title: Satellite glial cell P2Y12 receptor in the trigeminal ganglion is involved in lingual neuropathic pain mechanisms in rats.
abstract: BACKGROUND
  It has been reported that the P2Y12 receptor (P2Y12R) is involved in satellite glial cells (SGCs) activation, indicating that P2Y12R expressed in SGCs may play functional roles in orofacial neuropathic pain mechanisms. However, the involvement of P2Y12R in orofacial neuropathic pain mechanisms is still unknown. We therefore studied the reflex to noxious mechanical or heat stimulation of the tongue, P2Y12R and glial fibrillary acidic protein (GFAP) immunohistochemistries in the trigeminal ganglion (TG) in a rat model of unilateral lingual nerve crush (LNC) to evaluate role of P2Y12R in SGC in lingual neuropathic pain.
  
  
  RESULTS
  The head-withdrawal reflex thresholds to mechanical and heat stimulation of the lateral tongue were significantly decreased in LNC-rats compared to sham-rats. These nocifensive effects were apparent on day 1 after LNC and lasted for 17 days. On days 3, 9, 15 and 21 after LNC, the mean relative number of TG neurons encircled with GFAP-immunoreactive (IR) cells significantly increased in the ophthalmic, maxillary and mandibular branch regions of TG. On day 3 after LNC, P2Y12R expression occurred in GFAP-IR cells but not neuronal nuclei (NeuN)-IR cells (i.e. neurons) in TG. After 3 days of successive administration of the P2Y12R antagonist MRS2395 into TG in LNC-rats, the mean relative number of TG neurons encircled with GFAP-IR cells was significantly decreased coincident with a significant reversal of the lowered head-withdrawal reflex thresholds to mechanical and heat stimulation of the tongue compared to vehicle-injected rats. Furthermore, after 3 days of successive administration of the P2YR agonist 2-MeSADP into the TG in naïve rats, the mean relative number of TG neurons encircled with GFAP-IR cells was significantly increased and head-withdrawal reflex thresholds to mechanical and heat stimulation of the tongue were significantly decreased in a dose-dependent manner compared to vehicle-injected rats.
  
  
  CONCLUSIONS
  The present findings provide the first evidence that the activation of P2Y12R in SGCs of TG following lingual nerve injury is involved in the enhancement of TG neuron activity and nocifensive reflex behavior, resulting in neuropathic pain in the tongue.
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, Tokyo, Japan.
authors.forename: Ayano
authors.initials: A
authors.lastname: Katagiri
authors.forename: Masamichi
authors.initials: M
authors.lastname: Shinoda
authors.forename: Kuniya
authors.initials: K
authors.lastname: Honda
authors.forename: Akira
authors.initials: A
authors.lastname: Toyofuku
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Sessle
authors.forename: Koichi
authors.initials: K
authors.lastname: Iwata
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D061222:Lingual Nerve Injuries / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009437:Neuralgia / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1 / Q000378:metabolism; D058925:Receptors, Purinergic P2Y12 / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000378:metabolism*
chemical_list: D034961:Antigens, Nuclear; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C486690:P2ry13 protein, rat; C546339:Rbfox3 protein, rat; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12