Hunter College and The Graduate Center, The City University of New York, New York 10065, USA.
Synapse. 2011 Jul;65(7):643-51. doi: 10.1002/syn.20890. Epub 2011 Feb 25.
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.
雌激素调节疼痛感知，但具体机制尚不完全清楚。本研究旨在确定雌激素是否通过下丘脑-垂体-肾上腺 (HPA) 轴调节环氧化酶 (COX)-1/COX-2 活性来降低伤害性反应。第一项研究考察了雌二醇 (20%) 或同时注射非甾体抗炎药 (NSAIDs) 的载体对去卵巢 (OVX) 大鼠福尔马林诱导的伤害性反应 (退缩) 的影响。这些药物是布洛芬 (COX-1 和 COX-2 抑制剂)、SC560 (COX-1 抑制剂) 或 NS398 (COX-2 抑制剂)。在第二项研究中，在肾上腺切除术 (ADX)、OVX 和 ADX+OVX 大鼠中测试了雌二醇对福尔马林诱导的伤害性感受的影响。测量了前列腺素 (PG) PGE2 和皮质酮的血清水平。雌二醇显著降低 OVX 大鼠的伤害性反应，对福尔马林测试的第一和第二阶段均有影响。在此使用的剂量下，非甾体抗炎药 (NSAIDs) 不会改变伤害性感受。肾上腺切除术既不改变雌性大鼠的退缩反应，也不逆转雌二醇诱导的抗伤害性反应。雌二醇本身对皮质酮 (CORT) 或前列腺素水平在福尔马林测试后没有影响，将雌二醇对行为和这些血清标志物的影响分开。布洛芬和 NS398 显著降低 PGE2 水平。OVX 手术或雌二醇不会降低 CORT 水平低于 ADX。只有 IBU 显著增加皮质酮水平。总之，我们的结果表明，雌二醇诱导的雌性大鼠的镇痛作用独立于 COX 活性和 HPA 轴激活。
