Analgesic properties of S100A9 C-terminal domain: a mechanism dependent on calcium channel inhibition

Analgesic properties of S100A9 C-terminal domain: a mechanism dependent on calcium channel inhibition

Author Dale, Camila Squarzoni Google Scholar
Altier, Christophe Google Scholar
Cenac, Nicolas Google Scholar
Giorgi, Renata Google Scholar
Juliano, Maria Aparecida Autor UNIFESP Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Zamponi, Gerald W. Google Scholar
Vergnolle, Nathalie Google Scholar
Institution INSERM
Univ Toulouse 3
Univ Calgary
Butantan Inst
Universidade Federal de São Paulo (UNIFESP)
Abstract Calcium-binding protein S100A9 and its C-terminus peptide (mS100A9p) are anti-inflammatory and induce antinociception in rodents. We investigated the mechanisms involved in this effect, and whether they depend or not on the anti-inflammatory properties of mS100A9p. in mice, mS100A9p inhibited thermal and mechanical hyperalgesia and allodynia induced by either carrageenan or formalin, without interfering with paw edema. mS100A9p also inhibited myeloperoxidase activity (MPO), a marker of granulocyte infiltration, induced by carrageenan, but increased MPO after formalin intraplantar injection. the in vivo analgesic properties of mS100A9p were independent of opioid receptor activation. Calcium flux into dorsal root ganglia neurons induced by KCl was inhibited by mS100A9p, suggesting that this protein is able to inhibit signaling, in sensory neurons. the inhibitory effects of mS100A9p on primary afferent signaling were neither due to intracellular calcium store inhibition nor to calcium chelating properties. However, mS100A9p was able to inhibit calcium currents carried by transiently expressed N-type, but not L-type calcium channels, as demonstrated both by gene transfection techniques and electrophysiology. These data demonstrate that mS100A9p interferes with mechanisms involved in nociception, hyperalgesia and calcium signaling in sensory neurons, modulating primary afferent nociceptive signal by inhibiting activation of N-type voltage operated calcium channels.
Keywords antinociception
dorsal root ganglia neurons
N-type calcium channels
voltage operated calcium channels
Language English
Date 2009-08-01
Published in Fundamental & Clinical Pharmacology. Malden: Wiley-Blackwell Publishing, Inc, v. 23, n. 4, p. 427-438, 2009.
ISSN 0767-3981 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 427-438
Access rights Closed access
Type Article
Web of Science ID WOS:000268588700006

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