-Original-

Involvement of Tachykinins and NK₁ Receptor in the Joint Inflammation with Collagen Type II-Specific Monoclonal Antibody-Induced Arthritis in Mice

Akira Makino¹, Atsushi Sakai², Hiromoto Ito¹ and Hidenori Suzuki²

¹Department of Restorative Medicine of Neuro-musculoskeletal System, Orthopaedic Surgery, Graduate School of Medicine, Nippon Medical School
²Department of Neuropharmacology, Graduate School of Medicine, Nippon Medical School

Rheumatoid arthritis (RA) is a chronic multisystem disease characterized by persistent joint inflammation associated with severe pain. Because RA is an immune-mediated joint disease and because type II collagen is considered an autoantigen, rodent models of arthritis using collagen type II-specific monoclonal antibodies are valuable for studying the pathogenesis of autoimmune arthritis and for evaluating therapeutic strategies. The tachykinin family peptides, substance P (SP) and hemokinin-1 (HK-1), are expressed in the nervous systems and in many peripheral organs and immunocompetent cells and activate tachykinin NK₁ receptors with similar affinities. NK₁ receptors are involved in the inflammation and hyperalgesia associated with a variety of inflammatory diseases. In the present study, we examined the involvement of SP and HK-1 in the joint inflammation and hyperalgesia in a collagen antibody-induced arthritis (CAIA) model in mice. The messenger RNA expression levels of the TAC1 gene encoding SP and of the TAC4 gene encoding HK-1 were decreased in the dorsal root ganglia and spinal cord at the peak of the inflammatory symptoms in CAIA. Systemic injection of an NK₁ receptor antagonist, WIN 51708, significantly inhibited the joint swelling, but not the mechanical allodynia, on day 7 in CAIA mice. The messenger RNA expression levels of TAC1 and TAC4 in the dorsal root ganglia and dorsal spinal cord were unaffected by treatment with WIN 51708. These findings suggest that tachykinins and NK₁ receptors play a key role in joint inflammation, rather than in nociceptive sensitization, in CAIA.

J Nippon Med Sch 2012; 79: 129-138

Keywords
allodynia, collagen antibody-induced arthritis, hemokinin-1, NK₁ receptor, substance P

Correspondence to
Hidenori Suzuki, MD, PhD, Department of Pharmacology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan
hsuzuki@nms.ac.jp

Received, October 6, 2011
Accepted, November 8, 2011