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Lysophosphatidic acid-induced, pertussis toxin-sensitive nociception through a substance P release from peripheral
1Department of Molecular Pharmacology and Neuroscience, Nagasaki University School of Pharmaceutical Sciences, Japan.
Abstract:
The intraplantar injection of lysophosphatidic acid (LPA) at doses of 0.1-100 pmol into the hind limb of mice showed dose-dependent nociceptive flexor responses. Repeated challenges of LPA at 100 pmol every 5 min showed constant responses at least for 30 min. The prior application of pertussis toxin (PTX) at a dose of 10 ng markedly reduced the following LPA (100 pmol) actions. In addition, the intraplantar application of CP-99994 (1 pmol), a substance P (NK1) receptor antagonist, but not CP-100263 (1 pmol), an inactive derivative, also markedly reduced the LPA responses. These findings suggest that LPA has a nociception-producing activity on sensory neurons through G(i/o) activation and substance P release from nociceptor endings.