The absence of the leukotriene B4 receptor BLT1 attenuates peripheral inflammation and spinal nociceptive processing following intraplantar formalin injury.

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.

• Authors: Miho Asahara, Nobuko Ito, Takehiko Yokomizo, Motonao Nakamura, Takao Shimizu, Yoshitsugu Yamada
• Journal: Molecular pain (Mol Pain) Vol. 11 Pg. 11 (Mar 12 2015) ISSN: 1744-8069 [Electronic] United States
• PMID: 25889478 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclic AMP Response Element-Binding Protein
• Ltb4r1 protein, mouse
• Receptors, Leukotriene B4
• Formaldehyde

Topics

• Animals
• Cyclic AMP Response Element-Binding Protein (metabolism)
• Formaldehyde (toxicity)
• Inflammation (metabolism)
• Mice
• Mice, Knockout
• Pain (metabolism)
• Receptors, Leukotriene B4 (deficiency, metabolism)
• Signal Transduction (drug effects)
• Spinal Cord (metabolism)