Unilateral carrageenan injection into muscle or joint induces chronic bilateral hyperalgesia in rats
Unilateral carrageenan injection into muscle or joint induces chronic bilateral hyperalgesia in rats
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DOI：
10.1016/s0304-3959(03)00114-3
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发表时间：
2003-08-01
期刊：
影响因子：
7.4
通讯作者：
Sluka, KA
中科院分区：
文献类型：
--
作者：
Radhakrishnan, R;Moore, SA;Sluka, KA
慢性肌肉骨骼疼痛是一个主要的临床问题，目前普遍缺乏动物模型来研究这种情况。角叉菜胶通常用于在动物模型中产生短暂的急性炎症和痛觉过敏。然而，角叉菜胶产生慢性、持久痛觉过敏的潜力尚未得到评估。在本研究中，我们研究了角叉菜胶注射到大鼠关节或肌肉中的长期影响。在大鼠的一个膝关节或腓肠肌中注射0.3%、1%或3%角叉菜胶，并在注射前和注射后的不同时间评估两个爪对机械（测量为降低的退缩阈值）和热（测量为降低的退缩潜伏期）刺激的痛觉过敏，直至8周。仅在注射3%角叉菜胶后检查组织学变化。将3%角叉菜胶注射于肌肉或膝关节，对机械刺激和热刺激产生痛觉过敏，持续7-8周，注射后1-2周扩散至对侧。1%角叉菜胶注射于膝关节或腓肠肌引起的痛觉过敏持续时间较短，且保持在同侧，0.3%角叉菜胶注射于膝关节或腓肠肌没有影响。将3%的角叉菜胶注射到膝关节周围的皮肤中不会产生痛觉过敏。在组织学上观察到关节和肌肉组织的炎症变化模式相似。在前24小时观察到急性炎症，早在4小时就观察到水肿和嗜中性粒细胞浸润。在1周时，炎症转化为主要的巨噬细胞反应，伴有散在的肥大细胞。数据表明，在膝关节或腓肠肌中注射1%或3%角叉菜胶的动物可用作24小时内的急性炎症和1周后的慢性炎症模型。此外，3%角叉菜胶注射到深部组织产生痛觉过敏，蔓延到对侧，在同一时间段的炎症从急性转化为慢性。(C)2003年国际疼痛研究协会。由Elsevier Science B. V.出版，版权所有。
Chronic musculoskeletal pain is a major clinical problem and there is a general lack of animal models to study this condition. Carrageenan is commonly used to produce short-lasting acute inflammation and hyperalgesia in animal models. However, the potential of carrageenan to produce chronic, long-lasting hyperalgesia has not been evaluated. In the present study, we investigated the long-term effects of carrageenan injected into joint or muscle in rats. Rats were injected with 0.3, 1 or 3% carrageenan in one knee joint or gastrocnemius muscle and hyperalgesia to mechanical (measured as decreased withdrawal threshold) and heat (measured as decreased withdrawal latency) stimuli of both paws assessed before and at varying times after injection, through 8 weeks. Histological changes were examined only after injection of 3% carrageenan. Three percent carrageenan injected ill the Muscle or knee produced hyperalgesia to mechanical and heat stimuli ipsilaterally, which lasted 7-8 weeks and spread to the contralateral side 1-2 weeks after injection. One percent carrageenan injected to the knee joint or gastrocnemius Muscle, produced hyperalgesia that was shorter-lasting and remained ipsilateral, 0.3% carrageenan injected into the knee joint or gastrocnemius muscle had no effect. Three percent carrageenan injected into the skin surrounding the knee joint did not produce hyperalgesia. A similar pattern of inflammatory changes was observed histologically for both the joint and muscle tissues. Acute inflammation was observed for the first 24 h with edema and neutrophilic infiltration evident as early as 4 h. At 1 week, the inflammation converted to primarily a macrophage response with scattered mast cells. The data suggest that animals injected with 1 or 3% carrageenan in the knee joint or gastrocnemius muscle could be used as models of acute inflammation through 24 h and chronic inflammation after I week. Furthermore, 3% carrageenan injected into deep tissues produces hyperalgesia that spreads to the contralateral side, at the same time period as the inflammation transforms from acute to chronic. (C) 2003 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.