ArticleMolecular pain
Preoperative anxiety-induced glucocorticoid signaling reduces GABAergic markers in spinal cord and promotes postoperative hyperalgesia by affecting neuronal PAS domain protein 4.
Article in Molecular pain. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- Repeated restraint stress-induced increase in post-surgical somatosensory hypersensitivity and affective responding is mediated by β-adrenergic receptor activation and spinal NLRP3-IL1β signalling in male rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Construction and evaluation of a PONV prediction model in patients undergoing orthopedic surgery under spinal anesthesia: a prospective cohort study.BMC anesthesiology · 2026Article
- Reactive Microglia-Mediated Synaptic Engulfment in the Basolateral Amygdala may Contribute to Preoperative Anxiety-Induced Postoperative Hyperalgesia.Neurochemical research · 2026Article
- Transcriptomic signatures of the insular cortex in a mouse model of neuropathic pain.Frontiers in molecular neuroscience · 2026Article
- Ventral Anterior-Lateral Complex of the Thalamus Mediates Chronic Stress-Induced Pain Hypersensitivity and Underlies Electroacupuncture Analgesia.Brain and behavior · 2025Article
- Electroacupuncture Mechanisms in Managing Preoperative Anxiety and Postoperative Pain Chronification: A Review.Journal of pain research · 2024Review
- Preoperative Anxiety in Patients with Pancreatic Cancer: What Contributes to Anxiety Levels in Patients Waiting for Surgical Intervention.Healthcare (Basel, Switzerland) · 2023Article
- Duration of Reduction in Enduring Stress-Induced Hyperalgesia Via FKBP51 Inhibition Depends on Timing of Administration Relative to Traumatic Stress Exposure.The journal of pain · 2022Article
- Stress-induced changes in nociceptive responding post-surgery in preclinical rodent models.Frontiers in pain research (Lausanne, Switzerland) · 2022Review
- Genetic and epigenetic mechanisms influencing acute to chronic postsurgical pain transitions in pediatrics: Preclinical to clinical evidence.Canadian journal of pain = Revue canadienne de la douleur · 2022Review
- Essential Functions of the Transcription Factor Npas4 in Neural Circuit Development, Plasticity, and Diseases.Frontiers in neuroscience · 2020Review
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Preoperative anxiety is common in patients undergoing elective surgery and is closely related to postoperative hyperalgesia. In this study, a single prolonged stress model was used to induce preoperative anxiety-like behavior in rats 24 h before the surgery. We found that single prolonged stress exacerbated the postoperative pain and elevated the level of serum corticosterone. Previous studies have shown that glucocorticoid is associated with synaptic plasticity, and decreased spinal GABAergic activity can cause hyperalgesia in rodents. Here, single prolonged stress rats' lumbar spinal cord showed reduced glutamic acid decarboxylase-65, glutamic acid decarboxylase-67, GABA type A receptor alpha 1 subunit, and GABA type A receptor gamma 2 subunit, indicating an impairment of GABAergic system. Furthermore, neuronal PAS domain protein 4 was also reduced in rats after single prolonged stress stimulation, which has been reported to promote GABAergic synapse development. Then, intraperitoneal injection of RU486 (a glucocorticoid receptor antagonist) rather than spironolactone (a mineralocorticoid receptor antagonist) was found to relieve single prolonged stress-induced hyperalgesia and reverse neuronal PAS domain protein 4 reduction and the impairment of GABAergic system. Furthermore, overexpressing neuronal PAS domain protein 4 could also restore the damage of GABAergic system caused by single prolonged stress while interfering with neuronal PAS domain protein 4 caused an opposite effect. Finally, after stimulation of rat primary spinal cord neurons with exogenous corticosterone in vitro, neuronal PAS domain protein 4 and GABAergic markers were also downregulated, and RU486 reversed that. Together, our results demonstrated that preoperative anxiety led to GABAergic system impairment in spinal cord and thus caused hyperalgesia due to glucocorticoid-induced downregulation of neuronal PAS domain protein 4.
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