Low-intensity muscle contraction exercise reduces pain sensitivity by modulating peripheral pathology and spinal sensitization in end-stage knee osteoarthritis rats

Satoko Motokawa¹Junya Sakamoto^2,3*Ryo Sasaki^2,4Yuki Nishi^2,3Yuichiro Honda^2,3Ayumi Takahashi^2,3Minoru Okita^2,3

• ¹Sakurajuji Fukuoka Byoin, Fukuoka, Japan
• ²Department of Physical Therapy Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
• ³Institute of Biomedical Sciences (Health Sciences), Nagasaki University, Nagasaki, Japan
• ⁴Japan Society for the Promotion of Science, Tokyo, Japan

This study evaluated the effects of low-intensity muscle contraction exercise on pain sensitivity, peripheral pathology, and central sensitization in the spinal dorsal horn in a rat model of end-stage knee osteoarthritis (OA) induced by monosodium iodoacetate (MIA). Sixty-two male Wistar rats were assigned to three groups: OA, Exercise, and Sham. The Exercise group underwent quadriceps muscle contractions induced by electrical stimulation (50 Hz, 250 µs, 2-3 mA) with a duty cycle of 1:2 (2 sec On, 4 sec Off) for 20 minutes daily, five days per week, from day 29 to day 56 post-MIA administration. Pain sensitivity was assessed by measuring knee joint pressure pain thresholds (PPT) and paw withdrawal thresholds using von Frey filaments. Histological and immunohistochemical analyses of the knee joint and spinal cord included toluidine blue staining, tartrate-resistant acid phosphatase staining, and markers for CD68, CD11c, CD206, osteoclasts, nerve growth factor (NGF), calcitonin gene-related peptide (CGRP), and phosphorylated NR1 (pNR1). Knee joint PPTs were significantly higher in the Exercise group after day 35, accompanied by reductions in CD68-, CD11c-positive cells, NGF-positive cells, CGRP-positive fibers, osteoclasts, and pNR1-positive cells, as well as an increase in CD206-positive cells, compared to the OA group. Despite no significant changes in cartilage or subchondral bone degeneration, these findings suggest that low-intensity muscle contraction exercise alleviates pain sensitivity by modulating peripheral pathology and central sensitization. This study highlights the potential of therapeutic exercise as a strategy for OA pain management.