ArticleThe Journal of pharmacology and experimental therapeutics2013
Sex, pain, and opioids: interdependent influences of sex and pain modality on dynorphin-mediated antinociception in rats.
Article in The Journal of pharmacology and experimental therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Morphine-Induced Antinociception Is Potentiated and Dopamine Elevations Are Inhibited by the Biased Kappa Opioid Receptor Agonist Triazole 1.1.ACS chemical neuroscience · 2025Article
- 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
- Dezocine relieves the postoperative hyperalgesia in rats through suppressing the hyper-action of Akt1/GSK-3β pathway.Experimental brain research · 2022Article
- Sex differences in kappa opioid receptor antinociception is influenced by the number of X chromosomes in mouse.Journal of neuroscience research · 2022Article
- Endogenous Opioid Dynorphin Is a Potential Link between Traumatic Brain Injury, Chronic Pain, and Substance Use Disorder.Journal of neurotrauma · 2022Review
- The kappa-opioid receptor agonist, triazole 1.1, reduces oxycodone self-administration and enhances oxycodone-induced thermal antinociception in male rats.Psychopharmacology · 2021Article
- Arbiters of endogenous opioid analgesia: role of CNS estrogenic and glutamatergic systems.Translational research : the journal of laboratory and clinical medicine · 2021Review
- Qualitative sex differences in pain processing: emerging evidence of a biased literature.Nature reviews. Neuroscience · 2020Review
- Targeting opioid dysregulation in depression for the development of novel therapeutics.Pharmacology & therapeutics · 2019Review
- Plasticity of Signaling by Spinal Estrogen Receptor α, κ-Opioid Receptor, and Metabotropic Glutamate Receptors over the Rat Reproductive Cycle Regulates Spinal Endomorphin 2 Antinociception: Relevance of Endogenous-Biased Agonism.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Bullatine A stimulates spinal microglial dynorphin A expression to produce anti-hypersensitivity in a variety of rat pain models.Journal of neuroinflammation · 2016Article
- Contribution of Endogenous Spinal Endomorphin 2 to Intrathecal Opioid Antinociception in Rats Is Agonist Dependent and Sexually Dimorphic.The journal of pain · 2015Article
- Examination of sex and minocycline treatment on acute morphine-induced analgesia and inflammatory gene expression along the pain pathway in Sprague-Dawley rats.Biology of sex differences · 2015Article
- Estrogens Suppress Spinal Endomorphin 2 Release in Female Rats in Phase with the Estrous Cycle.Neuroendocrinology · 2015Article
- The neuroanatomy of sexual dimorphism in opioid analgesia.Experimental neurology · 2014Review
- Effects of kappa opioid receptors on conditioned place aversion and social interaction in males and females.Behavioural brain research · 2014Article
- On the g-protein-coupled receptor heteromers and their allosteric receptor-receptor interactions in the central nervous system: focus on their role in pain modulation.Evidence-based complementary and alternative medicine : eCAM · 2013Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The role of dynorphin A (1-17; Dyn) and its associated kappa opioid receptor (KOR) in nociception represents a longstanding scientific conundrum: Dyn and KOR (Dyn/KOR) have variously been reported to inhibit, facilitate, or have no effect on pain. We investigated whether interactions between sex and pain type (which are usually ignored) influenced Dyn/KOR-mediated antinociception. Blockade of the spinal α(2)-noradrenergic receptor (α(2)-NAR) using yohimbine elicited comparable spinal Dyn release in females and males. Nevertheless, the yohimbine-induced antinociception exhibited sexual dimorphism that depended on the pain test used: in the intraperitoneal acetic acid-induced writhing test, yohimbine produced antinociception only in females, whereas in the intraplantar formalin-induced paw flinch test, antinociception was observed only in males. In females and males, both intrathecal Dyn antibodies and spinal KOR blockade eliminated the yohimbine-induced antinociception, indicating that Dyn/KOR mediated it. However, despite the conditional nature of spinal Dyn/KOR-mediated yohimbine antinociception, both intraplantar formalin and intraperitoneal acetic acid activated spinal Dyn neurons that expressed α(2)-NARs. Moreover, Dyn terminals apposed KOR-expressing spinal nociceptive neurons in both sexes. This similar organization suggests that the sexually dimorphic interdependent effects of sex and pain type may result from the presence of nonfunctional (silent) KORs on nociceptive spinal neurons that are responsive to intraplantar formalin (in females) versus intraperitoneal acetic acid (in males). Our findings that spinal Dyn/KOR-mediated antinociception depends on interactions between sex and pain type underscore the importance of using both sexes and multiple pain models when investigating Dyn/KOR antinociception.
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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.