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

• DOI: 10.1016/j.neuroscience.2013.09.012
• Publication Date: 2013-09-14T01:47:23Z
• Authors: J.D. Figueroa; K. Cordero; M. Serrano-Illan; A. Almeyda; K. Baldeosingh; F.G. Almaguel; M. De Leon
• Keywords: 0301 basic medicine; dietary fatty acids; Neuroscience(all); Fluorescent Antibody Technique; EPA; Dietary Fats; spinal cord injury; endocannabinoid metabolome; Rats; DHA; Rats, Sprague-Dawley; Disease Models, Animal; 03 medical and health sciences; Hyperalgesia; Tandem Mass Spectrometry; Fatty Acids, Omega-3; Animals; Metabolomics; Female; chronic pain; Chromatography, High Pressure Liquid; Spinal Cord Injuries

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