Pharmacological modulation of colorectal distension evoked potentials in conscious rats


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Abstract

Background:Cerebral evoked potentials (CEP) induced by colorectal distension (CRD) in conscious rats provides a novel method in studies of visceral sensitivity. The aim of this study was to explore the pharmacological effect on CEP of compounds known to reduce the visceromotor response to CRD.Methods:Epidural electrodes were chronically implanted in eight female Sprague-Dawley rats. Evoked potentials were elicited by colorectal rapid balloon distensions (100 ms, 80 mmHg) and the effect of WIN55 (cannabinoid CB receptor agonist), clonidine (adrenergic α2 receptor agonist), MPEP (mGluR5 receptor antagonist), pregabalin (ligand of α2δ subunits in voltage-gated calcium channels) and baclofen (GABA-B receptor agonist) on amplitudes and latency of CEP were determined.Results:WIN55 (0.1 μmol kg−1), clonidine (0.05 μmol kg−1), MPEP (10 μmol kg−1) and pregabalin (200 μmol kg−1) caused a significant, p < 0.05, reduction of the N2 to P2 peak-to-peak amplitude by 23 ± 8%, 25 ± 8%, 39 ± 5%, and 47 ± 6% respectively. Baclofen (9 μmol kg−1) induced a prolongation of the N2 peak latency of 18 ± 4% but had no significant effect on the amplitudes.Conclusion:The obtained results suggest that MPEP, WIN55, clonidine, and pregabalin reduce visceral nociceptive input to the brain, whereas the lack of effect of baclofen on CRD evoked CEP amplitudes suggest that the effect on VMR is not due to a direct analgesic effect.Brain responses to colorectal distension provide a useful tool to evaluate pharmacological effects in rats and may serve as a valuable preclinical model for understanding pharmacological mechanisms related to visceral sensitivity.HighlightsCRD evoked potentials in rats provides a novel method to assess pharmacological effects on supraspinal response to visceral stimulation.MPEP, WIN55, clonidine, and pregabalin reduce visceral nociceptive input to the brain.Baclofen had no significant effect on the amplitudes of the CRD evoked potentials.The results suggest that the effect of baclofen on CRD-induced VMR is through a different mechanism than MPEP, WIN55, clonidine, and pregabalin.Brain responses to colorectal distension in rats provide a useful tool to evaluate effects of visceral analgesic drugs.

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