title: PLGA-Curcumin Attenuates Opioid-Induced Hyperalgesia and Inhibits Spinal CaMKIIα.
abstract: Opioid-induced hyperalgesia (OIH) is one of the major problems associated with prolonged use of opioids for the treatment of chronic pain. Effective treatment for OIH is lacking. In this study, we examined the efficacy and preliminary mechanism of curcumin in attenuating OIH. We employed a newly developed PLGA-curcumin nanoformulation (PLGA-curcumin) in order to improve the solubility of curcumin, which has been a major obstacle in properly characterizing curcumin's mechanism of action and efficacy. We found that curcumin administered intrathecally or orally significantly attenuated hyperalgesia in mice with morphine-induced OIH. Furthermore, we demonstrated that the effects of curcumin on OIH correlated with the suppression of chronic morphine-induced CaMKIIα activation in the superficial laminae of the spinal dorsal horn. These data suggest that PLGA-curcumin may reverse OIH possibly by inhibiting CaMKIIα and its downstream signaling.
authors.affiliation: Department of Biopharmaceutical Sciences and Cancer Center, University of Illinois, Chicago, Illinois, United States of America.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Biopharmaceutical Sciences and Cancer Center, University of Illinois, Chicago, Illinois, United States of America.
authors.forename: Fang
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Chemical Engineering, University of Illinois, Chicago, Illinois, United States of America.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Szymusiak
authors.affiliation: Department of Biopharmaceutical Sciences and Cancer Center, University of Illinois, Chicago, Illinois, United States of America.|Department of Anesthesiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xuebi
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Biopharmaceutical Sciences and Cancer Center, University of Illinois, Chicago, Illinois, United States of America.|Department of Chemical Engineering, University of Illinois, Chicago, Illinois, United States of America.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biopharmaceutical Sciences and Cancer Center, University of Illinois, Chicago, Illinois, United States of America.
authors.forename: Zaijie Jim
authors.initials: ZJ
authors.lastname: Wang
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects*; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D059350:Chronic Pain / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods; D004361:Drug Tolerance; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000009:adverse effects*; D049329:Nanostructures / Q000737:chemistry; D010147:Pain Measurement; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000701:Analgesics, Opioid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D009020:Morphine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D003474:Curcumin