ArticleBritish journal of pharmacology2008
Activation of the spinal sigma-1 receptor enhances NMDA-induced pain via PKC- and PKA-dependent phosphorylation of the NR1 subunit in mice.
Article in British journal of pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- A neuroprotective target in the shadows: a scoping review of pharmacological gaps in σ1R agonists for glutamate-induced neurotoxicity.Frontiers in pharmacology · 2026Pooled it
- Review
- Targeting Sigma-1 and Sigma-2 Receptors in Neuropathic Pain: Pharmacology, Ligand Development, and Translational Progress.Brain sciences · 2026Review
- Characterization of Novel Sigma Receptor Ligands Derived from Multicomponent Reactions as Efficacious Treatments for Neuropathic Pain.Pharmaceuticals (Basel, Switzerland) · 2026Article
- AIM2 promotes excitatory glutamate receptor expression by inhibiting STING and contributes to bone cancer pain in male mice.Scientific reports · 2024Article
- Current understanding of the link between angiotensin-converting enzyme and pain perception.Drug discovery today · 2024Review
- Novel drug treatments for pain in advanced cancer and serious illness: a focus on neuropathic pain and chemotherapy-induced peripheral neuropathy.Palliative care and social practice · 2024Review
- A Practical Guide to Sigma-1 Receptor Positron Emission Tomography/Magnetic Resonance Imaging: A New Clinical Molecular Imaging Method to Identify Peripheral Pain Generators in Patients with Chronic Pain.Seminars in musculoskeletal radiology · 2023Article
- Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids.Acta pharmaceutica Sinica. B · 2023Article
- Long-lasting visceral hypersensitivity in a model of DSS-induced colitis in rats.Neurogastroenterology and motility · 2022Article
- Long-Lasting Nociplastic Pain Modulation by Repeated Administration of Sigma-1 Receptor Antagonist BD1063 in Fibromyalgia-like Mouse Models.International journal of molecular sciences · 2022Article
- Characterization of CM-398, a Novel Selective Sigma-2 Receptor Ligand, as a Potential Therapeutic for Neuropathic Pain.Molecules (Basel, Switzerland) · 2022Article
- Sigma-1 Receptors in Depression: Mechanism and Therapeutic Development.Frontiers in pharmacology · 2022Review
- Antagonism of Sigma-1 receptor blocks heavy alcohol drinking and associated hyperalgesia in male mice.Alcoholism, clinical and experimental research · 2021Article
- Chaperone Sigma1R and Antidepressant Effect.International journal of molecular sciences · 2020Review
- Tyrosine Kinase Inhibitors Reduce NMDA NR1 Subunit Expression, Nuclear Translocation, and Behavioral Pain Measures in Experimental Arthritis.Frontiers in physiology · 2020Article
- Progesterone and Allopregnanolone Rapidly Attenuate Estrogen-Associated Mechanical Allodynia in Rats with Persistent Temporomandibular Joint Inflammation.Frontiers in integrative neuroscience · 2020Article
- Role of Sigma Receptors in Alcohol Addiction.Frontiers in pharmacology · 2019Review
- Characterization of Sigma 1 Receptor Antagonist CM-304 and Its Analog, AZ-66: Novel Therapeutics Against Allodynia and Induced Pain.Frontiers in pharmacology · 2019Article
- Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposePreviously we demonstrated that the spinal sigma-1 receptor (Sig-1 R) plays an important role in pain transmission, although the exact mechanism is still unclear. It has been suggested that Sig-1 R agonists increase glutamate-induced calcium influx through N-methyl-D-aspartate (NMDA) receptors. Despite data suggesting a link between Sig-1 Rs and NMDA receptors, there are no studies addressing whether Sig-1 R activation directly affects NMDA receptor sensitivity. EXPERIMENTAL APPROACH: We studied the effect of intrathecal (i.t.) administration of Sig-1 R agonists on protein kinase C (PKC) and protein kinase A (PKA) dependent phosphorylation of the NMDA receptor subunit NR1 (pNR1) as a marker of NMDA receptor sensitization. In addition, we examined whether this Sig-1 R mediated phosphorylation of NR1 plays an important role in sensory function using a model of NMDA-induced pain. KEY
resultsBoth Western blot assays and image analysis of pNR1 immunohistochemical staining in the spinal cord indicated that i.t. injection of the Sig-1 R agonists, PRE-084 or carbetapentane dose dependently enhanced pNR1 expression in the murine dorsal horn. This increased pNR1 expression was significantly reduced by pretreatment with the specific Sig-1 R antagonist, BD-1047. In another set of experiments Sig-1 R agonists further potentiated NMDA-induced pain behaviour and pNR1 immunoreactivity and this was also reversed with BD-1047. CONCLUSIONS AND IMPLICATIONS: The results of this study suggest that the activation of spinal Sig-1 R enhances NMDA-induced pain via PKC- and PKA-dependent phosphorylation of the NMDA receptor NR 1 subunit.
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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.