Translational Aspects of Rectal Evoked Potentials: A Comparative Study in Rats and Humans

Background: 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. Methods: Twelve rats received rectal balloon distensions on two different days separated by 24.3 (SD 24.6) days. Rectal balloon distension were also performed in eighteen humans (mean age: 34 years; range: 21-56; 12 males) on two separate occasions, separated by 9.3 (SD 5.5) days. In rats cerebral evoked potentials (CEP's) were recorded using 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 with wavelet analysis. Within- and between days reproducibility was assessed in terms of latencies, amplitudes and frequency content. Results: In rats CEP's showed tri-phasic 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 CEP's showed a tri-phasic 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) were the most reproducible characteristic within and between days. Conclusion: 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.