Chun L. Kwan

An fMRI study of the anterior cingulate cortex and surrounding medial wall activations evoked by noxious cutaneous heat and cold stimuli

&NA; The anterior cingulate cortex (ACC) and adjacent regions in the medial wall have been implicated in sensory, motor and cognitive processes, including pain. Our previous functional magnetic resonance imaging (fMRI) studies have demonstrated pain‐related activation of the posterior portion of the ACC during transcutaneous electrical nerve stimulation (TENS) and variable patterns of cortical activation with innocuous and noxious thermal stimuli in individual subjects. The present study represents the companion paper to our recent study of pain‐ and thermal‐related cortical activations with the aim to use fMRI to delineate the activations in the ACC and surrounding regions of the medial wall during application of innocuous and noxious thermal stimuli as well as during performance of a motor task in individual subjects. Ten normal subjects were imaged on a conventional 1.5 T GE ‘echospeed’ system. Functional images were obtained from sagittal sections through each hemisphere centered at approximately 3–5 and 7–9 mm from midline. Each subject was imaged during innocuous (cool, warm) and noxious thermal (cold, hot) stimulation of the thenar eminence, and execution of a motor (sequential finger‐thumb opposition) task. Task‐related activations were mostly confined to contralateral and medial ipsilateral images. Although the present results demonstrate intersubject variability in the task‐related activations, some general modality‐specific patterns were apparent: (i) innocuous thermal‐related activations were located mainly in the anterior ACC; (ii) noxious thermal‐related activations were primarily located in the anterior ACC, the ventral portion of the posterior ACC, and the supplementary motor area (SMA); (iii) motor‐related activations were primarily located in the SMA and dorsal portion of the posterior ACC. These results indicate that specific spatial patterns of activation exist within the ACC and surrounding regions of the medial wall for innocuous and noxious thermal stimuli, and that noxious thermal‐ and motor‐related activations appear to be segregated within the ACC. Therefore, we propose a segregation of the ACC into an anterior non‐specific attention/arousal system and a posterior pain system.

Altered central somatosensory processing in chronic pain patients with “hysterical” anesthesia

Objective: The authors hypothesized that central factors may underlie sensory deficits in patients with nondermatomal somatosensory deficits (NDSD) and that functional brain imaging would reveal altered responses in supraspinal nuclei. Background: Patients with chronic pain frequently present with NDSD, ranging from hypoesthesia to complete anesthesia in the absence of substantial pathology and often in association with motor weakness and occasional paralysis. Patients with pain and such pseudoneurologic symptoms can be classified as having both a pain disorder and a conversion disorder (Diagnostic and Statistical Manual of Mental Disorders–IV classification). Methods: The authors tested their hypothesis with functional MRI (fMRI) of brush and noxious stimulation-evoked brain responses in four patients with chronic pain and NDSD. Results: The fMRI findings revealed altered somatosensory-evoked responses in specific forebrain areas. Unperceived stimuli failed to activate areas that were activated with perceived touch and pain: notably, the thalamus, posterior region of the anterior cingulate cortex (ACC), and Brodmann area 44/45. Furthermore, unperceived stimuli were associated with deactivations in primary and secondary somatosensory cortex (S1, S2), posterior parietal cortex, and prefrontal cortex. Finally, unperceived (but not perceived) stimuli activated the rostral ACC. Conclusions: Diminished perception of innocuous and noxious stimuli is associated with altered activity in many parts of the somatosensory pathway or other supraspinal areas. The cortical findings indicate a neurobiological component for at least part of the symptoms in patients presenting with nondermatomal somatosensory deficits.

CORTICAL THINNING IN IBS: IMPLICATIONS FOR HOMEOSTATIC, ATTENTION, AND PAIN PROCESSING

Chronic pain may be accompanied by abnormal functioning in pain, attention, or homeostatic systems. We recently identified abnormal rectal-evoked functional MRI responses in patients with irritable bowel syndrome (IBS) in brain regions associated with such systems, including the insula and anterior cingulate cortex (ACC).1 However, it is not known whether structural brain abnormalities contribute to these responses. We tested the hypothesis that abnormal cortical responses in IBS are at least partly due to structural differences within the insula and ACC. ### Methods. Right-handed healthy control subjects (n = 11, 7 women, 4 men; 24 to 50 years old) and patients with IBS (n = 9, 6 women, 3 men; 30 to 58 years old) provided written consent to procedures approved by the University Health Network Research Ethics Board. Control subjects were excluded if they had a history of bowel disorders, chronic pain, fibromyalgia, diabetes, or psychiatric illness. Patients were recruited from the Toronto Western Hospital Gastrointestinal Unit, met Rome III criteria2 for diagnosis of IBS, and had mild to moderate symptoms and pain for more than 2 years. Exclusion criteria were a history of …

Abnormal forebrain activity in functional bowel disorder patients with chronic pain.

Background: Abnormal cortical pain responses in patients with fibromyalgia and conversion disorder raise the possibility of a neurobiologic basis underlying so-called “functional” chronic pain. Objective: To use percept-related fMRI to test the hypothesis that patients with a painful functional bowel disorder do not process visceral input or sensations normally or effectively at the cortical level. Methods: Eleven healthy subjects and nine patients with irritable bowel syndrome (IBS) underwent fMRI during rectal distensions that elicited either a moderate level of urge to defecate or pain. Subjects continuously rated their rectal stimulus–evoked urge or pain sensations during fMRI acquisition. fMRI data were interrogated for activity related to stimulus presence and to specific sensations. Results: In IBS, abnormal responses associated with rectal-evoked sensations were identified in five brain regions. In primary sensory cortex, there were urge-related responses in the IBS but not control group. In the medial thalamus and hippocampus, there were pain-related responses in the IBS but not control group. However, pronounced urge- and pain-related activations were present in the right anterior insula and the right anterior cingulate cortex in the control group but not the IBS group. Conclusions: Percept-related fMRI revealed abnormal urge- and pain-related forebrain activity during rectal distension in patients with irritable bowel syndrome (IBS). As visceral stimulation evokes pain and triggers unconscious processes related to homeostasis and reflexes, abnormal brain responses in IBS may reflect the sensory symptoms of rectal pain and hypersensitivity, visceromotor dysfunction, and abnormal interoceptive processing.

Abnormal rectal motor physiology in patients with irritable bowel syndrome.

Abstract  A contentious issue is whether irritable bowel syndrome (IBS) patients have abnormal rectal motor physiology. Our aim was to determine whether IBS patients have abnormal rectal responses to low (urge producing) or high (pain producing) distension pressures. The IBS patients and healthy controls underwent five series of isobaric rectal distensions to examine volume–pressure relationships and rectal accommodation: (i) ascending stepwise distensions terminating upon report of moderate pain, (ii) phasic and (iii) tonic distensions at a single low pressure producing a moderate sensation of urge to defecate (iv) phasic and (v) tonic distensions at a single high pressure producing a moderate pain sensation. The IBS patients demonstrated a lower rectal volume–pressure ratio during repetitive single‐pressure phasic distensions, and a slower rate of rectal accommodation during low (but not high) pressure tonic distensions. However, dynamic compliance during ascending stepwise distensions and the change in rectal volume during tonic distension were not significantly different from controls. Rectal abnormality was readily demonstrated by determining the volume–pressure ratio using a small number of repetitive single‐pressure distensions, supporting the hypothesis that IBS patients have abnormal rectal motor physiology. We propose that a peripheral neuromuscular substrate may contribute to the pathogenesis of IBS.

Characteristics of rectal perception are altered in irritable bowel syndrome.

&NA; A hallmark symptom of irritable bowel syndrome (IBS) is a lower pain threshold during rectal distension, but the mechanism underlying this disorder remains unclear. Examining the relationship between physiological and perceptual responses to rectal distension can provide insight into the underlying peripheral or central dysfunction in IBS. Therefore, we carried out a study of the rectal sensations of urge to defecate, pain and unpleasantness in relation to the varying states of the rectum. Ten IBS patients and 13 healthy controls underwent six sets of isobaric rectal distensions. The first set was ascending stepwise distensions terminating upon report of moderate pain where verbal ratings of urge, pain, and unpleasantness were acquired. The remaining sets were phasic or tonic distensions at a single pressure eliciting either moderate urge or moderate pain intensity where subjects gave continuous ratings of urge or pain percepts. The McGill Pain Questionnaire (MPQ) was used to assess different qualities of the pain experience during single pressure distensions. Abnormalities in IBS patients included: (1) higher incidence of distensions where unpleasantness is greater than pain intensity, (2) significantly longer persistence of ratings after stimulus termination during phasic distensions eliciting either moderate urge or moderate pain, (3) significantly smaller ratings fluctuations during tonic distensions, and (4) significantly higher MPQ scores for painful tonic distensions. Our study demonstrates that IBS patients have abnormal temporal and intensity properties of rectal sensation. These can be accounted for by either altered peripheral neuromuscular processing and/or processing of ascending rectal input in the central nervous system.

The relationship between rectal pain, unpleasantness, and urge to defecate in normal subjects.

&NA; Rectal stimulation under normal or pathological conditions evokes numerous sensations. Previous studies have examined rectal stimulation‐evoked pain and urge to defecate, but discrepancies in the findings remain because of the different methodologies used in each study and the reporting of sensations only at the end of or after the applied stimuli. Therefore, we conducted a psychophysical study of various aspects of rectal sensation in normal subjects using a variety of distension stimuli and continuous on‐line rating of sensation. Ten normal healthy subjects (eight female and two male) were given rectal distension stimuli delivered by a computer‐driven barostat. For some experiments, sensation was continuously monitored and rated on a visual analog scale. Subjects first underwent an ascending series of phasic (30 s) distensions to determine how urge, unpleasantness, and pain intensity varied and interrelated as rectal volume and pressure changed. A second series of distensions examined rectal physiology and perception during short phasic (30 s) or long (300 s) distensions at pressures that elicit either moderate urge or moderate pain and while continuously rating these sensations. The McGill Pain Questionnaire was used to assess the multidimensional aspects of rectal pain with each type of distension. The results of the ascending series revealed significant relationships between sensations as pressure and volume increased. The ratings of urge were double that of pain and unpleasantness, whereas unpleasantness and pain ratings were comparable. Isobaric phasic and tonic distensions were associated with an increase in volume (i.e. accommodation) with time. The magnitude of urge with repetitive short isobaric (30 s) distensions was overall not related to the slight increase in rectal volume, while phasic distensions at moderate pain intensity revealed a significant overall relationship between rectal volume and both unpleasantness and pain intensity. Long isobaric distensions evoked sensations that varied over time despite progressive increases in volume, but less variation in sensation was observed during short phasic distensions which also demonstrated a similar increase in rectal volume. Differences in temporal characteristics of sensations evoked by low‐pressure distensions eliciting moderate urge versus high‐pressure distensions eliciting moderate pain were illustrated by a significantly longer delay to the diminution of non‐painful urge versus pain. Therefore, we conclude (1) Differences in the discrimination and the temporal characteristics of urge at subpainful rectal pressures and of pain at noxious pressures suggest that noxious and non‐noxious stimuli are processed differently. (2) The overall unpleasantness and pain correlate with rectal volume during accommodation. However, instantaneous evoked sensations can vary independent of volume changes during constant pressure distension. (3) The reported sensation‐related responses to tension and stretch will likely be different depending on the degree of accommodation that is occurring. Moreover, the peripheral receptor mechanisms which contribute to controlling this accommodation will also affect the perception of rectal stimuli. (4) Continuous ratings of rectal sensations are valuable in investigating rectal physiology and the multidimensional nature of rectal symptoms.

Electrical Nerve Stimulation Can Be Used as a Tool in fMRI Studies of Pain- and Tingling-Evoked Activations

OBJECTIVES/HYPOTHESES: To determine whether transcutaneous electrical nerve stimulation (TENS) provides adequate, inexpensive and simple means to image innocuous and pain-related activations in the thalamus and cortex.