Imaging Studies in Freund's Complete Adjuvant Model of Regional Polyarthritis, a Model Suitable for the Study of Pain Mechanisms, in the Rat

Objective. 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. Methods. 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. Results. 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. Conclusion. 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.