期刊
PAIN
卷 161, 期 12, 页码 2786-2797出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/j.pain.0000000000001992
关键词
Mitochondria; Pain; Astrocytes; Microglia; Dichloroacetate
资金
- Agencia Nacional de Investigacion e Innovacion (ANII) fellowship
- Comision Sectorial de Investigacion Cientifica (CSIC)-Universidad de la Republica (UDELAR), Programa Iniciacion a la Investigacion [87]
- CSIC-UDELAR, Programa Grupos I+D [1104]
- Fondo para la Convergencia Estructural del MERCOSUR (FOCEM), COF [03/1111]
Glial reactivity in the dorsal horn of the spinal cord is a hallmark in most chronic pain conditions. Neuroinflammation-associated reactive glia, in particular astrocytes, have been shown to exhibit reduced mitochondrial respiratory function. Here, we studied the mitochondrial function at the lumbar spinal cord tissue from complete Freund's adjuvant-induced inflammatory pain rat and chronic constriction injury mouse models by high-resolution respirometry. A significant decrease in mitochondrial bioenergetic parameters at the injury-related spinal cord level coincided with highest astrocytosis. Oral administration of dichloroacetate (DCA) significantly increased mitochondrial respiratory function by inhibiting pyruvate dehydrogenase kinase and decreased glial fibrillary acidic protein and Iba-1 immunoreactivity in spinal cord. Importantly, DCA treatment significantly reduced the ipsilateral pain-related behavior without affecting contralateral sensitivity in both pain models. Our results indicate that mitochondrial metabolic modulation with DCA may offer an alternative therapeutic strategy to alleviate chronic and persistent inflammatory pain.
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