Peripheral Neurokinin-1 Receptors Contribute to Kaolin-Induced Acute Monoarthritis in Rats

NeuroImmunoModulation - Tập 22 Số 6 - Trang 373-384 - 2015
Lívia L. Camargo1, Alexandre Denadai‐Souza1, Lidia Yshii1, Filiphe P.N. Mesquita1, António G. Soares1, Carla Lima2, André Almeida Schenka3, Andrew Grant4, Elizabeth S. Fernandes5,6, Marcelo N. Muscará1, Soraia K.P. Costa1
1Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo (USP), and
2Special Laboratory of Applied Toxinology (CAT/CEPID), Butantan Institute, São Paulo,
3Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, and
4Wolfson Wing, Hodgkin Building, Guy's Campus, and
5BHF Cardiovascular Centre of Excellence and Centre of Integrative Biomedicine, Cardiovascular Division, Waterloo Campus, King's College, London, UK
6Programa de Pós-Graduação em Biologia Parasitária, Universidade Ceuma, São Luís, Brazil

Tóm tắt

<b><i>Objective:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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 (NK<sub>1</sub>) 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. <b><i>Conclusions:</i></b> 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 NK<sub>1</sub> 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.

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NeuroImmunoModulation

Tập 22 Số 6

373-384

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