title: Inhibition of the cAMP/PKA/CREB Pathway Contributes to the Analgesic Effects of Electroacupuncture in the Anterior Cingulate Cortex in a Rat Pain Memory Model.
abstract: Pain memory is considered as endopathic factor underlying stubborn chronic pain. Our previous study demonstrated that electroacupuncture (EA) can alleviate retrieval of pain memory. This study was designed to observe the different effects between EA and indomethacin (a kind of nonsteroid anti-inflammatory drugs, NSAIDs) in a rat pain memory model. To explore the critical role of protein kinase A (PKA) in pain memory, a PKA inhibitor was microinjected into anterior cingulate cortex (ACC) in model rats. We further investigated the roles of the cyclic adenosine monophosphate (cAMP), PKA, cAMP response element-binding protein (CREB), and cAMP/PKA/CREB pathway in pain memory to explore the potential molecular mechanism. The results showed that EA alleviates the retrieval of pain memory while indomethacin failed. Intra-ACC microinjection of a PKA inhibitor blocked the occurrence of pain memory. EA reduced the activation of cAMP, PKA, and CREB and the coexpression levels of cAMP/PKA and PKA/CREB in the ACC of pain memory model rats, but indomethacin failed. The present findings identified a critical role of PKA in ACC in retrieval of pain memory. We propose that the proper mechanism of EA on pain memory is possibly due to the partial inhibition of cAMP/PKA/CREB signaling pathway by EA.
authors.affiliation: Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Xiao-Mei
authors.identifier: 0000-0002-1637-1178
authors.initials: XM
authors.lastname: Shao
authors.affiliation: Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Yong-Liang
authors.identifier: 0000-0002-9937-7398
authors.initials: YL
authors.lastname: Jiang
authors.affiliation: Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Bo-Yi
authors.initials: BY
authors.lastname: Liu
authors.affiliation: Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Zui
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Acupuncture and Moxibustion, Wenzhou Hospital Affiliated to Zhejiang University of Traditional Chinese Medicine, Wenzhou, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Jun-Ying
authors.identifier: 0000-0002-0997-5379
authors.initials: JY
authors.lastname: Du
authors.affiliation: Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Yuan-Yuan
authors.identifier: 0000-0001-8884-0802
authors.initials: YY
authors.lastname: Wu
authors.affiliation: Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Jia-Ling
authors.initials: JL
authors.lastname: Wang
authors.affiliation: Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Jian-Qiao
authors.identifier: 0000-0003-2124-5130
authors.initials: JQ
authors.lastname: Fang
mesh_terms: D000698:Analgesia / Q000379:methods; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis*; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004195:Disease Models, Animal; D015671:Electroacupuncture / Q000379:methods*; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism*; D007213:Indomethacin / Q000008:administration & dosage; D007276:Injections, Intraventricular; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000188:drug therapy / Q000378:metabolism*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D047428:Protein Kinase Inhibitors; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D007213:Indomethacin