PDF(Pubmed)
Abstract：
Chronic pain is a prevalent and persistent ailment that affects individuals worldwide. Conventional medications employed in the treatment of chronic pain typically demonstrate limited analgesic effectiveness and frequently give rise to debilitating side effects, such as tolerance and addiction, thereby diminishing patient compliance with medication. Consequently, there is an urgent need for the development of efficacious novel analgesics and innovative methodologies to address chronic pain. Recently, a growing body of evidence has suggested that multireceptor ligands targeting opioid receptors (ORs) are favorable for improving analgesic efficacy, decreasing the risk of adverse effects, and occasionally yielding additional advantages. In this study, the intrathecal injection of a recently developed peptide (VYWEMEDKN) at nanomolar concentrations decreased pain sensitivity in naïve mice and effectively reduced pain-related behaviors in nociceptive pain model mice with minimal opioid-related side effects. Importantly, the compound exerted significant rapid-acting antidepressant effects in both the forced swim test and tail suspension test. It is possible that the rapid antihyperalgesic and antidepressant effects of the peptide are mediated through the OR pathway. Overall, this peptide could both effectively provide pain relief and alleviate depression with fewer side effects, suggesting that it is a potential agent for chronic pain and depression comorbidities from the perspective of pharmaceutical development.
摘要：
慢性疼痛是影响全世界个体的普遍且持续的疾病。用于治疗慢性疼痛的常规药物通常表现出有限的镇痛效果，并经常引起使人衰弱的副作用。比如宽容和成瘾，从而降低患者对药物的依从性。因此,迫切需要开发有效的新型镇痛药和创新方法来解决慢性疼痛。最近,越来越多的证据表明，靶向阿片受体（ORs）的多受体配体有利于提高镇痛疗效，降低不良反应的风险，偶尔会产生额外的优势。在这项研究中,鞘内注射纳摩尔浓度的最近开发的肽(VYWEMEDKN)降低了初治小鼠的疼痛敏感性,并有效降低了伤害性疼痛模型小鼠的疼痛相关行为,且阿片类药物相关副作用最小.重要的是,该化合物在强迫游泳试验和尾部悬吊试验中均具有显着的速效抗抑郁作用。肽的快速抗痛觉过敏和抗抑郁作用可能是通过OR途径介导的。总的来说,这种肽既能有效缓解疼痛，又能缓解抑郁，副作用少，表明从药物开发的角度来看，它是慢性疼痛和抑郁症合并症的潜在药物。
