Curcumin blocks chronic morphine analgesic tolerance and brain-derived neurotrophic factor upregulation.
This study was carried out based on the assumption that brain-derived neurotrophic factor (BDNF) may counterbalance the action of morphine in the brain. Morphine analgesic tolerance after daily administrations for six days was blocked by intracerebroventricular injection of anti-BDNF IgG on day 5, but not by administrations on days 1-4. Chronic morphine treatment significantly increased the expression of exon I and IV BDNF transcripts, indicating differential regulation of BDNF gene expression. Daily administration of the CREB-binding protein inhibitor curcumin abolished the upregulation of BDNF transcription and morphine analgesic tolerance. These results suggest that curcumin might be a promising adjuvant to reduce morphine analgesic tolerance, and that epigenetic control could be a new strategy useful for the control of this problem.
Matsushita
Yosuke
Y
aDivision of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Ueda
Hiroshi
H
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000276:immunology; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D004361:Drug Tolerance; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005091:Exons / Q000235:genetics; D006358:Hot Temperature / Q000009:adverse effects; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D010812:Physical Stimulation / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics
D000701:Analgesics, Opioid; D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D007074:Immunoglobulin G; D012333:RNA, Messenger; D009020:Morphine; D003474:Curcumin