Sensitization of the tail-flick reflex following exposure to either a single prolonged test trial or behavioral testing under the analgesic influence of morphine

Pain. 1996 Sep;67(1):163-172. doi: 10.1016/0304-3959(96)03084-9.


Although the tail-flick response to radiant heat is widely used in nociceptive research, there are indications that this benchmark test possesses some undesirable characteristics. Of present concern is the possibility that the supra-threshold stimuli associated with behavioral testing while under the influence of an effective hypoalgesic manipulation can alter subsequent tail-flick responses. To examine the effects of supra-threshold heating of the tail, we exposed anesthetized rats to either (1) manual restraint of the tail during a single tail-flick trial to a 5- or 7-sec cut-off, or (2) testing while under the analgesic effects of morphine (5 mg/kg/ml). A single prolonged trial produced hyperalgesia which lasted for 30 min. Following naltrexone injection, hyperalgesia was also found in animals that had been tested while under morphine analgesia. In contrast, animals that received morphine but were not tested under its influence did not exhibit hyperalgesia of similar magnitude. Analyses of tail temperature data in the second experiment indicate that these results are not dependent on shifts in tail temperature. These results suggest that, in anesthetized animals, exposure to prolonged tail-flick trials can produce hyperalgesia.

MeSH terms

  • Analgesics, Opioid / pharmacology*
  • Animals
  • Behavior, Animal / drug effects*
  • Body Temperature
  • Hot Temperature
  • Hyperalgesia / chemically induced*
  • Hyperalgesia / physiopathology*
  • Male
  • Morphine / pharmacology*
  • Naltrexone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Pain Threshold
  • Physical Stimulation
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time
  • Reflex / physiology*
  • Restraint, Physical
  • Tail / physiology*
  • Time Factors


  • Analgesics, Opioid
  • Narcotic Antagonists
  • Naltrexone
  • Morphine