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mTOR, a new potential target for chronic pain and opioid-induced tolerance and hyperalgesia

机译:mTOR,慢性疼痛和阿片类药物引起的耐受性和痛觉过敏的新潜在靶点

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摘要

Chronic pain is a major public health problem with limited treatment options. Opioids remain a routine treatment for chronic pain, but extended exposure to opioid therapy can produce opioid tolerance and hyperalgesia. Although the mechanisms underlying chronic pain, opioid-induced tolerance, and opioid-induced hyperalgesia remain to be uncovered, mammalian target of rapamycin (mTOR) is involved in these disorders. The mTOR complex 1 and its triggered protein translation are required for the initiation and maintenance of chronic pain (including cancer pain) and opioid-induced tolerance/hyperalgesia. Given that mTOR inhibitors are FDA-approved drugs and an mTOR inhibitor is approved for the treatment of several cancers, these findings suggest that mTOR inhibitors will likely have multiple clinical benefits, including anticancer, antinociception/anti-cancer pain, and antitolerance/hyperalgesia. This paper compares the role of mTOR complex 1 in chronic pain, opioid-induced tolerance, and opioid-induced hyperalgesia.
机译:慢性疼痛是主要的公共卫生问题,治疗选择有限。阿片类药物仍然是治疗慢性疼痛的常规方法,但是长期接触阿片类药物可产生阿片类药物耐受性和痛觉过敏。尽管仍未发现引起慢性疼痛,阿片样物质引起的耐受性和阿片样物质引起的痛觉过敏的机制,但雷帕霉素(mTOR)的哺乳动物靶点参与了这些疾病。引发和维持慢性疼痛(包括癌症疼痛)和阿片类药物诱导的耐受/痛觉过敏需要mTOR复合物1及其触发的蛋白质翻译。鉴于mTOR抑制剂是FDA批准的药物,并且mTOR抑制剂被批准用于治疗多种癌症,这些发现表明mTOR抑制剂可能具有多种临床益处,包括抗癌,抗伤害感/抗癌痛以及抗耐受/痛觉过敏。本文比较了mTOR complex 1在慢性疼痛,阿片类药物引起的耐受性和阿片类药物引起的痛觉过敏中的作用。

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