Central neural contribution to the perception of chest pain in cardiac syndrome X

Abstract

Objective: To investigate the central neural contribution to chest pain perception in cardiac syndrome X (angina-like pain, ECG changes during stress, angiographically normal coronary arteriogram).

Subjects: Eight syndrome X patients and eight healthy volunteers.

Methods: Dobutamine stress using echocardiography to assess myocardial function, and positron emission tomography to measure changes in regional cerebral blood flow, as an index of neuronal activity.

Results: During similar doses of dobutamine, syndrome X patients and controls showed comparable regional cerebral blood flow changes in the hypothalamus, thalami, right orbito-frontal cortex, and anterior temporal poles, associated with the sensation of a fast or powerful heart beat. In patients, but not controls, the stress also generated severe chest pain associated with increased activity in the right anterior insula/frontal operculum junction. There were ischaemia-like ECG changes in the syndrome X patients, but no left ventricular dysfunction on echocardiography. Activation of the right insula during chest pain clearly distinguished the syndrome X patients from a group of patients with known coronary disease.

Conclusions: Chest pain and ECG changes were not accompanied by demonstrable myocardial dysfunction in syndrome X patients, but altered central neural handling of afferent signals may contribute to the abnormal pain perception in these patients.

Figure 1

Activation of the right anterior insula during dobutamine induced chest pain. This feature distinguishes the syndrome X patients from (on the left) patients with coronary artery disease and (on the right) normal controls. The images are obtained by projecting the results obtained from the SPM analysis onto an MRI template. The colour coding shows degree of statistical significance (Z score) and the physical extent of those volume elements (voxels) in which regional cerebral blood flow was significantly different between the patient groups for the comparison high dose dobutamine v rest. MRI, magnetic resonance imaging; L, left; R, right. For the stereotactic coordinates, see text.

Figure 2

Time course of regional cerebral blood flow changes in the right insula region of interest. The differences in activation between the syndrome X and coronary disease patients (left of figure) and between the syndrome X patients and the normal controls (right of figure) can be seen to occur maximally during day (dy) 5, the high dose dobutamine scan. (The sequence of dynamic scans, dy1–dy6, is as described in the text.) *p<0.001;**p<0.0001. CAD, coronary artery disease; SX, syndrome X.

Figure 3

Schematic description of our hypothesis on the perception of cardiac pain. A full description is in the text.