Investigating the functional properties of the somatosensory cortex during experimental visceral pain using magnetoencephalography

Background The somatosensory cortex has been inconsistently activated in pain studies and the functional properties of subregions within this cortical area are poorly understood. To address this we used magnetoencephalography (MEG), a brain imaging technique capable of recording changes in cortical neural activity in real-time, to investigate the functional properties of the somatosensory cortex during different phases of the visceral pain experience. Methods In eight participants (4 male), 151-channel whole cortex MEG was used to detect cortical neural activity during 25 trials lasting 20 seconds each. Each trial comprised four separate periods of 5 seconds in duration. During each of the periods, different visual cues were presented, indicating that period 1=rest, period 2=anticipation, period 3=pain and period 4=post pain. During period 3, participants received painful oesophageal balloon distensions (four at 1 Hz). Regions of cortical activity were identified using Synthetic Aperture Magnetometry (SAM) and by the placement of virtual electrodes in regions of interest within the somatosensory cortex, time-frequency wavelet plots were generated. Results SAM analysis revealed significant activation with the primary (S1) and secondary (S2) somatosensory cortices. The time-frequency wavelet spectrograms showed that activation in S1 increased during the anticipation phase and continued during the presentation of the stimulus. In S2, activation was tightly time and phase-locked to the stimulus within the pain period. Activations in both regions predominantly occurred within the 10–15 Hz and 20–30 Hz frequency bandwidths. Discussion These data are consistent with the role of S1 and S2 in the sensory discriminatory aspects of pain processing. Activation of S1 during anticipation and then pain may be linked to its proposed role in attentional as well as sensory processing. The stimulus-related phasic activity seen in S2 demonstrates that this region predominantly encodes information pertaining to the nature and intensity of the stimulus.

Neurophysiologic assessment of esophageal sensory processing in noncardiac chest pain

Background & Aims: Esophageal hypersensitivity is thought to be important in the generation and maintenance of symptoms in noncardiac chest pain (NCCP). In this study, we explored the neurophysiologic basis of esophageal hypersensitivity in a cohort of NCCP patients. Methods: We studied 12 healthy controls (9 women; mean age, 37.1 ± 8.7 y) and 32 NCCP patients (23 women; mean age, 47.2 ± 10 y). All had esophageal manometry, esophageal evoked potentials to electrical stimulation, and NCCP patients had 24-hour ambulatory pH testing. Results: The NCCP patients had reduced pain thresholds (PT) (72.1 ± 19.4 vs 54.2 ± 23.6, P = .02) and increased P1 latencies (P1 = 105.5 ± 11.1 vs 118.1 ± 23.4, P = .02). Subanalysis showed that the NCCP group could be divided into 3 distinct phenotypic classifications. Group 1 had reduced pain thresholds in conjunction with normal/reduced latency P1 latencies (n = 9). Group 2 had reduced pain thresholds in conjunction with increased (>2.5 SD) P1 latencies (n = 7), and group 3 had normal pain thresholds in conjunction with either normal (n = 10) or increased (>2.5 SD, n = 3) P1 latencies. Conclusions: Normal esophageal evoked potential latencies with reduced PT, as seen in group 1 patients, is indicative of enhanced afferent transmission and therefore increased esophageal afferent pathway sensitivity. Increased esophageal evoked potential latencies with reduced PT in group 2 patients implies normal afferent transmission to the cortex but heightened secondary cortical processing of this information, most likely owing to psychologic factors such as hypervigilance. This study shows that NCCP patients with esophageal hypersensitivity may be subclassified into distinct phenotypic subclasses based on sensory responsiveness and objective neurophysiologic profiles. © 2006 by the American Gastroenterological Association.

Real-time imaging of human cortical activity evoked by painful esophageal stimulation

Background & Aims: Current models of visceral pain processing derived from metabolic brain imaging techniques fail to differentiate between exogenous (stimulus-dependent) and endogenous (non-stimulus-specific) neural activity. The aim of this study was to determine the spatiotemporal correlates of exogenous neural activity evoked by painful esophageal stimulation. Methods: In 16 healthy subjects (8 men; mean age, 30.2 ± 2.2 years), we recorded magnetoencephalographic responses to 2 runs of 50 painful esophageal electrical stimuli originating from 8 brain subregions. Subsequently, 11 subjects (6 men; mean age, 31.2 ± 1.8 years) had esophageal cortical evoked potentials recorded on a separate occasion by using similar experimental parameters. Results: Earliest cortical activity (P1) was recorded in parallel in the primary/secondary somatosensory cortex and posterior insula (∼85 ms). Significantly later activity was seen in the anterior insula (∼103 ms) and cingulate cortex (∼106 ms; P = .0001). There was no difference between the P1 latency for magnetoencephalography and cortical evoked potential (P = .16); however, neural activity recorded with cortical evoked potential was longer than with magnetoencephalography (P = .001). No sex differences were seen for psychophysical or neurophysiological measures. Conclusions: This study shows that exogenous cortical neural activity evoked by experimental esophageal pain is processed simultaneously in somatosensory and posterior insula regions. Activity in the anterior insula and cingulate - brain regions that process the affective aspects of esophageal pain - occurs significantly later than in the somatosensory regions, and no sex differences were observed with this experimental paradigm. Cortical evoked potential reflects the summation of cortical activity from these brain regions and has sufficient temporal resolution to separate exogenous and endogenous neural activity. © 2005 by the American Gastroenterological Association.

Development of esophageal hypersensitivity following experimental duodenal acidification

OBJECTIVES: As visceral afferents from different regions of the gastrointestinal tract converge at the level of the spinal cord, we hypothesized that sensitization of one gut organ would induce visceral hypersensitivity in another gut organ, remote to the sensitizing stimulus. METHODS: Protocol 1: Eight healthy male volunteers, age 30 +/- 8.2 yr, underwent three studies on different days. Esophageal pain thresholds (PT) were recorded at 10-min intervals prior to and for 2 h following a 30-min duodenal infusion of either 0.15 M hydrochloric acid (HCl), saline, or no infusion. Five subjects repeated the study to demonstrate reproducibility. Protocol 2: Esophageal evoked potentials (EEP) were studied in six subjects on two occasions prior to and 1 h after a 30-min duodenal infusion of 0.15 M HCl or saline. RESULTS: Protocol 1: After acid infusion, there were reproducible reductions in esophageal PT (ICC = 0.88), which were maximal at 110 min (15.05 +/- 2.25 mA) (p < 0.002). Following saline infusion there was an increase in esophageal PT (ICC = 0.71), which was similar to the no-infusion condition (6.21 +/- 1.54 mA vs 8.5 + 7.6 mA; p > 0.05). Protocol 2: Esophageal sensation scores increased (p= 0.02) after acid, but not after saline infusion (p= 0.1). A comparison of the latencies of EEP components prior to and following acid and saline infusion revealed a reduction in the N1 (p= 0.02) and P2 components (p= 0.04). CONCLUSION: This study provides the first objective evidence that duodenal acidification can induce esophageal hypersensitivity associated with changes in sensitivity of the central visceral pain pathway. As the esophagus was remote from the sensitizing stimulus, central sensitization of spinal dorsal horn neurons is likely to have contributed to these changes.