title: Inhibition of CaMKIIα in the Central Nucleus of Amygdala Attenuates Fentanyl-Induced Hyperalgesia in Rats.
abstract: Opioid-induced hyperalgesia (OIH) is a less-studied phenomenon that has been reported in both preclinical and clinical studies. Although the underlying cause is not entirely understood, OIH is a real-life problem that affects millions of patients on a daily basis. Research has implicated the important contribution of Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα) to OIH at the level of spinal nociceptors. To expand our understanding of the entire brain circuitry driving OIH, in this study we investigated the role of CaMKIIα in the laterocapcular division of the central amygdala (CeLC), the conjunctive point between the spinal cord and rostro-ventral medulla. OIH was produced by repeated fentanyl administration in the rat. Correlating with the development of mechanical allodynia and thermal hyperalgesia, CaMKIIα activity was significantly elevated in the CeLC in OIH. In addition, the frequency and amplitude of spontaneous miniature excitatory postsynaptic currents (mEPSCs) in CeLC neurons were significantly increased in OIH. 2-[N-(2-hidroxyethyl)-N-(4-methoxy-benzenesulfonyl)]-amino-N-(4-chlorocinnamyl)-N-methylbenzylamine, a CaMKIIα inhibitor, dose dependently reversed sensory hypersensitivity, activation of CeLC CaMKIIα, and mEPSCs in OIH. Taken together, our data for the first time implicate a critical role of CeLC CaMKIIα in OIH.
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Z.L., P.Y, F.L.); Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science, State Ethnic Affairs Commission, College of Biomedical Engineering, South-Central University for Nationalities, Wuhan, China (C. L.); and Department of Biopharmaceutical Sciences and Cancer Center, University of Illinois, Chicago, Illinois (Z.J.W).
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Z.L., P.Y, F.L.); Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science, State Ethnic Affairs Commission, College of Biomedical Engineering, South-Central University for Nationalities, Wuhan, China (C. L.); and Department of Biopharmaceutical Sciences and Cancer Center, University of Illinois, Chicago, Illinois (Z.J.W).
authors.forename: Chenhong
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Z.L., P.Y, F.L.); Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science, State Ethnic Affairs Commission, College of Biomedical Engineering, South-Central University for Nationalities, Wuhan, China (C. L.); and Department of Biopharmaceutical Sciences and Cancer Center, University of Illinois, Chicago, Illinois (Z.J.W).
authors.forename: Pingping
authors.initials: P
authors.lastname: Yin
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Z.L., P.Y, F.L.); Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science, State Ethnic Affairs Commission, College of Biomedical Engineering, South-Central University for Nationalities, Wuhan, China (C. L.); and Department of Biopharmaceutical Sciences and Cancer Center, University of Illinois, Chicago, Illinois (Z.J.W).
authors.forename: Zaijie Jim
authors.initials: ZJ
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Z.L., P.Y, F.L.); Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science, State Ethnic Affairs Commission, College of Biomedical Engineering, South-Central University for Nationalities, Wuhan, China (C. L.); and Department of Biopharmaceutical Sciences and Cancer Center, University of Illinois, Chicago, Illinois (Z.J.W) luofang0909@hotmail.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Luo
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000494:pharmacology / Q000627:therapeutic use; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors*; D066274:Central Amygdaloid Nucleus / Q000187:drug effects* / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005283:Fentanyl / Q000494:pharmacology*; D006930:Hyperalgesia / Q000139:chemically induced* / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D001596:Benzylamines; D047428:Protein Kinase Inhibitors; C030796:benzylamine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D005283:Fentanyl