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Mechanisms involved in the nociception triggered by the venom of the armed spider Phoneutria nigriventer.

Abstract：

BACKGROUND:The frequency of accidental spider bites in Brazil is growing, and poisoning due to bites from the spider genus Phoneutria nigriventer is the second most frequent source of such accidents. Intense local pain is the major symptom reported after bites of P. nigriventer, although the mechanisms involved are still poorly understood. Therefore, the aim of this study was to identify the mechanisms involved in nociception triggered by the venom of Phoneutria nigriventer (PNV). METHODOLOGY/PRINCIPAL FINDINGS:Twenty microliters of PNV or PBS was injected into the mouse paw (intraplantar, i.pl.). The time spent licking the injected paw was considered indicative of the level of nociception. I.pl. injection of PNV produced spontaneous nociception, which was reduced by arachnid antivenin (ArAv), local anaesthetics, opioids, acetaminophen and dipyrone, but not indomethacin. Boiling or dialysing the venom reduced the nociception induced by the venom. PNV-induced nociception is not dependent on glutamate or histamine receptors or on mast cell degranulation, but it is mediated by the stimulation of sensory fibres that contain serotonin 4 (5-HT4) and vanilloid receptors (TRPV1). We detected a kallikrein-like kinin-generating enzyme activity in tissue treated with PNV, which also contributes to nociception. Inhibition of enzymatic activity or administration of a receptor antagonist for kinin B2 was able to inhibit the nociception induced by PNV. PNV nociception was also reduced by the blockade of tetrodotoxin-sensitive Na(+) channels, acid-sensitive ion channels (ASIC) and TRPV1 receptors. CONCLUSION/SIGNIFICANCE:Results suggest that both low- and high-molecular-weight toxins of PNV produce spontaneous nociception through direct or indirect action of kinin B2, TRPV1, 5-HT4 or ASIC receptors and voltage-dependent sodium channels present in sensory neurons but not in mast cells. Understanding the mechanisms involved in nociception caused by PNV are of interest not only for better treating poisoning by P. nigriventer but also appreciating the diversity of targets triggered by PNV toxins.

journal_name

PLoS Negl Trop Dis

journal_title

PLoS neglected tropical diseases

authors

Gewehr C,Oliveira SM,Rossato MF,Trevisan G,Dalmolin GD,Rigo FK,de Castro Júnior CJ,Cordeiro MN,Ferreira J,Gomez MV

doi

10.1371/journal.pntd.0002198

subject

Has Abstract

pub_date

2013-04-25 00:00:00

pages

e2198

issue

eissn

1935-2727

issn

1935-2735

pii

PNTD-D-12-01033

journal_volume

pub_type

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Mechanisms involved in the nociception triggered by the venom of the armed spider Phoneutria nigriventer.