Forced treadmill running suppresses postincisional pain and inhibits upregulation of substance P and cytokines in rat dorsal root ganglion

J Pain. 2014 Aug;15(8):827-34. doi: 10.1016/j.jpain.2014.04.010. Epub 2014 May 20.


Exercise causes a variety of psychophysical effects (eg, alterations in pain sensation). Tissue injury induces mediator releases in the spinal cord resulting in pain hypersensitivity; however, the contribution of the dorsal root ganglion (DRG) is poorly understood. In this study, we tested if forced treadmill running can attenuate postoperative pain and alter substance P (SP) or proinflammatory cytokine level in the DRG by using a rat model of skin/muscle incision and retraction (SMIR). We evaluated mechanical sensitivity to von Frey stimuli (6 and 15 g) and expression of SP, interleukin-1β, and interleukin-6 in the DRG of sham-operated sedentary rats, SMIR sedentary rats, sham-operated rats with forced treadmill running, and SMIR rats with forced treadmill running. At postoperative day 8, trained rats ran for 5 days per week for 4 weeks on a treadmill 70 minutes/d with an intensity of 18 m/min. On postoperative day 6, SMIR sedentary rats displayed a significant mechanical hypersensitivity that persisted until postoperative day 35. By comparison, SMIR-operated rats, which received forced treadmill running, exhibited a quick recovery from mechanical hypersensitivity. SMIR sedentary rats showed an upregulation of SP, interleukin-1β, and interleukin-6 in the DRG at postoperative days 14 and 28, whereas SMIR-operated rats receiving forced treadmill running reversed this upregulation at postoperative day 28. We concluded that forced treadmill running alleviated persistent postincisional pain caused by SMIR surgery. This appears to be protective against postoperative pain, which probably relates to the downturn in excess SP, interleukin-1β, and interleukin-6 in the DRG.

Perspective: Controlling the expression of SP, interleukin-6, and interleukin-1β in the DRG can help manage postoperative pain. This finding could potentially help clinicians and physical therapists who seek to examine how exercise may attenuate postsurgical pain and its mechanism.

Keywords: Skin/muscle incision and retraction; forced treadmill running; interleukin-1β; interleukin-6; mechanical hypersensitivity; substance P.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Exercise Test
  • Ganglia, Spinal / metabolism*
  • Gene Expression Regulation / physiology*
  • Hyperalgesia
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Pain Measurement
  • Pain Threshold / physiology
  • Pain, Postoperative* / metabolism
  • Pain, Postoperative* / pathology
  • Pain, Postoperative* / rehabilitation
  • Physical Conditioning, Animal*
  • Rats
  • Rats, Sprague-Dawley
  • Substance P / metabolism*
  • Time Factors


  • Cytokines
  • Interleukin-1beta
  • Interleukin-6
  • Substance P