Naloxone-sensitive hyperalgesia follows analgesia induced by morphine and environmental stimulation

Abstract

Manipulations of attack parameters in murine agonistic encounters have shown that moderate attack terminating at the first unambiguous display of the upright submissive posture results in nonopioid analgesia. By contrast, attack continuing significantly beyond this behavioural marker results in decreases in nociception mediated by opiodergic mechanisms. However, these effects have only been demonstrated immediately upon termination of encounters. As such, little is known of the influences of agonistic encounters on nociceptive responding beyond this. Tail-flick latencies of male DBA/2 mice that had been exposed to opioid activating attack parameters were established at 15-minute intervals up to 90 min postattack. Data suggest the existence of at least two distinct phases in nociceptive responding with 1) analgesia being evident in the early phase (0-45 min) and 2) short-lasting (detectable only at 75 min postattack) hyperalgesia in the late phase. Further studies revealed both of these effects to be reversed by low (1-10 mg/kg) doses of naloxone. Interestingly, alterations in responsivity to noxious stimulation postmorphine (1-20 mg/kg) administration followed a similar pattern, with analgesia being detectable 0-2 hr and hyperalgesia being evident at 4 hr postinjection of either 10 or 20 mg/kg morphine. However, only the hyperalgesia induced by 20 mg/kg morphine was reversed by 10 but not 1 mg/kg naloxone. These data together suggest a relationship between the dose of morphine required to induce hyperalgesia and the amount of naloxone needed to reverse this response. The naloxone-reversibility of postencounter or morphine-induced hyperalgesia suggests that these effects are not a consequence of the absence of opiates/opioids per se.(ABSTRACT TRUNCATED AT 250 WORDS)