Asahara,M., Ito,N., Yokomizo,T., Nakamura,M. Shimizu,T., and Yamada Y.
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Abstract
Background: Leukotriene B4 (LTB4) is a potent lipid mediator of inflammation, and its biological effects are mediated
primarily through the high affinity LTB4 receptor BLT1. Although numerous studies have reported that LTB4-BLT1
signaling is involved in inflammatory diseases, the role of BLT1 signaling in pain remains undefined. To clarify the role
of LTB4-BLT1 signaling in acute inflammatory pain induced by tissue injury, we performed pain behavioral analysis and
assessment of local inflammation induced by peripheral formalin injections in BLT1 knockout mice. We examined the
phosphorylation of cAMP response element-binding protein (CREB) in the spinal cord both in wild-type and BLT1
knockout mice because phosphorylation of CREB in spinal cord neurons is important for nociceptive sensitization
following peripheral injury. We also examined the effect of a BLT1 antagonist on formalin-induced pain responses
in mice.
Results: BLT1 knockout mice exhibited markedly attenuated nociceptive responses induced by intraplantar formalin
injections. Edema formation and neutrophil infiltration in the paw were significantly decreased in BLT1 knockout mice
compared with wild-type mice. Phosphorylation of CREB in the spinal cord after the intraplantar formalin injection was
decreased in BLT1 knockout mice. In addition, mice pretreated with a BLT1 antagonist showed reduced nociception
and attenuated CREB phosphorylation in the spinal cord after the formalin injection.
Conclusions: Our data suggest that LTB4-BLT1 axis contributes not only to the peripheral inflammation but also to
the neuronal activation in the spinal cord induced by intraplantar formalin injections. Thus, LTB4-BLT1 signaling is a
potential target for therapeutic intervention of acute and persistent pain induced by tissue injury.
Keywords: Inflammation, Leukotriene, Formalin test, Sensitization
Research papers (academic journals)
