Premium
GT 1b functions as a novel endogenous agonist of toll‐like receptor 2 inducing neuropathic pain
Author(s) -
Lim Hyoungsub,
Lee Jaesung,
You Byunghyun,
Oh Jae Hoon,
Mok Hyuck Jun,
Kim Yoo Sung,
Yoon BoEun,
Kim Byung Gon,
Back Seung Keun,
Park JongSang,
Kim Kwang Pyo,
Schnaar Ronald L,
Lee Sung Joong
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2019102214
Subject(s) - library science , toll , medicine , chemistry , medical education , neuroscience , psychology , computer science , immunology
Spinal cord microglia contribute to nerve injury‐induced neuropathic pain. We have previously demonstrated that toll‐like receptor 2 ( TLR 2) signaling is critical for nerve injury‐induced activation of spinal cord microglia, but the responsible endogenous TLR 2 agonist has not been identified. Here, we show that nerve injury‐induced upregulation of sialyltransferase St3gal2 in sensory neurons leads to an increase in expression of the sialylated glycosphingolipid, GT 1b. GT 1b ganglioside is axonally transported to the spinal cord dorsal horn and contributes to characteristics of neuropathic pain such as mechanical and thermal hypersensitivity. Spinal cord GT 1b functions as an TLR 2 agonist and induces proinflammatory microglia activation and central sensitization. Pharmacological inhibition of GT 1b synthesis attenuates nerve injury‐induced spinal cord microglia activation and pain hypersensitivity. Thus, the St3gal2 ‐ GT 1b‐ TLR 2 axis may offer a novel therapeutic target for the treatment of neuropathic pain.