Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats

J Neurosci Methods. 2016 Apr 1:263:115-22. doi: 10.1016/j.jneumeth.2016.02.013. Epub 2016 Feb 15.


Background: The assessment of nociception in preclinical studies is undergoing a transformation from pain-evoked to pain-depressed tests to more closely mimic the effects of clinical pain. Many inflammatory pain-depressed behaviors (reward seeking, locomotion) have been examined, but these tests are limited because of confounds such as stress and difficulties in quantifying behavior.

New method: The present study evaluates home cage wheel running as an objective method to assess the magnitude and duration of inflammatory pain in male and female rats.

Results: Injection of Complete Freund's Adjuvant (CFA) into the right hindpaw to induce inflammatory pain almost completely inhibited wheel running for 2 days in male and female rats. Wheel running gradually returned to baseline levels within 12 days despite persistent mechanical hypersensitivity (von Frey test).

Comparison with existing methods: Continuously monitoring home cage wheel running improves on previous studies examining inflammatory pain-depressed wheel running because it is more sensitive to noxious stimuli, avoids the stress of removing the rat from its cage for testing, and provides a complete analysis of the time course for changes in nociception.

Conclusions: The present data indicate that home cage wheel running is a clinically relevant method to assess inflammatory pain in the rat. The decrease in activity caused by inflammatory pain and subsequent gradual recovery mimics the changes in activity caused by pain in humans. The tendency for pain-depressed wheel running to be greater in female than male rats is consistent with the tendency for women to be at greater risk of chronic pain than men.

Keywords: Inflammatory pain; Nociception; Pain-depressed behavior; Sex differences; Wheel running.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Freund's Adjuvant / toxicity
  • Hyperalgesia / physiopathology
  • Inflammation / chemically induced
  • Inflammation / complications*
  • Male
  • Nociception / physiology*
  • Pain / diagnosis*
  • Pain / etiology*
  • Pain Threshold / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Rotarod Performance Test
  • Running / physiology*
  • Sex Characteristics*
  • Time Factors


  • Freund's Adjuvant