Work

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

Year: 2024

Type: article

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-Na v 1.8 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 Na v 1.7 expression, thus attenuating chronic mechanical allodynia.

Source: iScience

DOI: 10.1016/j.isci.2024.110955

Authors: Shih-Ping Dai, Chun-Chieh Yang, Yin Chin, Wei-Hsin Sun

Institutions: National Yang Ming Chiao Tung University, Academia Sinica

Language: English

Topic: Pain Mechanisms and Treatments

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,150