Exercise-Induced Changes to the Macrophage Response in the Dorsal Root Ganglia Prevent Neuropathic Pain after Unilateral Cervical Spinal Cord Injury in Adult Female Rats

STUDY PURPOSE: The purpose of this experiment was two fold: 1) underlying immune differences in the spinal cord and DRG between rats with and without pain and 2) immunomodulatory effects of exercise in pain reduction. DATA COLLECTED: Adult, female, Sprague-Dawley rats were randomly assigned to the following experimental groups: Naive (n=5), spinal cord injury (SCI n=25), or SCI with Exercise (SCI Ex; n=20). Six additional SCI rats were included as histological controls at 5 days post SCI to observe the immune environment at the time of exercise initiation. SCI and SCI Ex rats were subjected to a moderate, unilateral contusion at C5. The SCI Ex group was exercised on forced running wheels for 20 minutes per day, 5 days per week, starting at 5 days post-injury for 4 weeks. All rats were tested for pain development using von Frey and mechanical conflict-avoidance paradigms. The degree of white and grey matter sparing at the lesion epicenter was measured on histological preparations of the C4-C6 spinal cord stained with euriochrome cyanine using the Cavalieri estimator on StereoInvestigator software. The phagocytic immune cell response was measured at C4-6 and C7-8 spinal cord as the proportional area of ED1 positive tissue. The microglial response was measured in the C7-8 spinal cord via proportional area analysis of Iba-1 stained tissue. The number of ED1+ immune cells were counted in the ipsilesional C7 or C8 dorsal root ganglia. DATA USAGE NOTES: Our data suggest that macrophage presence in the DRG may be an important effector of pain development, and early wheel walking exercise may prevent pain development by modulating the injury-induced macrophage response in the DRG. Collectively, these data suggest that macrophage presence in the DRG may be an amenable cellular target for future therapies.