PERIPHERAL SOMATOSTATIN CONTROLS INFLAMMATORY PAIN

描述：（改编自研究者摘要） 这项建议的总体目标是确定外周生长抑素 (SST)受体活化在控制伤害感受器兴奋性中是关键的， 减少外周致敏和促进镇痛。SST，发现的肽 在初级传入，或其长效激动剂奥曲肽，已被证明， 防止外周致敏。伤害感受器的外周敏化是一种 不仅是外周原发性痛觉过敏的基础， 也有助于中枢敏感化。该提案探讨了使用 外周中的SST激动剂以减少炎性细胞中的外周致敏作用 痛苦假设是外周SST受体在以下过程中起关键作用： 调节正常和发炎皮肤中的伤害感受器敏化。其宗旨是 表明1）SST受体位于外周传入神经上，并在 2）外周SST受体激活减少了伤害性炎症; 炎症过程中伤害感受器的反应和敏化; 3）外周 SST受体激活抑制正常人和正常人的伤害性行为反应， 4）SST受体对炎症动物产生紧张性抑制作用， 外周伤害感受器; 5）SST激动剂通过非阿片机制起作用; 6） 外周给予SST激动剂不会产生神经毒性; 7)内源性SST可以被释放以帮助身体应对炎性疼痛。 初步数据表明，SST 2a受体定位于伤害感受器上， 老鼠光滑的皮肤。奥曲肽激活这些受体 使用体外方法减弱缓激肽诱导的伤害感受器敏化 皮肤-神经制备和足底注射奥曲肽减弱 福尔马林-和完全弗氏镇痛剂诱导的伤害感受器行为。的 初步的数据表明，SST发挥紧张性抑制控制， 外周伤害感受器和内源性SST释放，以帮助身体 应对炎性疼痛。外周SST受体提供了新的靶点， 伤害感受器调制，并可能是进一步发展的目标， 非阿片类药物治疗，以帮助减少疼痛和长期有害的 可能伴随炎症的变化。

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.