Satellite glial cell P2Y12 receptor in the trigeminal ganglion is involved in lingual neuropathic pain mechanisms in rats.
Satellite glial cell P2Y12 receptor in the trigeminal ganglion is involved in lingual neuropathic pain mechanisms in rats.
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DOI：
10.1186/1744-8069-8-23
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发表时间：
2012-03-30
期刊：
影响因子：
3.3
通讯作者：
Iwata K
中科院分区：
文献类型：
--
作者：
Katagiri A;Shinoda M;Honda K;Toyofuku A;Sessle BJ;Iwata K
P2 Y12受体（P2 Y12 R）参与了卫星胶质细胞（SGCs）的活化，提示SGCs表达的P2 Y12 R可能在口面神经病理性疼痛机制中发挥作用。然而，P2 Y12 R参与口面神经病理性疼痛机制仍然是未知的。因此，我们研究了对舌头的伤害性机械或热刺激的反射，P2 Y12 R和胶质细胞酸性蛋白（GFAP）在三叉神经节（TG）在单侧舌神经挤压（LNC）大鼠模型的化学反应，以评估P2 Y12 R在舌神经病理性疼痛中的作用。与假手术大鼠相比，LNC大鼠对机械和热刺激侧舌的缩头反射阈值显著降低。这些伤害性反应在LNC后第1天明显，并持续17天。LNC后3、9、15和21 d，TG眼、上颌和下颌分支区GFAP免疫反应阳性（IR）细胞环绕的TG神经元平均相对数量显著增加。在LNC后第3天，在TG中，P2 Y12 R表达发生在GFAP-IR细胞中，而不是神经元核（NeuN）-IR细胞（即神经元）中。在将P2 Y12 R拮抗剂MRS 2395连续施用到LNC大鼠的TG中3天后，与注射媒介物的大鼠相比，用GFAP-IR细胞包围的TG神经元的平均相对数量显著降低，这与降低的头部缩回反射阈值对舌的机械和热刺激的显著逆转一致。此外，在向未处理大鼠的TG中连续给予P2 YR激动剂2-MeSADP 3天后，与注射溶剂的大鼠相比，GFAP-IR细胞包围的TG神经元的平均相对数量显著增加，并且对舌的机械和热刺激的头回缩反射阈值以剂量依赖性方式显著降低。本研究结果首次证明舌神经损伤后TG SGCs中P2 Y12 R的激活参与了TG神经元活性的增强和伤害性反射行为，导致舌神经病理性疼痛。
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. 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. 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.
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影响因子：
4.7
作者：
Kushnir, Raya;Cherkas, Pavel S.;Hanani, Menachem
通讯作者：
Hanani, Menachem
DOI：
10.1523/jneurosci.3365-09.2009
发表时间：
2009-09-09
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Okada-Ogawa A;Suzuki I;Sessle BJ;Chiang CY;Salter MW;Dostrovsky JO;Tsuboi Y;Kondo M;Kitagawa J;Kobayashi A;Noma N;Imamura Y;Iwata K
通讯作者：
Iwata K
影响因子：
4
作者：
Ceruti, Stefania;Furnagalli, Marta;Abbracchio, Maria P.
通讯作者：
Abbracchio, Maria P.
影响因子：
2.5
作者：
Iwata, K;Imai, T;Hu, J
通讯作者：
Hu, J
影响因子：
7.4
作者：
BENNETT, GJ;XIE, YK
通讯作者：
XIE, YK