THE ROLE OF CORTICOSTERONE IN THE BLOCKADE OF TOLERANCE TO MORPHINE ANALGESIA BY FORMALIN-INDUCED PAIN IN THE RAT

We previously reported that morphine fails to produce analgesic tolera nce when administered in the presence of formalin-induced pain, which may be related to activity of the hypothalamic-pituitary-adrenal axis. In the present study, we examined whether suppression of corticostero ne secretion during pain prevents the blockade of tolerance to morphin e analgesia. Male Long-Evans rats were injected with morphine (20 mg/k g) or saline for 4 consecutive days in the presence or absence of form alin-induced pain. To suppress corticosterone activity, some animals w ere injected daily with the corticosterone synthesis inhibitor, metyra pone (100 mg/kg), 24 h and 30 min before formalin injections. The anal gesic effect of a test dose of morphine (IO mg/kg) was then measured i n the tail-flick test 24 h after tolerance induction (i.e. day 5). The presence of pain during tolerance induction prevented the development of analgesic tolerance. Furthermore, inhibition of corticosterone syn thesis by metyrapone prevented the blockade of tolerance by pain. Thes e results suggest that the blockade of tolerance to morphine analgesia by formalin-induced pain depends on stress-induced corticosterone inc reases. (C) 1997 Elsevier Science Ireland Ltd.