title: 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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Programa de Pós-graduação em Ciências da Saúde: Biomedicina e Medicina, Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Grupo Santa Casa de Belo Horizonte, Belo Horizonte, Minas Gerais, Brazil.
authors: Camila
authors: C
authors: Gewehr
authors: Sara Marchesan
authors: SM
authors: Oliveira
authors: Mateus Fortes
authors: MF
authors: Rossato
authors: Gabriela
authors: G
authors: Trevisan
authors: Gerusa Duarte
authors: GD
authors: Dalmolin
authors: Flávia Karine
authors: FK
authors: Rigo
authors: Célio José
authors: CJ
authors: de Castro Júnior
authors: Marta Nascimento
authors: MN
authors: Cordeiro
authors: Juliano
authors: J
authors: Ferreira
authors: Marcus V
authors: MV
authors: Gomez
mesh_terms: D000818:Animals; D008297:Male; D051379:Mice; D059225:Nociception / Q000502:physiology*; D010146:Pain / Q000139:chemically induced / Q000378:metabolism*; D013111:Spider Venoms / Q000633:toxicity*
chemical_list: D013111:Spider Venoms
references: J Allergy Clin Immunol. 2009 Jul;124(1):143-9
references: 19342086
references: Neuroreport. 2004 May 19;15(7):1187-90
references: 15129171
references: Br J Pharmacol. 2004 Mar;141(5):787-94
references: 14967737
references: Eur J Pharmacol. 2011 Dec 15;672(1-3):88-95
references: 22004612
references: Anal Biochem. 1976 May 7;72:248-54
references: 942051
references: Pain. 1983 Jun;16(2):109-110
references: 6877845
references: Pain. 2000 Dec 15;89(1):53-63
references: 11113293
references: Naunyn Schmiedebergs Arch Pharmacol. 1993 Feb;347(2):205-8
references: 8386326
references: Peptides. 1989 Nov-Dec;10(6):1147-52
references: 2482964
references: Biochem Pharmacol. 2004 Dec 1;68(11):2151-7
references: 15498505
references: Toxicon. 2008 Feb;51(2):163-73
references: 18061640
references: Neuropharmacology. 2004 Mar;46(4):590-7
references: 14975683
references: J Pain. 2010 Jun;11(6):570-8
references: 20338819
references: Anal Biochem. 1963 Nov;6:393-403
references: 14077633
references: Nature. 2006 Nov 9;444(7116):208-12
references: 17093448
references: J Pharmacol Exp Ther. 1969 Apr;166(2):285-90
references: 5776986
references: Biochem Pharmacol. 2011 Feb 15;81(4):544-51
references: 21087598
references: Lancet. 2011 Dec 10;378(9808):2039-2047
references: 21762981
references: Pain. 2005 Sep;117(1-2):171-81
references: 16099101
references: Pain. 1975 Mar;1(1):3-49
references: 800636
references: J Biol Chem. 2007 Jun 15;282(24):17325-9
references: 17430882
references: Inflamm Res. 2003 Mar;52(3):132-9
references: 12755378
references: Pain. 2008 Nov 15;140(1):115-126
references: 18774645
references: Biochem J. 1993 Dec 1;296 ( Pt 2):313-9
references: 7504921
references: Br J Pharmacol. 1991 Aug;103(4):1958-62
references: 1717093
references: Rev Inst Med Trop Sao Paulo. 2000 Jan-Feb;42(1):17-21
references: 10742722
references: Br J Dermatol. 2005 Apr;152(4):650-7
references: 15840094
references: Pain. 2002 Oct;99(3):397-406
references: 12406514
references: J Neurosci. 2002 Feb 1;22(3):1010-9
references: 11826129
references: J Hum Hypertens. 1999 Nov;13(11):771-5
references: 10578222
references: Pain. 1999 Dec;83(3):561-569
references: 10568865
references: Neuroscience. 2007 Mar 16;145(2):686-98
references: 17258862
references: Biochemistry. 2009 Apr 14;48(14):3078-88
references: 19231838
references: Nat Rev Neurosci. 2009 Apr;10(4):283-94
references: 19259101
references: Mem Inst Butantan. 1966;33(2):627-38
references: 6012216
references: Behav Pharmacol. 2011 Sep;22(5-6):390-404
references: 21808193
references: Toxicon. 1992 Sep;30(9):1011-6
references: 1359680
references: Pharmacol Biochem Behav. 2011 Oct;99(4):775-81
references: 21763717
references: Pharmacol Rev. 2005 Mar;57(1):27-77
references: 15734727
references: J Pharmacol Exp Ther. 2012 Oct;343(1):44-52
references: 22736506
references: Brain Res. 2002 Jan 11;924(2):219-28
references: 11750907
references: Eur J Pharmacol. 2009 Jan 28;603(1-3):56-61
references: 19109946
references: Neurosci Lett. 1998 Oct 30;256(1):17-20
references: 9832206
references: Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):E1578-86
references: 22586118
references: Br J Pharmacol. 1996 May;118(2):295-8
references: 8735630
references: Pain. 2011 Aug;152(8):1777-1788
references: 21550723
references: Br J Pharmacol. 2003 May;139(1):59-64
references: 12746223
references: Br J Rheumatol. 1994 Mar;33(3):215-23
references: 7512421
references: Peptides. 2011 Oct;32(10):2122-6
references: 21939705
references: Pain. 2000 Jul;87(1):1-5
references: 10863040
references: Toxicon. 1988;26(9):759-72
references: 3059583
references: Somatosens Res. 1987;5(2):81-92
references: 3423533
references: Braz J Med Biol Res. 2004 Mar;37(3):401-7
references: 15060710
references: Br J Pharmacol. 1993 Jun;109(2):539-43
references: 8395291
references: Nature. 2011 Nov 16;479(7373):410-4
references: 22094702
references: Eur J Pharmacol. 2008 Feb 26;581(1-2):86-96
references: 18190906
references: Mem Inst Butantan. 1953;25(1):153-74
references: 13193521
references: J Comp Neurol. 2005 Dec 26;493(4):596-606
references: 16304633
references: Life Sci. 2001 Aug 17;69(13):1573-85
references: 11554618
references: Neuropeptides. 1997 Aug;31(4):381-9
references: 9308027
references: Basic Clin Pharmacol Toxicol. 2009 Feb;104(2):122-9
references: 19143754
references: Cell. 2010 May 28;141(5):834-45
references: 20510930
references: J Med Entomol. 2009 Jan;46(1):58-66
references: 19198518
references: Comp Biochem Physiol C Toxicol Pharmacol. 2006 Mar-Apr;142(3-4):173-187
references: 16278100
references: Eur J Pharmacol. 2003 Apr 25;467(1-3):111-8
references: 12706463
references: J Neuropathol Exp Neurol. 2008 Feb;67(2):93-104
references: 18219259
references: Toxicon. 1982;20(6):1059-67
references: 7164108