Spinal cord NMDA receptor-mediated activation of mammalian target of rapamycin is required for the development and maintenance of bone cancer-induced pain hypersensitivities in rats.

The Journal of Pain : Official Journal of the American Pain Society
Ming-Hung ShihYuan-Xiang Tao

Abstract

Mammalian target of rapamycin (mTOR) controls mRNA translation and is critical for neuronal plasticity. However, how it participates in central sensitization underlying chronic pain is unclear. Here, we show that NMDA receptors are required for the functional role of spinal cord mTOR in bone cancer pain induced by injecting prostate cancer cells (PCCs) into the tibia. Intrathecal rapamycin, a specific mTOR inhibitor, dose dependently attenuated the development and maintenance of PCC-induced mechanical allodynia and thermal hyperalgesia. Rapamycin alone did not affect locomotor activity and acute responses to thermal or mechanical stimuli. Phosphorylation of mTOR and p70S6K (a downstream effector) was increased time dependently in L(4-5) dorsal horn and transiently in L(4-5) dorsal root ganglions on the ipsilateral side after PCC injection, although total expression of mTOR or p70S6K was not changed in these regions. The increases in dorsal horn were abolished by intrathecal infusion of DL-AP5, an NMDA receptor antagonist. Moreover, NMDA receptor subunit NR1 colocalized with mTOR and p70S6K in dorsal horn neurons. These findings suggest that PCC-induced dorsal horn activation of the mTOR pathway participates in NMDA receptor-tri...Continue Reading

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Citations

Jul 9, 2013·Neuroscience Letters·Theodore J Price, Gregory Dussor
Jan 3, 2014·The Journal of Clinical Investigation·Ji-Tian XuYuan-Xiang Tao
Dec 12, 2013·CNS Drugs·Leandro Francisco Silva Bastos, Márcio Matos Coelho
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Dec 19, 2015·ELife·Arkady KhoutorskyNahum Sonenberg
May 15, 2013·The Journal of Pain : Official Journal of the American Pain Society·Luiz F FerrariJon D Levine
May 7, 2013·The Journal of Pain : Official Journal of the American Pain Society·Lingli LiangYuan-Xiang Tao
Jul 26, 2015·Breast Cancer Research and Treatment·Dareen M AbdelazizSvetlana V Komarova
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Nov 22, 2018·Frontiers in Genetics·Sonali UttamArkady Khoutorsky

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