Targeting sensory neuron GPCRs for peripheral neuropathic pain

Ankit Uniyal, Vinod Tiwari, Takashi Tsukamoto, Xinzhong Dong, Yun Guan, Srinivasa N. Raja

Research output: Contribution to journalReview articlepeer-review

Abstract

Despite the high prevalence of peripheral neuropathic pain (NP) conditions and significant progress in understanding its underlying mechanisms, the management of peripheral NP remains inadequate. Existing pharmacotherapies for NP act primarily on the central nervous system (CNS) and are often associated with CNS-related adverse effects, limiting their clinical effectiveness. Mounting preclinical evidence indicates that reducing the heightened activity in primary sensory neurons by targeting G-protein-coupled receptors (GPCRs), without activating these receptors in the CNS, relieves pain without central adverse effects. In this review, we focus on recent advancements in GPCR-mediated peripheral pain relief and discuss strategies to advance the development of more effective and safer therapies for peripheral NP by shifting from traditional CNS modulatory approaches toward selective targeting of GPCRs on primary sensory neurons.

Original languageEnglish (US)
Pages (from-to)1009-1027
Number of pages19
JournalTrends in Pharmacological Sciences
Volume44
Issue number12
DOIs
StatePublished - Dec 2023

Keywords

  • G-protein-coupled receptors
  • drug discovery
  • neuropathic pain
  • peripheral nervous system
  • primary sensory neurons
  • spontaneous discharge

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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