Pharmacological modulation of colorectal distension evoked potentials in conscious rats

NEUROPHARMACOLOGY

卷:140

Article

Nissen, Thomas Dahl^1,2,3  Brock, Christina²  Lykkesfeldt, Jens³  Lindstrom, Erik⁴  Hultin, Leif¹ 

[1] AstraZeneca, IMED Biotech Unit, Lab Anim Sci Drug Safety & Metab, Gothenburg, Sweden

[2] Aalborg Univ Hosp, Dept Gastroenterol & Hepatol, Mech Sense, Aalborg, Denmark

[3] Univ Copenhagen, Fac Hlth & Med Sci, Dept Vet Dis Biol, Copenhagen, Denmark

[4] Zealand Pharma AS, Glostrup, Denmark

关键词: Analgesics;    Cerebral evoked potential;    Colorectal distension;    Rats;    Visceral pain;   

DOI  :  10.1016/j.neuropharm.2018.07.028

来源: Elsevier

【 摘 要 】

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 alpha(2) receptor agonist), MPEP (mGluR5 receptor antagonist), pregabalin (ligand of alpha(2)delta subunits in voltage-gated calcium channels) and baclofen (GABA-B receptor agonist) on amplitudes and latency of CEP were determined. Results: WIN55 (0.1 mu mol kg(-1)), clonidine (0.05 mu mol kg(-1)), MPEP (10 mu mol kg(-1)) and pregabalin (200 mu mol 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 mu mol 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. (C) 2018 Published by Elsevier Ltd.

【 授权许可】

Free