Rapid balloon distension as a tool to study cortical processing of visceral sensations and pain.

BACKGROUND: The processing of discomfort and pain in the central nervous system is normally studied with experimental methods, but it is mandatory that they are reliable over time to ensure that any interventions will result in valid results. We investigated reliability of rapid balloon distension in the rectum to elicit cortical evoked potentials (CEPs) to study the reliability of central processing of visceral sensation and discomfort/pain. METHODS: Eighteen healthy volunteers had two series of rectal balloon distensions performed on two separate days. Individualized balloon pressure, corresponding to pain detection threshold or to the maximum possible distension (30 psi), was used. Within- and between days reliability was measured in terms of amplitudes and latencies of the CEP global field power, topography and underlying brain networks. KEY RESULTS: There were two prominent peaks in the CEP recordings at mean latencies of 157 and 322 ms. There were no differences in latencies or amplitudes (p = 0.3) and they passed the Bland-Altman test for reproducibility. There were no differences in topographies (p > 0.7). Brain source connectivity revealed the cingulate-operculum network as the most consistent network within and between subjects. There were no differences in the location of brain sources in this network (p = 0.9) and the source coordinates were reproducible. Finally, the cingulate source generally had higher strength than operculum source (p < 0.001). CONCLUSIONS & INFERENCES: A reliable method to study central mechanisms underlying visceral sensation and pain was established. The method may improve our understanding of visceral pain and could be an objective method for studying efficacy of analgesics on visceral pain.

Cortical evoked potentials in response to rapid balloon distension of the rectum and anal canal.

BACKGROUND: Neurophysiological evaluation of anorectal sensory function is hampered by a paucity of methods. Rapid balloon distension (RBD) has been introduced to describe the cerebral response to rectal distension, but it has not successfully been applied to the anal canal. METHODS: Nineteen healthy women received 30 RBDs in the rectum and the anal canal at intensities corresponding to sensory and unpleasantness thresholds, and response was recorded as cortical evoked potentials (CEPs) in 64-channels. The anal canal stimulations at unpleasantness level were repeated after 4 min to test the within-day reproducibility. CEPs were averaged, and to overcome latency variation related to jitter the spectral content of single sweeps was also computed. KEY RESULTS: Repeated stimulation of the anal canal generated CEPs with similar latencies but smaller amplitudes compared to those from the rectum. Due to latency jitter, reproducibility of averaged CEPs was lower than what was found in the rectum. The most reproducible feature was N2P2 peak-to-peak amplitude with intra-class correlation coefficient (ICC) of 0.7 and coefficient of variation (CV) of 18%. Spectral content of the single sweeps showed reproducibility with ICCs for all bands >0.8 and corresponding CVs <7%. CONCLUSIONS & INFERENCES: Cortical potentials evoked from the anal canal are challenged by latency jitter likely related to variability in muscle tone due to the distensions. Using single-sweep analysis, anal CEPs proved to be reproducible and should be used in future evaluation of the anal function.

Reproducibility of psychophysics and electroencephalography during offset analgesia.

BACKGROUND: Offset analgesia (OA) is a pain-inhibiting mechanism, defined as a disproportionately large decrease in pain perception in response to a discrete decrease in noxious stimulus intensity. Hence, the aims were (1) to investigate whether psychophysics and electroencephalography (EEG) can be assessed simultaneously during OA and (2) to assess whether OA is reproducible within the same day as well as between different days. METHODS: Two separate studies investigated OA: Study I (13 healthy volunteers; seven men; 25.5 ± 0.65 years) aimed at determining the feasibility of recording psychophysics and EEG simultaneously during OA. Study II (18 healthy volunteers; 12 men; 34 ± 3.15 years) assessed reproducibility of OA in terms of psychophysics and EEG. Subjects were presented to a 30-s OA heat stimulus paradigm on the volar forearm and psychophysics, and EEG recordings were obtained throughout the procedure. Reproducibility was assessed within the same day and between different days, using intraclass correlation coefficients (ICCs). Additionally, the reproducible psychophysical parameters were correlated to relevant EEG frequency bands. RESULTS: Simultaneous recording of psychophysics and EEG affects the frequency distribution in terms of alpha suppression. Reproducibility was proven for the psychophysics and EEG frequency bands both within the same day (all ICCs > 0.62) and between different days (all ICCs > 0.66, except for the delta band). Correlations between psychophysics and EEG were found in the theta (4-8 Hz), alpha (8-12 Hz) and gamma (32-80 Hz) bands (all p < 0.01). CONCLUSION: OA is a robust and reproducible model for experimental pain research, making it suitable for future research.

Colorectal distension-evoked potentials in awake rats: a novel method for studies of visceral sensitivity.

BACKGROUND: Quantification of the visceromotor response induced by colorectal distension (CRD) in rodents is commonly used for preclinical studies of visceral pain. The model is well established but does not fully assess the central response to stimulation. The aim of this study was to establish a novel model assessing cerebral evoked potentials (CEPs) in response to CRD in awake rats. METHODS: Epidural recording electrodes were chronically implanted in the skull of female Sprague-Dawley rats. Colorectal distension-induced CEPs were recorded using either rapid balloon distensions (100 ms, 20-80 mmHg) or electric stimulation (1 ms, 1-4 mA) using stimulation probes placed in the distal colon. KEY RESULTS: Colorectal distension-induced CEPs were separated in three partly temporally overlapping components consisting of five prominent peaks. Peak latencies at 80 mmHg were (P1, N1) 23 ± 1 and 55 ± 4 ms, (N2, P2a, P2b) 91 ± 3, 143 ± 5 and 174 ± 3 ms, and (P3) 297 ± 3 ms. Amplitudes and latencies were, except for the early component, intensity dependent. Intrarectal administration of lidocaine significantly reduced the amplitude of N2 (by 42 ± 6%, P < 0.001) and P2 (by 34 ± 6%, P < 0.001). Electrically induced CEPs were intensity dependent and had similar topography and latencies as the mechanical evoked potentials (P1: 26 ± 2 ms; N1: 61 ± 1 ms; P2: 84 ± 6 ms; N2: 154 ± 6 ms; P3: 326 ± 10 ms), but there were large variations in amplitudes in between repeated electrical stimulations. CONCLUSIONS & INFERENCES: Colorectal distension-induced CEPs can be recorded reliably in awake rats and may serve as a surrogate marker of colonic sensation and be a useful parameter in studies of visceral sensitivity.

Multimodal sensory testing of the rectum and rectosigmoid: development and reproducibility of a new method.

Evaluation of rectal and rectosigmoid sensation is important in basic, clinical and pharmacological studies. New methods to evoke and assess multimodal (electrical, thermal and mechanical) experimental pain of the upper gut activate distinct pathways and mimics clinical pain. The aims of the current study were to characterize the sensory response and reproducibility to multimodal stimulation of rectum and the rectosigmoid. A multimodal rectal probe was developed. Mucosal electrostimulation was delivered at the recto-sigmoid junction. In Rectum, impedance planimetry was used for measurement of cross-sectional area (CSA) during distension. Circulation of water within the bag at either 4 or 60 degrees C was applied for thermal stimulation. The method was tested in 12 healthy volunteers (six men mean age 32 years) on two subsequent days. Mechanical and sensory responses and referred pain areas were assessed. Stimulation with electrical, thermal and mechanical modalities resulted in different sensory perceptions. The relationship between stimulus intensity and sensory response was linear for all modalities. Sensory response to different modalities did not differ between investigation days (all P-values > 0.1). Approximately 75% of subjects felt referred pain in distinct skin locations. Between-days reproducibility was good for all modalities [intra-class correlation (ICC) > or = 0.6]. At sensory threshold, CSA showed best reproducibility (ICC > or = 0.9). At pain detection threshold stretch ratio, CSA and electrostimulation showed best reproducibility (ICC = 1.0; 0.9; 0.9). The present model was easily implemented, robust and showed good reproducibility. It can be used to study pathophysiology or pharmacological interventions in healthy controls and in patients with diseases involving the distal hindgut.