Exploring mechanisms of inflammatory hyperalgesia in murine collagen-induced arthritis

Rheumatoid arthritis (RA) is an autoimmune inflammatory disorder, characterised by joint swelling and diffuse chronic pain. RA patients display both hyperalgesia (an exaggerated painful response to a noxious stimulus) and allodynia (a painful response to a non-noxious stimulus). Collagen-induced arthritis (CIA) in the mouse is a well-established model of RA that may be useful in the study of inflammatory hyperalgesia.

The aim of this study was to establish CIA as a model for studying inflammatory hyperalgesia, and to assess cellular changes that occur in the nociceptive system during the course of arthritis.

Arthritis was induced by injection of 2 mg/ml bovine type II collagen in complete Freund's adjuvant into the base of the tail of male DBA/1 mice (n = 30). Behavioural analysis was performed for 28 days following arthritis onset. Mechanical and thermal hyperalgesia was assessed using the Plantar Von-Frey microprocessor system and the Hargreaves Plantar test, respectively. Animals were sacrificed at intervals after arthritis onset, and the lumbar spinal cord was collected and immunostained for astrocytes using antibodies to glial fibrillary acidic protein.

Prior to onset of inflammation (post immunisation), little hyperalgesia occurred. Following arthritis onset there was a rapid decrease in both mechanical (Fig. 1) and thermal thresholds, reaching a maximum at 7–10 days after onset. Thermal threshold returned to naïve levels 24 days following arthritis onset, while mechanical hyperalgesia remained throughout the study.

Figure 1

The development of mechanical hyperalgesia in mice with collagen-induced arthritis.

Increased glial fibrillary acidic protein expression was detected in the spinal cord from the day of arthritis onset, indicating that astrocytic activation occurs in CIA. This is in agreement with a well-established inflammatory model used for the study of pain, complete Freund's adjuvant-induced monoarthritis.

Our results indicate that CIA can be used in the study of pain, and that changes occur in the nociceptive system during inflammation. As CIA is a well-established and validated model of RA, it may be of benefit to test analgesics aimed at inflammatory pain in this model and to understand the mechanisms involved in inflammatory hyperalgesia.