Rapid reperfusion is crucial to reduce mortality in patients with ST elevation myocardial infarction. Prehospital patient delay, defined as time from symptoms onset to the decision to seek medical attention, accounts for a large proportion of cases with delayed reperfusion. However, whether pain modulation processes are involved in this phenomenon is not known. We hypothesized that prehospital patient delay may be affected by a reduction of perceived pain perception and pain modulation pattern. Pain threshold, magnitude estimation of suprathreshold stimulation, mechanical temporal summation and conditioned pain modulation (CPM), and recalls of pain magnitude at the onset of chest pain were obtained in 67 patients with first ST elevation myocardial infarction. The study's primary outcome was prehospital patient delay. The median patient delay was 24 (interquartile range, 0.5-72) hours. Of all psychophysical pain measures including pain threshold, magnitude estimation of suprathreshold stimulation, mechanical temporal summation, as well as CPM, only warm sensation threshold was independently associated with lower clinical chest pain intensity (P = 0.01). Multivariable regression analysis (R2 = 0.449; P < 0.0001) revealed an inverse independent association between chest pain intensity (P < 0.001) and patient delay, whereas efficient CPM was positively associated with prolonged patient delay (P = 0.034). The electrocardiography-derived myocardial ischemic area was not associated with chest pain intensity or patient delay, indicating that the affected ischemic tissue is not a dominant component that determines pain response. In conclusion, beyond the perceived chest pain intensity, the activation pattern of descending inhibition pathways during coronary occlusion affects pain interpretation and behavior during acute coronary occlusion.