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

Purpose: 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. Materials and Methods: Trigeminal neuropathic pain was established by partial infraorbital nerve ligation (pIONL) in wild-type and Cxcr3^−/− mice. Facial mechanical allodynia was evaluated by behavioral testing. A lentivirus containing Cxcr3 shRNA (LV-Cxcr3 shRNA) was microinjected into the trigeminal ganglion (TG) to knock down Cxcr3 expression. Quantitative polymerase chain reaction assays and immunofluorescence staining were used to examine Cxcl10/Cxcr3 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. Results: pIONL induced persistent trigeminal neuropathic pain, which was alleviated in Cxcr3^−/− mice. Intra-TG injection of LV-Cxcr3 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 Cxcr3^−/− 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 Cxcr3^−/− mice. Intra-TG injection of the AKT inhibitor alleviated pIONL-induced mechanical allodynia in WT mice but not in Cxcr3^−/− mice. Conclusion: CXCL10 acts on CXCR3 to induce ERK and AKT activation in TG neurons and contributes to the maintenance of trigeminal neuropathic pain. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Pain Research is the property of Dove Medical Press Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)