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 15min before
carrageenan injection blocked
carrageenan-induced
pain hypersensitivity for more than 6h. In addition, i.t. injection of DHA at 3h 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-α - TNF-α and
interleukin-1β - IL-1β) 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-α, IL-1β, 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.