ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
A transient receptor potential vanilloid 4-dependent mechanism of hyperalgesia is engaged by concerted action of inflammatory mediators.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 225 citations in OpenAlex.
- TRPV4 activation by TGFβ2 enhances cellular contractility and drives ocular hypertension.eLife · 2025Article
- A synthetic peptide, derived from neurotoxin GsMTx4, acts as a non-opioid analgesic to alleviate mechanical and neuropathic pain through the TRPV4 channel.Acta pharmaceutica Sinica. B · 2025Article
- TRPV4-A Multifunctional Cellular Sensor Protein with Therapeutic Potential.Sensors (Basel, Switzerland) · 2024Review
- Potential of cannabidiol as acne and acne scar treatment: novel insights into molecular pathways of pathophysiological factors.Archives of dermatological research · 2024Article
- TRPV4 Activation and its Intracellular Modulation Mediated by Kinin Receptors Contribute to Painful Symptoms Induced by Anastrozole.Molecular neurobiology · 2024Article
- The Multifaceted Functions of TRPV4 and Calcium Oscillations in Tissue Repair.International journal of molecular sciences · 2024Review
- Roles of mechanosensitive ion channels in immune cells.Heliyon · 2024Review
- Structural determinants of TRPV4 inhibition and identification of new antagonists with antiviral activity.British journal of pharmacology · 2022Article
- The role of TRPV4 channels in cutaneous epithelia.Current topics in membranes · 2022Article
- Article
- Transient Receptor Potential-Vanilloid (TRPV1-TRPV4) Channels in the Atlantic Salmon,Frontiers in physiology · 2021Article
- Taxane-induced neurotoxicity: Pathophysiology and therapeutic perspectives.British journal of pharmacology · 2020Review
- Role of Transient Receptor Potential Vanilloid 4 Channel in Skin Physiology and Pathology.Sultan Qaboos University medical journal · 2020Review
- Elevated TRPV4 Levels Contribute to Endothelial Damage and Scarring in Experimental Spinal Cord Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Molecular mechanisms underlying the actions of arachidonic acid-derived prostaglandins on peripheral nociception.Journal of neuroinflammation · 2020Review
- Transient Receptor Potential vanilloid 4 ion channel in C-fibres is involved in mechanonociception of the normal and inflamed joint.Scientific reports · 2019Article
- Pain and immunity: implications for host defence.Nature reviews. Immunology · 2019Review
- Ion Channels Involved in Tooth Pain.International journal of molecular sciences · 2019Review
- The Role of Transient Receptor Potential (TRP) Channels in the Transduction of Dental Pain.International journal of molecular sciences · 2019Review
- Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The transient receptor potential vanilloid 4 (TRPV4) is a primary afferent transducer that plays a crucial role in neuropathic hyperalgesia for osmotic and mechanical stimuli, as well as in inflammatory mediator-induced hyperalgesia for osmotic stimuli. In view of the clinical importance of mechanical hyperalgesia in inflammatory states, the present study investigated the role of TRPV4 in mechanical hyperalgesia induced by inflammatory mediators and the second-messenger pathways involved. Intradermal injection of either the inflammogen carrageenan or a soup of inflammatory mediators enhanced the nocifensive paw-withdrawal reflex elicited by hypotonic or mechanical stimuli in rat. Spinal administration of TRPV4 antisense oligodeoxynucleotide blocked the enhancement without altering baseline nociceptive threshold. Similarly, in TRPV4(-/-) knock-out mice, inflammatory soup failed to induce any significant mechanical or osmotic hyperalgesia. In vitro investigation showed that inflammatory mediators engage the TRPV4-mediated mechanism of sensitization by direct action on dissociated primary afferent neurons. Additional behavioral observations suggested that multiple mediators are necessary to achieve sufficient activation of the cAMP pathway to engage the TRPV4-dependent mechanism of hyperalgesia. In addition, direct activation of protein kinase A or protein kinase C epsilon, two pathways that mediate inflammation-induced mechanical hyperalgesia, also induced hyperalgesia for both hypotonic and mechanical stimuli that was decreased by TRPV4 antisense and absent in TRPV4(-/-) mice. We conclude that TRPV4 plays a crucial role in the mechanical hyperalgesia that is generated by the concerted action of inflammatory mediators present in inflamed tissues.
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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.