CXCL10 and CXCR3 in the Trigeminal Ganglion Contribute to Trigeminal Neuropathic Pain in Mice

• Published in: Journal of pain research Vol. 14; pp. 41 - 51
• Main Authors: Ju, Yuan-Yuan, Jiang, Ming, Xu, Feifei, Wang, Dongqin, Ding, Bixiao, Ma, Ling-Jie, Wu, Hao
• Format: Journal Article
• Language: English
• Published: New Zealand Taylor & Francis Ltd 2021; Dove; Dove Medical Press
• Subjects: Antibodies; Behavior; Chemokines; cxcl10; cxcr3; Inflammation; Kinases; mice; neuropathic pain; Original Research; Pain; Polymerase chain reaction; Proteins; Spinal cord; Surgery; trigeminal ganglion; United States > US; trigeminal ganglion; CXCL10; neuropathic pain; mice; CXCR3
• ISSN: 1178-7090; 1178-7090
• DOI: 10.2147/JPR.S288292

Trigeminal neuropathic pain is very common clinically, but effective treatments are lacking. Chemokines and their receptors have been implicated in the pathogenesis of chronic pain. This study explored the role of the chemokine CXCL10 and its receptor, CXCR3, in trigeminal neuropathic pain in mice. Trigeminal neuropathic pain was established by partial infraorbital nerve ligation (pIONL) in wild-type and mice. Facial mechanical allodynia was evaluated by behavioral testing. A lentivirus containing shRNA (LV- shRNA) was microinjected into the trigeminal ganglion (TG) to knock down expression. Quantitative polymerase chain reaction assays and immunofluorescence staining were used to examine mRNA expression and protein distribution. Western blotting was performed to examine activation of extracellular signal-regulated kinase (ERK) and AKT in the TG. Intra-TG injection of an AKT inhibitor was performed to examine the role of AKT in trigeminal neuropathic pain. pIONL induced persistent trigeminal neuropathic pain, which was alleviated in mice. Intra-TG injection of LV- shRNA attenuated pIONL-induced mechanical allodynia. Furthermore, pIONL increased the expression of CXCR3 and its major ligand, CXCL10, in TG neurons. Intra-TG injection of CXCL10 induced pain hypersensitivity in wild-type mice but not in mice. CXCL10 also induced activation of ERK and AKT in the TG of wild-type mice. Finally, pIONL-induced activation of ERK and AKT was reduced in mice. Intra-TG injection of the AKT inhibitor alleviated pIONL-induced mechanical allodynia in WT mice but not in mice. CXCL10 acts on CXCR3 to induce ERK and AKT activation in TG neurons and contributes to the maintenance of trigeminal neuropathic pain.