137: Treadmill Exercise Downregulates Pro-algesic Neurotrophins in an Osteoarthritis Pain Model

Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic secondary musculoskeletal pain, , , , , , , , , , Non-pharmacological interventions

Background and Aims: Osteoarthritis is the most common rheumatic disorder and a leading cause of disability worldwide1. Exercise is recommended as a first-line non-pharmacological intervention as it reduces pain and improves function in those with the condition1,2,3. However, the biological mechanisms underlying these effects are not yet fully understood. Neurotrophic factors have emerged as promising targets for the treatment of musculoskeletal pain4. Therefore, we aimed to examine the effects of exercise on pain-related behavior and the gene expression of neurotrophins (NGF and BDNF) in the dorsal root ganglia (DRG) and spinal cord in a rodent model of osteoarthritis induced by monoiodoacetate (MIA).

Methods: Knee osteoarthritis was induced by intra-articular injection of monoiodoacetate (2 mg) in male and female Wistar rats. After 7 days, the rats were randomly assigned to low-to-moderate (12 m/min) or moderate-to-high (18 m/min) exercise intensity groups. Treadmill exercise was performed for 2 weeks (30 min/day for 5 days). Pain-related behavior was assessed using the von Frey test; measurements were conducted before osteoarthritis induction and at weekly intervals. On day 28, animals were sacrificed; the DRG and spinal cord were collected for qRT-PCR analysis of NGF and BDNF. The results were analyzed by one-way/two-way repeated-measures ANOVA (Tukey post-hoc analysis).

Results: Both exercise intensities reduced MIA-induced mechanical hypersensitivity in male and female rats. The effects of higher intensity exercise were evident after 7 days, whereas those of lower intensity exercise appeared after 14 days (all P ≤ 0.013 vs MIA-control at day 21). The beneficial effects on pain-related behavior were also observed on day 28, one week after exercise cessation (all P ≤ 0.008 vs MIA-control). Additionally, both exercise intensities reversed the upregulation of Ngf and Bdnf in the DRG and Bdnf in the spinal cord in both sexes (all P ≤ 0.04 vs MIA-control).

Conclusions: We have demonstrated that both exercise intensities effectively reduce pain-related behavior (mechanical hypersensitivity) in male and female animals, with effects persisting after exercise cessation. In addition, this study expands current understanding of exercise-induced analgesia. We have shown that exercise-induced analgesia in a rat model of osteoarthritis is at least partially due to downregulation of neurotrophic factors in the DRG and spinal cord. This work contributes to understanding the molecular basis of the most recommended non-pharmacological intervention for the treatment of osteoarthritis pain.

References: 1. Tang S, Zhang C, Oo WM, et al. Osteoarthritis. Nat Rev Dis Primers. 2025;11(1):10. Published 2025 Feb 13. d
2. Moseng T, Vliet Vlieland TPM, Battista S, et al. EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis: 2023 update. Ann Rheum Dis. 2024;83(6):730-740. Published 2024 May 15.
3. Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Rheumatol. 2020;72(2):220-233.
4. Malfait AM, Miller RE, Block JA. Targeting neurotrophic factors: Novel approaches to musculoskeletal pain. Pharmacol Ther. 2020 Jul;211:107553.

Presenting Author: Katarina Nastić
Submitting Author: Katarina Nastić

Senior Author: Radica Stepanović-Petrović

IASP 2026 Global Year theme of Neuropathic Pain: No

• Uroš Pecikoza: Ph.D. - University of Belgrade – Faculty of Pharmacy, Department of Pharmacology
• Miroslav Dinić: Ph.D - Institute of Molecular Genetics and Genetic Engineering (IMGGE) - University of Belgrade
• Emilija Brdarić: Ph.D - Institute of Molecular Genetics and Genetic Engineering (IMGGE) - University of Belgrade
• Aleksandar Jovanović: Ph.D - University of Nicosia – Medical School, Department of Basic and Clinical Sciences
• Maja Tomić: Ph.D - University of Belgrade – Faculty of Pharmacy, Department of Pharmacology
• Radica Stepanović-Petrović: Ph.D - University of Belgrade – Faculty of Pharmacy, Department of Pharmacology