PITUITARY-ADRENOCORTICAL RESPONSES TO PERSISTENT NOXIOUS STIMULI IN THE AWAKE RAT - ENDOGENOUS CORTICOSTERONE DOES NOT REDUCE NOCICEPTION IN THE FORMALIN TEST

Although glucocorticoids inhibit inflammation and are used to treat pa inful inflammatory rheumatic diseases, the contribution, if any, of en dogenous pituitary-adrenocortical activity to the control of pain rema ins unclear. We report that injection of dilute formalin into the hind paw not only evokes inflammation and pain-related behavior, but it als o increases ACTH and corticosterone to a greater extent than restraint and saline injection alone. This difference was particularly robust d uring the final periods of pain-related behavior in the formalin test, when the ACTH and corticosterone (B) levels in the restraint/saline c ontrol group had returned to normal. These results indicate that forma lin-evoked increases in ACTH and B reflect nociceptive input, rather t han the stress associated with handling. To test the hypothesis that t he formalin-induced increase in corticosterone reduces pain and inflam mation, we next evaluated the effect of adrenalectomy (to prevent acti vation of glucocorticoid receptors) or high-dose dexamethasone (to sat urate glucocorticoid receptors) on nociceptive processing in the forma lin test. Neither adrenalectomy nor dexamethasone changed behavioral o r cardiovascular nociceptive responses. Furthermore, the increases in blood pressure and heart rate produced by formalin may not be mediated by adrenomedullary catecholamine release. In addition, we conclude th at the nociceptive component of the formalin stimulus is sufficient to activate the pituitary-adrenocortical system in the awake rat, but th at the resulting release of corticosterone does not feed back and redu ce nociceptive processing.