ArticleProceedings of the National Academy of Sciences of the United States of America2018
TRPV1 channels and the progesterone receptor Sig-1R interact to regulate pain.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 93 citations in OpenAlex.
- Capsaicin suppresses microglial inflammation through TRPV1-SSR4 interaction.Translational neurodegeneration · 2026Article
- Current and Developing Therapeutics for Dry Eye Disease: Targeting Ion Channels.Current issues in molecular biology · 2026Review
- Article
- Review
- Mitochondria-Associated Membranes: A Key Point of Neurodegenerative Diseases.CNS neuroscience & therapeutics · 2025Review
- Sigma-1 Receptor Modulates CFA-Induced Inflammatory Pain via Sodium Channels in Small DRG Neurons.Biomolecules · 2025Article
- The role of mitochondria-associated ER membranes in disease pathology: protein complex and therapeutic targets.Frontiers in cell and developmental biology · 2025Review
- Heat acclimation defense against exertional heat stroke by improving the function of preoptic TRPV1 neurons.Theranostics · 2025Article
- Crucial role for sensory nerves and Na/H exchanger inhibition in dapagliflozin- and empagliflozin-induced arterial relaxation.Cardiovascular research · 2024Article
- Article
- The Influence of Sex Steroid Hormone Fluctuations on Capsaicin-Induced Pain and TRPV1 Expression.International journal of molecular sciences · 2024Article
- Transient receptor potential vanilloid 1 involved in the analgesic effects of total flavonoids extracted from Longxuejie ().Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2024Article
- Supportive care of female hormones in brain health: what and how?Frontiers in pharmacology · 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
- The dual role of TRPV1 in peripheral neuropathic pain: pain switches caused by its sensitization or desensitization.Frontiers in molecular neuroscience · 2024Review
- GnRH peripherally modulates nociceptor functions, exacerbating mechanical pain.Frontiers in molecular neuroscience · 2024Article
- 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
- Efficacy of the Multi-Target Compound E153 in Relieving Pain and Pruritus of Different Origins.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Genetic and Pharmacological Blockade of Sigma-1 Receptors Attenuates Inflammation-Associated Hypersensitivity during Acute Colitis in CD1 Mice.Biomedicines · 2023Article
- Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Transient Receptor Potential Vanilloid 1 (TRPV1) ion channel is expressed in nociceptors where, when activated by chemical or thermal stimuli, it functions as an important transducer of painful and itch-related stimuli. Although the interaction of TRPV1 with proteins that regulate its function has been previously explored, their modulation by chaperones has not been elucidated, as is the case for other mammalian TRP channels. Here we show that TRPV1 physically interacts with the Sigma 1 Receptor (Sig-1R), a chaperone that binds progesterone, an antagonist of Sig-1R and an important neurosteroid associated to the modulation of pain. Antagonism of Sig-1R by progesterone results in the down-regulation of TRPV1 expression in the plasma membrane of sensory neurons and, consequently, a decrease in capsaicin-induced nociceptive responses. This is observed both in males treated with a synthetic antagonist of Sig-1R and in pregnant females where progesterone levels are elevated. This constitutes a previously undescribed mechanism by which TRPV1-dependent nociception and pain can be regulated.
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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.