Inflammation Research

, Volume 65, Issue 9, pp 725–736

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
Original Research Paper

DOI: 10.1007/s00011-016-0954-x

Cite this article as:
Borbély, É., Sándor, K., Markovics, A. et al. Inflamm. Res. (2016) 65: 725. doi:10.1007/s00011-016-0954-x

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.

Keywords

Capsaicin-sensitive sensory nerves Arthritis Inflammation Pain Oedema Synovial microcirculation 

Abbreviations

CGRP

Calcitonin gene-related peptide

IL-1β

Interleukin-1β

MCT

Mast cell tryptase

NK1

Tachykinin NK1 receptor

NKA

Neurokinin A

PAR2

Protease-activated receptor 2

TRPV1

Transient receptor potential vanilloid 1

RTX

Resiniferatoxin

SP

Substance P

Tac1

Preprotachykinin 1 gene

Tacr1

Tachykinin NK1 receptor encoding gene

TNFα

Tumour necrosis factor α

Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  • Éva Borbély
    • 1
    • 2
  • Katalin Sándor
    • 1
  • Adrienn Markovics
    • 1
    • 2
  • Ágnes Kemény
    • 1
    • 2
  • Erika Pintér
    • 1
    • 2
  • János Szolcsányi
    • 1
    • 2
  • John P. Quinn
    • 4
  • Jason J. McDougall
    • 5
  • Zsuzsanna Helyes
    • 1
    • 2
    • 3
  1. 1.Department of Pharmacology and Pharmacotherapy, Medical SchoolUniversity of PécsPecsHungary
  2. 2.János Szentágothai Research Centre, Molecular Pharmacology Research GroupCentre for Neuroscience, University of PécsPecsHungary
  3. 3.MTA-PTE NAP B Chronic Pain Research GroupPecsHungary
  4. 4.School of Biomedical SciencesLiverpool UniversityLiverpoolUK
  5. 5.Department of PharmacologyDalhousie UniversityHalifaxCanada

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