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

Éva Borbély, Katalin Sándor, Adrienn Markovics, Ágnes Kemény, Erika Pintér, János Szolcsányi, John P. Quinn, Jason J. McDougall, Zsuzsanna Helyes

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)725-736
Number of pages12
JournalInflammation Research
Volume65
Issue number9
DOIs
Publication statusPublished - Sep 1 2016

Keywords

  • Arthritis
  • Capsaicin-sensitive sensory nerves
  • Inflammation
  • Oedema
  • Pain
  • Synovial microcirculation

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

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