Targeting Peripheral μ-opioid Receptors or μ-opioid Receptor-Expressing Neurons Does not Prevent Morphine-induced Mechanical Allodynia and Anti-allodynic Tolerance  

作　　者：Feng Du Guangjuan Yin Lei Han Xi Liu Dong Dong Kaifang Duan Jiantao Huo Yanyan Sun Longzhen Cheng 

机构地区：[1]School of Life Science and Technology,Harbin Institute of Technology,Harbin 150001,China [2]Shenzhen Key Laboratory of Gene Regulation and Systems Biology,School of Life Sciences,Southern University of Science and Technology,Shenzhen 518055,China [3]Department of Biology,Brain Research Center,Southern University of Science and Technology,Shenzhen 518055,China [4]Department of Anesthesiology,Shenzhen University General Hospital,Shenzhen University,Shenzhen 518055,China [5]Department of Biology,School of Life Sciences,Southern University of Science and Technology,Shenzhen 518055,China

出　　处：《Neuroscience Bulletin》2023年第8期1210-1228,共19页神经科学通报（英文版）

基　　金：supported by grants from the Ministry of Science and Technology of China(2021ZD0203302);the National Natural Science Foundation of China(32170996);Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(2021SHIBS0002);the Guangdong Science and Technology Committee(2019A1515010041,A2021319);the Shenzhen Innovation Committee of Science and Technology(ZDSYS20200811144002008);the Natural Science Foundation of Shenzhen University General Hospital(SUGH2018QD024);the Basic Research Project of Shenzhen Science and Technology Innovation Commission(JCYJ20210324100206017).

摘　　要：The chronic use of morphine and other opioids is associated with opioid-induced hypersensitivity(OIH)and analgesic tolerance.Among the different forms of OIH and tolerance,the opioid receptors and cell types mediating opioid-induced mechanical allodynia and anti-allodynic tolerance remain unresolved.Here we demonstrated that the loss of peripheralμ-opioid receptors(MORs)or MOR-expressing neurons attenuated thermal tolerance,but did not affect the expression and maintenance of morphine-induced mechanical allodynia and anti-allodynic tolerance.To confirm this result,we made dorsal root ganglia-dorsal roots-sagittal spinal cord slice preparations and recorded low-threshold Aβ-fiber stimulation-evoked inputs and outputs in superficial dorsal horn neurons.Consistent with the behavioral results,peripheral MOR loss did not prevent the opening of Aβmechanical allodynia pathways in the spinal dorsal horn.Therefore,the peripheral MOR signaling pathway may not be an optimal target for preventing mechanical OIH and analgesic tolerance.Future studies should focus more on central mechanisms.

关 键 词：μ-opioid receptor MORPHINE Mechanical allodynia Punctate allodynia Dynamic allodynia OIH TOLERANCE Aβ-fber 

分 类 号：R749.64[医药卫生—神经病学与精神病学]