Inflammation Research

, Volume 65, Issue 9, pp 725–736 | Cite as

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 HelyesEmail author
Original Research Paper


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).


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).


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.


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.


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.


Capsaicin-sensitive sensory nerves Arthritis Inflammation Pain Oedema Synovial microcirculation 



Calcitonin gene-related peptide




Mast cell tryptase


Tachykinin NK1 receptor


Neurokinin A


Protease-activated receptor 2


Transient receptor potential vanilloid 1




Substance P


Preprotachykinin 1 gene


Tachykinin NK1 receptor encoding gene


Tumour necrosis factor α



This work was supported by KTIA_NAP_13-2014-0022 (MTA-PTE NAP B Pain Research Group, identification number: 888819, Zs. Helyes) and OTKA NN-114458 (E. Pintér). The present scientific contribution is dedicated to the 650th anniversary of the foundation of the University of Pécs, Hungary. The authors are grateful to Teréz Bagoly for the CGRP and SP measurements.


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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
    Email author
  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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