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生长抑素sst4受体选择性激动剂J-2156在急慢性疼痛模型中的镇痛作用

Analgesic effects of the somatostatin sst4 receptor selective agonist J-2156 in acute and chronic pain models.

作者信息

Sándor Katalin, Elekes Krisztián, Szabó Arpád, Pintér Erika, Engström Mia, Wurster Siegfried, Szolcsányi János, Helyes Zsuzsanna

机构信息

Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Pécs-7624 Szigeti str. 12, Hungary.

出版信息

Eur J Pharmacol. 2006 Jun 6;539(1-2):71-5. doi: 10.1016/j.ejphar.2006.03.082. Epub 2006 Apr 18.

Abstract

Somatostatin released from capsaicin-sensitive afferents exerts systemic anti-nociceptive actions, presumably via somatostatin receptor subtype 4 (sst4). In the present study, the antinociceptive effects of a novel somatostatin sst4 receptor selective peptidomimetic compound, J-2156 (1-100 microg/kg i.p.), were examined. J-2156 inhibited nocifensive behaviour of mice in the second phase of the formalin test. Adjuvant-evoked chronic inflammatory mechanical allodynia was decreased in rats treated with J-2156 for 21 days. Sciatic nerve ligation-induced neuropathic mechanical hyperalgesia was inhibited by J-2156 on the seventh postoperative day. Results obtained using this highly selective agonist suggest that somatostatin sst4 receptors represent a promising target for new perspectives in analgesic therapy.

摘要

从辣椒素敏感传入神经释放的生长抑素发挥全身抗伤害感受作用,推测是通过生长抑素受体亚型4(sst4)实现的。在本研究中,检测了一种新型生长抑素sst4受体选择性拟肽化合物J-2156(腹腔注射1-100微克/千克)的抗伤害感受作用。J-2156抑制了福尔马林试验第二阶段小鼠的伤害防御行为。用J-2156治疗21天的大鼠,佐剂诱发的慢性炎性机械性异常性疼痛减轻。坐骨神经结扎诱导的神经性机械性痛觉过敏在术后第7天被J-2156抑制。使用这种高选择性激动剂获得的结果表明,生长抑素sst4受体是镇痛治疗新视角的一个有前景的靶点。

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