Role of capsaicin-sensitive nerves and tachykinins in mast cell tryptase-induced inflammation of murine knees

Borbely, Eva, Sandor, Katalin, Markovics, Adrienn, Kemeny, Agnes, Pinter, Erika, Szolcsanyi, Janos, Quinn, John P ORCID: 0000-0003-3551-7803, McDougall, Jason J and Helyes, Zsuzsanna (2016) Role of capsaicin-sensitive nerves and tachykinins in mast cell tryptase-induced inflammation of murine knees INFLAMMATION RESEARCH, 65 (9). pp. 725-736. ISSN 1023-3830, 1420-908X

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Abstract

Objective, design: Mast cell tryptase (MCT) is elevated in arthritic joints, but its direct effects are not known. Here, we investigated MCT-evoked acute inflammatory and nociceptive mechanisms with behavioural, in vivo imaging and immunological techniques. Material and subjects: Neurogenic inflammation involving capsaicin-sensitive afferents, transient receptor potential vanilloid 1 receptor (TRPV1), substance P (SP), neurokinin A (NKA) and their NK1 tachykinin receptor were studied using gene-deleted mice compared to C57Bl/6 wildtypes (n = 5–8/group). Treatment: MCT was administered intraarticularly or topically (20 μl, 12 μg/ml). Capsaicin-sensitive afferents were defunctionalized with the TRPV1 agonist resiniferatoxin (RTX; 30–70–100 μg/kg s.c. pretreatment). Methods: Knee diameter was measured with a caliper, synovial perfusion with laser Doppler imaging, mechanonociception with aesthesiometry and weight distribution with incapacitance tester over 6 h. Cytokines and neuropeptides were determined with immunoassays. Results: MCT induced synovial vasodilatation, oedema, impaired weight distribution and mechanical hyperalgesia, but cytokine or neuropeptide levels were not altered at the 6-h timepoint. Hyperaemia was reduced in RTX-treated and TRPV1-deleted animals, and oedema was absent in NK1-deficient mice. Hyperalgesia was decreased in SP/NKA- and NK1-deficient mice, weight bearing impairment in RTX-pretreated, TRPV1- and NK1-deficient animals. Conclusions: MCT evokes synovial hyperaemia, oedema, hyperalgesia and spontaneous pain. Capsaicin-sensitive afferents and TRPV1 receptors are essential for vasodilatation, while tachykinins mediate oedema and pain.

Item Type:	Article
Uncontrolled Keywords:	Capsaicin-sensitive sensory nerves, Arthritis, Inflammation, Pain, Oedema, Synovial microcirculation
Depositing User:	Symplectic Admin
Date Deposited:	27 Oct 2016 11:04
Last Modified:	24 Jun 2026 13:41
DOI:	10.1007/s00011-016-0954-x
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3004021
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