title: Peripheral neurokinin-1 receptors contribute to kaolin-induced acute monoarthritis in rats.
abstract: OBJECTIVE
  intra-articular co-injection of kaolin with carrageenan (CGN) in rodents is widely used as an experimental model of arthritis. However, the ability of kaolin to cause arthritis and related immune responses when administered alone is unclear. We evaluated the contribution of prostanoids and sensory C-fibres (and their neuropeptide substance P) to kaolin-induced inflammation in the rat knee.
  
  
  METHODS
  Wistar rats, 8-10 weeks old, received an intra-articular injection of kaolin (1-10 μg/joint) or saline into the knee joint. Knee inflammation, proinflammatory cytokines, pain behaviour and secondary tactile allodynia were assessed over 5 h, when synovial leukocyte counts, histopathological changes and proinflammatory cytokine levels were evaluated.
  
  
  RESULTS
  The intra-articular injection of kaolin caused a dose- and time-dependent knee swelling and impairment of motion that were associated with secondary tactile allodynia, elevated concentrations of IL-1β, IL-6 and TNFα, leukocyte infiltration, and histopathological changes in the ipsilateral hindpaw. The neurokinin-1 (NK1) receptor antagonist SR140333 or neonatal treatment with capsaicin markedly reduced the inflammatory parameters, cytokines and allodynia but failed to significantly inhibit the impaired motion. The cyclo-oxygenase inhibitor indomethacin partially inhibited knee oedema and allodynia but did not affect the leukocyte influx, myeloperoxidase activity or impaired motion in the kaolin-injected rat.
  
  
  CONCLUSIONS
  We show the first evidence that intra-articular injection of kaolin without CGN produced severe acute monoarthritis. This was highly dependent on substance P (released from C-fibres) and NK1 receptor activation, which stimulated local production of proinflammatory cytokines. This model may be of critical importance for mechanistic studies and screening new anti-inflammatory/analgesic drugs.
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of Sx00E3;o Paulo (USP), Sx00E3;o Paulo, Brazil.
authors.forename: Livia L
authors.initials: LL
authors.lastname: Camargo
authors.forename: Alexandre
authors.initials: A
authors.lastname: Denadai-Souza
authors.forename: Lidia M
authors.initials: LM
authors.lastname: Yshii
authors.forename: Filiphe P N
authors.initials: FP
authors.lastname: Mesquita
authors.forename: Antonio G
authors.initials: AG
authors.lastname: Soares
authors.forename: Carla
authors.initials: C
authors.lastname: Lima
authors.forename: André
authors.initials: A
authors.lastname: Schenka
authors.forename: Andrew
authors.initials: A
authors.lastname: Grant
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fernandes
authors.forename: Marcelo N
authors.initials: MN
authors.lastname: Muscará
authors.forename: Soraia K P
authors.initials: SK
authors.lastname: Costa
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000930:Antidiarrheals / Q000633:toxicity*; D001168:Arthritis / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy; D002211:Capsaicin / Q000633:toxicity; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004487:Edema / Q000209:etiology; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006930:Hyperalgesia / Q000209:etiology; D007213:Indomethacin / Q000627:therapeutic use; D007616:Kaolin / Q000633:toxicity*; D007719:Knee Joint / Q000473:pathology; D008297:Male; D010147:Pain Measurement; D009195:Peroxidase / Q000378:metabolism; D010880:Piperidines / Q000627:therapeutic use; D011812:Quinuclidines / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D013582:Synovial Fluid / Q000378:metabolism
chemical_list: D000930:Antidiarrheals; D016207:Cytokines; D004791:Enzyme Inhibitors; D010880:Piperidines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; C085215:SR 140333; D007616:Kaolin; D009195:Peroxidase; D002211:Capsaicin; D007213:Indomethacin