ArticleEuropean journal of pain (London, England)2022
Role of Src kinase in regulating protein kinase C mediated phosphorylation of TRPV1.
Article in European journal of pain (London, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- Molecular target for neuroinflammation and pain management: transient receptor potential vanilloid 1.Inflammopharmacology · 2026Review
- Untangling neuropathic pain: pathophysiological insights and future directions for targeted therapy.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Review
- The Multi-Dimensional Role of Vitamin D in the Pathophysiology and Treatment of Diabetic Foot Ulcers: From Molecular Mechanisms to Clinical Translation.International journal of molecular sciences · 2025Review
- Gender-different effect of Src family kinases antagonism on photophobia and trigeminal ganglion activity.The journal of headache and pain · 2024Article
- Antinociceptive and anti-inflammatory activity of extracts and α-pyrones isolated from Cantinoa stricta.Inflammopharmacology · 2024Article
- Targeting TRPV1 for Cancer Pain Relief: Can It Work?Cancers · 2024Review
- Gastric protective effect ofPharmaceutical biology · 2023Article
- Modification of the TRP Channel TRPA1 as a Relevant Factor in Migraine-Related Intracranial Hypersensitivity.International journal of molecular sciences · 2023Review
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4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundTransient receptor potential vanilloid-1 (TRPV1), activated by heat, acidic pH, endogenous vanilloids and capsaicin, is essential for thermal hyperalgesia. Under inflammatory conditions, phosphorylation of TRPV1 by protein kinase C (PKC) can sensitize the channel and decrease the activation threshold. Src kinase also phosphorylates TRPV1, promoting channel trafficking to the plasma membrane. These post-translational modifications are important for several chronic pain conditions. This study presents a previously undescribed relationship between Src and PKC phosphorylation of TRPV1, influencing the thermal hypersensitivity associated with TRPV1 activation.
methodsWe assessed TRPV1 channel activity using intracellular calcium imaging and patch-clamp electrophysiology in mouse dorsal root ganglion cultures. Additionally, we used behavioural experiments to evaluate plantar thermal sensitivity following intraplantar injections of activators of known modulators of TRPV1 with and without an Src antagonist.
resultsUsing calcium imaging and patch-clamp techniques, we demonstrated that pharmacological inhibition of Src kinase or mutation of the Src phosphorylation site on TRPV1 prevented PKC but not PKA-mediated sensitization of TRPV1 in vitro. We found that intraplantar injection of the PKC activator phorbol 12-myristate 13-acetate (PMA) or bradykinin produces thermal hypersensitivity that can be attenuated by pharmacological inhibition of Src. Additionally, complete Freund's Adjuvant (CFA)-induced inflammatory hypersensitivity could also be attenuated by local Src kinase inhibition.
conclusionsOur data demonstrate that Src phosphorylation is critical for PKC-mediated sensitization of TRPV1. Further, in a model of inflammatory pain, CFA, Src kinase inhibition could reduce thermal hypersensitivity. Targeting of Src kinase may have analgesic benefits in inflammatory pain conditions. SIGNIFICANCE: Src kinase-mediated phosphorylation of TRPV1 is a critical regulator of the PKC-induced sensitization induced by multiple inflammatory mediators. This suggest a new regulatory mechanism governing TRPV1 function and a potential therapeutic target for inflammatory type pain, including cancer pain where Src antagonists are currently utilized.
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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 Socratic graph.