RESUMO
The aim of this work was to verify whether formalin would induce leukocyte recruitment following intraperitoneal (i.p.) injection in rats. Formalin (1.25 - 2.5%) induced cell recruitment, which was concentration- and time-dependent (0 - 24 h). Two peaks of leukocyte recruitment were observed. The first peak (from 2 to 4 h) was characterized by a mixed polymorphonuclear and lymphocyte cell population (representing an increase of 100 - 220% and 55 - 60%, respectively), whereas the second peak was characterized by a marked increase in lymphocytes at 24 h (representing an increase of 230%). Pretreatment of animals with specific antagonists for neurokinin NK(1), NK(2), and NK(3) receptors (SR140333, SR48968, and SR142801 compounds, respectively) reduced the early leukocyte increase (representing a significant reduction of 65%, 51%, and 46%, respectively), whereas only the treatment with NK(2)-specific antagonist reduced the late cell increase induced by formalin injection (amounting to a significant reduction of 48%). These results suggested that substance P, neurokinin A, and neurokinin B release accounted for formalin-induced cell migratory activity. The anti-inflammatory drug dexamethasone also reduced cell recruitment, which was mainly related to a reduction in 79% of the neutrophils at 4 h following 1.25% formalin injection, suggesting also a release of lipid mediators (eicosanoids and/or platelet-activating factor) and/or cytokines/chemokines by the formalin injection.
Assuntos
Formaldeído/administração & dosagem , Formaldeído/farmacologia , Leucócitos/fisiologia , Cavidade Peritoneal/fisiologia , Receptores de Taquicininas/antagonistas & inibidores , Animais , Benzamidas/farmacologia , Movimento Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Injeções Intraperitoneais , Leucócitos/citologia , Leucócitos/efeitos dos fármacos , Modelos Biológicos , Neurocinina A/metabolismo , Neurocinina B/metabolismo , Antagonistas dos Receptores de Neurocinina-1 , Lavagem Peritoneal , Piperidinas/farmacologia , Quinuclidinas/farmacologia , Ratos , Ratos Endogâmicos , Receptores da Neurocinina-1/efeitos dos fármacos , Receptores da Neurocinina-2/antagonistas & inibidores , Receptores da Neurocinina-2/efeitos dos fármacos , Receptores da Neurocinina-3/antagonistas & inibidores , Receptores da Neurocinina-3/efeitos dos fármacos , Receptores de Taquicininas/efeitos dos fármacos , Substância P/metabolismo , Fatores de TempoRESUMO
We investigated the involvement of endogenous gamma-aminobutyric acid (GABA) in the modulation of secondary hyperalgesia induced by intraplantar (i.pl.) injection of 5% formalin in the rat tail-flick test. Intraplantar injection of gabamimetic drugs such as gabapentin (150-600 microg/site) or phenobarbital (20-80 microg/site) reversed secondary hyperalgesia, as measured by an increase in the tail-flick latency, thus displaying a peripheral antihyperalgesic effect. Central inhibition of the secondary hyperalgesia response by gabapentin was obtained following injection of either 200 microg intrathecally (i.t.) or 50 mg intraperitoneally (i.p.). The effects induced by gabamimetics were blocked locally or centrally by prior treatment with the specific GABA(A) receptor antagonist, bicuculline (80 ng/paw or 20 ng, i.t.). These data indicate the participation of endogenous GABA in the modulation of secondary hyperalgesia, through either a peripheral and/or a central action. They also indicate that GABA(A) receptors might be involved since a specific antagonist of these receptors (bicuculline) blocked this response.