Role of capsaicin-sensitive nerves and tachykinins in mast cell tryptase-induced inflammation of murine knees
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- Borbély, É., Sándor, K., Markovics, A. et al. Inflamm. Res. (2016) 65: 725. doi:10.1007/s00011-016-0954-x
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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.
KeywordsCapsaicin-sensitive sensory nerves Arthritis Inflammation Pain Oedema Synovial microcirculation
Calcitonin gene-related peptide
Mast cell tryptase
Tachykinin NK1 receptor
Protease-activated receptor 2
Transient receptor potential vanilloid 1
Preprotachykinin 1 gene
Tachykinin NK1 receptor encoding gene
Tumour necrosis factor α