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 painful inflammatory rheumatic diseases, the contribution, if any, of endogenous pituitary-adrenocortical activity to the control of pain remains unclear. We report that injection of dilute formalin into the hindpaw not only evokes inflammation and pain-related behavior, but it also increases ACTH and corticosterone to a greater extent than restraint and saline injection alone. This difference was particularly robust during the final periods of pain-related behavior in the formalin test, when the ACTH and corticosterone (B) levels in the restraint/saline control group had returned to normal. These results indicate that formalin-evoked increases in ACTH and B reflect nociceptive input, rather than the stress associated with handling. To test the hypothesis that the formalin-induced increase in corticosterone reduces pain and inflammation, we next evaluated the effect of adrenalectomy (to prevent activation of glucocorticoid receptors) or high-dose dexamethasone (to saturate glucocorticoid receptors) on nociceptive processing in the formalin test. Neither adrenalectomy nor dexamethasone changed behavioral or 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 that the nociceptive component of the formalin stimulus is sufficient to activate the pituitary-adrenocortical system in the awake rat, but that the resulting release of corticosterone does not feed back and reduce nociceptive processing.
Taylor
B K
BK
W. M. Keck Foundation Center for Integrative Neuroscience, and Department of Anatomy, University of California, San Francisco, 94143-0452, USA. brad@phy.ucsf.edu
Akana
S F
SF
Peterson
M A
MA
Dallman
M F
MF
Basbaum
A I
AI
D000302:Adrenal Cortex / Q000502:physiology*; D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003345:Corticosterone / Q000097:blood / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D005557:Formaldehyde / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced; D008297:Male; D009619:Nociceptors / Q000502:physiology*; D010146:Pain; D010902:Pituitary Gland / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005938:Glucocorticoids; D005557:Formaldehyde; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone