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

Mayur J. Patil, Margaux Salas, Siarhei Bialuhin, Jacob T. Boyd, Nathaniel A. Jeske, Armen N. Akopian

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)287-302
Number of pages16
JournalFASEB Journal
Volume34
Issue number1
DOIs
StatePublished - Jan 1 2020

Keywords

  • TRPA1
  • TRPV1
  • pain
  • sensitization
  • sensory neurons

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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