Cold Suppresses Agonist-induced Activation of TRPV1

Chung, Man‐Kyo; Wang, S.

doi:10.1177/0022034511412074

Cited by 24 publications

(27 citation statements)

References 23 publications

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“…The rate of capsaicin-induced desensitization increases as temperature increase (44). In a TRPV1 mutant that shows limited heat-evoked activation (TRPV1 N628K/N652T/Y653T), desensitization of capsaicin-induced current is enhanced by the superimposed application of heat, suggesting that heat accelerates the rate of capsaicin-induced desensitization even with little preceding heat activation (22). Heat can enhance agonistinduced desensitization not only in heat-gated channels but also in cold-gated channels.…”

Section: Discussionmentioning

confidence: 99%

“…Cell Culture and Transfection-HEK293 cells were cultured and transfected using Lipofectamine 2000 (Invitrogen) as previously described (9,22). Plasmids containing cDNA encoding TRPV1 or TRPV1 mutants were co-transfected with cDNA encoding mCherry or GFP.…”

Section: Methodsmentioning

confidence: 99%

“…Whole Cell Patch Clamp-Whole cell voltage clamp techniques were performed as described previously (22). The recording pipettes (2-3 M⍀) were pulled from borosilicate glass using a P-97 (Sutter Instrument).…”

Section: Methodsmentioning

confidence: 99%

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Carboxyl-terminal Domain of Transient Receptor Potential Vanilloid 1 Contains Distinct Segments Differentially Involved in Capsaicin- and Heat-induced Desensitization

Joseph

Wang

Lee

et al. 2013

Journal of Biological Chemistry

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Background: Mechanisms of TRPV1 desensitization by heat are not fully understood. Results: Distinct segments of the TRPV1 carboxyl-terminal domain are differentially involved in capsaicin-and heat-induced desensitization. Conclusion: Capsaicin and heat desensitizes TRPV1 through a distinct structural basis. Significances: Selective enhancement of desensitization could be a novel strategy for suppressing heat hyperalgesia.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Carboxyl-terminal Domain of Transient Receptor Potential Vanilloid 1 Contains Distinct Segments Differentially Involved in Capsaicin- and Heat-induced Desensitization

Joseph

Wang

Lee

et al. 2013

Journal of Biological Chemistry

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“…Whole-cell voltage clamp techniques were performed as described previously 8, 34 . The recording pipettes (2–3 MΩ) were pulled from borosilicate glass using a P-97 (Sutter Instrument).…”

Section: Methodsmentioning

confidence: 99%

Peripheral Group I Metabotropic Glutamate Receptor Activation Leads to Muscle Mechanical Hyperalgesia Through TRPV1 Phosphorylation in the Rat

Chung

Lee

Joseph

et al. 2015

The Journal of Pain

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Elevated glutamate levels within injured muscle play important roles in muscle pain and hyperalgesia. In this study, we hypothesized that PKC-dependent TRPV1 phosphorylation contributes to the muscle mechanical hyperalgesia following activation of Group I metabotropic glutamate receptors (mGlu1/5). Mechanical hyperalgesia induced by dihydroxyphenylglycine (DHPG), an mGlu1/5 agonist, in the masseter muscle was attenuated by AMG9810, a specific TRPV1 antagonist. AMG9810 also suppressed mechanical hyperalgesia evoked by pharmacological activation of PKC. DHPG-induced mechanical hyperalgesia was suppressed by pretreatment with a decoy peptide that disrupted interactions between TRPV1 and A-kinase anchoring protein (AKAP), which facilitates phosphorylation of TRPV1. In dissociated trigeminal ganglia (TG), DHPG upregulated serine phosphorylation of TRPV1 (S800) during which DHPG-induced mechanical hyperalgesia was prominent. The TRPV1 phosphorylation at S800 was suppressed by a PKC inhibitor. Electrophysiological measurements in TG neurons demonstrated that TRPV1 sensitivity was enhanced by pretreatment with DHPG, and this was prevented by a PKC, but not by a PKA, inhibitor. These results suggest that mGlu1/5 activation in masseter afferents invoke phosphorylation of TRPV1 serine residues including S800, and that phosphorylation-induced sensitization of TRPV1 is involved in masseter mechanical hyperalgesia. These data support a role of TRPV1 as an integrator of glutamate receptor signaling in muscle nociceptors. PERSPECTIVE This article demonstrates that activation of mGlu1/5 leads to phosphorylation of a specific TRPV1 residue via PKC and AKAP150 in trigeminal sensory neurons, and that functional interactions between glutamate receptors and TRPV1 mediate mechanical hyperalgesia in the muscle tissue.

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“…Cold temperature slows down the kinetics of TRPV1 activation by capsaicin [74]. In addition, voltage-gated sodium channels, such as Nav1.7, are largely inactivated at cold temperature, which may reduce the conduction of action potentials [75].…”

Section: Functional and Histological Effectsmentioning

confidence: 99%

Use of Capsaicin to Treat Pain: Mechanistic and Therapeutic Considerations

Chung

Campbell

2016

Pharmaceuticals

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Capsaicin is the pungent ingredient of chili peppers and is approved as a topical treatment of neuropathic pain. The analgesia lasts for several months after a single treatment. Capsaicin selectively activates TRPV1, a Ca2+-permeable cationic ion channel that is enriched in the terminals of certain nociceptors. Activation is followed by a prolonged decreased response to noxious stimuli. Interest also exists in the use of injectable capsaicin as a treatment for focal pain conditions, such as arthritis and other musculoskeletal conditions. Recently injection of capsaicin showed therapeutic efficacy in patients with Morton’s neuroma, a painful foot condition associated with compression of one of the digital nerves. The relief of pain was associated with no change in tactile sensibility. Though injection evokes short term pain, the brief systemic exposure and potential to establish long term analgesia without other sensory changes creates an attractive clinical profile. Short-term and long-term effects arise from both functional and structural changes in nociceptive terminals. In this review, we discuss how local administration of capsaicin may induce ablation of nociceptive terminals and the clinical implications.

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Cold Suppresses Agonist-induced Activation of TRPV1

Abstract: A supplemental appendix to this article is published electronically only at http://jdr.sagepub.com/supplemental.

Cited by 24 publications

References 23 publications

Carboxyl-terminal Domain of Transient Receptor Potential Vanilloid 1 Contains Distinct Segments Differentially Involved in Capsaicin- and Heat-induced Desensitization

Carboxyl-terminal Domain of Transient Receptor Potential Vanilloid 1 Contains Distinct Segments Differentially Involved in Capsaicin- and Heat-induced Desensitization

Peripheral Group I Metabotropic Glutamate Receptor Activation Leads to Muscle Mechanical Hyperalgesia Through TRPV1 Phosphorylation in the Rat

Use of Capsaicin to Treat Pain: Mechanistic and Therapeutic Considerations

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