Stress Induces Pain Transition by Potentiation of AMPA Receptor Phosphorylation

Chronic postsurgical pain is a serious issue in clinical practice. After surgery, patients experience ongoing pain or become sensitive to incident, normally nonpainful stimulation. The intensity and duration of postsurgical pain vary. However, it is unclear how the transition from acute to chronic pain occurs. Here we showed that social defeat stress enhanced plantar incision-induced AMPA receptor GluA1 phosphorylation at the Ser831 site in the spinal cord and greatly prolonged plantar incision-induced pain. Interestingly, targeted mutation of the GluA1 phosphorylation site Ser831 significantly inhibited stress-induced prolongation of incisional pain. In addition, stress hormones enhanced GluA1 phosphorylation and AMPA receptor-mediated electrical activity in the spinal cord. Subthreshold stimulation induced spinal long-term potentiation in GluA1 phosphomimetic mutant mice, but not in wild-type mice. Therefore, spinal AMPA receptor phosphorylation contributes to the mechanisms underlying stress-induced pain transition.

• Publication year

  2014

• Venue

  Journal of Neuroscience

• Publication date

  2014-10-08

• Fields of study

  Medicine, Psychology

• Identifiers
  DOI 10.1523/JNEUROSCI.2130-14.2014PMID 25297100PMCID PMC4188971
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The transition from acute to chronic pain: understanding how different biological systems interact

  2014cited by this paper
• Stress-induced hyperalgesia.

  2014cited by this paper
• The noradrenergic pain regulation system: a potential target for pain therapy.

  2013cited by this paper
• Stress-Induced Allodynia – Evidence of Increased Pain Sensitivity in Healthy Humans and Patients with Chronic Pain after Experimentally Induced Psychosocial Stress

  2013cited by this paper
• Acute Stress Contributes to Individual Differences in Pain and Pain-Related Brain Activity in Healthy and Chronic Pain Patients

  2013cited by this paper
• Antagonism of orexin-1 receptors attenuates swim- and restraint stress-induced antinociceptive behaviors in formalin test.

  2012cited by this paper
• Naloxone inhibits not only stress‐induced analgesia but also sympathetic activation and baroreceptor‐reflex sensitivity

  2012cited by this paper
• Experimental hypoglycemia is a human model of stress‐induced hyperalgesia

  2012cited by this paper
• A role for repressive histone methylation in cocaine-induced vulnerability to stress.

  2011cited by this paper
• Stress‐induced hyperalgesia is associated with a reduced and delayed GABA inhibitory control that enhances post‐synaptic NMDA receptor activation in the spinal cord

  2011cited by this paper
• Enhanced synaptic plasticity in mice with phosphomimetic mutation of the GluA1 AMPA receptor

  2011cited by this paper
• Endogenous opioids released during non-nociceptive environmental stress induce latent pain sensitization Via a NMDA-dependent process.

  2011cited by this paper
• A Novel Role of the WNT-Dishevelled-GSK3β Signaling Cascade in the Mouse Nucleus Accumbens in a Social Defeat Model of Depression

  2011cited by this paper
• Enhanced cytokine-induced mechanical hyperalgesia in skeletal muscle produced by a novel mechanism in rats exposed to unpredictable sound stress.

  2011cited by this paper
• Stress hormones and AMPA receptor trafficking in synaptic plasticity and memory

  2010influential reference
• The effects of acute restraint stress on nociceptive responses evoked by the injection of formalin into the temporomandibular joint of female rats

  2010cited by this paper
• Involvement of NTS2 receptors in stress-induced analgesia.

  2010cited by this paper
• Stress-induced analgesia.

  2009cited by this paper
• Nitric oxide mechanism in protective effect of imipramine and venlafaxine against acute immobilization stress-induced behavioral and biochemical alteration in mice.

  2009cited by this paper
• Persistent Inflammation Induces GluR2 Internalization via NMDA Receptor-Triggered PKC Activation in Dorsal Horn Neurons

  2009cited by this paper
• Sound stress-induced long-term enhancement of mechanical hyperalgesia in rats is maintained by sympathoadrenal catecholamines.

  2009cited by this paper
• Transition from acute to chronic postsurgical pain: risk factors and protective factors

  2009cited by this paper
• Chronic restraint stress induces mechanical and cold allodynia, and enhances inflammatory pain in rat: Relevance to human stress-associated painful pathologies.

  2009cited by this paper
• Quercetin Protects Against Acute Immobilization Stress-Induced Behaviors and Biochemical Alterations in Mice

  2008cited by this paper
• Neuronal nitric oxide synthase gene inactivation reduces the expression of vasopressin in the hypothalamic paraventricular nucleus and of catecholamine biosynthetic enzymes in the adrenal gland of the mouse

  2008cited by this paper
• Enhanced LTP of primary afferent neurotransmission in AMPA receptor GluR2‐deficient mice

  2008cited by this paper
• N‐ethylmaleimide‐sensitive fusion protein (NSF) is involved in central sensitization in the spinal cord through GluR2 subunit composition switch after inflammation

  2008cited by this paper
• The stress hormone corticosterone conditions AMPAR surface trafficking and synaptic potentiation

  2008cited by this paper
• Emotion enhances learning via norepinephrine regulation of AMPA-receptor trafficking.

  2007cited by this paper
• The cell biology of synaptic plasticity: AMPA receptor trafficking.

  2007cited by this paper
• The Neural Cell Adhesion Molecule Antibody Blocks Cold Water Swim Stress-Induced Analgesia and Cell Adhesion Between Lymphocytes and Cultured Dorsal Root Ganglion Neurons

  2006cited by this paper
• New role for spinal Stargazin in α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor‐mediated pain sensitization after inflammation

  2006cited by this paper
• Persistent postsurgical pain: risk factors and prevention.

  2006cited by this paper
• Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action

  2006cited by this paper
• Involvement of Cholecystokininergic Systems in Anxiety-Induced Hyperalgesia in Male Rats: Behavioral and Biochemical Studies

  2005cited by this paper
• Mineralocorticoid receptors are indispensable for nongenomic modulation of hippocampal glutamate transmission by corticosterone.

  2005influential reference
• Stress and the brain: from adaptation to disease

  2005cited by this paper
• Acute noise stress analgesia in relation to 5-HT2 and mu-opioid receptor changes in the frontal cortex of young mice.

  2005cited by this paper
• Expression of Central Glucocorticoid Receptors after Peripheral Nerve Injury Contributes to Neuropathic Pain Behaviors in Rats

  2004cited by this paper
• Sustained &bgr;1-Adrenergic Stimulation Modulates Cardiac Contractility by Ca2+/Calmodulin Kinase Signaling Pathway

  2004cited by this paper
• Sustained beta1-adrenergic stimulation modulates cardiac contractility by Ca2+/calmodulin kinase signaling pathway.

  2004cited by this paper
• The AMPA receptor subunits GluR-A and GluR-B reciprocally modulate spinal synaptic plasticity and inflammatory pain.

  2004cited by this paper
• β-Adrenergic receptors and their interacting proteins

  2004cited by this paper
• Beta-adrenergic receptors and their interacting proteins.

  2004cited by this paper
• Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory.

  2003cited by this paper
• A Mouse Model of Incisional Pain

  2003cited by this paper
• AMPA receptor trafficking at excitatory synapses.

  2003cited by this paper
• Spinal glutamate receptor antagonists differentiate primary and secondary mechanical hyperalgesia caused by incision

  2003cited by this paper
• NMDA and β1-Adrenergic Receptors Differentially Signal Phosphorylation of Glutamate Receptor Type 1 in Area CA1 of Hippocampus

  2003cited by this paper
• Alpha 2 adrenoceptor-mediated presynaptic inhibition of primary afferent glutamatergic transmission in rat substantia gelatinosa neurons.

  2003cited by this paper
• Impaired NMDA Receptor-Mediated Postsynaptic Function and Blunted NMDA Receptor-Dependent Persistent Pain in Mice Lacking Postsynaptic Density-93 Protein

  2003cited by this paper
• Analysis of Glutamate Receptor Surface Expression in Acute Hippocampal Slices

  2002cited by this paper
• AMPA receptor trafficking and synaptic plasticity.

  2002cited by this paper
• Yeast and apoptosis

  2002cited by this paper
• Regulation of AMPA receptors during synaptic plasticity.

  2002cited by this paper
• LTP leads to rapid surface expression of NMDA but not AMPA receptors in adult rat CA1

  2002cited by this paper
• The stressed hippocampus, synaptic plasticity and lost memories

  2002cited by this paper
• Norepinephrine Facilitates Inhibitory Transmission in Substantia Gelatinosa of Adult Rat Spinal Cord (Part 1): Effects on Axon Terminals of GABAergic and Glycinergic Neurons

  2000cited by this paper
• Norepinephrine Facilitates Inhibitory Transmission in Substantia Gelatinosa of Adult Rat Spinal Cord (Part 2): Effects on Somatodendritic Sites of GABAergic Neurons

  2000cited by this paper
• Phosphorylation of the α-Amino-3-hydroxy-5-methylisoxazole4-propionic Acid Receptor GluR1 Subunit by Calcium/ Calmodulin-dependent Kinase II*

  1997cited by this paper
• The alpha2a adrenergic receptor subtype mediates spinal analgesia evoked by alpha2 agonists and is necessary for spinal adrenergic-opioid synergy.

  1997cited by this paper
• Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation.

  1997cited by this paper
• Mapping of punctuate hyperalgesia around a surgical incision demonstrates that ketamine is a powerful suppressor of central sensitization to pain following surgery

  1997cited by this paper
• The α2a Adrenergic Receptor Subtype Mediates Spinal Analgesia Evoked by α2 Agonists and Is Necessary for Spinal Adrenergic–Opioid Synergy

  1997cited by this paper
• Characterization of multiple phosphorylation sites on the AMPA receptor GluR1 subunit.

  1996cited by this paper
• Colocalization of Fos- and glucocorticoid receptor-immunoreactivities is present only in a very restricted population of dorsal horn neurons of the rat spinal cord after nociceptive stimulation.

  1993influential reference
• Preoperative morphine pre‐empts postoperative pain

  1993cited by this paper
• OPEN ACCESS Research Article Modulation of formalin-induced Fos-like immunoreactivity

  year unknowncited by this paper

• [Temporal changes of chronic postsurgical pain in mice: the regulatory role of CX3CL1 in the dorsal root ganglion].

  2026cites this paper
• Mechanisms of chronic postsurgical pain

  2025cites this paper
• Decoding pain chronification: mechanisms of the acute-to-chronic transition

  2025influential citation
• 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

  2025cites this paper
• Ketogenic diet mitigates opioid-induced hyperalgesia by restoring short-chain fatty acids-producing bacteria in the gut.

  2024cites this paper
• New Insights into Contradictory Changes in Brain-Derived Neurotrophic Factor (BDNF) in Rodent Models of Posttraumatic Stress Disorder (PTSD)

  2024cites this paper
• Specific Activation of Dopamine Receptor D1 Expressing Neurons in the PrL Alleviates CSDS-Induced Anxiety-Like Behavior Comorbidity with Postoperative Hyperalgesia in Male Mice

  2024influential citation
• Ventral tegmental area dopaminergic circuits participates in stress-induced chronic postsurgical pain in male mice

  2024cites this paper
• Stress-Induced Changes in the Endogenous Opioid System Cause Dysfunction of Pain and Emotion Regulation

  2023cites this paper
• Ferroptosis: a new regulatory mechanism in neuropathic pain

  2023cites this paper
• Stress induces prolonged pain recovery after surgery: involvement of glucocorticoid related pathway.

  2023cites this paper
• Stress-induced changes in nociceptive responding post-surgery in preclinical rodent models

  2023influential citation
• Antinociceptive and Analgesic Effects of (2R,6R)-Hydroxynorketamine

  2022cites this paper
• Green light exposure elicits anti-inflammation, endogenous opioid release and dampens synaptic potentiation to relieve post-surgical pain.

  2022cites this paper
• TNFα Enhances Calcium Influx by Interacting with AMPA Receptors in the Spinal Dorsal Horn Neurons

  2022cites this paper
• (2R,6R)-hydroxynorketamine (HNK) reverses mechanical hypersensitivity in a model of localized inflammatory pain.

  2022cites this paper
• Effect of daily treadmill running exercise on masseter muscle nociception associated with social defeat stress in mice.

  2022cites this paper
• Sciatic nerve block downregulates the BDNF pathway to alleviate the neonatal incision-induced exaggeration of incisional pain via decreasing microglial activation.

  2022cites this paper
• Differential Effects of Sevoflurane Exposure on Long-Term Fear Memory in Neonatal and Adult Rats

  2022cites this paper
• Spinal microglial activation promotes perioperative social defeat stress-induced prolonged postoperative pain in a sex-dependent manner.

  2021cites this paper
• Patient and Surgery-Related Predictors of Acute Postoperative Pain

  2020cites this paper
• Emotional Stress Induces Structural Plasticity in Bergmann Glial Cells via an AC5–CPEB3–GluA1 Pathway

  2020cites this paper
• Congrès de la SFETD, Strasbourg, 27–29 septembre 2019

  2020cites this paper
• Pathophysiology of Postoperative Pain

  2020cites this paper
• Spinal N-Cadherin/CREB Signaling Contributes to Chronic Alcohol Consumption-Enhanced Postsurgical Pain

  2020cites this paper
• Mode of delivery alters dental pulp nociception and pain-induced changes in cognitive performance in adults' male rats.

  2020cites this paper
• Can I Get a Witness? Using Vicarious Defeat Stress to Study Mood-Related Illnesses in Traditionally Understudied Populations.

  2020cites this paper
• Differential impact of psychological and psychophysical stress on low back pain in mice.

  2020cites this paper
• PGE2/EP4 receptor and TRPV1 channel are involved in repeated restraint stress-induced prolongation of sensitization pain evoked by subsequent PGE2 challenge.

  2019cites this paper
• Preoperative anxiety-induced glucocorticoid signaling reduces GABAergic markers in spinal cord and promotes postoperative hyperalgesia by affecting neuronal PAS domain protein 4

  2019cites this paper
• Gut Microbiota Dysbiosis Enhances Migraine-Like Pain Via TNFα Upregulation

  2019cites this paper
• New Developments in Neuroscience. A Review

  2019cites this paper
• The Effects of Chronic Stress on Migraine Relevant Phenotypes in Male Mice

  2018cites this paper
• Psychosocial Stress Delays Recovery of Postoperative Pain Following Incisional Surgery in the Rat.

  2018cites this paper
• The role of glutamate and its receptors in central nervous system in stress-induced hyperalgesia

  2018cites this paper
• Pathophysiology and Preventative Pharmacologic Considerations

  2018cites this paper
• PKMζ Is Not Required for Development of Postsurgical Pain

  2018cites this paper
• Persistent Postsurgical Pain: Pathophysiology and Preventative Pharmacologic Considerations

  2018cites this paper
• TNFα in the Trigeminal Nociceptive System Is Critical for Temporomandibular Joint Pain

  2018cites this paper
• AMPA receptor GluA1 Ser831 phosphorylation is critical for nitroglycerin‐induced migraine‐like pain

  2018cites this paper
• Spinal AMPA Receptor GluA1 Ser831 Phosphorylation Controls Chronic Alcohol Consumption-Produced Prolongation of Postsurgical Pain

  2017cites this paper
• Dexmedetomidine Alleviates Presurgical

  2017cites this paper
• Postoperative pain—from mechanisms to treatment

  2017cites this paper
• Dysfunctional GPR40/FFAR1 signaling exacerbates pain behavior in mice

  2017cites this paper
• Role of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor regulation in stress-induced pain chronification

  2017cites this paper
• Current Status of Animal Models of Posttraumatic Stress Disorder: Behavioral and Biological Phenotypes, and Future Challenges in Improving Translation.

  2017cites this paper
• Inflammation‐induced GluA1 trafficking and membrane insertion of Ca2 + permeable AMPA receptors in dorsal horn neurons is dependent on spinal tumor necrosis factor, PI3 kinase and protein kinase A

  2017cites this paper
• Journal of Integrated Creative Studies 1 New Developments in Neuroscience

  2016cites this paper
• The Transition of Acute Postoperative Pain to Acute Persistent Pain to Chronic Pain: Assessing and Managing the Risks

  2016cites this paper
• Traumatic Stress Promotes Hyperalgesia via Corticotropin-Releasing Factor-1 Receptor (CRFR1) Signaling in Central Amygdala

  2016cites this paper
• Common Brain Mechanisms of Chronic Pain and Addiction.

  2016cites this paper
• Influence of hypophysectomy, ovariectomy and gonadectomy on postoperative hypersensitivity in rats

  2016cites this paper
• Effect of parecoxib sodium on propofol combined with fentanyl anesthesia effect and postoperative recovery in elderly patients with laparoscopic surgery

  2016cites this paper
• New Developments in Neuroscience

  2015cites this paper
• Potassium Channel Allele Modulates Chronic Pain Experience

  2015cites this paper
• Social stress in mice induces urinary bladder overactivity and increases TRPV1 channel-dependent afferent nerve activity.

  2015cites this paper