title: Involvement of circulating platelets on the hyperalgesic response evoked by carrageenan and Bothrops jararaca snake venom.
abstract: BACKGROUND
  The role of platelets in hemostasis is well known, but few papers have reported their role in pain and edema induced by inflammatory agents.
  
  
  OBJECTIVE
  To evaluate the role of circulating platelets in the local injury induced by two diverse inflammatory agents, Bothrops jararaca venom (Bjv) and carrageenan.
  
  
  METHODS
  Rats were (i) rendered thrombocytopenic by administration of polyclonal anti-rat platelet IgG (ARPI) or busulfan, or (ii) treated with platelet inhibitors (aspirin or clopidogrel). Edema formation, local hemorrhage and the pain threshold were assessed after intraplantar injection of Bjv or carrageenan in rat hind paws. Additionally, whole platelets or platelet releasate were tested whether they directly induced hyperalgesia.
  
  
  RESULTS
  Platelet counts were markedly diminished in rats administered with either ARPI (± 88%) or busulfan (± 96%). Previous treatment with ARPI or busulfan slightly reduced edema induced by Bjv or carrageenan. Injection of Bjv, but not of carrageenan, induced a statistically significance increase in hemorrhage in the hind paws of thrombocytopenic rats. Remarkably, hyperalgesia evoked by Bjv or carrageenan was completely blocked in animals treated with ARPI or busulfan, or pre-treated with aspirin or clopidogrel. On the other hand, intraplantar administration of whole platelets or platelet releasate evoked hyperalgesia, which was inhibited by pre-incubation with alkaline phosphatase.
  
  
  CONCLUSIONS
  Thrombocytopenia or inhibition of platelet function drastically reduced hyperalgesia induced by injection of carrageenan or Bjv; moreover, platelets per se secrete phosphorylated compounds involved in pain mediation. Thus, blood platelets are crucial cells involved in the pain genesis, and their role therein has been underestimated.
authors.affiliation: Laboratory of Pathophysiology, Institute Butantan, São Paulo, Brazil.
authors.forename: K M
authors.initials: KM
authors.lastname: Yamashita
authors.forename: T O
authors.initials: TO
authors.lastname: Nogueira
authors.forename: L V
authors.initials: LV
authors.lastname: Senise
authors.forename: M C
authors.initials: MC
authors.lastname: Cirillo
authors.forename: L R C
authors.initials: LR
authors.lastname: Gonçalves
authors.forename: I S
authors.initials: IS
authors.lastname: Sano-Martins
authors.forename: R
authors.initials: R
authors.lastname: Giorgi
authors.forename: M L
authors.initials: ML
authors.lastname: Santoro
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology* / Q000201:enzymology; D017837:Bothrops; D002066:Busulfan / Q000633:toxicity; D002351:Carrageenan / Q000494:pharmacology*; D000077144:Clopidogrel; D003435:Crotalid Venoms / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000187:drug effects; D006930:Hyperalgesia / Q000139:chemically induced* / Q000517:prevention & control; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013921:Thrombocytopenia / Q000139:chemically induced; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D003435:Crotalid Venoms; D002351:Carrageenan; D000077144:Clopidogrel; D051545:Cyclooxygenase 1; D002066:Busulfan; D013988:Ticlopidine; D001241:Aspirin