1. Common alterations in parallel metabolomic profiling of serum and spinal cord and mechanistic studies on neuropathic pain following PPARα administration.
- Author
-
Zhao YY, Wu ZJ, Hao SJ, Dong BB, Zheng YX, Liu B, and Li J
- Subjects
- Animals, Male, Mice, Hyperalgesia drug therapy, Hyperalgesia metabolism, Metabolomics, Microglia drug effects, Microglia metabolism, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, NLR Family, Pyrin Domain-Containing 3 Protein antagonists & inhibitors, Neuroinflammatory Diseases drug therapy, Neuroinflammatory Diseases metabolism, Dendritic Spines drug effects, Dendritic Spines metabolism, Dendritic Spines pathology, Inflammasomes metabolism, Inflammasomes drug effects, PPAR alpha metabolism, Neuralgia drug therapy, Neuralgia metabolism, Spinal Cord metabolism, Spinal Cord drug effects, Mice, Inbred C57BL
- Abstract
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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF