title: Chronic morphine treatment increased the expression of myeloid differentiation primary response protein 88 in rat spinal cord.
abstract: Chronic 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.
authors.affiliation: Department of Anesthesiology, Shanghai Jiaotong University, Affiliated Shanghai Sixth People's Hospital, Shanghai 200233, P. R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.forename: Xia-Qing
authors.initials: XQ
authors.lastname: Ma
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D053594:Myeloid Differentiation Factor 88; D009020:Morphine
keywords: Morphine; mitogen-activated protein kinases; myeloid differentiation primary response protein 88, MyD88; tolerance; toll-like receptors