Participação de canais de k+atp na resposta antinociceptiva periférica da via Heme-oxigenase/monóxido de carbono

Abstract

Carbon monoxide (CO) is one of the oldest molecules found in the atmosphere, being popularly associated to asphyxia by its high binding to hemoglobin. However, studies have also demonstrated its involvement in various physiological functions through the endogenous production by the enzyme heme-oxygenase (HO), which catalyzes the metabolism of heme in equimolar amounts of CO, biliverdin and iron. Of these, the CO is one of its most active and may act as a neurotransmitter and neuromodulator nervous system, cardiovascular signaling molecule with vasoactive properties and potential involvement in nociceptive processes. Numerous research associate of the mechanisms of action of the HO/CO pathway by activation of the enzyme guanylate cyclase, cGMP or direct modulation of potassium channels, the latter being widely described as involved in various nociceptive mechanisms in particular its class ATP-sensitive (K+ATP). Thus, our goal in this study was to investigate the possible involvement of K+ATP in an antinociceptive via triggered by the HO/CO after hyperalgesia induced by administration of carrageen and exposure to electronic Von Frey and Randall Selitto. The results obtained in our experiments suggest that i.pl. treatment with the substrate of HO (hemin) caused a dose-dependent antinociception, and the possible systemic action was excluded by treating contralateral paw via. In turn, the administration HO pathway inhibitor (Tin protoporphyrin IX dichloride) increased the hyperalgesia caused by carrageen. Similar effects were not observed by the administration of the other two products, biliverdin, iron, showing the CO as the more active pathway in the modulation of nociceptive processes. Since the joint administration of glibenclamide (blocker of K+ATP) and hemin, caused the blockage of antinociceptive action caused by hemin, and the joint administration of the lowest dose-response diazoxide (potassium channel activator) and hemin caused a synergistic action between drugs, and potentiate the antinociceptive response to the pathway substrate. We also observed that the antinociceptive effect of hemin was not altered by the administration of naloxone (opioid antagonist), suggesting the exclusion of the opioid system in the antinociceptive response of the HO/CO. Thus, the results presented in this study strongly suggest that the peripheral antinociceptive action via the HO/CO may be related to the activation of potassium channels sensitive to ATP