title: Genetic elimination of behavioral sensitization in mice lacking calmodulin-stimulated adenylyl cyclases.
abstract: Adenylyl cyclase types 1 (AC1) and 8 (AC8), the two major calmodulin-stimulated adenylyl cyclases in the brain, couple NMDA receptor activation to cAMP signaling pathways. Cyclic AMP signaling pathways are important for many brain functions, such as learning and memory, drug addiction, and development. Here we show that wild-type, AC1, AC8, or AC1&8 double knockout (DKO) mice were indistinguishable in tests of acute pain, whereas behavioral responses to peripheral injection of two inflammatory stimuli, formalin and complete Freund's adjuvant, were reduced or abolished in AC1&8 DKO mice. AC1 and AC8 are highly expressed in the anterior cingulate cortex (ACC), and contribute to inflammation-induced activation of CREB. Intra-ACC administration of forskolin rescued behavioral allodynia defective in the AC1&8 DKO mice. Our studies suggest that AC1 and AC8 in the ACC selectively contribute to behavioral allodynia.
authors.affiliation: Department of Anesthesiology, Washington University Pain Center, Washington University, St. Louis, MO 63108, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Wei
authors.forename: Chang Shen
authors.initials: CS
authors.lastname: Qiu
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Kim
authors.forename: Lisa
authors.initials: L
authors.lastname: Muglia
authors.forename: James W
authors.initials: JW
authors.lastname: Maas
authors.forename: Victor V
authors.initials: VV
authors.lastname: Pineda
authors.forename: Hai Ming
authors.initials: HM
authors.lastname: Xu
authors.forename: Zhou Feng
authors.initials: ZF
authors.lastname: Chen
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Storm
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Muglia
authors.forename: Min
authors.initials: M
authors.lastname: Zhuo
mesh_terms: D000262:Adenylyl Cyclases / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000201:enzymology* / Q000503:physiopathology; D002147:Calmodulin / Q000378:metabolism*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005620:Freund's Adjuvant; D006930:Hyperalgesia / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009434:Neural Pathways / Q000201:enzymology* / Q000503:physiopathology; D010146:Pain / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D010147:Pain Measurement; D012333:RNA, Messenger / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: D002147:Calmodulin; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D005620:Freund's Adjuvant; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1; C118292:adenylyl cyclase 8