Opioid footshock-induced analgesia in mice acutely falls by stress prolongation

Abstract The application of 80 footshocks (S-80) to mice induces a decrease in nociceptive responses as measured by the tail-flick test, which is opioid mediated as well as prevented by naloxone (10 mg/kg, SC). When the stress is prolonged up to 240 shocks (S-240) (i.e., from 6 min 40 s to 20 min), no analgesia can be seen immediately after the stress. We have examined the two most obvious possibilities, but they do not seem to be responsible for this fact. When morphine (1–5 mg/kg IP) is injected in the S-240 situation, a potentiation of its analgesic effects is seen, so that a desensitization of mu opioid receptors is unlikely. On the other hand, although cortisol (3–30 mg/kg IP) inhibits the analgesic response to S-80, metyrapone (40 and 80 mg/kg IP) and cortexolone (3–18 mg/kg IP) do not cause S-240 to be analgesic. Thus, an increase of endogenous glucocorticoids released during the long-duration stress does not seem responsible for the lack of analgesia after S-240.