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

Feng Du ¹Guangjuan Yin ²Lei Han ³Xi Liu ²Dong Dong ²Kaifang Duan ²Jiantao Huo ²Yanyan Sun ³Longzhen Cheng⁴

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作者信息

1. School of Life Science and Technology,Harbin Institute of Technology,Harbin 150001,China;Shenzhen Key Laboratory of Gene Regulation and Systems Biology,School of Life Sciences,Southern University of Science and Technology,Shenzhen 518055,China;Department of Biology,Brain Research Center,Southern University of Science and Technology,Shenzhen 518055,China
2. Shenzhen Key Laboratory of Gene Regulation and Systems Biology,School of Life Sciences,Southern University of Science and Technology,Shenzhen 518055,China;Department of Biology,Brain Research Center,Southern University of Science and Technology,Shenzhen 518055,China
3. Department of Anesthesiology,Shenzhen University General Hospital,Shenzhen University,Shenzhen 518055,China
4. Shenzhen Key Laboratory of Gene Regulation and Systems Biology,School of Life Sciences,Southern University of Science and Technology,Shenzhen 518055,China;Department of Biology,Brain Research Center,Southern University of Science and Technology,Shenzhen 518055,China;Department of Biology,School of Life Sciences,Southern University of Science and Technology,Shenzhen 518055,China
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Abstract

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 mediat-ing opioid-induced mechanical allodynia and anti-allo-dynic tolerance remain unresolved.Here we demonstrated that the loss of peripheral μ-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 out-puts in superficial dorsal horn neurons.Consistent with the behavioral results,peripheral MOR loss did not prevent the opening of Aβ mechanical allodynia pathways in the spinal dorsal horn.Therefore,the peripheral MOR signaling path-way may not be an optimal target for preventing mechanical OIH and analgesic tolerance.Future studies should focus more on central mechanisms.

Key words

μ-opioid receptor/Morphine/Mechanical allodynia/Punctate allodynia/Dynamic allodynia/OIH/Tolerance/Aβ-fiber

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基金项目

Ministry of Science and Technology of China(2021ZD0203302)

National Natural Science Foundation of China(32170996)

Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(2021SHIBS0002)

Guangdong Science and Technology Committee(2019A1515010041)

Guangdong Science and Technology Committee(A2021319)

Shenzhen Innovation Committee of Science and Technology(ZDSYS20200811144002008)

Natural Science Foundation of Shenzhen University General Hospital(SUGH2018QD024)

Basic Research Project of Shenzhen Science and Technology Innovation Commission(JCYJ20210324100206017)

出版年

2023

神经科学通报(英文版)

中国科学院上海生命科学研究院

神经科学通报(英文版)

CSTPCDCSCD

影响因子：0.741

ISSN：1673-7067

参考文献量53

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