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

## TL;DR

Low-intensity muscle exercise reduces pain in rats with severe knee osteoarthritis by changing tissue and spinal responses.

## Contribution

Shows that low-intensity muscle exercise can reduce pain by modulating peripheral and spinal mechanisms in end-stage OA.

## Key findings

- Exercise increased pain thresholds and reduced markers of inflammation and nerve sensitivity in the knee joint.
- Spinal cord changes included fewer pain-related cells and increased anti-inflammatory markers in the exercise group.
- No significant cartilage or bone degeneration changes were observed, but pain sensitivity was reduced.

## Abstract

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 s On, 4 s Off) for 20 min 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.