Regular physical activity reduces the percentage of spinally projecting neurons that express mu-opioid receptors from the RVM

Regular physical activity/exercise is an effective non-pharmacological treatment for individuals with chronic pain. Central inhibitory mechanisms, involving serotonin and opioids, are critical to analgesia produced by regular physical activity. The RVM sends projections to the spinal cord to inhibit or facilitate nociceptive neurons and plays a key role in exercise-induced analgesia. The goal of these studies was to examine if regular physical activity modifies RVM-spinal cord circuitry. Male and female mice received Fluoro-Gold placed on the spinal cord to identify spinally projecting neurons from the rostral ventromedial medulla (RVM) and the nucleus raphe obscuris/nucleus raphe pallidus (NRO/NRP), dermorphin-488 into caudal medulla to identify mu-opioid receptors, and were immunohistochemically stained for either phosphorylated-N-methyl-D-aspartate subunit NR1 (p-NR1) to identify excitatory neurons or tryptophan hydroxylase (TPH) to identify serotonin neurons. The percentage of dermorphin-488-positive cells that stained for p-NR1 (or TPH), and the percentage of dermorphin-488-positive cells that stained for p-NR1 (or TPH) and Fluoro-Gold was calculated. Physically active animals were provided running wheels in their cages for 8 weeks and compared to sedentary animals without running wheels. Animals with chronic muscle pain, induced by two intramuscular injections of pH 4.0, were compared to sham controls (pH 7.2). Physically active animals had less mu-opioid expressing neurons projecting to the spinal cord when compared to sedentary animals in the RVM, but not the NRO/NRP. No changes were observed for TPH. These data suggest that regular exercise alters central facilitation so that there is less descending facilitation to result in a net increase in inhibition. Summary StatementPhysically active animals has less mu-opioid expressing neurons projecting to the spinal cord in the RVM, but not the NRO/NRP, when compared to sedentary animals.