Receptors in Endosomes Mediate Chronic Pain Associated with Trauma and Stress: Non-Opioid Targets for Pain

Abstract

The grant seeks to determine whether G protein-coupled receptors (GPCRs) in endosomes, rather than at the plasma membrane, are mediators and therapeutic targets for chronic pain. Aim 1 examines whether GPCRs in endosomes control activity of ion channels and expression of genes that induce sustained neuronal excitation. Aim 2 determines whether endosomally-targeted antagonists inhibit channel activity, gene expression and hyperexcitability of neurons. Aim 3 evaluates the therapeutic potential of endosomally-targeted GPCR antagonists in trauma- and stress-induced pain relevant to militarypersonnel. Progress has been made in all aims. Neuropeptides (substance P, calcitonin gene-related peptide) and proteases(trypsin) stimulated GPCR endocytosis and evoked sustained signals and hyperexcitability in pain-sensing neurons. Dynamin and clathrin inhibitors suppressed endocytosis, signaling and hyperexcitability.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2020
Accession Number
AD1118513

Entities

People

  • Nigel W Bunnett

Organizations

  • New York University

Tags

DTIC Thesaurus Topics

  • Cells
  • Chemical Synthesis
  • Chemistry
  • Health Services
  • Medical Personnel
  • Pain
  • Proteins

Fields of Study

  • Biology
  • Chemistry

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Molecular and Cellular Biochemistry
  • Neurotrauma and Rehabilitation Medicine.