Contribution of Spinal Cord mTORC1 to Chronic Opioid Tolerance and Hyperalgesia

Linlin Sun, Brianna M. Lutz, Yuan Xiang Tao

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Morphine and related opiates are commonly used in the clinical treatment of various types of moderate to severe pain. However, this treatment is often limited by a rapid development of opiate tolerance and hyperalgesia. A number of studies reported that mammalian target of rapamycin (mTOR), an enzyme that controls most protein translation, is required for the genesis of opioid tolerance and hyperalgesia. Repeated intrathecal morphine injections activated spinal dorsal horn mTOR through ? opioid receptor-triggered PI3K/Akt signaling. The resulting increase in mTOR activation led to an increase in translation initiation activity and nascent protein synthesis. Blocking this activation either by the specific mTOR inhibitor rapamycin or specific mTOR siRNA attenuated the development and maintenance of morphine analgesic tolerance and hyperalgesia. Mimicking this increase decreased morphine analgesia and produced pain hypersensitivity. These findings identify mTOR as a likely target for treatment of chronic opioid tolerance and hyperalgesia.

Original languageEnglish (US)
Title of host publicationGeneral Processes and Mechanisms, Prescription Medications, Caffeine and Areca, Polydrug Misuse, Emerging Addictions and Non-Drug Addictions
PublisherElsevier Inc.
Pages482-489
Number of pages8
Volume3
ISBN (Electronic)9780128006771
ISBN (Print)9780128006344
DOIs
StatePublished - May 13 2016
Externally publishedYes

Keywords

  • Akt
  • Hyperalgesia
  • MTORC1
  • Opioids
  • Pain
  • PI3K
  • Rapamycin
  • Tolerance
  • μOpioid receptor

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Sun, L., Lutz, B. M., & Tao, Y. X. (2016). Contribution of Spinal Cord mTORC1 to Chronic Opioid Tolerance and Hyperalgesia. In General Processes and Mechanisms, Prescription Medications, Caffeine and Areca, Polydrug Misuse, Emerging Addictions and Non-Drug Addictions (Vol. 3, pp. 482-489). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-800634-4.00048-2