TLR8 in the Trigeminal Ganglion Contributes to the Maintenance of Trigeminal Neuropathic Pain in Mice
Lin-Xia Zhao 1,2 • Ming Jiang 2 • Xue-Qiang Bai 1 • De-Li Cao 2 • Xiao-Bo Wu 2 • Jing Zhang 2 • Jian-Shuang Guo 2 • Tong-Tong Chen 1 • Juan Wang 1 • Hao Wu 3 • Yong-Jing Gao 2,4 • Zhi-Jun Zhang 1,2
1 Department of Human Anatomy, School of Medicine, Nantong University, Nantong 226001, China
2 Institute of Pain Medicine, Institute of Nautical Medicine, Nantong University, Nantong 226019, China
3 Department of Otolaryngology Head Neck Surgery, The Affiliated Hospital of Nantong University, Nantong 226001, China
4 Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
Abstract
Trigeminal neuropathic pain (TNP) is a significant health problem but the involved mechanism has not been completely elucidated. Toll-like receptors (TLRs) have recently been demonstrated to be expressed in the dorsal root ganglion and involved in chronic pain. Here, we show that TLR8 was persistently increased in the trigeminal ganglion (TG) neurons in model of TNP induced by partial infraorbital nerve ligation (pIONL). In addition, deletion or knockdown of Tlr8 in the TG attenuated pIONL-induced mechanical allodynia, reduced the activation of ERK and p38-MAPK, and decreased the expression of pro-inflammatory cytokines in the TG. Furthermore, intra-TG injection of the TLR8 agonist VTX-2337 induced pain hypersensitivity. VTX-2337 also increased the intracellular Ca2+ concentration, induced the activation of ERK and p38, and increased the expression of pro-inflammatory cytokines in the TG. These data indicate that TLR8 contributes to the maintenance of TNP through increasing MAPK-mediated neuroinflammation. Targeting TLR8 signaling may be effective for the treatment of TNP.
Keywords
TLR8 ; ERK; p38 ; Pro-inflammatory cytokine; Trigeminal ganglion ; Trigeminal neuropathic pain; Mouse
