Effects of Treadmill Exercise on Advanced Osteoarthritis Pain in Rats.
Effects of Treadmill Exercise on Advanced Osteoarthritis Pain in Rats.
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DOI：
10.1002/art.40101
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发表时间：
2017-07
期刊：
影响因子：
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通讯作者：
King T
中科院分区：
文献类型：
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作者：
Allen J;Imbert I;Havelin J;Henderson T;Stevenson G;Liaw L;King T
运动通常被推荐用于骨关节炎（OA）疼痛患者。然而，运动是否有益于改善与晚期OA相关的持续性NSAID耐药持续疼痛尚不清楚。用关节内碘乙酸盐（MIA）或盐水处理的大鼠在注射后10天开始进行跑步机运动或保持久坐。触觉感觉阈值和负重进行了评估，然后每周进行一次X光片检查。运动4周后，使用条件性位置偏爱（CPP）对关节内或延髓头端腹内侧（RVM）利多卡因进行持续疼痛评估。通过全身给药纳洛酮，研究内源性阿片类物质在运动性疼痛缓解中的可能作用。收集膝关节进行μCT分析，以检查胫骨软骨下骨和干骺端的病理变化。跑步机运动4周逆转MIA诱导的触觉过敏和体重不对称。MIA后关节内和RVM利多卡因D35在久坐但未运动的MIA治疗大鼠中诱导CPP，表明运动阻断MIA诱导的持续疼痛。纳洛酮在MIA治疗的大鼠中重新建立了体重不对称性，并诱导了条件性位置厌恶（CPA），表明运动诱导的疼痛缓解依赖于内源性阿片类药物。运动并没有改变OA的影像学证据。然而，μCT分析表明，运动阻止了MIA诱导的内侧，而不是外侧软骨下骨丢失和干骺端骨小梁丢失。这些发现支持运动可能通过增加内源性阿片样物质信号传导诱导晚期NSAID耐药OA疼痛缓解的结论。此外，在该模型中，跑步机运动阻断了MIA诱导的骨丢失，表明运动对OA关节具有潜在的骨稳定作用。
Exercise is commonly recommended for patients with osteoarthritis (OA) pain. However, whether exercise is beneficial in ameliorating persistent NSAID-resistant ongoing pain associated with advanced OA is unknown. Rats treated with intra-articular monosodium iodoacetate (MIA) or saline underwent treadmill exercise or remained sedentary starting 10 days post-injection. Tactile sensory thresholds and weight bearing were assessed followed by radiographs at weekly intervals. After 4 weeks of exercise, ongoing pain was assessed using conditioned place preference (CPP) to intra-articular or rostral ventromedial medulla (RVM) lidocaine. The possible role of endogenous opioids in exercise-induced pain relief was examined by systemic administration of naloxone. Knee joints were collected for μCT analysis to examine pathological changes to subchondral bone and metaphysis of the tibia. Treadmill exercise for 4 weeks reversed MIA-induced tactile hypersensitivity and weight asymmetry. Both intra-articular and RVM lidocaine D35 post-MIA induced CPP in sedentary but not exercised MIA-treated rats, indicating that exercise blocks MIA-induced ongoing pain. Naloxone re-established weight asymmetry in MIA-treated rats undergoing exercise and induced conditioned place aversion (CPA), indicating exercise-induced pain relief is dependent on endogenous opioids. Exercise did not alter radiographic evidence of OA. However, μCT analysis indicates that exercise blocked MIA-induced medial, but not lateral subchondral bone loss and trabecular bone loss in the metaphysis. These findings support the conclusion that exercise induces pain relief in advanced, NSAID resistant OA, likely through increased endogenous opioid signaling. In addition, treadmill exercise blocked MIA-induced bone loss in this model, indicating a potential bone stabilizing effect of exercise on the OA joint.