An Exploratory Investigation Utilizing Repetitive Transcranial Magnetic Stimulation (rTMS) as a Tool to Decrease Pain and Improve Functioning in Veterans with Opioid Use Disorder

阿片类药物使用障碍（OUD）在退伍军人中很常见。尽管有阿片类药物替代品 尽管有许多人在接受治疗，但仍有许多人继续滥用类阿片，复发率仍然很高。退伍军人是近两倍 死于意外阿片类药物过量的可能性比一般人群高。约60%的退伍军人 从中东返回，超过50%的退伍军人在VA医疗保健系统的老年退伍军人有慢性 痛苦此外，创伤后应激障碍是退伍军人群体中常见的合并症， 对OUD治疗的早期参与和保留产生负面影响。与其他情况一样， 物质使用障碍，阿片类药物渴求通常由禁欲患者描述，无论他们是否 在丁丙诺啡上稳定（Northrup等，2015; Tsui等人，2014）。随后，一种治疗方法， 疼痛和渴望，同时也改善早期参与和保留治疗，将改善恢复 阿片类药物成瘾 重复经颅磁刺激（rTMS）能够非侵入性地改变皮质功能。rTMS 是FDA批准的治疗重度抑郁症的药物初步证据表明，rTMS也可以 减少慢性疼痛状况下的疼痛和物质使用障碍中的渴望。单次rTMS产生 小的暂时性影响，而多次rTMS会产生更大，更持久的影响。我们组最近 在非寻求治疗的OUD参与者中完成了一项盲法、假对照交叉试验。单个 rTMS的会话减少了线索诱导的渴望和增加的热痛阈值。鉴于多个 与单次rTMS相比，rTMS的疗程产生更大和更持久的治疗效果，因此， 对OUD患者进行多次治疗可能会导致疼痛和提示的临床相关减轻， 诱发渴望，这可能会改善临床和功能结果。 在这项SPiRE试点计划中，我们将进行一项随机、双盲、假对照试验， rTMS的加速过程中，一个队列的OUD退伍军人与慢性疼痛接受治疗，通过拉尔夫 H.约翰逊VA医疗中心物质治疗和康复计划。本提案的目的是 评估将rTMS输送到退伍军人背外侧前额叶皮层的可行性和可接受性， OUD和慢性疼痛。我们也将初步探讨评估潜在结果的可行性 为更大规模的试验做准备的测量，包括禁欲、治疗保留、重返社区 和功能结果疼痛和阿片类药物渴求该试点项目的积极成果将为未来的 MERIT的应用，并有可能显着改善这种难以治疗的治疗结果 退伍军人

Opioid use disorders (OUDs) are common among Veterans. Despite the availability of opioid replacement therapies, many individuals continue to abuse opioids and relapse rates remain high. Veterans are nearly twice as likely to die from accidental opioid overdose than the general population. Approximately 60% of Veterans returning from the Middle East and more than 50% of older Veterans in the VA health care system have chronic pain. Further, post-traumatic stress disorder, a common comorbidity in the Veteran population, has been shown to negatively impact early engagement and retention of individuals in OUD treatment. As is the case with other substance use disorders, opioid craving is commonly described by abstinent patients whether or not they are stabilized on buprenorphine (Northrup et al., 2015; Tsui et al., 2014). Subsequently, a treatment that reduces pain and craving, while also improving early engagement and retention in treatment, would improve recovery from opioid addiction. Repetitive Transcranial Magnetic Stimulation (rTMS) is capable of non-invasively altering cortical function. rTMS is an FDA-approved treatment for major depressive disorder. Preliminary evidence suggests that rTMS can also reduce pain in chronic pain conditions and craving in substance use disorders. Single sessions of rTMS produce small temporary effects, while multiple sessions of rTMS result in larger, more durable effects. Our group recently completed a blinded, sham-controlled crossover trial in non-treatment seeking OUD participants. A single session of rTMS reduced cue-induced craving and increased thermal pain thresholds. Given that multiple sessions of rTMS produce larger and more durable treatment effects than single sessions of rTMS, it follows that multiple treatment sessions applied to OUD patients may result in a clinically relevant reduction in pain and cue- induced craving, which could improve clinical and functional outcomes. In this SPiRE pilot proposal, we will perform a randomized, double-blind, sham-controlled trial delivering an accelerated course of rTMS to a cohort of OUD Veterans with chronic pain receiving treatment through the Ralph H. Johnson VA Medical Center Substance Treatment and Recovery program. The goal of this proposal is to evaluate the feasibility and acceptability of delivering rTMS to the dorsolateral pre-frontal cortex in Veterans with OUD and chronic pain. We will also preliminarily explore the feasibility of evaluating potential outcome measurements in preparation for a larger trial, including abstinence, treatment retention, community reintegration and functional outcomes, pain, and opioid craving. Positive results from this pilot project will inform a future MERIT application and have the potential to significantly improve treatment outcomes in this difficult to treat Veteran population.