Rutin antinociception involves opioidergic mechanism and descending modulation of ventrolateral periaqueductal grey matter in rats. 2016

A Hernandez-Leon, and A Fernández-Guasti, and M E González-Trujano
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados-Sede Sur, Mexico.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008845 Microinjections The injection of very small amounts of fluid, often with the aid of a microscope and microsyringes. Microinjection
D009020 Morphine The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. Morphine Sulfate,Duramorph,MS Contin,Morphia,Morphine Chloride,Morphine Sulfate (2:1), Anhydrous,Morphine Sulfate (2:1), Pentahydrate,Oramorph SR,SDZ 202-250,SDZ202-250,Chloride, Morphine,Contin, MS,SDZ 202 250,SDZ 202250,SDZ202 250,SDZ202250,Sulfate, Morphine
D009271 Naltrexone Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. Antaxone,Celupan,EN-1639A,Nalorex,Naltrexone Hydrochloride,Nemexin,ReVia,Trexan,EN 1639A,EN1639A
D009292 Narcotic Antagonists Agents inhibiting the effect of narcotics on the central nervous system. Competitive Opioid Antagonist,Narcotic Antagonist,Opioid Antagonist,Opioid Antagonists,Opioid Receptor Antagonist,Opioid Reversal Agent,Competitive Opioid Antagonists,Opioid Receptor Antagonists,Opioid Reversal Agents,Agent, Opioid Reversal,Agents, Opioid Reversal,Antagonist, Competitive Opioid,Antagonist, Narcotic,Antagonist, Opioid,Antagonist, Opioid Receptor,Antagonists, Competitive Opioid,Antagonists, Narcotic,Antagonists, Opioid,Antagonists, Opioid Receptor,Opioid Antagonist, Competitive,Opioid Antagonists, Competitive,Receptor Antagonist, Opioid,Receptor Antagonists, Opioid,Reversal Agent, Opioid,Reversal Agents, Opioid
D009294 Narcotics Agents that induce NARCOSIS. Narcotics include agents that cause somnolence or induced sleep (STUPOR); natural or synthetic derivatives of OPIUM or MORPHINE or any substance that has such effects. They are potent inducers of ANALGESIA and OPIOID-RELATED DISORDERS. Analgesics, Narcotic,Narcotic Analgesics,Narcotic,Narcotic Effect,Narcotic Effects,Effect, Narcotic,Effects, Narcotic
D010146 Pain An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS. Suffering, Physical,Ache,Pain, Burning,Pain, Crushing,Pain, Migratory,Pain, Radiating,Pain, Splitting,Aches,Burning Pain,Burning Pains,Crushing Pain,Crushing Pains,Migratory Pain,Migratory Pains,Pains, Burning,Pains, Crushing,Pains, Migratory,Pains, Radiating,Pains, Splitting,Physical Suffering,Physical Sufferings,Radiating Pain,Radiating Pains,Splitting Pain,Splitting Pains,Sufferings, Physical
D010147 Pain Measurement Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies. Analgesia Tests,Analogue Pain Scale,Formalin Test,McGill Pain Questionnaire,Nociception Tests,Pain Assessment,Pain Intensity,Pain Severity,Tourniquet Pain Test,Visual Analogue Pain Scale,Analog Pain Scale,Assessment, Pain,McGill Pain Scale,Visual Analog Pain Scale,Analgesia Test,Analog Pain Scales,Analogue Pain Scales,Formalin Tests,Intensity, Pain,Measurement, Pain,Nociception Test,Pain Assessments,Pain Intensities,Pain Measurements,Pain Questionnaire, McGill,Pain Scale, Analog,Pain Scale, Analogue,Pain Scale, McGill,Pain Severities,Pain Test, Tourniquet,Questionnaire, McGill Pain,Scale, Analog Pain,Scale, Analogue Pain,Scale, McGill Pain,Severity, Pain,Test, Analgesia,Test, Formalin,Test, Nociception,Test, Tourniquet Pain,Tests, Nociception,Tourniquet Pain Tests
D010487 Periaqueductal Gray Central gray matter surrounding the CEREBRAL AQUEDUCT in the MESENCEPHALON. Physiologically it is probably involved in RAGE reactions, the LORDOSIS REFLEX; FEEDING responses, bladder tonus, and pain. Mesencephalic Central Gray,Midbrain Central Gray,Central Gray Substance of Midbrain,Central Periaqueductal Gray,Griseum Centrale,Griseum Centrale Mesencephali,Periaqueductal Gray Matter,Substantia Grisea Centralis,Substantia Grisea Centralis Mesencephali,Central Gray, Mesencephalic,Central Gray, Midbrain,Gray Matter, Periaqueductal,Gray, Central Periaqueductal,Griseum Centrale Mesencephalus,Periaqueductal Grays, Central
D011957 Receptors, Opioid Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known. Endorphin Receptors,Enkephalin Receptors,Narcotic Receptors,Opioid Receptors,Receptors, Endorphin,Receptors, Enkephalin,Receptors, Narcotic,Receptors, Opiate,Endorphin Receptor,Enkephalin Receptor,Normorphine Receptors,Opiate Receptor,Opiate Receptors,Opioid Receptor,Receptors, Normorphine,Receptors, beta-Endorphin,beta-Endorphin Receptor,Receptor, Endorphin,Receptor, Enkephalin,Receptor, Opiate,Receptor, Opioid,Receptor, beta-Endorphin,Receptors, beta Endorphin,beta Endorphin Receptor,beta-Endorphin Receptors

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