ArticleSynapse (New York, N.Y.)2011
Estradiol-induced antinociceptive responses on formalin-induced nociception are independent of COX and HPA activation.
Article in Synapse (New York, N.Y.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Oxylipins as Biomarkers for Aromatase Inhibitor-Induced Arthralgia (AIA) in Breast Cancer Patients.Metabolites · 2023Article
- Estrogen alters baseline and inflammatory-induced cytokine levels independent from hypothalamic-pituitary-adrenal axis activity.Cytokine · 2015Article
- Activation of estrogen receptor α enhances bradykinin signaling in peripheral sensory neurons of female rats.The Journal of pharmacology and experimental therapeutics · 2014Article
- Ovariectomy results in variable changes in nociception, mood and depression in adult female rats.PloS one · 2014Article
- Sex differences and hormonal modulation of deep tissue pain.Frontiers in neuroendocrinology · 2013Review
- Estrogen receptor β activation is antinociceptive in a model of visceral pain in the rat.The journal of pain · 2012Article
- Estrogen receptors and the regulation of neural stress responses.Neuroendocrinology · 2012Review
- Interactions of estradiol and NSAIDS on carrageenan-induced hyperalgesia.Brain research · 2011Article
- Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
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.
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Registered trials
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