Characterization of the Visceral Antinociceptive Effect of Glial Glutamate Transporter GLT-1 Upregulation by Ceftriaxone.
Characterization of the Visceral Antinociceptive Effect of Glial Glutamate Transporter GLT-1 Upregulation by Ceftriaxone.
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DOI：
10.1155/2013/726891
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Stephens RL Jr
中科院分区：
文献类型：
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作者：
Roman K;Yang M;Stephens RL Jr
最近的研究表明，胶质细胞谷氨酸转运体-1（GLT-1）上调减弱内脏伤害性感受。本工作进一步表征了头孢曲松-（CTX-）介导的GLT-1上调对内脏痛觉过敏的影响。鞘内预处理与二氢红藻氨酸，选择性GLT-1拮抗剂，产生了一个逆转的抗伤害性反应，由CTX产生的膀胱扩张。由于囊内丙烯醛引起的膀胱扩张的痛觉过敏反应也被CTX治疗减弱，因为由于囊内丙烯醛增加了舔腹部区域的时间。通过环磷酰胺注射的膀胱炎症增强了对膀胱扩张的伤害性;给予CTX和伴随环磷酰胺的队列显示痛觉过敏反应降低。环磷酰胺诱导的膀胱痛觉过敏与腰骶脊髓膜部分中GluR 1 AMPA受体亚单位表达显著增加22%相关，而CTX联合给药可使其减弱。最后，在P9和P11结肠内给予芥子油（2%）引起的新生儿结肠损伤诱导的痛觉过敏被CTX减弱。这些研究表明，GLT-1上调（1）减弱由膀胱刺激/炎症或新生儿结肠损伤引起的痛觉过敏，（2）作用于脊髓部位，（3）可能通过减弱GluR 1膜运输产生抗伤害效应。这些发现支持进一步考虑这种FDA批准的药物治疗慢性盆腔疼痛综合征。
Recent studies demonstrate that glial glutamate transporter-1 (GLT-1) upregulation attenuates visceral nociception. The present work further characterized the effect of ceftriaxone- (CTX-) mediated GLT-1 upregulation on visceral hyperalgesia. Intrathecal pretreatment with dihydrokainate, a selective GLT-1 antagonist, produced a reversal of the antinociceptive response to bladder distension produced by CTX. The hyperalgesic response to urinary bladder distension caused by intravesicular acrolein was also attenuated by CTX treatment as was the enhanced time spent licking of abdominal area due to intravesicular acrolein. Bladder inflammation via cyclophosphamide injections enhanced the nociceptive to bladder distension; cohorts administered CTX and concomitant cyclophosphamide showed reduced hyperalgesic response. Cyclophosphamide-induced bladder hyperalgesia correlated with a significant 22% increase in GluR1 AMPA receptor subunit expression in the membrane fraction of the lumbosacral spinal cord, which was attenuated by CTX coadministration. Finally, neonatal colon insult-induced hyperalgesia caused by intracolonic mustard oil (2%) administration at P9 and P11 was attenuated by CTX. These studies suggest that GLT-1 upregulation (1) attenuates the hyperalgesia caused by bladder irritation/inflammation or by neonatal colonic insult, (2) acts at a spinal site, and (3) may produce antinociceptive effects by attenuating GluR1 membrane trafficking. These findings support further consideration of this FDA-approved drug to treat chronic pelvic pain syndromes.