Elsevier

Neuroscience Letters

Volume 369, Issue 1, 7 October 2004, Pages 59-63
Neuroscience Letters

Activation of peroxisome proliferator-activated receptor alpha in rat spinal cord after peripheral noxious stimulation

https://doi.org/10.1016/j.neulet.2004.07.056Get rights and content

Abstract

Following recurrent noxious stimulation, both functional modification and structural reorganization such as activation of the arachidonate cascade or axon sprouting occur in the central nervous system (CNS). It has been recently proposed that these alterations observed during chronic pain state were supported by an intensification of the lipid metabolism. In this regard, it has been shown that mRNA coding for several fatty acid metabolizing enzymes are up-regulated in the rat lumbar spinal cord in response to persistent nociception induced by a peripheral inflammation. As peroxisome proliferators-activated receptor (PPAR) could mediate such effects, we therefore investigated the activation of this transcription factor in the rat spinal cord following subcutaneous injection of complete Freund's adjuvant (CFA) into a hind paw. In this study, we compared the DNA-binding activity of nuclear proteins extracted from healthy and inflamed rats toward a PPAR response element. Using electrophoretic mobility-shift assay (EMSA), we found that only the PPARα isoform was activated in the rat spinal cord after CFA injection. This activation occurred rapidly, as early as 30 min post-CFA injection, and was persistent up to 10 h, reaching a maximum at 6 h after CFA injection. In view of the consequences of PPARα activation in other tissues, these results suggest that fatty acid utilization is enhanced in the CNS during chronic pain state. Although the physiopathological relevance of PPARα activation during hyperalgesia needs further investigation, we provided here a new player in the molecular modeling of pain pathways.

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Acknowledgments

This work is supported by grants from the Région Lorraine and from the “Communauté Urbaine du Grand Nancy”. We thank Professor M. Dauça for the generous gift of the PPAR antibodies (Laboratoire de Biologie du Peroxysome, EA 3446, Faculté des Sciences, Vandoeuvre-les-Nancy, France).

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