title: Translational aspects of rectal evoked potentials: a comparative study in rats and humans.
abstract: Inconsistencies between species has stunted the progress of developing new analgesics. To increase the success of translating results between species, improved comparable models are required. Twelve rats received rectal balloon distensions on 2 different days separated by 24.3 (SD 24.6) days. Rectal balloon distensions were also performed in 18 humans (mean age: 34 yr; range: 21-56 yr; 12 men) on two separate occasions, separated by 9.3 (SD 5.5) days. In rats, cerebral evoked potentials (CEPs) were recorded by use of implanted skull-electrodes to distension pressure of 80 mmHg. In humans surface electrodes and individualized pressure, corresponding to pain detection threshold, were used. Comparison of morphology was assessed by wavelet analysis. Within- and between-day reproducibility was assessed in terms of latencies, amplitudes, and frequency content. In rats CEPs showed triphasic morphology. No differences in latencies, amplitudes, and power distribution were seen within or between days (all P ≥ 0.5). Peak-to-peak amplitude between the first positive and negative potential were the most reproducible characteristic within and between days (evaluated by intraclass correlation coefficients, ICC) (ICC = 0.99 and ICC = 9.98, respectively). In humans CEPs showed a triphasic morphology. No differences in latencies, amplitudes, or power distribution were seen within or between days (all P ≥ 0.2). Latency to the second negative potential (ICC = 0.98) and the second positive potential (ICC = 0.95) was the most reproducible characteristic within and between days. A unique and reliable translational platform was established assessing visceral sensitivity in rats and humans, which may improve the translational process of developing new drugs targeting visceral pain.
authors.affiliation: Section of Biomedicine, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thomas Dahl
authors.initials: TD
authors.lastname: Nissen
authors.forename: Christina
authors.initials: C
authors.lastname: Brock
authors.forename: Carina
authors.initials: C
authors.lastname: Graversen
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Coen
authors.forename: Leif
authors.initials: L
authors.lastname: Hultin
authors.forename: Qasim
authors.initials: Q
authors.lastname: Aziz
authors.forename: Jens
authors.initials: J
authors.lastname: Lykkesfeldt
authors.forename: Asbjørn Mohr
authors.initials: AM
authors.lastname: Drewes
mesh_terms: D000328:Adult; D000818:Animals; D001007:Anxiety; D002540:Cerebral Cortex / Q000502:physiology; D004569:Electroencephalography; D005071:Evoked Potentials / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017288:Pain Threshold / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum / Q000502:physiology*; D015203:Reproducibility of Results; D055815:Young Adult
keywords: evoked potentials; mechanical rectal distension; reproducibility; translation