Aerobic Exercise Alters Analgesia and Neurotrophin-3 Synthesis in an Animal Model of Chronic Widespread Pain

Abstract

Background Present literature and clinical practice provide strong support for the use of aerobic exercise in reducing pain and improving function for individuals with chronic musculoskeletal pain syndromes. However, the molecular basis for the positive actions of exercise remains poorly understood. Recent studies suggest that neurotrophin-3 (NT-3) may act in an analgesic fashion in various pain states. Objective The purpose of the present study was to examine the effects of moderate-intensity aerobic exercise on pain-like behavior and NT-3 in an animal model of widespread pain. Design This was a repeated-measures, observational cross-sectional study. Methods Forty female mice were injected with either normal (pH 7.2; n=20) or acidic (pH 4.0; n=20) saline in the gastrocnemius muscle to induce widespread hyperalgesia and exercised for 3 weeks. Cutaneous (von Frey monofilament) and muscular (forceps compression) mechanical sensitivity were assessed. Neurotrophin-3 was quantified in 2 hind-limb skeletal muscles for both messenger RNA (mRNA) and protein levels after exercise training. Data were analyzed with 2-factor analysis of variance for repeated measures (group × time). Results Moderate-intensity aerobic exercise reduced cutaneous and deep tissue hyperalgesia induced by acidic saline and stimulated NT-3 synthesis in skeletal muscle. The increase in NT-3 was more pronounced at the protein level compared with mRNA expression. In addition, the increase in NT-3 protein was significant in the gastrocnemius muscle but not in the soleus muscle, suggesting that exercise can preferentially target NT-3 synthesis in specific muscle types. Limitations Results are limited to animal models and cannot be generalized to chronic pain syndromes in humans. Conclusions This is the first study demonstrating the effect of exercise on deep tissue mechanical hyperalgesia in a rodent model of pain and providing a possible molecular basis for exercise training in reducing muscular pain.