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iScience

IF: 4.6
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TDAG8-mediated distinct signaling pathways modulate the early and late phases of neuropathic pain

Published:13 September 2024 DOI: 10.1016/j.isci.2024.110955
Shih-Ping Dai , Chun-Chieh Yang , Yin Chin , Wei-Hsin Sun

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.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
5-(4-Chlorophenyl)-furan-2-carboxylic acid 3,5
-dimethoxyphenylamide
944261-79-4 C19H16ClNO4 150 suppliers $37.00-$2445.00
5-(4-Chlorophenyl)-furan-2-carboxylic acid 3,5
-dimethoxyphenylamide
944261-79-4 C19H16ClNO4 150 suppliers $37.00-$2445.00
5-(4-Chlorophenyl)-furan-2-carboxylic acid 3,5
-dimethoxyphenylamide
944261-79-4 C19H16ClNO4 150 suppliers $37.00-$2445.00
5-(4-Chlorophenyl)-furan-2-carboxylic acid 3,5
-dimethoxyphenylamide
944261-79-4 C19H16ClNO4 150 suppliers $37.00-$2445.00

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