Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1590/S0034-70942009000400008
Brazilian Journal of Anesthesiology
Scientific Article

Efeito analgésico de antagonistas do receptor da histamina H1 em modelo de dor provocada por formalina em ratos

Analgesic effects of H1 receptor antagonists in the rat model of formalin-induced pain

Hazem Adel Ashmawi; Leandro Mamede Braun; Angela Maria Sousa; Irimar de Paula Posso

http://dx.doi.org/10.1590/S0034-70942009000400008 Braz J Anesthesiol, vol.59, n4, p.461-470, 2009
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Resumo

JUSTIFICATIVA E OBJETIVOS: Os receptores de histamina mediam vias nociceptivas principalmente no sistema nervoso central. Alguns estudos mostraram efeito analgésico de antagonistas de receptor de histamina no sistema nervoso periférico. Não está claro se o efeito analgésico local é classe específico ou droga específico. MÉTODO: Para responder a essa questão, utilizamos três diferentes antagonistas do receptor H1 (pirilamina, prometazina e cetirizina) administrados diretamente na pata do rato, pela via intraperitoneal ou por bloqueio de nervo periférico em modelo de dor induzida por formalina. Observamos o efeito das drogas no comportamento do número de elevações da pata. RESULTADOS: Na fase I, a pirilamina local diminuiu o número de elevações da pata de forma dose-dependente. Na dose mais alta, a diminuição foi de 97,8%. Para a prometazina, a diminuição foi de 92% e para cetizirina, 23,9%. Na fase II, a pirilamina diminuiu o número de elevações da pata em 93,5%, a prometazina em 78,2% e a cetirizina em 80,1%. A administração dos fármacos por via intraperitoneal não alterou o comportamento doloroso. Quando utilizadas para bloqueio de nervo periférico, na fase I, a pirilamina diminuiu o número de elevações da pata em 96,7%, a prometazina em 73,3% e a cetirizina em 23,9%. Na fase II, a pirilamina levou à diminuição de 86,6%, a prometazina de 64,4% e a cetirizina de 19,9%. CONCLUSÕES: Os resultados mostraram que os antagonistas de receptor da histamina H1 apresentam efeitos analgésicos locais, diferentes do efeito sistêmico, sendo um deles anti-inflamatório e classe específico e o outro específico para prometazina e pirilamina, semelhante a efeito clínico anestésico local.

Palavras-chave

ANIMAIS, DOR, Experimental, DROGAS, DROGAS, DROGAS

Abstract

BACKGROUND AND OBJECTIVES: Histamine receptors mediate nociceptive pathways, especially in the central nervous system. Some studies have demonstrated the analgesic effects of histamine receptor antagonists in the peripheral nervous system. It is not clear whether the local analgesic effect is class-specific or drug-specific. METHODS: To answer this question, we used three different H1 receptor antagonists (pyrilamine, promethazine, and cetirizine) administered directly in the paw of the rat, intraperitoneally, or in peripheral nerve blockade in the formalin-induced pain model. The effects of the drugs on the number of paw elevations were observed. RESULTS: In phase I, the local administration of pyrilamine caused a dose-dependent reduction on the number of paw elevations; in the highest dose, the number of paw elevations was reduced by 97.8%. Promethazine decreased it by 92%, while cetirizine decreased by 23.9%. In phase II, pyrilamine decreased the number of paw elevations by 93.5%, promethazine by 78.2%, and cetirizine by 80.1%. Intraperitoneal administration of drugs did not change painful behavior. When used in peripheral nerve block, in phase I pyrilamine reduced the number of paw elevations by 96.7%, promethazine by 73.3%, and cetirizine by 23.9%. In phase II, pyrilamine reduced the number of paw elevations by 86.6%, promethazine by 64.4%, and cetirizine by 19.9%. CONCLUSIONS: The results demonstrate that H1 receptor antagonists have local analgesic effects, different from the systemic effects, one of them an anti-inflammatory and class-specific effect and the other similarly to the local anesthetic effect, specific for promethazine and pyrilamine

Keywords

ANIMALS, DRUGS, DRUGS, pyrilamine, PAIN, Experimental

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