2. Academic Validation
  3. T cell death-associated gene 8-mediated distinct signaling pathways modulate the early and late phases of neuropathic pain

T cell death-associated gene 8-mediated distinct signaling pathways modulate the early and late phases of neuropathic pain

  • iScience. 2024 Sep 13;27(10):110955. doi: 10.1016/j.isci.2024.110955.
Shih-Ping Dai 1,  Chun-Chieh Yang 1 2,  Yin Chin 1,  Wei-Hsin Sun 1 2
Affiliations

Affiliations

  • 1 Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • 2 Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan.
PMID: 39381739 DOI: 10.1016/j.isci.2024.110955
Abstract

Peripheral nerve injury alters the transduction of nociceptive signaling. The coordination of neurons, glia, and immune cells results in persistent pain and inflammation. T cell death-associated gene 8 (TDAG8), located at nociceptors and immune cells, is involved in inflammatory pain and arthritis-induced pain. Here, we employed TDAG8-deficient mice, pharmacological approaches, and calcium/sodium imaging to elucidate how TDAG8-mediated signaling modulates neuron activities in a mouse model of chronic constriction injury-induced neuropathic pain. We demonstrated that TDAG8 participated alone in mechanical allodynia induced by constriction injury. (1) TDAG8-Nav1.8 signaling in small-diameter isolectin B4-positive [IB4(+)] neurons initiates mechanical allodynia; it also modulated substance P release from IB4(-) neurons to facilitate the development of early mechanical allodynia. (2) TDAG8-mediated signaling increased medium-to large-diameter IB4(-) neuron activity to maintain late mechanical allodynia; it also modulated substance P release in soma to reduce satellite glial number and Nav1.7 expression, thus attenuating chronic mechanical allodynia.

Keywords

Molecular biology; Neuroscience.

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