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Astrocytic pyruvate dehydrogenase kinase-lactic acid axis involvement in glia-neuron crosstalk contributes to morphine-induced hyperalgesia in mice

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Fundamental Research 2024年第4期4卷 820-828页

作者： Xiaqing Ma Qi Qi Wenying Wang Min Huang Haiyan Wang Limin Luo Xiaotao Xu Tifei Yuan Haibo Shi Wei Jiang Tao Xu Department of Anesthesiology Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200233China Department of Anesthesiology Suzhou Hospital of Anhui Medical UniversitySuzhou 234000China Department of Anesthesiology Affliated Hospital of Nantong UniversityMedical School of Nantong UniversityNantong 226001China Shanghai Key Laboratory of Psychotic Disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai 200030China Shanghai Key Laboratory of Sleep Disordered Breathing Shanghai 200233China

The activation of spinal astrocytes accounts for opioid-induced hyperalgesia(OIH),but the underlying mechanisms remain *** presence of astrocyte-neuron lactate shuttle(ANLS)makes astrocytes necessary for some neural function and *** aim of this study was to explore the role of ANLS in the occurrence and maintenance of *** 7 days consecutive morphine injection,a mice OIH model was established and astrocytic pyruvate dehydrogenase kinase 4(PDK4),phosphorylated pyruvate dehydrogenase(p-PDH)and accumulation of L-lactate was elevated in the spinal dorsal *** administration of inhibitors of PDK,lactate dehydrogenase 5 and monocarboxylate transporters to decrease the supply of L-lactate on neurons was observed to attenuate hypersensitivity behaviors induced by repeated morphine administration and downregulate the expression of markers of central sensitization in the spinal dorsal *** astrocyte line and the neuronal line were co-cultured to investigate the mechanisms in *** this study,we demonstrated that morphine-induced hyperalgesia was sustained by lactate overload consequent upon aberrant function of spinal *** this process,PDK-p-PDH-lactate axis serves a pivotal role,which might therefore be a new target to improve long-term opioid treatment strategy in clinical practice.

关键词： pyruvate dehydrogenase kinase 4 phosphorylated pyruvate dehydrogenase Astrocyte-neuron lactate shuttle Opioid-induced hyperalgesia Lactate

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