Collagen antibody-induced arthritis evokes persistent pain with spinal glial involvement and transient prostaglandin dependency

• Published in: Arthritis & rheumatology (Hoboken, N.J.) Vol. 64; no. 12; pp. 3886 - 3896
• Main Authors: Bas, Duygu B., Su, Jie, Sandor, Katalin, Agalave, Nilesh M., Lundberg, Johanna, Codeluppi, Simone, Baharpoor, Azar, Nandakumar, Kutty S., Holmdahl, Rikard, Svensson, Camilla I.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.12.2012; Wiley; Wiley Subscription Services, Inc
• Subjects: Amines - therapeutic use; Analgesics - therapeutic use; Animal; Animals; Arthralgia - drug therapy; Arthralgia - etiology; Arthralgia - metabolism; Arthralgia/drug therapy/etiology/metabolism; Arthritis; Arthritis, Experimental - complications; Arthritis, Experimental - metabolism; Arthritis, Experimental - pathology; Biological and medical sciences; Buprenorphine - therapeutic use; Collagen; Cyclohexanecarboxylic Acids - therapeutic use; Diclofenac - therapeutic use; Disease Models; Disease Models, Animal; Diseases of the osteoarticular system; Experimental/complications/metabolism/pathology; Gabapentin; gamma-Aminobutyric Acid - therapeutic use; Inbred BALB C; Inbred CBA; Inflammatory joint diseases; Male; Medical research; Medical sciences; Medicin och hälsovetenskap; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Neuroglia - metabolism; Neuroglia - pathology; Neuroglia/metabolism/pathology; Pain; Prostaglandins - metabolism; Spine - metabolism; Spine - pathology; Spine/metabolism/pathology; Time Factors; Treatment Outcome; Immunopathology; Chronic; Pain; Prostaglandin; Antibody; Spine; Rheumatoid arthritis; Diseases of the osteoarticular system; Rheumatology; Autoimmune disease; Inflammatory joint disease; Transitory
• ISSN: 0004-3591; 2326-5191; 2326-5205; 1529-0131; 1529-0131; 2326-5205
• DOI: 10.1002/art.37686

Objective Pain is one of the most debilitating symptoms reported by rheumatoid arthritis (RA) patients. While the collagen antibody–induced arthritis (CAIA) model is used for studying the effector phase of RA pathologic progression, it has not been evaluated as a model for studies of pain. Thus, this study was undertaken to examine pain‐like behavior induced by anticollagen antibodies and to assess the effect of currently prescribed analgesics for RA. In addition, the involvement of spinal glia in antibody‐induced pain was explored. Methods CAIA was induced in mice by intravenous injection of a collagen antibody cocktail, followed by intraperitoneal injection of lipopolysaccharide. Disease severity was assessed by visual and histologic examination. Pain‐like behavior and the antinociceptive effect of diclofenac, buprenorphine, gabapentin, pentoxifylline, and JNK‐interacting protein 1 were examined in mechanical stimulation experiments. Spinal astrocyte and microglia reactivity were investigated by real‐time polymerase chain reaction and immunohistochemistry. Results Following the induction of CAIA, mice developed transient joint inflammation. In contrast, pain‐like behavior was observed prior to, and outlasted, the visual signs of arthritis. Whereas gabapentin and buprenorphine attenuated mechanical hypersensitivity during both the inflammatory and postinflammatory phases of arthritis, diclofenac was antinociceptive only during the inflammatory phase. Spinal astrocytes and microglia displayed time‐dependent signs of activation, and inhibition of glial activity reversed CAIA‐induced mechanical hypersensitivity. Conclusion CAIA represents a multifaceted model for studies exploring the mechanisms of pain induced by inflammation in the articular joint. Our findings of a time‐dependent prostaglandin and spinal glial contribution to antibody‐induced pain highlight the importance of using appropriate disease models to assess joint‐related pain.