PERIPHERAL SOMATOSTATIN CONTROLS INFLAMMATORY PAIN

描述：(改编自《调查者摘要》) 该提案的总体目标是确定外周生长抑素 (SST)受体激活在控制伤害性感受器兴奋性方面起着关键作用。 减少外周敏感化，促进镇痛。SST，一种被发现的多肽 在初级传入，或其长期持续的激动剂奥曲肽，已被证明 防止外周敏感化。伤害性感受器的外周敏化是一种 不仅是导致外周原发性痛觉过敏的关键因素，而且 也有助于中枢敏感化。该提案探讨了如何使用 外周应用SST激动剂减轻炎症外周致敏作用 疼痛。该假说认为，外周SST受体在 调节正常和发炎皮肤的伤害性感受器敏化。我们的目标是 为了表明1)SST受体位于外周传入神经上，并在 炎症；2)外周SST受体激活减少伤害性反应 炎症时伤害性感受器的反应和敏化；3)外周 SST受体激活抑制正常和大鼠伤害性行为反应 4)SST受体具有紧张性抑制作用。 外周伤害性感受器；5)SST激动剂通过非阿片类机制起作用；6) SST激动剂外周给药不会产生神经毒性； 7)内源性SST可被释放，帮助身体应对炎性疼痛。 初步数据表明，SST2a受体定位于伤害性感受器。 老鼠身上无毛的皮肤。奥曲肽对上述受体的激活 阿司匹林体外减轻缓激肽对伤害性感受器的敏化作用 皮肤神经准备和足底注射奥曲肽减毒药 福尔马林和完全弗洛因德的佐剂诱导的伤害性感受器行为。这个 初步数据表明，海温对海温具有紧张性抑制作用 外周伤害性感受器和内源性SST被释放以帮助身体 应对炎症性疼痛。外周SST受体提供新的靶点 伤害性感受器的调制，可能是进一步发展的目标 非阿片类药物治疗有助于减轻疼痛和长期有害 伴随炎症而来的变化。

DESCRIPTION: (Adapted from the Investigator's Abstract) The overall goal of this proposal is to determine that peripheral somatostatin (SST) receptor activation is critical in controlling nociceptor excitability, reducing peripheral sensitization and promoting analgesia. SST, a peptide found in primary afferents, or its long lasting agonist Octreotide, has been shown to prevent peripheral sensitization. Peripheral sensitization of nociceptors is a key element that not only underlies primary hyperalgesia in the peripheral but also contributes to central sensitization. The proposal explores the use of an SST agonist in the periphery to reduce peripheral sensitization in inflammatory pain. The hypothesis is that peripheral SST receptors play a critical role in modulating nociceptor sensitization in normal and inflamed skin. The aims are to show that 1) SST receptors are on peripheral afferents and increase during inflammation; 2) peripheral SST receptor activation reduces the nociceptive responses and sensitization of nociceptors during inflammation; 3) peripheral SST receptor activation inhibits nociceptive behavioral responses in normal and inflamed animals; 4) SST receptors exert a tonic inhibitory influence over peripheral nociceptors; 5) SST agonists acts through non-opioid mechanisms; 6) that peripheral administration of SST agonists does not produce neurotoxicity; 7) endogenous SST can be released to help the body cope with inflammatory pain. Preliminary data suggest that SST2a receptors are localized on nociceptors in the glabrous skin in the rat. Activation of these receptors with Octreotide attenuates bradykinin-induced sensitization of nociceptors using an in vitro skin-nerve preparation and intraplantar injection of Octreotide attenuates formalin- and complete Freund's adjuvant-inducted nociceptor behaviors. The preliminary data suggests that SST exerts a tonic inhibitory control over peripheral nociceptors and that endogenous SST is released to help the body cope with inflammatory pain. Peripheral SST receptors offer novel targets for nociceptor modulation and are likely targets for further development of non-opioid therapies to aid in reducing the pain and long-term deleterious changes that can accompany inflammation.