Match and mismatch: Identifying the neuronal determinants of pain

Despite the increased intensity and sophistication of research on pain mechanisms in the past three decades, serious uncertainties remain about the neuronal origin of pain, especially in painful clinical conditions. Although a positive correlation between nociceptive afferent activity and the subjective perception of pain has been seen under controlled experimental conditions, important mismatches point to the critical importance of central nervous system processes as determinants of pain. Multiple peripheral, segmental, and supraspinal neuronal activities control nociceptive processing at all levels of the neuraxis. Three studies in this issue highlight the problem of identifying the neuronal determinants of pain by addressing contrasting mismatches: angina-like chest pain without an obvious cause and a potential source of angina (myocardial ischemia) without pain. The results of these studies suggest that selective visceral hyperalgesia and hypoalgesia of peripheral or central origin may be present without other clinical evidence for neurologic abnormality. Complex mechanisms interacting at several levels of the nervous system appear to be involved.