Pain information pathways from the periphery to the cerebral cortex

Abstract

A recent PET study revealed that the first and second somatosensory cortices (SI, SII), and the anterior cingulate cortex are activated by painful peripheral stimulation in humans. It has become clear that painful signals (nociceptive information) evoked at the periphery are transmitted via various circuits to the multiple cerebral cortices where pain signals are processed and perceived. Human or clinical pain is not merely a modality of somatic sensation, but associated with the affect that accompanies sensation. Consequently, pain has a somatosensory-discriminative aspect and an affective-cognitive aspect that are processed in different but correlated brain structures in the ascending circuits. Considering the physiologic characteristics and fiber connections, the SI and SII cortices appear to be involved in somatosensory-discriminative pain, and the anterior cingulate cortex (area 24) in the affective-cognitive aspect of pain. This paper deals with the ascending pain pathways from the periphery to these cortices and their interconnections. Our recent findings on the protease-activated receptors 1 and 2 (PAR-1, and -2), which are confirmed to exist in the dorsal root ganglion cells, are also described. Activation of PAR-2 during inflammation or tissue injury at the periphery is pronociceptive, while PAR-1 appears to be antinociceptive. Based on the these findings, PAR-1 and PAR-2 are attracting interest as target molecules for new drug development.