TY - JOUR
T1 - Pharmacological modulation of colorectal distension evoked potentials in conscious rats
AU - Nissen, Thomas Dahl
AU - Brock, Christina
AU - Lykkesfeldt, Jens
AU - Lindström, Erik
AU - Hultin, Leif
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - (2-methyl-6-(phenylethynyl)-pyridine) hydrochloride
KW - Analgesics
KW - Cannabinoid receptor 1
KW - CB1
KW - CEP
KW - Cerebral evoked potential
KW - Colorectal distension
KW - CRD
KW - GABAB
KW - IBS
KW - ICC
KW - Intra-class correlation coefficients
KW - Irritable bowel syndrome
KW - MPEP
KW - Rats
KW - Visceral pain
KW - Visceromotor response
KW - VMR
KW - WIN55
KW - WIN55,212-2 [[(R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinyl-methyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-napthalenyl-methanone], mesylate form]
KW - γ-aminobutyric acid B receptor
U2 - 10.1016/j.neuropharm.2018.07.028
DO - 10.1016/j.neuropharm.2018.07.028
M3 - Journal article
C2 - 30059662
AN - SCOPUS:85051400594
SN - 0028-3908
VL - 140
SP - 193
EP - 200
JO - Neuropharmacology
JF - Neuropharmacology
ER -