ArticlePain2012
Functional interactions between NMDA receptors and TRPV1 in trigeminal sensory neurons mediate mechanical hyperalgesia in the rat masseter muscle.
Article in Pain, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- The efficacy and mechanisms of low-intensity transcranial ultrasound stimulation on pain: a systematic review of human and animal studies.The journal of headache and pain · 2025Pooled it
- The effects of physical exercise on inflammation-induced maladaptive neuroplasticity in post-traumatic headache.Neuroscience · 2026Review
- Molecular landscape connecting complications of dry eye disease: mechanisms, therapeutic targets, biomarkers, and future innovations.International ophthalmology · 2026Review
- Article
- Neuro-immune crosstalk in cancer: mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2025Review
- Activation of NR2A-Wnt-TLR2 Signaling Axis in Satellite Glial Cells of the Dorsal Root Ganglion Contributes to Neuropathic Pain Induced by Nerve Injury in Diabetic Mice.Molecular neurobiology · 2025Article
- Unmasking the relationship between CGRP and glutamate: from peripheral excitation to central sensitization in migraine.The journal of headache and pain · 2025Review
- TRP Channels in Excitotoxicity.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2025Review
- N-methyl-D-aspartate Receptor Subunits 2A and 2B Mediate Connexins and Pannexins in the Trigeminal Ganglion Involved in Orofacial Inflammatory Allodynia during Temporomandibular Joint Inflammation.Molecular neurobiology · 2025Article
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- Protein Kinase A Inhibitor Attenuates the Antinociceptive Effect of NMDA-Receptor Channel Antagonists in the Capsaicin Test in Mice.Bulletin of experimental biology and medicine · 2024Article
- Low-Affinity NMDA Receptor Antagonist Hemantane in a Topical Formulation Attenuates Arthritis Induced by Freund's Complete Adjuvant in Rats.Advanced pharmaceutical bulletin · 2024Article
- Involvement of the Transient Receptor Channels in Preclinical Models of Musculoskeletal Pain.Current neuropharmacology · 2024Review
- From pain to tumor immunity: influence of peripheral sensory neurons in cancer.Frontiers in immunology · 2024Review
- Aspartame Safety as a Food Sweetener and Related Health Hazards.Nutrients · 2023Review
- The role of protein kinases in diabetic neuropathic pain: an update review.Journal of diabetes and metabolic disorders · 2023Review
- CaMolecules and cells · 2023Article
- Recent advances in the study of anesthesia-and analgesia-related mechanisms of S-ketamine.Frontiers in pharmacology · 2023Review
- TRP Channels: Recent Development in Translational Research and Potential Therapeutic Targets in Migraine.International journal of molecular sciences · 2022Review
- Activation of Meningeal Afferents Relevant to Trigeminal Headache Pain after Photothrombotic Stroke Lesion: A Pilot Study in Mice.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The NMDA and TRPV1 receptors that are expressed in sensory neurons have been independently demonstrated to play important roles in peripheral pain mechanisms. In the present study, we investigated whether the 2 receptor-channel systems form a functional complex that provides the basis for the development of mechanical hyperalgesia. In the masseter muscle, direct application of NMDA induced a time-dependent increase in mechanical sensitivity, which was significantly blocked when the muscle was pretreated with a specific TRPV1 antagonist, AMG9810. The NR1 subunit of the NMDA receptor and TRPV1 were coexpressed in 32% of masseter afferents in trigeminal ganglia (TG). Furthermore, NR1 and NR2B formed protein-protein complexes with TRPV1 in TG as demonstrated by coimmunoprecipitation experiments. Calcium imaging analyses further corroborated that NMDA and TRPV1 receptors functionally interact. In TG culture, application of NMDA resulted in phosphorylation of serine, but not threonine or tyrosine, residues of TRPV1 in a time course similar to that of the development of NMDA-induced mechanical hyperalgesia. The NMDA-induced phosphorylation was significantly attenuated by CaMKII and PKC inhibitors, but not by a PKA inhibitor. Consistent with the biochemical data, the NMDA-induced mechanical hyperalgesia was also effectively blocked when the muscle was pretreated with a CaMKII or PKC inhibitor. Thus, NMDA receptors and TRPV1 functionally interact via CaMKII and PKC signaling cascades and contribute to mechanical hyperalgesia. These data offer novel mechanisms by which 2 ligand-gated channels in sensory neurons interact and reinforce the notion that TRPV1 functions as a signal integrator under pathological conditions.
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What OpenQuestion holds
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.