A comparative behavioural study of mechanical hypersensitivity in 2 pain models in rats and humans

Pain. 2016 Jun;157(6):1248-1258. doi: 10.1097/j.pain.0000000000000515.

Abstract

The assessment of pain sensitivity in humans has been standardized using quantitative sensory testing, whereas in animals mostly paw withdrawal thresholds to diverse stimuli are measured. This study directly compares tests used in quantitative sensory testing (pinpricks, pressure algometer) with tests used in animal studies (electronic von Frey test: evF), which we applied to the dorsal hind limbs of humans after high frequency stimulation and rats after tibial nerve transection. Both experimental models induce profound mechanical hypersensitivity. At baseline, humans and rats showed a similar sensitivity to evF with 0.2 mm diameter tips, but significant differences for other test stimuli (all P < 0.001). When expressed as force divided by circumference, baseline thresholds for 0.8 mm probes were higher than for 0.2 mm in both species (both P < 0.001) suggesting spatial summation. At similar probe diameters, ramped stimuli showed higher baseline thresholds than stepped stimuli (P < 0.01) but similar sensitivity to change. For ramped stimuli sensitivity to change was higher with small probe tips than large blunt tips in both pain models (P < 0.01 in rat, P < 0.05 in humans). These data show that rat paw withdrawal threshold to punctate stimuli (0.2 mm diameter) can be used as surrogate parameters for human mechanical pain sensitivity, but probe size and shape should be standardized. Hypersensitivity to blunt pressure-the leading positive sensory sign after peripheral nerve injury in humans-is a novel finding in the tibial nerve transection model. By testing outside the primary zone of nerve damage (rat) or activation (humans), our methods likely involve effects of central sensitization in both species.

MeSH terms

  • Adult
  • Animals
  • Disease Models, Animal
  • Electric Stimulation
  • Humans
  • Hyperalgesia / etiology
  • Hyperalgesia / physiopathology*
  • Male
  • Pain Measurement
  • Pain Threshold / physiology*
  • Peripheral Nerve Injuries / complications
  • Peripheral Nerve Injuries / physiopathology*
  • Physical Stimulation
  • Rats
  • Rats, Wistar