Antinociceptive effects of hyaluronic acid on monoiodoacetate-induced ankle osteoarthritis in rats

Shunsuke Jimbo,1 Yoshinori Terashima,1,2 Atsushi Teramoto,1 Tsuneo Takebayashi,3 Izaya Ogon,1 Kota Watanabe,4 Tatsuya Sato,2,5 Nobutoshi Ichise,2 Noritsugu Tohse,2 Toshihiko Yamashita1 1Department of Orthopaedic surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; 2Department of Cellular Physiology and Signal Transduction, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; 3Sapporo Maruyama Orthopaedic Hospital, Sapporo 060-0007, Japan; 4Department of Second Division of Physical Therapy, Sapporo Medical University School of Health Sciences, Sapporo 060-8556, Japan; 5Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan Purpose: Ankle osteoarthritis (OA) causes significant pain and debilitation; yet, its underlying mechanisms remain unclear. Clinically, hyaluronic acid (HA) is widely used to treat OA. The present study aimed to investigate the roles of HA in pain-related behavior, joint function, swelling, and pathological changes in cartilage in a rat model of monoiodoacetate (MIA)-induced ankle OA. Materials and methods: Male Sprague Dawley rats were assigned to three experimental groups as follows: 1) MIA rats injected with 1 mg MIA in the right tibiotarsal joint for two consecutive days; 2) sham rats injected with saline instead of MIA; and 3) MIA-HA rats injected with HA in the tibiotarsal joint at 7, 14, and 21 days after MIA injection. Joint swelling, range of motion (ROM), and pain-related behavior were evaluated 1 day before and on the 7th, 14th, 21st, and 28th day after MIA or saline injection. Pathological changes in the ankle joint were assessed 28 days after MIA or saline injection. Results: No significant difference in the degree of ankle swelling or ROM reduction was observed between MIA rats and MIA-HA rats. However, compared with those in MIA rats, mechanical and thermal hypersensitivity was significantly reduced and stride length significantly improved in MIA-HA rats. Histologic analysis revealed that cartilage degeneration was significantly suppressed in MIA-HA rats compared with that in MIA rats, reflecting the chondroprotective effects of HA. Conclusion: HA improved pain-related behavior and stride length and suppressed MIA-induced cartilage degeneration. HA may thus inhibit OA progression and suppress peripheral and/or central sensitization. Keywords: ankle osteoarthritis, monoiodoacetate, osteoarthritis pain, hyaluronic acid