title: Role of neuroinflammation in morphine tolerance: effect of tumor necrosis factor-α.
abstract: Opioids have been used as potent analgesics in clinics for decades; however, their long-term administration leads to tolerance. Two possible mechanisms for drug tolerance are postulated as within-system and between-systems adaptation. The within-system tolerance is involved in the signal transduction of opioid receptors, including downregulation of opioid receptors, uncoupling of G-protein from opioid receptors, and β-arrestin recruitment to opioid receptors, which causes receptor desensitization and internalization/endocytosis. The between-systems tolerance comprehends the glutamatergic receptor system and glial activation with the release of proinflammatory cytokines, and thus the analgesic effect of morphine is reduced. Tumor necrosis factor-α (TNF-α) is a vital proinflammatory cytokine and exerts either a neurotoxic or neuroprotective effect on different diseases of the central nervous system. TNF-α has also been demonstrated to correlate with neuronal plasticity via activation of spinal glial cells and enhancement of glutamatergic transmission. Previous studies had revealed an increased expression of TNF-α in morphine tolerance. This review article focuses on the role of TNF-α in neuroinflammation and the glutamatergic receptor system in morphine tolerance. It may provide another adjuvant therapy for morphine tolerance, which extends the effectiveness of opioids in clinical pain management.
authors: Department of Anesthesiology, Veterans General Hospital, Taichung, Taiwan.
authors: Ching-Hui
authors: CH
authors: Shen
authors: Ru-Ying
authors: RY
authors: Tsai
authors: Chih-Shung
authors: CS
authors: Wong
mesh_terms: D004361:Drug Tolerance; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007249:Inflammation / Q000503:physiopathology*; D009020:Morphine / Q000494:pharmacology*; D009457:Neuroglia / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D007074:Immunoglobulin G; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D009020:Morphine; D000068800:Etanercept