Estradiol-induced antinociceptive responses on formalin-induced nociception are independent of COX and HPA activation.
Estrogen modulates pain perception but how it does so is not fully understood. The aim of this study was to determine if estradiol reduces nociceptive responses in part via hypothalamic-pituitary-adrenal (HPA) axis regulation of cyclooxygenase (COX)-1/COX-2 activity. The first study examined the effects of estradiol (20%) or vehicle with concurrent injection nonsteroidal antiinflammatory drugs (NSAIDs) on formalin-induced nociceptive responding (flinching) in ovariectomized (OVX) rats. The drugs were ibuprofen (COX-1 and COX-2 inhibitor), SC560 (COX-1 inhibitor), or NS398 (COX-2 inhibitor). In a second study, estradiol's effects on formalin-induced nociception were tested in adrenalectomized (ADX), OVX, and ADX+OVX rats. Serum levels of prostaglandins (PG) PGE(2) and corticosterone were measured. Estradiol significantly decreased nociceptive responses in OVX rats with effects during both the first and the second phase of the formalin test. The nonsteroidal antiinflammatory drugs (NSAIDs) did not alter nociception at the doses used here. Adrenalectomy neither altered flinching responses in female rats nor reversed estradiol-induced antinociceptive responses. Estradiol alone had no effect on corticosterone (CORT) or prostaglandin levels after the formalin test, dissociating the effects of estradiol on behavior and these serum markers. Ibuprofen and NS398 significantly reduced PGE2 levels. CORT was not decreased by OVX surgery or by estradiol below that of ADX. Only IBU significantly increased corticosterone levels. Taken together, our results suggest that estradiol-induced antinociception in female rats is independent of COX activity and HPA axis activation.
Hunter College and The Graduate Center, The City University of New York, New York 10065, USA. hunterd@pi.cpmc.columbia.edu
Deirtra A
DA
Hunter
Gordon A
GA
Barr
Nicole
N
Amador
Kai-Yvonne
KY
Shivers
Lynne
L
Kemen
Christopher M
CM
Kreiter
Shirzad
S
Jenab
Charles E
CE
Inturrisi
Vanya
V
Quinones-Jenab
D000818:Animals; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005557:Formaldehyde / Q000633:toxicity; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D007509:Irritants / Q000633:toxicity; D010052:Ovariectomy; D010146:Pain / Q000503:physiopathology*; D058748:Pain Perception / Q000187:drug effects* / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D007509:Irritants; D005557:Formaldehyde; D004958:Estradiol; D011451:Prostaglandin-Endoperoxide Synthases