Chemokine-mediated Modulaton of Opioid-induced Pain

吗啡目前是治疗剧烈疼痛和 慢性疼痛状态。长期使用鸦片类药物通常会产生对永远- 增加剂量以维持止痛，也称为止痛耐受。这个 与止痛耐受有关的机制被认为是由于吗啡- 引起细胞适应，产生高度疼痛或痛觉过敏的状态。 最近的研究表明，通过Mu-阿片受体作用的阿片剂可以诱导 趋化因子及其受体的表达。我们实验室以前的工作 证明这些相同的趋化因子/受体中的一些已经被证明发挥作用 在慢性疼痛状态中的中心作用。以发现证据表明 慢性吗啡治疗、趋化因子信号转导与止痛耐受 阿片类药物诱导的趋化因子信号传导是止痛耐受的中心假说。 我们的具体目标包括1)描述细胞/信号的年表 与阿片剂诱导的痛觉过敏相关的事件2)探索 吗啡诱导背根神经节趋化因子/受体表达 研究慢性吗啡治疗的细胞/分子机制 增强趋化因子信号。更好地了解这些趋化因子/受体- 中介事件可以为设计代理提供必要的框架 对抗有害的阿片剂诱导的细胞适应，有效地减少 止痛耐受性。

Morphine currently represents the best option for the management of severe pain and chronic pain states. Prolonged use of opiates often produces the need for ever- increasing doses to maintain pain relief, also known as analgesic tolerance. The mechanisms associated with analgesic tolerance are thought to due to morphine- induced cellular adaptations that produce a state of heightened pain or hyperalgesia. Recent studies suggest that opiates acting via the mu-opioid receptor can induce expression of chemokines and their receptors. Previous works from our laboratory demonstrate that some of these same chemokines/receptors have been shown to play central roles in chronic pain states. To uncover evidence of possible links between chronic morophine treatment, chemokine signaling and analgesic tolerance, we propose the hypothesis that opiate-induced chemokine signaling is central to analgesic tolerance. Our specific aims include 1) a characterization of the chronology of cellular/signaling events associated with opiate-induced hyperalgesia 2) explore mechanisms by which morphine induces chemokine/receptor expression in the dorsal root ganglia and 3) examine the cellular/molecular mechanisms by which chronic morphine treatment enhances chemokine signaling. Better understanding of these chemokine/receptor- mediated events may provide the necessary framework for the design of agents that counteract deleterious opiate-induced cellular adaptations and effectively reduce analgesic tolerance.