I am a
Home I AM A Search Login

Papers of the Week


Papers: 6 May 2023 - 12 May 2023

RESEARCH TYPE:
Basic Science


Animal Studies, Genetics, Molecular/Cellular, Neurobiology, Pharmacology/Drug Development

PAIN TYPE:
Neuropathic Pain


2023 Apr 27


Neuron


37146610

Editor's Pick

Tiam1 coordinates synaptic structural and functional plasticity underpinning the pathophysiology of neuropathic pain.

Authors

Li L, Ru Q, Lu Y, Fang X, Chen G, Saifullah AB, Yao C, Tolias KF

Abstract

Neuropathic pain is a common, debilitating chronic pain condition caused by damage or a disease affecting the somatosensory nervous system. Understanding the pathophysiological mechanisms underlying neuropathic pain is critical for developing new therapeutic strategies to treat chronic pain effectively. Tiam1 is a Rac1 guanine nucleotide exchange factor (GEF) that promotes dendritic and synaptic growth during hippocampal development by inducing actin cytoskeletal remodeling. Here, using multiple neuropathic pain animal models, we show that Tiam1 coordinates synaptic structural and functional plasticity in the spinal dorsal horn via actin cytoskeleton reorganization and synaptic NMDAR stabilization and that these actions are essential for the initiation, transition, and maintenance of neuropathic pain. Furthermore, an antisense oligonucleotides (ASO) targeting spinal Tiam1 persistently alleviate neuropathic pain sensitivity. Our findings suggest that Tiam1-coordinated synaptic functional and structural plasticity underlies the pathophysiology of neuropathic pain and that intervention of Tiam1-mediated maladaptive synaptic plasticity has long-lasting consequences in neuropathic pain management.