ArticlePain2010
Sex-specificity and estrogen-dependence of kappa opioid receptor-mediated antinociception and antihyperalgesia.
Article in Pain, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- A review of the kappa opioid receptor system in opioid use.Neuroscience and biobehavioral reviews · 2024Pooled it
- Sex Differences in the Regulation of Interleukins in Chronic Pain: A Widely Recognized but Difficult-to-Tackle Factor.International journal of molecular sciences · 2025Review
- Morphine-Induced Antinociception Is Potentiated and Dopamine Elevations Are Inhibited by the Biased Kappa Opioid Receptor Agonist Triazole 1.1.ACS chemical neuroscience · 2025Article
- The Dynorphin/-Opioid Receptor System at the Interface of Hyperalgesia/Hyperkatifeia and Addiction.Current addiction reports · 2025Review
- The role of gonadal hormones in regulating opioid antinociception.Annals of medicine · 2024Review
- Sex Differences in Brain Region-Specific Activation of c-Fos following Kappa Opioid Receptor Stimulation or Acute Stress in Mice.International journal of molecular sciences · 2023Article
- Sex differences in pain along the neuraxis.Neuropharmacology · 2022Review
- Traumatic Stress-Induced Vulnerability to Addiction: Critical Role of the Dynorphin/Kappa Opioid Receptor System.Frontiers in pharmacology · 2022Review
- The kappa-opioid receptor agonist, triazole 1.1, reduces oxycodone self-administration and enhances oxycodone-induced thermal antinociception in male rats.Psychopharmacology · 2021Article
- Sex Differences in Protein Kinase A Signaling of the Latent Postoperative Pain Sensitization That Is Masked by Kappa Opioid Receptors in the Spinal Cord.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Arbiters of endogenous opioid analgesia: role of CNS estrogenic and glutamatergic systems.Translational research : the journal of laboratory and clinical medicine · 2021Review
- Sex differences in the modulation of mouse nest building behavior by kappa opioid receptor signaling.Neuropharmacology · 2020Article
- Qualitative sex differences in pain processing: emerging evidence of a biased literature.Nature reviews. Neuroscience · 2020Review
- Sex differences in kappa opioid receptor inhibition of latent postoperative pain sensitization in dorsal horn.Neuropharmacology · 2020Article
- Activation of Membrane Estrogen Receptors Attenuates NOP-Mediated Tactile Antihypersensitivity in a Rodent Model of Neuropathic Pain.Brain sciences · 2019Article
- Article
- Pharmacological Modulation of Endogenous Opioid Activity to Attenuate Neuropathic Pain in Rats.The journal of pain · 2019Article
- Estrogens as arbiters of sex-specific and reproductive cycle-dependent opioid analgesic mechanisms.Vitamins and hormones · 2019Article
- Estrogen Regulation of GRK2 Inactivates Kappa Opioid Receptor Signaling Mediating Analgesia, But Not Aversion.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Article
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
This investigation determined whether the activation of the kappa opioid receptor (KOR) in the spinal cord produces estrogen-dependent, sex-specific modulation of acute and inflammation-induced persistent nociception. We demonstrate for the first time that KOR antinociception and gene expression are enhanced by exogenous or endogenous estrogen in the female. The lack of KOR antinociception and KOR gene expression are not altered by the hormonal status (testosterone or estrogen) in males. Cannulae were implanted intrathecally in male, gonadectomized male (GDX), intact and ovariectomized female (OVX) Sprague-Dawley rats. Estradiol was injected subcutaneously, 48h before testing (GDX+E and OVX+E). Intrathecal injection of U50,488H, a selective KOR agonist, dose dependently increased heat-evoked tail flick latencies (TFLs) in proestrous and OVX+E groups, but not in male, GDX, GDX+E, OVX, and diestrous groups. Further, estrogen dose-dependently enhanced the effect of U50,488H in OVX rats. KOR selective antagonist, nor-binaltorphimine (Nor-BNI), blocked the antinociceptive effect of U50,488H. U50,488H reversed the carrageenan-induced thermal hyperalgesia in OVX+E rats, but not in male or OVX rats. However, U50,488H treatment did not alter mechanical thresholds in any group, with or without inflammation. KOR gene expression was enhanced in proestrous and OVX+E groups as compared to any other group. We conclude that selective activation of KOR in the spinal cord produces sex-specific, stimulus- and estrogen-dependent attenuation of acute and inflammatory pain in the rat via estrogen-induced upregulation of the KOR gene expression in the spinal cord. These findings may further implicate estrogen dependence of KOR effects in learning, epilepsy, stress response, addiction etc.
Indexed as
Identifiers
What OpenQuestion holds
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.