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Papers of the Week

Papers: 18 Nov 2023 - 24 Nov 2023

2023 Dec

Trends Pharmacol Sci




Targeting sensory neuron GPCRs for peripheral neuropathic pain.


Uniyal A, Tiwari V, Tsukamoto T, Dong X, Guan Y, Raja SN


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.