Translational aspects of rectal evoked potentials: a comparative study in rats and humans

Thomas Dahl Nissen, Christina Brock, Carina Graversen, Steven J. Coen, Leif Hultin, Qasim Aziz, Jens Lykkesfeldt, Asbjørn Mohr Drewes

13 Citationer (Scopus)
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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.

OriginalsprogEngelsk
TidsskriftAmerican Journal of Physiology: Gastrointestinal and Liver Physiology
Vol/bind305
Sider (fra-til)G119-G128
Antal sider10
ISSN0193-1857
DOI
StatusUdgivet - 15 jul. 2013

Emneord

  • Det Sundhedsvidenskabelige Fakultet
  • evoked potentials
  • mechanical rectal distension
  • reproducibility
  • translation studies

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