Acta Physiologica 2011; Volume 202, Supplement 684
The Joint Conference (FAMÉ 2011) of the LXXVth Meeting of the Hungarian Physiological Society, XVIth Meeting of the Hungarian Society of Anatomists, Experimental Section of the Hungarian Society for Experimental and Clinical Pharmacology and Hungarian Society for Microcirculation and Vascular Biology
ROLE OF CAPSAICIN-SENSITIVE SENSORY NERVES AND TACHYKININS IN MAST CELL TRYPTASE-INDUCED ACUTE ARTHRITIS OF THE MOUSE
Abstract number: P8
Borbely1 É., Sandor1 K., Markovics1 A., Pinter1 E., Szolcsanyi1 J., Quinn2 J. P., McDougall3 J. J., Helyes1 Zs.
Protease-activated receptors (PARs) are activated through proteolytic cleavage and coupled to G-proteins. They are localized on epithelial, endothelial/inflammatory cells, and transient receptor potential vanilloid 1 (TRPV1)-expressing capsaicin-sensitive afferents. Tachykinins, encoded by the TAC1 gene (substance P; neurokinin A) are released from these fibres and mediate inflammation and pain. We investigated the role of capsaicin-sensitive fibres, TRPV1 channels, NK1 receptors and TAC1-encoded tachykinins in mast cell tryptase (MCT)-induced acute joint swelling, hyperalgesia and synovial microcirculation.
Knee diameter was measured with a digital micrometer, mechanonociceptive threshold with dynamic plantar aesthesiometry and spontaneous weight distribution with incapacitance tester. Synovial bloodflow was determined by laser Doppler imaging. Resiniferatoxin (RTX)-desensitized, TRPV1, TAC1 and NK1 gene-deficient (-/-)animals were studied compared to their wildtype (WT) C57Bl/6 counterparts.
MCT-induced joint swelling and secondary hyperalgesia were significantly reduced in TAC1-/- and NK1-/- mice, but not in the other groups. Spontaneous weight distribution decreased on the MCT injection site in WT mice, but not in any other groups. MCT-induced synovial vasodilatation was significantly reduced by capsaicin-sensitive fibre-destruction with RTX and the lack of TRPV1 receptors, but was not altered in TAC1 and NK1 deficient mice.
MCT-evoked acute edema and hyperalgesia are mediated by tachykinins via NK1 receptor activation. The lack of difference in RTX-desensitized and TRPV1-/- mice is explained by counteracting effects of simultaneously released inhibitory peptides (e.g. somatostatin, endomorphins). In contrast, these sensory nerves and TRPV1 channels are essential in acute synovial vasodilatation, but tachykinins are not involved in this response.
OTKA K72592, K73044, ETT 03-380/2009, SROP-4.2.1.B-10/2/KONV-2010-0002
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Acta Physiologica 2011; Volume 202, Supplement 684 :P8