SPINAL INJECTION OF DOCOSAHEXAENOIC ACID ATTENUATES CARRAGEENAN-INDUCED INFLAMMATORY PAIN THROUGH INHIBITION OF MICROGLIA-MEDIATED NEUROINFLAMMATION IN THE SPINAL CORD

Neuroinflammation in the spinal cord plays a critical role in the processing of inflammatory pain. Docosahexaenoic acid (DHA), a predominant omega-3 polyunsaturated fatty acid in the central nervous system, is known to modulate inflammatory responses in various neurodegenerative disorders. In this study, we investigated whether DHA could reduce inflammatory pain and inhibit neuroinflammation in the spinal cord following carrageenan injection in mice. Intrathecal (i.t.) injection of DHA at 15 min before carrageenan injection blocked carrageenan-induced pain hypersensitivity for more than 6 h. In addition, i.t. injection of DHA at 3 h after carrageenan transiently reversed carrageenan-induced heat hyperalgesia and mechanical allodynia. Furthermore, DHA treatment reduced carrageenan-induced activation of microglia, phosphorylation of p38 mitogen-activated protein kinase (MAPK), and production of proinflammatory cytokines (tumor necrosisfactor-alpha - TNF-alpha and interleukin-1 beta - IL-1 beta) in the L4-5 spinal cord. In cultured microglial cells, DHA dose-dependently reduced lipopolysaccharide (LPS)-induced phosphorylation of p38, production of proinflammatory cytokines (TNF-a, IL-1 beta, IL-6) and chemokines (CCL2, CCL3 and CXCL10). p38 inhibitor SB203580 inhibited LPS-induced expression of proinflammatory cytokines and chemokines in a dose-dependent manner. Taken together, these results provide evidence that DHA has antinociceptive effect in inflammatory pain, which may be attributed to, at least partially, suppressing a microglia-mediated inflammatory response through inhibition of p38 MAPK activation. (c) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.