Hyperalgesia induced by Bothrops jararaca venom in rats: role of eicosanoids and platelet activating factor (PAF).
In this study we investigated the ability of Bothrops jararaca venom (BjV) to induce hyperalgesia and the modulation of this effect by lipid mediators. It was found that intraplantar injection of BjV (1 to 25 micrograms) caused a dose and time-related hyperalgesia. The peak of the hyperalgesic response was 1 hr after injection of the venom and persisted for 24 hr with the higher dose. The BjV-induced hyperalgesia was markedly attenuated by dexamethasone. Dexamethasone blocks the generation of biologically active metabolites from arachidonic acid by inhibiting PLA2 activation. Inhibition of the cyclo-oxygenase pathway by indomethacin, or inhibition of lipoxygenases by NDGA both significantly inhibited BjV-induced hyperalgesia. Two antagonists of PAF, WEB2170 and BN52021, also significantly inhibited the initial phase of the hyperalgesia. These results suggest that hyperalgesia induced by BjV is, at least partially, mediated by lipid mediators such as prostaglandins, leukotrienes and PAF.
Teixeira
C F
CF
Laboratório de Farmacologia, Instituto Butantan, São Paulo, Brazil.
Cury
Y
Y
Oga
S
S
Jancar
S
S
D000818:Animals; D001381:Azepines / Q000627:therapeutic use; D017837:Bothrops; D003435:Crotalid Venoms / Q000037:antagonists & inhibitors / Q000633:toxicity*; D003907:Dexamethasone / Q000627:therapeutic use; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D015777:Eicosanoids / Q000096:biosynthesis / Q000502:physiology*; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D046934:Ginkgolides; D006930:Hyperalgesia / Q000139:chemically induced* / Q000188:drug therapy; D007213:Indomethacin / Q000627:therapeutic use; D007783:Lactones / Q000627:therapeutic use; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014230:Triazoles / Q000627:therapeutic use
D001381:Azepines; D003435:Crotalid Venoms; D004224:Diterpenes; D015777:Eicosanoids; D005343:Fibrinolytic Agents; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D014230:Triazoles; D003907:Dexamethasone; C063964:bepafant; C045856:ginkgolide B; D007213:Indomethacin