Regular physical activity prevents development of chronic pain and activation of central neurons

J Appl Physiol (1985). 2013 Mar 15;114(6):725-33. doi: 10.1152/japplphysiol.01317.2012. Epub 2012 Dec 27.


Chronic musculoskeletal pain is a significant health problem and is associated with increases in pain during acute physical activity. Regular physical activity is protective against many chronic diseases; however, it is unknown if it plays a role in development of chronic pain. The current study induced physical activity by placing running wheels in home cages of mice for 5 days or 8 wk and compared these to sedentary mice without running wheels in their home cages. Chronic muscle pain was induced by repeated intramuscular injection of pH 4.0 saline, exercise-enhanced pain was induced by combining a 2-h fatiguing exercise task with a low-dose muscle inflammation (0.03% carrageenan), and acute muscle inflammation was induced by 3% carrageenan. We tested the responses of the paw (response frequency) and muscle (withdrawal threshold) to nociceptive stimuli. Because the rostral ventromedial medulla (RVM) is involved in exercise-induced analgesia and chronic muscle pain, we tested for changes in phosphorylation of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor in the RVM. We demonstrate that regular physical activity prevents the development of chronic muscle pain and exercise-induced muscle pain by reducing phosphorylation of the NR1 subunit of the NMDA receptor in the central nervous system. However, regular physical activity has no effect on development of acute pain. Thus physical inactivity is a risk factor for development of chronic pain and may set the nervous system to respond in an exaggerated way to low-intensity muscle insults.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Behavior, Animal
  • Carrageenan
  • Chronic Pain / chemically induced
  • Chronic Pain / diagnosis
  • Chronic Pain / metabolism
  • Chronic Pain / physiopathology
  • Chronic Pain / prevention & control*
  • Disease Models, Animal
  • Down-Regulation
  • Hyperalgesia / chemically induced
  • Hyperalgesia / diagnosis
  • Hyperalgesia / metabolism
  • Hyperalgesia / physiopathology
  • Hyperalgesia / prevention & control*
  • Immunohistochemistry
  • Medulla Oblongata / metabolism
  • Medulla Oblongata / physiopathology*
  • Mice
  • Motor Activity
  • Muscular Diseases / chemically induced
  • Muscular Diseases / diagnosis
  • Muscular Diseases / metabolism
  • Muscular Diseases / physiopathology
  • Muscular Diseases / prevention & control*
  • Pain Measurement
  • Pain Perception
  • Pain Threshold
  • Phosphorylation
  • Physical Exertion*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Running
  • Sedentary Behavior
  • Sodium Chloride
  • Time Factors


  • NR1 NMDA receptor
  • Receptors, N-Methyl-D-Aspartate
  • Sodium Chloride
  • Carrageenan