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Sensitization of small-diameter sensory neurons is controlled by TRPV1 and TRPA1 association.


ABSTRACT: Unique features of sensory neuron subtypes are manifest by their distinct physiological and pathophysiological functions. Using patch-clamp electrophysiology, Ca2+ imaging, calcitonin gene-related peptide release assay from tissues, protein biochemistry approaches, and behavioral physiology on pain models, this study demonstrates the diversity of sensory neuron pathophysiology is due in part to subtype-dependent sensitization of TRPV1 and TRPA1. Differential sensitization is influenced by distinct expression of inflammatory mediators, such as prostaglandin E2 (PGE2), bradykinin (BK), and nerve growth factor (NGF) as well as multiple kinases, including protein kinase A (PKA) and C (PKC). However, the co-expression and interaction of TRPA1 with TRPV1 proved to be the most critical for differential sensitization of sensory neurons. We identified N- and C-terminal domains on TRPV1 responsible for TRPA1-TRPV1 (A1-V1) complex formation. Ablation of A1-V1 complex with dominant-negative peptides against these domains substantially reduced the sensitization of TRPA1, as well as BK- and CFA-induced hypersensitivity. These data indicate that often occurring TRP channel complexes regulate diversity in neuronal sensitization and may provide a therapeutic target for many neuroinflammatory pain conditions.

SUBMITTER: Patil MJ 

PROVIDER: S-EPMC7539696 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Sensitization of small-diameter sensory neurons is controlled by TRPV1 and TRPA1 association.

Patil Mayur J MJ   Salas Margaux M   Bialuhin Siarhei S   Boyd Jacob T JT   Jeske Nathaniel A NA   Akopian Armen N AN  

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20191121 1


Unique features of sensory neuron subtypes are manifest by their distinct physiological and pathophysiological functions. Using patch-clamp electrophysiology, Ca<sup>2+</sup> imaging, calcitonin gene-related peptide release assay from tissues, protein biochemistry approaches, and behavioral physiology on pain models, this study demonstrates the diversity of sensory neuron pathophysiology is due in part to subtype-dependent sensitization of TRPV1 and TRPA1. Differential sensitization is influence  ...[more]

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