Exercise training attenuates postoperative pain and expression of cytokines and N-methyl-D-aspartate receptor subunit 1 in rats

Reg Anesth Pain Med. Jul-Aug 2013;38(4):282-8. doi: 10.1097/AAP.0b013e31828df3f9.


Background: Exercise creates a variety of psychophysical effects, including altered pain perception. We investigated whether physical exercise reduces postincisional pain and cytokine and N-methyl-D-aspartate receptor 1 (NR1) expression in a rat model of skin/muscle incision and retraction (SMIR)-evoked pain.

Methods: Male Sprague-Dawley rats were divided randomly into 4 groups: sham operated, SMIR-sedentary (SS), SMIR-exercise, and sham operated-exercise. On postoperative day 8, trained rats started to run on a treadmill 55 min/d with an intensity of 18 meter/minute (m/min), 5 days per week for 4 weeks. NR1, tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) expressions in the spinal cord as well as mechanical hypersensitivity following SMIR surgery were assessed for 6 to 35 days.

Results: On postoperative day 6, SMIR-sedentary rats exhibited a marked hypersensitivity to von Frey stimuli. By contrast, SMIR-operated rats undergoing exercise demonstrated a quick recovery of mechanical hypersensitivity. The levels of TNF-α, IL-6, and NR1 in the spinal cord were significantly increased in SS rats when compared with sham-operated rats on postoperative days 6, 21, and 35 after SMIR surgery. After the 4-week exercise intervention, the SMIR-exercise group showed lower NR1, TNF-α, and IL-6 expression in the spinal cord than those in the SS group.

Conclusions: These results suggest that exercise training decreases persistent postsurgical pain caused by SMIR surgery. There appears to be a protective effect, probably relating to the decrease of NR1, TNF-α, and IL-6 expression in the spinal cord of SMIR rats, after exercise intervention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Down-Regulation
  • Interleukin-6 / metabolism
  • Male
  • Pain Measurement
  • Pain Perception*
  • Pain Threshold*
  • Pain, Postoperative / metabolism
  • Pain, Postoperative / physiopathology
  • Pain, Postoperative / prevention & control*
  • Pain, Postoperative / psychology
  • Physical Exertion*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Running
  • Spinal Cord / metabolism*
  • Spinal Cord / physiopathology
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism


  • Cytokines
  • Interleukin-6
  • NMDA receptor A1
  • Receptors, N-Methyl-D-Aspartate
  • Tumor Necrosis Factor-alpha