Naloxone and cold-water swim analgesia: Parametric considerations and individual differences

The role of endogenous opioids in the mediation of stress-induced analgesia has been studied using the opiate antagonist naloxone to reduce or eliminate the response. While the analgesic responses following some stressors are reduced by naloxone, other stressors, like cold-water swims, are altered minimally. However, in the case of inescapable foot shock analgesia, the temporal, numerical, and spatial arrangement of the shocks are critical parameters in determining whether naloxone is capable of altering the analgesic state. In assessing parametric variations of naloxone antagonism of cold-water swim analgesia, five experiments were performed. The first experiment showed that naloxone antagonized the analgesic response following a 3.5-min swim in a 15°C bath, but not in baths of 8°C and 2°C. The second experiment demonstrated dose-dependent antagonism of analgesia induced by 2°C swims for 2.5 and 3.5 min; shorter durations failed to increase thresholds. The third experiment indicated that naloxone decreased 2°C, 3.5-min swim analgesia when the pain test occurred 30 min after stress; longer intervals failed to produce analgesia. The fourth experiment showed that the temporal relationship between injections and swims had little bearing on resultant effects. Finally, since it appeared that naloxone decreased analgesia induced by the 2°C, 3.5-min swim in some animals, but not others, the fifth experiment found that the degree of naloxone antagonism was correlated with the magnitude of the analgesic response induced in individual animals. These results are discussed in terms of opioid and nonopioid mechanisms subserving pain inhibition.     

Tail-pinch hyperalgesia and analgesia: Test-specific opioid and nonopioid actions

Reactivity to noxious stimuli in rats is altered following acute exposure to tail-pinch. However, while our laboratory has reported that tail-pinch produces hyperalgesia as measured by the flinch-jump test and attenuates analgesic responses following morphine and cold-water swims, others have found that tail-pinch elicits an opioid-sensitive analgesia on the hot plate test and a nonopioid-sensitive analgesia on the writhing test. The first experiment of the present study examined whether tail-pinch altered responses on two somatic pain tests and showed that tail-pinch significantly decreased both jump thresholds and tail-flick latencies. In assessing whether tail-pinch hyperalgesia on the jump test was mediated by endogenous opioids, the second experiment indicated that low (0.1 and 0.5 mg/kg) doses of naloxone eliminated tail-pinch hyperalgesia by selectively lowering control thresholds and a high (10 mg/kg) dose of naloxone eliminated tail-pinch hyperalgesia by selectively increasing thresholds following tail-pinch. Further, the third experiment showed that morphine-tolerant rats (10 mg/kg morphine daily over 14 days) did not exhibit tail-pinch hyperalgesia on the 15th day, an effect attributable to a selective lowering of control thresholds. The fourth experiment was a direct replication of the observation that tail-pinch produces analgesia on the writhing test which is not antagonized by naloxone. These results demonstrate that the pain test employed and the amount of prior tail-pinch experience are critical variables in determining the direction of tail-pinch effects upon pain perception in rats.