• cardiac syndrome X
• chest pain
• pain perception

In cardiac syndrome X, the presence of ischaemic-like ST segment changes during chest pain, in the absence of epicardial coronary stenoses, suggests that myocardial ischaemia caused by coronary microvascular dysfunction is responsible for angina.¹ This view is supported by the documentation of abnormalities in myocardial perfusion on radionuclide studies^2,3 and abnormal coronary blood flow response to vasoactive stimuli.^4–7 Furthermore, several abnormalities able to cause microvascular dysfunction have been reported, including increased adrenergic function,⁸ increased stress induced coronary sinus release of endothelin-1,⁹ and increased activity of sodium–hydrogen countertransport.¹⁰ Yet several studies failed to show myocardial lactate production and left ventricular dysfunction^11–14 during angina and ST segment depression, thus casting some doubts on the ischaemic origin of chest pain and ECG changes.¹⁵

In 1988, Shapiro and colleagues reported the observation that syndrome X patients refer chest pain during intra-atrial saline injection, suggesting that an abnormally increased perception of pain during usually painless cardiac stimuli could be the mechanism responsible for chest pain in cardiac syndrome X.¹⁶ Several studies consistently confirmed this finding,^17–20 lending further support to the hypothesis that a reduced cardiac pain threshold might be the predominant cause of the syndrome. These observations generated some new questions:

1. Is enhanced perception of painful stimuli confined to the heart or is rather generalised?

2. Where does the abnormality responsible for enhanced …