ArticleBrain, behavior, and immunity2009
Stress exacerbates neuropathic pain via glucocorticoid and NMDA receptor activation.
Article in Brain, behavior, and immunity, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 134 citations in OpenAlex.
- Glucocorticoid-endocannabinoid crosstalk in the ventrolateral periaqueductal gray (vlPAG) promotes pain resolution.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Glucocorticoid-Mediated Astrocytic L-Lactate Release Drives Chronic Postsurgical Pain via Spinal Neuronal Sensitization.Neurochemical research · 2026Article
- Peptide Modulator of TRPV1 Channel Increases Long-Term Potentiation in the Hippocampus and Reduces Anxiety and Fear in Mice Under Acute Stress.Marine drugs · 2026Article
- Antioxidant Therapy Reverses Sound Stress-Induced Opioid Resistance in a Mouse Model of Mechanical Allodynia.Journal of pain research · 2026Article
- Sex differences in phenotypic modulation of microglia by early-life physical stress in a rat model of chronic primary low back pain.Pflugers Archiv : European journal of physiology · 2025Article
- Mind the GAPS: Glia associated with psychological stress.Journal of neuroendocrinology · 2025Review
- Article
- Spatial, transcriptomic, and epigenomic analyses link dorsal horn neurons to chronic pain genetic predisposition.Cell reports · 2024Article
- Influence of Early-Life Stress on the Excitability of Dynorphin Neurons in the Adult Mouse Dorsal Horn.The journal of pain · 2024Article
- Glucocorticoid signaling mediates stress-induced migraine-like behaviors in a preclinical mouse model.Cephalalgia : an international journal of headache · 2024Article
- Spatial, transcriptomic and epigenomic analyses link dorsal horn neurons to chronic pain genetic predisposition.bioRxiv : the preprint server for biology · 2024Article
- Effects of Corticosterone on the Excitability of Glutamatergic and GABAergic Neurons of the Adolescent Mouse Superficial Dorsal Horn.Neuroscience · 2023Article
- Effects of self-perceived psychological stress on clinical symptoms, cortisol, and cortisol/ACTH ratio in patients with burning mouth syndrome.BMC oral health · 2023Article
- Serotonin mediates stress-like effects on responses to non-nociceptive stimuli in the medicinal leech Hirudo verbana.The Journal of experimental biology · 2022Article
- The transcription factor CCAAT/enhancer-binding protein β in spinal microglia contributes to pre-operative stress-induced prolongation of postsurgical pain.Molecular pain · 2022Article
- The Importance of a Multi-Disciplinary Approach to the Endometriotic Patients: The Relationship between Endometriosis and Psychic Vulnerability.Journal of clinical medicine · 2021Review
- Neuroimmune Interactions in Pain and Stress: An Interdisciplinary Approach.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2021Review
- Opposing Changes in Synaptic and Extrasynaptic N-Methyl-D-Aspartate Receptor Function in Response to Acute and Chronic Restraint Stress.Frontiers in molecular neuroscience · 2021Article
- A Review of Inflammatory Bowel Disease: A Model of Microbial, Immune and Neuropsychological Integration.Public health reviews · 2021Review
- Physiopathological Role of Neuroactive Steroids in the Peripheral Nervous System.International journal of molecular sciences · 2020Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
There is growing recognition that psychological stress influences pain. Hormones that comprise the physiological response to stress (e.g., corticosterone; CORT) may interact with effectors of neuropathic pain. To test this hypothesis, mice received a spared nerve injury (SNI) after exposure to 60 min restraint stress. In stressed mice, allodynia was consistently increased. The mechanism(s) underlying the exacerbated pain response involves CORT acting via glucocorticoid receptors (GRs); RU486, a GR antagonist, prevented the stress-induced increase in allodynia whereas exogenous administration of CORT to non-stressed mice reproduced the allodynic response caused by stress. Since nerve injury-induced microglial activation has been implicated in the onset and propagation of neuropathic pain, we evaluated cellular and molecular indices of microglial activation in the context of stress. Activation of dorsal horn microglia was accelerated by stress; however, this effect was transient and was not associated with the onset or maintenance of a pro-inflammatory phenotype. Stress-enhanced allodynia was associated with increased dorsal horn extracellular signal-regulated kinase phosphorylation (pERK). ERK activation could indicate a stress-mediated increase in glutamatergic signaling, therefore mice were treated prior to SNI and stress with memantine, an N-methyl-D-aspartate receptor (NMDAR) antagonist. Memantine prevented stress-induced enhancement of allodynia after SNI. These data suggest that the hormonal responses elicited by stress exacerbate neuropathic pain through enhanced central sensitization. Moreover, drugs that inhibit glucocorticoids (GCs) and/or NMDAR signaling could ameliorate pain syndromes caused by stress.
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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.