title: Role of capsaicin-sensitive nerves and tachykinins in mast cell tryptase-induced inflammation of murine knees.
abstract: 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.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti u. 12, Pecs, 7624, Hungary.|János Szentágothai Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, University of Pécs, Pecs, Hungary.
authors.forename: Éva
authors.initials: É
authors.lastname: Borbély
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti u. 12, Pecs, 7624, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Sándor
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti u. 12, Pecs, 7624, Hungary.|János Szentágothai Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, University of Pécs, Pecs, Hungary.
authors.forename: Adrienn
authors.initials: A
authors.lastname: Markovics
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti u. 12, Pecs, 7624, Hungary.|János Szentágothai Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, University of Pécs, Pecs, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Kemény
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti u. 12, Pecs, 7624, Hungary.|János Szentágothai Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, University of Pécs, Pecs, Hungary.
authors.forename: Erika
authors.initials: E
authors.lastname: Pintér
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti u. 12, Pecs, 7624, Hungary.|János Szentágothai Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, University of Pécs, Pecs, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Szolcsányi
authors.affiliation: School of Biomedical Sciences, Liverpool University, Liverpool, UK.
authors.forename: John P
authors.initials: JP
authors.lastname: Quinn
authors.affiliation: Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: McDougall
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti u. 12, Pecs, 7624, Hungary. zsuzsanna.helyes@aok.pte.hu.|János Szentágothai Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, University of Pécs, Pecs, Hungary. zsuzsanna.helyes@aok.pte.hu.|MTA-PTE NAP B Chronic Pain Research Group, Pecs, Hungary. zsuzsanna.helyes@aok.pte.hu.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Helyes
mesh_terms: D000818:Animals; D001168:Arthritis / Q000139:chemically induced* / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin; D016207:Cytokines / Q000378:metabolism; D004487:Edema / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D006930:Hyperalgesia / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020078:Neurogenic Inflammation / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D010146:Pain / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D011498:Protein Precursors / Q000235:genetics; D044464:Receptor, PAR-2 / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000235:genetics; D013373:Substance P / Q000378:metabolism; D050916:TRPV Cation Channels / Q000235:genetics; D015320:Tachykinins / Q000235:genetics; D014110:Touch; D053802:Tryptases
chemical_list: D016207:Cytokines; D011498:Protein Precursors; D044464:Receptor, PAR-2; D018040:Receptors, Neurokinin-1; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P; D053802:Tryptases; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin
keywords: Arthritis; Capsaicin-sensitive sensory nerves; Inflammation; Oedema; Pain; Synovial microcirculation