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Common alterations in parallel metabolomic profiling of serum and spinal cord and mechanistic studies on neuropathic pain following PPARα administration

Zhao, Yu-Ying ; Wu, Zi-Jun ; Hao, Shu-jing ; Dong, Bei-bei ; Zheng, Yu-xin ; Liu, Bin ; Li, Jing

Neuropharmacology, 2024-08, Vol.254, p.109988, Article 109988 [Periódico revisado por pares]

England: Elsevier Ltd

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Título:
Common alterations in parallel metabolomic profiling of serum and spinal cord and mechanistic studies on neuropathic pain following PPARα administration
Autor: Zhao, Yu-Ying ; Wu, Zi-Jun ; Hao, Shu-jing ; Dong, Bei-bei ; Zheng, Yu-xin ; Liu, Bin ; Li, Jing
Assuntos: Animals ; Dendritic Spines - drug effects ; Dendritic Spines - metabolism ; Dendritic Spines - pathology ; Hyperalgesia - drug therapy ; Hyperalgesia - metabolism ; Inflammasomes - drug effects ; Inflammasomes - metabolism ; Male ; Metabolism ; Metabolomics ; Mice ; Mice, Inbred C57BL ; Microglia - drug effects ; Microglia - metabolism ; Neuralgia - drug therapy ; Neuralgia - metabolism ; Neuroinflammation ; Neuroinflammatory Diseases - drug therapy ; Neuroinflammatory Diseases - metabolism ; Neuropathic pain ; NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors ; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism ; NLRP3 ; PPAR alpha - metabolism ; PPARα ; Spinal Cord - drug effects ; Spinal Cord - metabolism
É parte de: Neuropharmacology, 2024-08, Vol.254, p.109988, Article 109988
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: Neuropathic pain (NP) is usually treated with analgesics and symptomatic therapy with poor efficacy and numerous side effects, highlighting the urgent need for effective treatment strategies. Recent studies have reported an important role for peroxisome proliferator-activated receptor alpha (PPARα) in regulating metabolism as well as inflammatory responses. Through pain behavioral assessment, we found that activation of PPARα prevented chronic constriction injury (CCI)-induced mechanical allodynia and thermal hyperalgesia. In addition, PPARα ameliorated inflammatory cell infiltration at the injury site and decreased microglial activation, NOD-like receptor protein 3 (NLRP3) inflammasome production, and spinal dendritic spine density, as well as improved serum and spinal cord metabolic levels in mice. Administration of PPARα antagonists eliminates the analgesic effect of PPARα agonists. PPARα relieves NP by inhibiting neuroinflammation and functional synaptic plasticity as well as modulating metabolic mechanisms, suggesting that PPARα may be a potential molecular target for NP alleviation. However, the effects of PPARα on neuroinflammation and synaptic plasticity should be further explored. •Neuropathic pain leads to reduced PPARα expression in the mouse spinal cord.•PPARα agonists/antagonists affect pain-related behavioral and histopathological changes in CCI mice.•The analgesic effect of GW7647 were reversed by GW6471.•PPARα agonists/antagonists affect pain-related behavioral and histopathological changes in CCI mice.•PPARα attenuates microglial activation in CCI mice.•PPARα attenuates NLRP3 inflammasome formation in CCI mice.•PPARα modulates synaptic plasticity in CCI mice.•Serum and spinal cord metabolism were significantly altered in CCI mice.•PPARα affects NP development by regulating serum and spinal cord metabolic mechanisms in mice.
Editor: England: Elsevier Ltd
Idioma: Inglês

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Common alterations in parallel metabolomic profiling of serum and spinal cord and mechanistic studies on neuropathic pain following PPARα administration

Zhao, Yu-Ying ; Wu, Zi-Jun ; Hao, Shu-jing ; Dong, Bei-bei ; Zheng, Yu-xin ; Liu, Bin ; Li, Jing

England: Elsevier Ltd

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