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


METHODS
The experimental design included groups of rats receiving rutin systemically (30-1000 mg/kg) or microinjected into the vlPAG (8-32 nmol/4 μL) alone or in the presence of an opioid antagonist, naltrexone (5 mg/kg, i.p. or 26 nmol/4 μL, respectively). Nociception was assessed using the formalin test and compared versus the reference drugs, tramadol and morphine.


RESULTS
Systemic 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.


CONCLUSIONS
Our results provide evidence that rutin produces antinociceptive effects involving central modulation of the vlPAG descending circuit partly mediated by an opioidergic mechanism.
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados-Sede Sur, Mexico.|Laboratorio de Neurofarmacología de Productos Naturales de la Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico.
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Hernandez-Leon
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados-Sede Sur, Mexico.
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Fernández-Guasti
Laboratorio de Neurofarmacología de Productos Naturales de la Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico.
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González-Trujano
D000818:Animals; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000494:pharmacology / Q000627:therapeutic use; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology / Q000627:therapeutic use; D059225:Nociception / Q000187:drug effects*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D010487:Periaqueductal Gray / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000819:agonists; D012431:Rutin / Q000494:pharmacology / Q000627:therapeutic use*; D014147:Tramadol / Q000494:pharmacology / Q000627:therapeutic use
D009292:Narcotic Antagonists; D009294:Narcotics; D011957:Receptors, Opioid; D014147:Tramadol; D012431:Rutin; D009271:Naltrexone; D009020:Morphine