The role of pituitary beta-endorphin in mediating corticotropin-releasing factor-induced antinociception.
The hypothesis that blood-borne beta-endorphin modulates nociception was examined with corticotropin-releasing factor (CRF) as a potent and selective agent to stimulate its release from the pituitary gland. Intravenously administered CRF produced a dose-related antinociception in rats as determined by measuring paw-lick latencies on a 50 degrees C hot plate. A dose of 25 nmol/kg of CRF was comparable in both magnitude and duration of antinociception to a 7,500 nmol/kg (= 2.5 mg/kg) dose of morphine sulfate. The antinociceptive effect of CRF was blocked by both hypophysectomy and dexamethasone pretreatment, suggesting that it was mediated by hormone release from the anterior pituitary corticotrophs. Furthermore, the effect of CRF was antagonized by 1) naltrexone, 2) naltrexone methyl bromide, and 3) passive immunization with anti-beta-endorphin antiserum. Together, these data support the hypothesis that opiate-active, beta-endorphin, released by pituitary corticotrophs, participates in the physiological modulation of nociception in rats.
Hargreaves
K M
KM
Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
Flores
C M
CM
Dionne
R A
RA
Mueller
G P
GP
D000700:Analgesics; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013997:Time Factors; D001615:beta-Endorphin / Q000097:blood / Q000502:physiology*
D000700:Analgesics; D009271:Naltrexone; D001615:beta-Endorphin; D009020:Morphine; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone