Trial of Minocycline to Reduce Pain after A1 Pulley and Carpal Tunnel Release

描述(由申请人提供)： 术后疼痛是一个巨大的问题。目前，10%的美国人会在手术后出现慢性疼痛，尽管组织有足够的愈合。在手外科手术中，大约20%的接受腕管松解术的患者术后疼痛时间较长。外科医生已经尝试改变他们的技术，但手术后疼痛的发生率几乎没有改善。现在有越来越多的文献表明，决定急性疼痛是否会进展为慢性疼痛的主导因素是患者特有的因素，而不是手术技术的因素。例如，在人类中，恐惧、焦虑和抑郁反映了似乎对疼痛有重大影响的大脑生理。神经胶质细胞的激活可能解释了为什么这些棘上状态最能预测谁会患上损伤后的慢性疼痛。神经胶质细胞是一种非神经细胞，在调节中枢和外周神经系统的激活方面发挥着积极的作用。这项研究着眼于“准备”神经胶质细胞的药物干预是否能减少腕管松解术后的疼痛。将要研究的药物将是米诺环素，这是一种四环素抗生素，是一种胶质细胞抑制剂，在动物模型中，米诺环素显示出抑制神经病理性疼痛的前景。这项研究的假设是，围术期服用米诺环素的受试者在腕管释放后疼痛缓解的时间更快。这将是一项随机的安慰剂对照试验。所有参与者都是在退伍军人帕洛阿尔托退伍军人医院使用局部麻醉剂进行腕管松解手术。参与者将被随机分组，干预组的患者将在手术前至少1小时服用200毫克的米诺环素，然后每天两次服用100毫克，连续5天。所有受试者每天都会被打电话，询问他们的疼痛水平和止痛药的使用情况。我们将有两个主端点。主要将是疼痛解决时间(TPR)，定义为连续三天的24小时平均零疼痛，由每日管理的简短疼痛清单评估。第二个将是处方阿片类药物停止时间，定义为连续三天零使用处方阿片类药物。我们计划通过使用TPR作为我们的主要终点和生存分析来明确研究疼痛的慢性化，以确定从急性疼痛过渡到慢性疼痛的预测因素。这项新颖的工作可能会为管理外科患者开辟新的途径，并对接受择期手术的退伍军人产生深远的影响。

DESCRIPTION (provided by applicant): Post-operative pain is an enormous problem. Currently 10% of Americans will develop chronic pain following surgery, despite adequate tissue healing. In hand surgery, about 20% of patients who undergo carpal tunnel release have prolonged post-operative pain. Surgeons have tried changing their technique with little improvement in the rate of post- operative pain. There is now a growing body of literature that suggests that the dominating factors, determining whether acute pain will progress to chronic pain, are patient specific factors rather than factors of surgical technique. For example, in humans, fear, anxiety, and depression reflect brain physiology that appears to have a significant impact on pain. Glial cell activation may explain why these supraspinal states best predict who will develop post-injury chronic pain. Glial cells are non-neuronal cells that play an active role in modulating the activation of the central and peripheral nervous system. This study looks at whether a pharmacologic intervention that would "prep" glial cells can reduce post-operative pain after carpal tunnel release. The drug to be studied will be minocycline, a tetracycline antibiotic that is a glial cell inhibitor and in animal models, minocycline has shown promise inhibiting neuropathic pain This study's hypothesis is that subjects who take peri-operative minocycline will have faster time to pain resolution after carpal tunnel release. This will be a randomized placebo controlled trial. All participants will be veterans undergoing carpal tunnel release at the Palo Alto VA using local anesthetic. Participants will be randomized and those in the intervention arm will receive 200mg of minocycline at least 1 hour prior to their procedure and then 100mg twice a day for 5 days. All subjects will be called daily and asked about their level of pain and pain medication use. We will have two primary endpoints. The primary will be the Time-to-Pain-Resolution (TPR) defined as zero 24- hour average pain for three consecutive days, as assessed by a daily-administered Brief Pain Inventory. The second will be time-to-prescription-opioid-cessation defined as the zero use of prescription opioids for three consecutive days. We plan to explicitly study pain chronicity by using TPR as our primary endpoint and survival analysis to identify predictors of transitioning from acute to chronic pain. This novel work could open new pathways to managing surgical patients and have a profound impact on veterans who undergo elective surgery.