title: Elevated Fractalkine (CX3CL1) Levels in the Trigeminal Ganglion Mechanically Sensitize Temporalis Muscle Nociceptors.
abstract: It has been proposed that after nerve injury or tissue inflammation, fractalkine (CX3CL1) released from dorsal root ganglion neurons acts on satellite glial cells (SGCs) through CX3C receptor 1 (CX3CR1) to induce neuroplastic changes. The existence and importance of fractalkine/CX3CR1 signaling in the trigeminal ganglia has not yet been clarified. This study investigated (1) whether trigeminal ganglion neurons that innervate temporalis muscle and their associated SGCs contain fractalkine and/or express CX3CR1, (2) if intraganglionic injection of fractalkine increases the mechanical sensitivity of temporalis muscle afferent fibers, (3) whether complete Freund's adjuvant (CFA)-induced inflammation of the temporalis muscle alters the expression of fractalkine or its receptor in the trigeminal ganglion, and (4) if intraganglionic administration of CX3CR1 antibodies alters afferent mechanical sensitivity. Immunohistochemistry and in vivo electrophysiological recordings in male and female rats were used to address these questions. It was found that ∼50 % of temporalis ganglion neurons and ∼25 % of their associated SGCs express CX3CR1, while only neurons expressed fractalkine. Temporalis muscle inflammation increased the expression of fractalkine, but only in male rats. Intraganglionic injection of fractalkine (25 g/ml; 3 μl) induced prolonged afferent mechanical sensitization. Intraganglionic injection of CX3CR1 antibody increased afferent mechanical threshold, but this effect was greater in controls than in rats with CFA-induced muscle inflammation. These findings raise the possibility that basal fractalkine signalling within the trigeminal ganglion plays an important role in mechanical sensitivity of masticatory muscle sensory afferent fibers and that inhibition of CX3CR1 signaling within the trigeminal ganglia may induce analgesia through a peripheral mechanism.
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada.|SMI®, Department of Health Science and Technology, The Faculty of Medicine, Aalborg University, Fredrik Bajers Vej 7-D3, 9220, Aalborg East, Denmark.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Cairns
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada.
authors.forename: Melissa
authors.initials: M
authors.lastname: O'Brien
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada.
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Dong
authors.affiliation: SMI®, Department of Health Science and Technology, The Faculty of Medicine, Aalborg University, Fredrik Bajers Vej 7-D3, 9220, Aalborg East, Denmark. gazerani@hst.aau.dk.
authors.forename: Parisa
authors.initials: P
authors.lastname: Gazerani
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000073883:CX3C Chemokine Receptor 1 / Q000378:metabolism; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D005260:Female; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000906:Antibodies; D000073883:CX3C Chemokine Receptor 1; C516305:CX3CR1 protein, rat; D054428:Chemokine CX3CL1
keywords: Fractalkine; Myositis; Sensory afferent fibers; Temporalis muscle; Trigeminal ganglion