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Exercise-Induced Pain Requires NMDA Receptor Activation in the Medullary Raphe Nuclei
Journal article   Open access   Peer reviewed

Exercise-Induced Pain Requires NMDA Receptor Activation in the Medullary Raphe Nuclei

Kathleen A SLUKA, Jessica DANIELSON, Lynn RASMUSSEN and Luis Felipe DASILVA
Medicine and science in sports and exercise, Vol.44(3), pp.420-427
2012
DOI: 10.1249/MSS.0b013e31822f490e
PMCID: PMC3955196
PMID: 21795998
url
https://doi.org/10.1249/MSS.0b013e31822f490eView
Published (Version of record) Open Access

Abstract

Purpose: Pain in response to physical activity is common in people with chronic musculoskeletal pain and is likely a barrier to regular exercise, which would lead to a sedentary lifestyle. We recently developed a model of exercise-induced pain that is associated with increased activation of neurons in the medullary raphe nuclei, i.e., the nucleus raphe obscurus (NRO) and nucleus raphe pallidus (NRP). Because the NRO and NRP not only modulate motor output but also respond to noxious stimuli, we hypothesized that the NRO and NRP were key nuclei in the interaction between pain and exercise. We tested whether exercise enhances hyperalgesia through activation of N-methyl D-aspartate (NMDA) receptors in the NRO/NRP. Methods: Muscle insult was induced by two injections of pH 5.0 saline 5 d apart into one gastrocnemius muscle. We initially tested whether hyperalgesia developed in mice injected with acidic saline (pH 5.0) into the gastrocnemius muscle immediately after a 30-min or 2-h exercise task or 2 h after a 2-h exercise task. Next, we tested whether blockade of NMDA receptors in the NRO/NRP during the exercise task prevented the development of exercise-induced hyperalgesia. Finally, we evaluated changes in phosphorylation of the NR1 subunit of the NMDA receptor (pNR1) after the exercise task at times in which muscle insult was given in behavioral experiments, i.e., immediately after a 30-min or 2-h exercise task or 2 h after the 2-h exercise task. Results: All exercise conditions enhanced nociception (hyperalgesia) after combining with two injections of pH 5.0 saline. Microinjection of AP5 (1.0-0.1 nmol; 2-amino-5-phophonopenanoate) dose-dependently prevented the development of exercise-induced hyperalgesia. All exercise conditions increased pNR1 in the NRO and NRP. Conclusions: Thus, exercise-induced pain in sedentary mice is associated with increased phosphorylation and activation of NMDA receptors in the NRO/NRP, suggesting that changes in central excitability mediate an interaction between unaccustomed exercise and pain.
 Fundamental and applied biological sciences. Psychology Vertebrates: body movement. Posture. Locomotion. Flight. Swimming. Physical exercise. Rest. Sports Biological and medical sciences

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