Efficacy of drugs with different mechanisms of action in relieving spontaneous pain at rest and during movement in a rat model of osteoarthritis
Efficacy of drugs with different mechanisms of action in relieving spontaneous pain at rest and during movement in a rat model of osteoarthritis
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DOI：
10.1016/j.ejphar.2014.05.048
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发表时间：
2014-09-05
影响因子：
5
通讯作者：
Shimizu, Yasuaki
中科院分区：
文献类型：
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作者：
Ishikawa, Go;Nagakura, Yukinori;Shimizu, Yasuaki
骨关节炎（OA）患者的关节疼痛会因运动而加剧，影响他们的生活质量。在本研究中，在关节内注射单碘乙酸钠（MIA）诱发单侧膝关节炎的大鼠中测试了静息疼痛的负重模式和运动期间疼痛的步态模式。注射 MIA（1 毫克/膝）后第 3 周，动物出现与疼痛相关的重量分布（负重）或足印参数（步态）左右不平衡。双氯芬酸，口服剂量高达 30 mg/kg（口服），对任一范例均没有显着影响。吗啡分别以 1 和 3 mg/kg 皮下注射纠正负重和步态不平衡。弱阿片类药物和血清素/去甲肾上腺素再摄取抑制剂 (SNRI) 曲马多也显着纠正了口服 10 mg/kg（负重）和 100 mg/kg 的指数。 （步态）。 SNRI 度洛西汀 30 mg/kg 口服可纠正负重不平衡，但不能纠正步态不平衡。我们评估了不同药物对 MIA 诱发的关节炎大鼠疼痛引起的体重分布和步态紊乱的影响。镇痛药物的作用机制不同，在纠正步态不平衡方面的效果不如纠正体重分布不平衡方面的效果。评估镇痛药不仅对静息痛而且对运动时疼痛的效果对于全面检查其对 OA 的治疗效果很有价值。 (C) 2014 Elsevier B.V. 保留所有权利。
Patients with osteoarthritis (OA) suffer from joint pain aggravated by movement, which affect their quality of life. In the present study, a weight bearing paradigm for pain at rest and a gait paradigm for pain during movement were tested in rats with unilateral knee arthritis induced by an intra-articular injection of sodium monoiodoacetate (MIA). At week 3 after MIA (1 mg/knee) injection, animals developed pain-associated, right-left imbalances of weight distribution (weight bearing) or foot print parameters (gait). Diclofenac, at doses up to 30 mg/kg orally (p o.), did not have a significant effect on either paradigm. Morphine rectified the weight bearing and gait imbalances at 1 and 3 mg/kg subcutaneously, respectively. The weak opioid and serotonin/norepinephrine reuptake inhibitor (SNRI) tramadol also significantly corrected the indices at 10 mg/kg (weight bearing) and 100 mg/kg p.o. (gait). The SNRI duloxetine at 30 mg/kg p.o corrected the weight bearing imbalance but not gait imbalance. We assessed the effect of different drugs on pain-induced disturbances in weight distribution and gait in MIA-induced arthritic rats. Analgesic drugs, each with different mechanisms of action, were less effective in rectifying the imbalance in gait than that in weight distribution. The assessment of the effect of analgesics on not only rest pain but pain during movement is valuable for the comprehensive examination of their therapeutic efficacies in OA. (C) 2014 Elsevier B.V. All rights reserved.