Rutin antinociception involves opioidergic mechanism and descending modulation of ventrolateral periaqueductal grey matter in rats

BackgroundRutin is a bioflavonoid found in fruits, vegetables and plants used in traditional medicine to alleviate pain. However, rutin's scientific evidence for the modulation of pain and its mechanism of action is lacking. It is well known that the periaqueductal grey matter (PAG) contains opioidergic neural circuits involved in the modulation of descending nociception. The aim of this study was to investigate if antinociceptive activity of rutin is modulated by the PAG circuitry involving participation of opioid receptors. MethodsThe experimental design included groups of rats receiving rutin systemically (30-1000mg/kg) or microinjected into the vlPAG (8-32nmol/4L) alone or in the presence of an opioid antagonist, naltrexone (5mg/kg, i.p. or 26nmol/4L, respectively). Nociception was assessed using the formalin test and compared versus the reference drugs, tramadol and morphine. ResultsSystemic or intra-vlPAG administration of rutin significantly decreased both phases of the formalin test. Antinociceptive responses of the reference drugs were prevented by naltrexone, whereas the antinociceptive effect of rutin was inhibited by this antagonist mainly in the phase II of the formalin test. ConclusionsOur results provide evidence that rutin produces antinociceptive effects involving central modulation of the vlPAG descending circuit partly mediated by an opioidergic mechanism.