• J Wang, Q Zhang, L Zhao, D Li, Z Fu, and L Liang.
• Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong University, Jinan City, Shandong Province 250021, China; Department of Pain Management, Qilu Hospital, Shandong University, Jinan City, Shandong Province 250012, China.
• Neuroscience. 2014 Oct 10;278:165-78.

AbstractObesity is associated with augmented peripheral inflammation and pain sensitivity in response to inflammatory stimulation, but the underlying mechanisms remain unclear. Emerging evidence has shown that activation of peroxisome proliferator-activated receptor-α (PPARα) in the central nervous system controls peripheral inflammation and pain. We hypothesized that obesity might down-regulate PPARα in the spinal cord, leading to enhanced peripheral inflammation and inflammatory hyperalgesia. Sprague-Dawley rats fed a high-fat diet (HF) for 12weeks developed metabolic disorder and displayed significantly decreased spinal PPARα expression and activity. Interestingly, intracerebroventricular (ICV) infusion of the PPARα activator palmitoylethanolamide (PEA) in HF-fed rats for 2weeks normalized spinal PPARα expression and activity without altering metabolic parameters. HF-fed rats were more sensitive to stimulation of the inflamed paw, and exhibited more severe paw edema following carrageenan injection, whereas HF-fed rats receiving ICV PEA had similar pain sensitivity and paw edema to LF-fed rats. No difference in the expression of inflammatory mediators or nuclear factor (NF)-κB activity was observed at baseline among groups. Carrageenan induced decreased PPARα expression and activity, increased spinal cord inflammatory mediator expression and NF-κB activity in both LF-and HF-fed rats. However, the increase was more pronounced in HF-fed rats and corrected by PEA. Intrathecal injection of small interfering RNA (siRNA) against PPARα in HF-fed rats completely abolished PEA effects on peripheral pain sensitivity and paw edema. These findings suggest that diet-induced obesity causes down-regulation of spinal PPARα, which facilitates the susceptibility to peripheral inflammatory challenge by increasing inflammatory response in the spinal cord, contributing to augmented peripheral inflammation and inflammatory hyperalgesia in obesity.Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

30 keywords...

hide…