RESUMEN
BACKGROUND: Chronic visceral hypersensitivity is closely associated with irritable bowel syndrome (IBS), a very common disorder which significantly impairs quality of life, characterized by abdominal pain, and distension. Imaging studies have found that IBS patients show higher metabolic activities and functional differences from normal controls in the anterior cingulate cortex (ACC), in response to visceral pain stimulation. Non-clinical data and clinical data suggest that medicinal products containing essential oils such as peppermint or caraway oil exert beneficial effects on IBS symptoms. METHODS: We assessed acute and long-term treatment effects of a mixture of peppermint and caraway essential oils (Menthacarin) on brain electrophysiological markers of gut pain sensitivity in two rat models of visceral hypersensitivity. KEY RESULTS: Chronic administration of corticosteroids and acute repeated mechanical hyperstimulation under anesthesia induced hyperalgesia and hypersensitivity, characterized by an increase in electrophysiological excitatory responses of ACC neurons to colorectal distension (CRD) and an increase in the proportion of neurons responding to otherwise subthreshold stimulation, respectively. Long-term, but not acute, oral administration of Menthacarin (60 mg kg-1 day-1) significantly reduced the net excitatory response to CRD in normally responsive control animals and counteracted the development of visceral hyperalgesia and hypersensitivity induced by repeated corticosterone administration and acute mechanical stimulation. CONCLUSIONS & INFERENCES: The present study shows that, using the CRD method, chronic Menthacarin administration at a clinically relevant dose attenuates the neuronal discharge associated with visceral pain stimuli in the rat ACC, particularly in models of hypersensitivity, suggesting a potential for treating exaggerated visceral pain sensitivity.
Asunto(s)
Síndrome del Colon Irritable , Aceites Volátiles , Dolor Visceral , Humanos , Ratas , Animales , Hiperalgesia/inducido químicamente , Hiperalgesia/tratamiento farmacológico , Síndrome del Colon Irritable/tratamiento farmacológico , Dolor Visceral/tratamiento farmacológico , Nocicepción , Calidad de Vida , Dolor Abdominal/inducido químicamente , Dolor Abdominal/tratamiento farmacológicoRESUMEN
We have previously shown that prebiotics (dietary fibres that augment the growth of indigenous beneficial gut bacteria) such as Bimuno™ galacto-oligosaccharides (B-GOS®), increased N-methyl-D-aspartate (NMDA) receptor levels in the rat brain. The current investigation examined the functional correlates of these changes in B-GOS®-fed rats by measuring cortical neuronal responses to NMDA using in vivo NMDA micro-iontophoresis electrophysiology, and performance in the attentional set-shifting task. Adult male rats were supplemented with B-GOS® in the drinking water 3 weeks prior to in vivo iontophoresis or behavioural testing. Cortical neuronal responses to NMDA iontophoresis, were greater (+30%) in B-GOS® administered rats compared to non-supplemented controls. The intake of B-GOS® also partially hindered the reduction of NMDA responses by the glycine site antagonist, HA-966. In the attentional set-shifting task, B-GOS® -fed rats shifted from an intra-dimensional to an extra-dimensional set in fewer trials than controls, thereby indicating greater cognitive flexibility. An initial exploration into the mechanisms revealed that rats ingesting B-GOS® had increased levels of plasma acetate, and cortical GluN2B subunits and Acetyl Co-A Carboxylase mRNA. These changes were also observed in rats fed daily for 3 weeks with glyceryl triacetate, though unlike B-GOS®, cortical histone deacetylase (HDAC1, HDAC2) mRNAs were also increased which suggested an additional epigenetic action of direct acetate supplementation. Our data demonstrate that a pro-cognitive effect of B-GOS® intake in rats is associated with an increase in cortical NMDA receptor function, but the role of circulating acetate derived from gut bacterial fermentation of this prebiotic requires further investigation.
Asunto(s)
Atención/fisiología , Corteza Cerebral/metabolismo , Suplementos Dietéticos , N-Metilaspartato/metabolismo , Neuronas/metabolismo , Prebióticos/administración & dosificación , Animales , Corteza Cerebral/efectos de los fármacos , Función Ejecutiva/fisiología , Masculino , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Neuronas/efectos de los fármacos , Neurotransmisores/farmacología , Distribución Aleatoria , Ratas Sprague-Dawley , Triglicéridos/administración & dosificaciónRESUMEN
The acute administration of the noncompetitive glutamate N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK 801) is known to increase central dopaminergic activity in rats and to elicit schizophreniform behavior in human. The current study was undertaken to compare the effects of different acute or chronic neuroleptic treatments, on the response of ventral tegmental area dopamine (DA) neurons to MK 801, using the in vivo electrophysiological paradigm in anesthetized preparations. Sprague Dawley male rats were treated, acutely or chronically during 3 weeks, with saline, olanzapine (10 mg/kg), haloperidol (1 mg/kg) or the combination of haloperidol with D-serine (1 mg/kg/300 mg/kg), a gliotransmitter coagonist of the NMDA receptor that has been shown to improve the efficacy of typical neuroleptics. In control animals, the acute administration of MK 801 (0.5 mg/kg, i.v.) increased significantly both the firing and burst activity of DA neurons by 20 and 26%, respectively, the latter effect being partially reversed by the selective 5-HT2A antagonist M 100,907 (0.4 mg/kg, i.v.). The acute preadministration of haloperidol (1 mg/kg, i.p.) and olanzapine (10 mg/kg, i.p.) failed to prevent or reverse the activatory effect of MK 801 on firing activity. On the other hand, MK 801-induced burst activity, was partially prevented by olanzapine, but not by haloperidol pretreatment. All antipsychotic treatments, when administered chronically, prevent the activatory effect of MK 801 on both firing and burst activity, and occasionally convert the response to MK 801 on burst activity to an inhibitory response, the latter occurring more predominantly in rats treated with the combination haloperidol/D-serine. These results suggest that a chronic antipsychotic regime alters the function of the NMDA receptors that tonically control the firing activity of midbrain dopaminergic neurons.