DREAMing about arthritic pain
DREAMing about arthritic pain
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DOI：
10.1136/ard.2004.029942
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发表时间：
2004-11-01
影响因子：
27.4
通讯作者：
Penninger, JM
中科院分区：
文献类型：
--
作者：
Cheng, HYM;Penninger, JM
急性疼痛的经历具有重要的生物学目的：它提醒生物体注意环境危险，诱导行为反应，保护生物体免受进一步损害。相比之下，由神经系统的疾病状态和/或病理功能引起的慢性疼痛没有提供任何优势，并且可能使那些受折磨的人衰弱。尽管我们对疼痛机制的理解有了新的进展，但病理性疼痛的满意治疗仍无法达到目前的治疗策略。我们已经证明了在以前的研究梦缺陷小鼠的关键作用下游调节元件拮抗调节剂（DREAM）在调节疼痛敏感性在许多行为模型，包括急性和慢性神经性疼痛。DREAM是一种新型的脊髓神经元强啡肽原基因的钙结合转录抑制因子。通过药理学和生物化学分析表明，梦（-/-）小鼠表现出的疼痛行为明显减弱是由于内源性κ-阿片系统的激活增加。重要的是，DREAM的丧失也减轻了炎症性疼痛。因此，DREAM和DREAM通路构成了治疗关节炎慢性疼痛的新的治疗范例。
The experience of acute pain serves a crucial biological purpose: it alerts a living organism to environmental dangers, inducing behavioural responses which protect the organism from further damage. In contrast, chronic pain arising from disease states and/or pathological functioning of the nervous system offers no advantage and may be debilitating to those afflicted. Despite recent advances in our understanding of pain mechanisms, the satisfactory management of pathological pain eludes current treatment strategies. We have demonstrated in a previous study on dream deficient mice the pivotal role of downstream regulatory element antagonistic modulator (DREAM) in modulating pain sensitivity in a number of behavioural models, including acute and chronic neuropathic pain. DREAM is a novel calcium binding transcriptional repressor for the prodynorphin gene in spinal cord neurones. The marked attenuation in pain behaviour exhibited by dream(-/-) mice was shown, by pharmacological and biochemical analyses, to be due to increased activation of the endogenous kappa-opioid system. Importantly, loss of DREAM also attenuated inflammatory pain. Thus, DREAM and the DREAM pathway constitute a novel therapeutic paradigm for the treatment of chronic pain in arthritis.