗(Sham-More)。集成 功能神经成像和心理物理学(毒热和行为疼痛评级)， 建议的R01研究的主要目标是：a)确定神经机制 支持More的即时止痛效果(与Sham-More和Treatment-as-as- 通常)，以及b)确定默认模式网络功能连通性的变化是否预测 治疗后cLBP缓解和阿片类药物剂量减少的个体差异。 最终，这项拟议的工作将深入了解基本的神经功能过程。 调节正念干预对慢性下腰痛的治疗效果，从而 促进对这种高度流行和 使慢性疼痛状况失灵，帮助助长了正在进行的阿片类药物危机。

ABSTRACT Chronic low back pain (cLBP) is the most common clinical pain condition worldwide, and the top chronic non-cancer condition for which opioids are prescribed. The current opioid crisis in the U.S. emerged in large part from overuse and misuse of opioids by patients with cLBP. Yet, there are few evidence-based interventions to reduce opioid use and misuse among patients with cLBP. Faced with a lack of effective treatment options, some cLBP patients become ensnared in a downward spiral of opioid dose escalation. Mindfulness-based interventions reduce chronic pain and opioid dosing. However, lack of mechanistic data has limited the deployment of these cost-effective and non-pharmacological treatment approaches. Multiple clinical trials indicate that Mindfulness-Oriented Recovery Enhancement (MORE), a novel mind-body therapy that integrates mindfulness with other affect regulation techniques, alleviates chronic pain symptoms as well as opioid use among people with cLBP. Yet, the active brain mechanisms of action underlying MORE’s analgesic and opioid sparing effects remain unknown. Further, no known placebo-controlled studies have disentangled the specific neural mechanisms of MORE or other mindfulness-based interventions for cLBP from nonspecific therapeutic factors like beliefs, expectancy, and social support. As such, the proposed study will employ one of the most rigorous control conditions in the mindfulness literature to date—a validated sham-mindfulness meditation technique combined with supportive psychotherapy (Sham-MORE). Integrating functional neuroimaging and psychophysics (noxious heat and behavioral pain ratings), the overarching aims of the proposed R01 study are to a) identify the neural mechanisms supporting the immediate analgesic effects of MORE (versus Sham-MORE and treatment-as- usual), and b) to determine if changes in default mode network functional connectivity predict individual differences in cLBP relief and opioid dose reduction following treatment with MORE. Ultimately, the proposed work will yield insight into the fundamental neuro-functional processes mediating the therapeutic effects of mindfulness-based interventions for cLBP, thereby facilitating the optimization of novel biobehavioral treatments for this highly prevalent and disabling chronic pain condition that helped to fuel the ongoing opioid crisis.