Modulation of mechanical and thermal nociceptive sensitivity in the laboratory mouse by behavioral state

Experienced basic (rodent) pain researchers appreciate the influence of subject behavior during nociceptive testing, but such factors are not commonly reported and have not been systematically studied. We examined here the modulatory effect of behavioral state (grooming, alert, resting, light sleep, deep sleep) on thermal and mechanical sensitivity on the radiant heat paw-withdrawal and von Frey tests, respectively, in 3 mouse strains (CD-1, C57BL/6, and 129P3) with or without neuropathic injury. We find that in all 3 strains, grooming mice are relatively hypoalgesic, and robustly so in the von Frey test such that even the largest usable fibers are met with indifference. This grooming-related "hypoalgesia" persists after spared nerve injury. This finding is problematic for algesiometric testing in the mouse due to the considerable time mice spend grooming (especially on a glass floor), and ethograms of mouse behavior within plexiglas testing cubicles are provided as evidence of this. Alone among the 3 strains tested, C57BL/6 mice also display robust relative hypoalgesia in deep sleep. Failure to consider behavioral state changes while testing may needlessly increase variability within and between experiments and lead to inaccurate conclusions in transgenic knockout studies of pain.

State of arousal and attention are important modulators of pain sensitivity in humans. In this report, we find evidence that these same factors influence nociceptive sensitivity in the laboratory mouse, providing a model for understanding the mechanistic underpinnings of these forms of modulation.