Antinociceptive effects of elevated plus-maze exposure: influence of opiate receptor manipulations

It has been suggested that anxiety may be a critical factor in certain forms of non-opioid environmental analgesia. In the present study, 5-min exposure to the elevated plus-maze test of anxiety (EPM) induced a mild, though enduring, elevation in tail-flick latencies in male mice. Pretreatment with the opiate antagonist naltrexone (0.1-10.0 mg/kg) failed to block EPM-induced antinociception: indeed, the highest dose actually enhanced the response. This effect could not be attributed to intrinsic analgetic activity of naltrexone. Rather, analysis of EPM behaviours suggested that it may have been secondary to an anxiogenic effect of the compound. The involvement of non-opioid substrates in the form of pain inhibition was further supported by the failure of chronic morphine treatment (7 days; 7.5 mg/kg) to alter either the antinociceptive or behavioural response to EPM exposure. Irrespective of treatment history, mice showed a retest EPM profile of enhanced anxiety, with tail-flick data suggesting a major contribution of anticipatory factors. Several important methodological variables are discussed and findings are contrasted with parallel studies on non-opioid defeat analgesia.