Intrathecal Fumagillin Alleviates Chronic Neuropathy-Induced Nociceptive Sensitization and Modulates Spinal Astrocyte-Neuronal Glycolytic and Angiogenic Proteins

Wen, Zhi-Hong; Wu, Zong-Sheng; Cheng, Hao-Jung; Huang, Shi-Ying; Tang, Shih-Hsuan; Teng, Wei-Nung; Su, Fu-Wei; Chen, Nan-Fu; Sung, Chun-Sung

doi:10.1007/s12035-024-04254-w

Mol Neurobiol

2024

DOI: 10.1007/s12035-024-04254-w

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Intrathecal Fumagillin Alleviates Chronic Neuropathy-Induced Nociceptive Sensitization and Modulates Spinal Astrocyte-Neuronal Glycolytic and Angiogenic Proteins

Zhi-Hong Wen,

Zong-Sheng Wu,

Hao-Jung Cheng

et al.

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2024

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Intrathecal lactate dehydrogenase A inhibitors FX11 and oxamate alleviate chronic constriction injury-induced nociceptive sensitization through neuroinflammation and angiogenesis

Cheng,

Chen,

Chen

et al. 2024

J Headache Pain

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Background Neuropathic pain involves neuroinflammation and upregulation of glycolysis in the central nervous system. Unfortunately, few effective treatments are available for managing this type of pain. The overactivation of lactate dehydrogenase A (LDHA), an essential enzyme in glycolysis, can cause neuroinflammation and nociception. This study investigated the spinal role of LDHA in neuropathic pain. Method Using immunohistochemical analysis, nociceptive behavior, and western blotting, we evaluated the cellular mechanisms of intrathecal administration of LDHA inhibitors, including FX11 and oxamate, in chronic constriction injury (CCI)-induced neuropathic rats. Result FX11 and oxamate attenuated CCI-induced neuronal LDHA upregulation and nociceptive sensitization. Moreover, CCI-induced neuroinflammation, microglial polarization, and angiogenesis were attenuated by LDHA inhibitors. These inhibitors regulate the TANK binding kinase-1 (TBK1)/hypoxia-inducible factor 1 subunit alpha (HIF-1α) axis, crucial for controlling inflammation and new blood vessel growth. Additionally, CCI-induced nuclear LDHA translocation, as associated with oxidative stress resistance, was attenuated by LDHA inhibitors. Conclusion In conclusion, LDHA may be a potential therapeutic target for treating neuropathic pain by regulating neuroinflammation and angiogenesis. Supplementary Information The online version contains supplementary material available at 10.1186/s10194-024-01916-x.

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Intrathecal lactate dehydrogenase A inhibitors FX11 and oxamate alleviate chronic constriction injury-induced nociceptive sensitization through neuroinflammation and angiogenesis

Cheng,

Chen,

Chen

et al. 2024

J Headache Pain

View full text Add to dashboard Cite

show abstract

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Intrathecal Fumagillin Alleviates Chronic Neuropathy-Induced Nociceptive Sensitization and Modulates Spinal Astrocyte-Neuronal Glycolytic and Angiogenic Proteins

Cited by 1 publication

References 98 publications

Intrathecal lactate dehydrogenase A inhibitors FX11 and oxamate alleviate chronic constriction injury-induced nociceptive sensitization through neuroinflammation and angiogenesis

Intrathecal lactate dehydrogenase A inhibitors FX11 and oxamate alleviate chronic constriction injury-induced nociceptive sensitization through neuroinflammation and angiogenesis

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