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Phenotypic change in trigeminal ganglion neurons associated with satellite cell activation via extracellular signal‐regulated kinase phosphorylation is involved in lingual neuropathic pain
Author(s) -
Mikuzuki Lou,
Saito Hiroto,
Katagiri Ayano,
Okada Shinji,
Sugawara Shiori,
Kubo Asako,
Ohara Kinuyo,
Lee Jun,
Toyofuku Akira,
Iwata Koichi
Publication year - 2017
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13667
Subject(s) - calcitonin gene related peptide , trigeminal ganglion , neuropathic pain , mapk/erk pathway , lingual nerve , kinase , medicine , endocrinology , dorsal root ganglion , glial fibrillary acidic protein , chemistry , neuropeptide , neuroscience , microbiology and biotechnology , pharmacology , biology , receptor , pathology , spinal cord , immunohistochemistry , tongue , sensory system
Iatrogenic trigeminal nerve injuries remain a common and complex clinical problem. Satellite glial cell ( SGC ) activation, associated phosphorylation of extracellular signal‐regulated kinase ( ERK ), and neuropeptide expression in the trigeminal ganglion ( TG ) are known to be involved in trigeminal neuropathic pain related to trigeminal nerve injury. However, the involvement of these molecules in orofacial neuropathic pain mechanisms is still unknown. Phosphorylation of ERK 1/2 in lingual nerve crush ( LNC ) rats was observed in SGC s. To evaluate the role of neuron– SGC interactions under neuropathic pain, calcitonin gene‐related peptide ( CGRP )‐immunoreactive ( IR ), phosphorylated ERK 1/2 ( pERK 1/2)‐ IR and glial fibrillary acidic protein ( GFAP )‐ IR cells in the TG were studied in LNC rats. The number of CGRP ‐ IR neurons and neurons encircled with pERK 1/2‐ IR SGC s was significantly larger in LNC rats compared with sham rats. The percentage of large‐sized CGRP ‐ IR neurons was significantly higher in LNC rats. The number of CGRP ‐ IR neurons, neurons encircled with pERK 1/2‐ IR SGC s, and neurons encircled with GFAP ‐ IR SGC s was decreased following CGRP receptor blocker CGRP 8‐37 or mitogen‐activated protein kinase/ ERK kinase 1 inhibitor PD 98059 administration into the TG after LNC . Reduced thresholds to mechanical and heat stimulation to the tongue in LNC rats were also significantly recovered following CGRP 8‐37 or PD 98059 administration. The present findings suggest that CGRP released from TG neurons activates SGC s through ERK 1/2 phosphorylation and TG neuronal activity is enhanced, resulting in the tongue hypersensitivity associated with lingual nerve injury. The phenotypic switching of large myelinated TG neurons expressing CGRP may account for the pathogenesis of tongue neuropathic pain.