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

doi:10.1152/ajpgi.00403.2012

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

Lifepharm

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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.

Original language	English
Journal	American Journal of Physiology: Gastrointestinal and Liver Physiology
Volume	305
Pages (from-to)	G119-G128
Number of pages	10
ISSN	0193-1857
DOIs	https://doi.org/10.1152/ajpgi.00403.2012
Publication status	Published - 15 Jul 2013

Keywords

Faculty of Health and Medical Sciences

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10.1152/ajpgi.00403.2012

AmJPhysiolGastLiverPhysiol305G119-128Submitted manuscript, 488 KB

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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.",

keywords = "Faculty of Health and Medical Sciences, evoked potentials, mechanical rectal distension, reproducibility, translation studies",

author = "Nissen, {Thomas Dahl} and Christina Brock and Carina Graversen and {J. Coen}, Steven and Leif Hultin and Qasim Aziz and Jens Lykkesfeldt and Drewes, {Asbj{\o}rn Mohr}",

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language = "English",

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TY - JOUR

T1 - Translational aspects of rectal evoked potentials

T2 - a comparative study in rats and humans

AU - Nissen, Thomas Dahl

AU - Brock, Christina

AU - Graversen, Carina

AU - J. Coen, Steven

AU - Hultin, Leif

AU - Aziz, Qasim

AU - Lykkesfeldt, Jens

AU - Drewes, Asbjørn Mohr

PY - 2013/7/15

Y1 - 2013/7/15

N2 - 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.

AB - 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.

KW - Faculty of Health and Medical Sciences

KW - evoked potentials

KW - mechanical rectal distension

KW - reproducibility

KW - translation studies

U2 - 10.1152/ajpgi.00403.2012

DO - 10.1152/ajpgi.00403.2012

M3 - Journal article

C2 - 23703652

SN - 0193-1857

VL - 305

SP - G119-G128

JO - American Journal of Physiology: Gastrointestinal and Liver Physiology

JF - American Journal of Physiology: Gastrointestinal and Liver Physiology

ER -

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

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Keywords

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