Satellite glial cell P2Y12 receptor in the trigeminal ganglion is involved in lingual neuropathic pain mechanisms in ratsReportar como inadecuado




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Molecular Pain

, 8:23

First Online: 30 March 2012Received: 13 October 2011Accepted: 30 March 2012

Abstract

BackgroundIt 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.

ResultsThe 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.

ConclusionsThe 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.

KeywordsNeuron-Glia interactions Lingual nerve injury Mechanical allodynia Heat hyperalgesia Purinergic receptor AbbreviationsP2Y12RP2Y12 receptor

P2Y1RP2Y1 receptor

P2Y13RP2Y13 receptor

SGCsatellite glial cell

GFAPglial fibrillary acidic protein

TGtrigeminal ganglion

LNClingual nerve crush

IRimmunoreactive

NeuNneuronal nuclei

ATPadenosine triphosphate

V1ophthalmic

V2maxillary

V3mandibular

MRS23952,2-dimethyl-propionic acid 3 - 2-chloro-6-methylaminopurin-9-yl - 2 - 2,2-dimethyl-propionyloxymethyl - propylester

2-MeSADP2-Methylthio adenosine5-diphosphate trisodium salt hydrate

DRGdorsal root ganglion

PBSphosphate-buffered saline

NGSnormal goat serum

ANOVAanalysis of variance.

Electronic supplementary materialThe online version of this article doi:10.1186-1744-8069-8-23 contains supplementary material, which is available to authorized users.

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Autor: Ayano Katagiri - Masamichi Shinoda - Kuniya Honda - Akira Toyofuku - Barry J Sessle - Koichi Iwata

Fuente: https://link.springer.com/







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