寻求实现为疼痛量身定制的药物

Pain Research Pub Date : 2020-03-31 DOI:10.11154/pain.35.24
Yoshinori Takemura, M. Narita, N. Kuzumaki, M. Yamazaki
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引用次数: 0

摘要

虽然疼痛因人而异是众所周知的,但为疼痛患者量身定制的药物尚未实现。麻醉师经常遇到手术后疼痛持续的病人,即使在手术前可以控制。一般来说,要缓解这种长期的疼痛是很困难的。在未来,为了对单个患者的疼痛做出反应,有必要分析疼痛相关信号,这些信号不仅反映了常规图像和检查中捕获的结果,还反映了患者的生理状态、遗传背景和疾病状态。我们一直在通过基础研究寻找与疼痛相关的信号。我们的功能性MRI研究表明,如果在手术中全身麻醉下不使用镇痛药,疼痛通路被激活。这引起了脊髓和大脑的表观基因组修饰,据推测,这导致了持续的疼痛以及继发性的情绪和睡眠障碍。我们还发现,手术引起的细胞因子风暴是长期疼痛的来源。此外,在microRNA (miRNA)研究中,早期周围神经病变显著增加了背根神经节中炎症细胞因子引起的几种miRNA的表达。这导致血液中炎症源性外泌体mirna的表达同时增加。我们相信这些发现将为下一代疼痛治疗提供新的信息。在未来,“分层”疼痛患者,将有必要从诸如液体活检等程序中收集信息。可以基于数学分析、数据压缩和聚类分析创建单独的和通用的参数。在此基础上,我们将通过单独引入疼痛参数诱导基因,建立高度有限和多样化的动物模型,并研究病理分析和治疗方法。如果这种转化性疼痛研究成为可能,那么针对疼痛的量身定制药物将更接近现实。
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Seeking to realize tailor–made medicine for pain
Although it is well known that pain varies from patient to patient, tailor–made medicine for patients in pain has not yet been realized. Anesthesiologists often encounter patients whose pain persists after surgery, even though could be managed before the operation. It can be difficult to alleviate such prolonged pain a generic. In the future, to respond to pain in individual patients, it will be necessary to analyze pain–related signals that reflect not only the findings captured in conventional images and examinations, but also the physiological state, genetic background, and the state of the disease in patients. We have been searching for pain–related signals through basic research. Our functional MRI studies showed that the pain pathway was activated if analgesics were not administered under general anesthesia during surgery. This induced epigenomic modification in the spinal cord and brain, which was speculated to lead to prolonged pain as well as secondary emotional and sleep disorders. We also found that cytokine storms caused by surgery were the source of prolonged pain. Furthermore, in microRNA (miRNA) studies, early peripheral neuropathy significantly increased the expression of several miRNAs caused by inflam matory cytokines in the dorsal root ganglia. This led to concomitant increases in the expression of inflammation–derived exosomal miRNAs in the blood. We believe these findings will provide new information for next–generation pain treatment. In the future, “stratify” pain patients, it will be necessary to collect informa tion from procedures such as liquid biopsies. Individual and common para meters can be created based on mathematical analysis, data compression, and clustering analysis. Based on this information, we will create highly limited and diverse animal models of by individually introducing pain parameter–induced genes, and study pathological analysis and treatment methods. If such translational pain research becomes possible, tailor–made medicine for pain will become closer to reality.
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Pain Research
Pain Research CLINICAL NEUROLOGY-
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