ArticleNeuroscience2008
Sex-specific modulation of spinal nociception by alpha2-adrenoceptors: differential regulation by estrogen and testosterone.
Article in Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Low-dose dexmedetomidine improves postoperative sleep and pain in gynecological surgery: a randomized trial.Frontiers in pharmacology · 2026Trial
- Trial
- Electrophysiological evidence about sexual dimorphism in the clonidine-induced inhibition of trigeminal wide dynamic range cell activity.The journal of headache and pain · 2026Article
- Influence of sex and gonadal hormones on pain perception in a neuropathic pain model in old rats.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas · 2026Article
- Sex Differences in the Regulation of Interleukins in Chronic Pain: A Widely Recognized but Difficult-to-Tackle Factor.International journal of molecular sciences · 2025Review
- Article
- Qualitative sex differences in pain processing: emerging evidence of a biased literature.Nature reviews. Neuroscience · 2020Review
- Sexual Dimorphism in Stress-induced Hyperthermia in SNAP25Δ3 mice, a mouse model with disabled Gβγ regulation of the exocytotic fusion apparatus.The European journal of neuroscience · 2020Article
- Article
- Propofol-sparing effect of different concentrations of dexmedetomidine : Comparison of gender differences.Der Anaesthesist · 2019Article
- TRP Channels as Potential Targets for Sex-Related Differences in Migraine Pain.Frontiers in molecular biosciences · 2018Review
- Activation of the trigeminal α2-adrenoceptor produces sex-specific, estrogen dependent thermal antinociception and antihyperalgesia using an operant pain assay in the rat.Behavioural brain research · 2016Article
- The effects of estrogen on the α2-adrenergic receptor subtypes in rat uterine function in late pregnancy in vitro.Croatian medical journal · 2016Article
- Article
- Activation of membrane estrogen receptors attenuates opioid receptor-like1 receptor-mediated antinociception via an ERK-dependent non-genomic mechanism.Neuroscience · 2013Article
- Mechanisms of G protein-coupled estrogen receptor-mediated spinal nociception.The journal of pain · 2012Article
- Effect of ovariectomy on external urethral sphincter activity in anesthetized female rats.The Journal of urology · 2011Article
- Article
- Neonatal androgen-dependent sex differences in lumbar spinal cord dopamine concentrations and the number of A11 diencephalospinal dopamine neurons.The Journal of comparative neurology · 2010Article
- Testosterone is essential for alpha(2)-adrenoceptor-induced antinociception in the trigeminal region of the male rat.Neuroscience letters · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Sex-related differences in antinociception produced by the activation of alpha(2)-adrenoceptors (alpha(2)-ARs) have been reported, however, the precise role of gonadal steroids is still unknown. Hence, we hypothesized that estrogen and testosterone modulate antinociceptive effects of clonidine (an alpha(2)-AR agonist) on N-methyl-D-aspartate- (NMDA) and heat-induced spinal nociception. We also investigated whether estrogen or testosterone alters the expression of alpha(2A)-adrenoceptors in the spinal cord. Sprague-Dawley (SD) rats were implanted with PE10 cannulae in the intrathecal space of the lumbosacral spinal cord and divided into male, proestrous and diestrous female, ovariectomized (OVX), estradiol-treated OVX (OVX+E), castrated male (GDX), testosterone (GDX+T) and estradiol-treated castrated male (GDX+E) groups. Clonidine dose-dependently inhibited NMDA-induced scratching behavior in the male and OVX groups but to a significantly lesser extent in the OVX+E group. It also increased the tail withdrawal latency in the male, OVX, diestrous and GDX+T groups but not in the OVX+E, proestrous, GDX and GDX+E groups. Levels of alpha(2A)-AR mRNA were significantly higher in the OVX, estradiol-treated OVX, GDX and GDX+E animals. In contrast, alpha(2A)-AR protein levels were higher in estradiol-treated OVX, GDX, GDX+T and GDX+E animals as compared with the male. Indeed, no correlations were observed between changes in the mRNA or protein levels of alpha(2A)-AR and behavioral observations. These results support our hypothesis that sex-related differences in alpha(2)-AR-mediated modulation of spinal nociception are gonadal hormone-dependent: estrogen attenuates antinociceptive effects in females whereas testosterone is required for the expression of antinociception in males. In addition, results also revealed that the mechanism of action of gonadal hormones may not involve a global alternation in expression of alpha(2A)-AR in the spinal cord. Estrogen-induced attenuation of alpha(2)-AR-mediated inhibition of nociception could contribute to the higher prevalence of pain syndromes in women.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.