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Canna~Fangled Abstracts

Metabolomics uncovers dietary omega-3 fatty acid-derived metabolites implicated in anti-nociceptive responses after experimental spinal cord injury.

By September 18, 2013No Comments
 [Epub ahead of print]

pm2Metabolomics uncovers dietary omega-3 fatty acid-derived metabolites implicated in anti-nociceptive responses after experimental spinal cord injury.

Source

Center for Health Disparities and Molecular Medicine; Departments of Basic Sciences and Pathology and Human Anatomy.

Abstract

Chronic neuropathic pain is a frequent comorbidity following spinal cord injury (SCI) and often fails to respond to conventional pain management strategies. Preventive administration of docosahexaenoic acid (DHA) or consumption of a diet rich in omega-3 polyunsaturated fatty acids (O3PUFAs) confers potent prophylaxis against SCI and improves functional recovery. The present study examines whether this novel dietary strategy provides significant antinociceptive benefits in rats experiencing SCI-induced pain. Rats were fed control chow or chow enriched with O3PUFAs for 8 weeks before being subjected to sham or cord contusion surgeries, continuing the same diets after surgery for another 8 more weeks. The paw sensitivity to noxious heat was quantified for at least 8 weeks post-SCI using the Hargreaves test. We found that SCI rats consuming the preventive O3PUFA-enriched diet exhibited a significant reduction in thermal hyperalgesia compared to those consuming the normal diet. Functional neurometabolomic profiling revealed a distinctive deregulation in the metabolism of endocannabinoids(eCB) and related N-acyl ethanolamines (NAEs) at 8 weeks post-SCI. We found that O3PUFAs consumption led to a robust accumulation of novel NAE precursors, including the glycerophospho-containing docosahexaenoyl ethanolamine (DHEA), docosapentaenoyl ethanolamine (DPEA), and eicosapentaenoyl ethanolamine (EPEA). The tissue levels of these metabolites were significantly correlated with the antihyperalgesic phenotype. In addition, rats consuming the O3PUFA-rich diet showed reduced sprouting of nociceptive fibers containing CGRP and dorsal horn neuron p38 MAPK expression, well-established biomarkers of pain. The spinal cord levels of inositols were positively correlated with thermal hyperalgesia, supporting their role as biomarkers of chronic neuropathic pain. Notably, the O3PUFA-rich dietary intervention reduced the levels of these metabolites. Collectively, these results demonstrate the prophylactic value of dietary O3PUFA against SCI-mediated chronic pain.
Copyright © 2013. Published by Elsevier Ltd.

KEYWORDS:

1-OG, 1-oleoyl glycerol, 2-AG, 2-PG, 2-arachidonoyl glycerol, 2-palmitoyl glycerol, AEA, Abh4, BBB, Basso Beattie and Bresnahan, CGRP, DHA, DHEA, DPEA, EG, EPA, EPEA, G3P, GAP43, GC/MS, GDE1, GP-NAEs, HWL, LEA, LPA, N-acyl ethanolamines, N-acyl phosphatidyl ethanolamine, NAEs, NAPE, O3PUFAs, PA, PEA, PLD, PLS-DA, SCI, Spinal cord injury, TH, UHPLC/MS/MS(2), arachidonoyl ethanolamine, calcitonin gene-related peptide, chronic pain, dietary fatty acids, docosahexaenoic acid, docosahexaenoyl ethanolamine/synaptamide, docosapentaenoyl ethanolamine, eCBs, eicosapentaenoyl ethanolamine, eicosenoyl glycerol, endocannabinoid metabolome, endocannabinoids, gas chromatography/mass spectrometry, glycerol-3-phosphate, glycerophospho-containing N-acyl ethanolamines, glycerophosphodiesterase, growth-associated protein 43, hindpaw withdrawal latency, linoleyl ethanolamine, lyso-phosphatidic, omega-3 polyunsaturated fatty acids, palmitoyl ethanolamine, partial least square-discriminant analysis, phosphatidic acid, phospholipase A/B or α-β-hydrolase 4, phospholipase D, spinal cord injury, thermal hyperalgesia, ultrahigh performance liquid chromatography/tandem mass spectrometry

PMID:

 

24042033

 

[PubMed – as supplied by publisher]
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