Opioid receptor-triggered spinal mTORC1 activation contributes to morphine tolerance and hyperalgesia.

ABSTRACT: The development of opioid-induced analgesic tolerance and hyperalgesia is a clinical challenge for managing chronic pain. Adaptive changes in protein translation in the nervous system are thought to promote opioid tolerance and hyperalgesia; however, how opioids drive such changes remains elusive. Here, we report that mammalian target of rapamycin (mTOR), which governs most protein translation, was activated in rat spinal dorsal horn neurons after repeated intrathecal morphine injections. Activation was triggered through μ opioid receptor and mediated by intracellular PI3K/Akt. Spinal mTOR inhibition blocked both induction and maintenance of morphine tolerance and hyperalgesia, without affecting basal pain perception or locomotor functions. These effects were attributed to the attenuation

SUBMITTER: Xu JT 

PROVIDER: S-EPMC3904613 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature