Naltrexone fails to increase pain affect in response to inflammatory pain in a novel escape/avoidance paradigm

The non-specific opioid antagonist naltrexone has traditionally been used as treatment for opioid overdose, as well as in research settings as an antagonist to examine opioid and non-opioid mediated analgesia. However, the mechanisms by which this drug operates are not well understood, and its exact effects on sensory and affective pain processes remain uncertain. Various studies have demonstrated that naltrexone behaves in a paradoxical manner, leading to analgesia, no discernable changes, or an increase in pain, depending on the circumstances of the study. This imprecise spectrum of effects leads to difficulty in interpreting results in studies where naltrexone was utilized as an antagonist. Therefore, the purpose of this experiment was to further examine whether naltrexone elicits dose-dependent effects in behavioral tests designed to quantify the sensory and affective components of pain. Naltrexone was not expected to have an effect on carrageenan-induced inflammatory pain in sensory pain measures, but a dose-dependent increase was predicted in behavior related to the affective component of pain. Eighty-eight male Sprague–Dawley rats were used to test these hypotheses by measuring Mechanical Paw Withdrawal Thresholds before and after naltrexone injection and by assessing performance in the Place Escape Avoidance Paradigm test, a novel paradigm to test pain affect, in which naltrexone had not been utilized. The results demonstrated that naltrexone failed to increase place/escape avoidance behavior as anticipated, but rather produced a slight, but non-significant, decrease in escape avoidance behavior. Further research is needed to elucidate the differential effects of naltrexone on various aspects of pain-related behavior.