• Hao Xu, Tao Xu, Xia-Qing Ma, and Wei Jiang.
• Department of Anesthesiology, Shanghai Jiaotong University, Affiliated Shanghai Sixth People's Hospital, Shanghai 200233, P. R. China.
• J Integr Neurosci. 2014 Dec 1; 13 (4): 607-15.

AbstractChronic morphine exposure leads to tolerance, which limits the clinical use of this potent analgesic in the treatment of severe and chronic pain. Compelling evidence suggest that neuro-immune activation (pro-inflammatory cytokines including IL-1β, IL-6 and TNF) as well as neuro-inflammation have been shown to mediate the development of morphine analgesic tolerance. Toll-like receptors (TLRs), especially TLR-4, have also been reported to contribute to the development of morphine analgesic tolerance. Besides, mitogen-activated protein kinases (MAPKs; especially p38 MAPK and c-Jun N -terminal kinase), as well as nuclear factor-κB (NF-κB) modulate the development of morphine antinociceptive tolerance. Hence, we hypothesis the possible involvement of myeloid differentiation primary response protein 88 (MyD88), a key adaptor protein for the TLR and IL-1R families, in the development of tolerance to morphine-induced analgesia. Our study demonstrated that chronic intrathecal morphine injection led to a robust increase of MyD88 expression in rat spinal cord. Sustained elevation of MyD88 may play a role in modulating the development of morphine antinociceptive tolerance.

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