Almarestani Lina, Fitzcharles Mary-Ann, Bennett Gary J, Ribeiro-da-Silva Alfredo
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Arthritis Rheum. 2011 Jun;63(6):1573-81. doi: 10.1002/art.30303.
In view of the extensive distribution in the spinal cord of primary afferent nociceptive nerve fibers from the rat hind paw, a model of regional inflammation would be useful in the study of arthritis pain. However, the subcutaneous intraplantar injection of a single low dose of Freund's complete adjuvant (CFA) has been used mostly as an inflammation model. We undertook this study to characterize this model by means of conventional radiography, microfocal computed tomography, and bone densitometry and by examining changes in pain-related behavior.
Male rats were injected unilaterally with CFA or saline subcutaneously in the hind paw and killed 7, 15, and 30 days after injection. Pain-related behavior was studied using the Hargreaves, von Frey, and acetone tests.
CFA-injected animals developed soft tissue inflammation and polyarthritis restricted to the joints of the injected hind paw. No signs of joint involvement were observed 7 days after CFA injection. On day 15 after CFA injection, there was widening of joint space indicative of joint effusion. By day 30 after CFA injection, there was evidence of joint damage with joint space narrowing, erosions, osteophyte formation, and joint deformity. There were no changes contralaterally or in saline-injected rats. Mechanical hyperalgesia and cold allodynia were present in the affected hind paw from day 1 through day 30.
Signs of arthritis were strictly unilateral and started only 2 weeks after injection. Since the affected area has a broad representation in the spinal cord, this model has advantages over monarthritis models for the study of plastic changes in the dorsal horn of the spinal cord.
鉴于来自大鼠后爪的初级传入伤害性神经纤维在脊髓中广泛分布,区域炎症模型将有助于关节炎疼痛的研究。然而,皮下足底内注射单一低剂量弗氏完全佐剂(CFA)大多被用作炎症模型。我们开展本研究,通过传统X线摄影、微焦点计算机断层扫描和骨密度测定,并通过检查疼痛相关行为的变化来表征该模型。
雄性大鼠单侧后爪皮下注射CFA或生理盐水,并在注射后7、15和30天处死。使用哈格里夫斯试验、von Frey试验和丙酮试验研究疼痛相关行为。
注射CFA的动物出现软组织炎症和多关节炎,局限于注射后爪的关节。注射CFA后7天未观察到关节受累迹象。注射CFA后第15天,关节间隙增宽表明有关节积液。注射CFA后第30天,有证据表明关节损伤,关节间隙变窄、糜烂、骨赘形成和关节畸形。对侧或注射生理盐水的大鼠无变化。从第1天到第30天,患侧后爪出现机械性痛觉过敏和冷觉异常。
关节炎体征严格单侧出现,且仅在注射后2周开始出现。由于受累区域在脊髓中有广泛的代表,该模型在研究脊髓背角的可塑性变化方面优于单关节炎模型。