The Effects of Different Intensities of Exercise on Behavioral and Molecular Pain-Related Reactions in Rats: Implications for Medication Development

Drug discovery for pain management is an important area of research given current limitations in medications for pain, including the addictive potential of opiates. While exercise may help worsen or lessen pain, the precise molecular mechanisms involved are incompletely understood. Thus, in the present study, we evaluated the effects of exercise intensity on pain via assessment of behavior and c-Fos expression. An animal model of moderate and high-intensity treadmill exercise was established. The specific nociceptive behaviors, such as flinches, favoring, lifting, and licking, were observed within 60 min following intraplantar injection of formalin. Lifting and licking times in the 1 h following formalin injection were shorter in the moderate/high-intensity exercise groups than the control group. The common pain scores in the exercise groups were significantly lower than those in the control group. There was no significant difference between the exercise groups. There was no significant difference in flinches among the three groups. Moderate/high-intensity exercise decreased c-Fos expression in the ipsilateral dorsal horn. These results suggest that different intensities of exercise may substantially influence pain-related responses. Exercise may reduce c-Fos expression and attenuate pain-related behaviors and provide insight into how exercise may reduce pain. Further research is needed to understand the precise mechanisms by which exercise may reduce c-Fos expression as the mediating entities may represent suitable targets for medication development for pain management, including medications that might be used in lieu of or in conjunction with exercise.