Nociceptive system - Nociceptors, fiber types, spinal pathways, and projection areas

In order to transform a nociceptive stimulus into a painful perception, a highly specialized chain of structural and functional elements is necessary. This system comprises nociceptors in the periphery with specific molecular properties for differential coding of noxious submodalities, ascending and descending tracts that can control the input into the dorsal horn of the spinal cord as well as supraspinal processing that regulates the integration of nociceptive information with other sensory modalities and autonomic function. In this article, structures involved in nociceptive signal processing starting from the periphery up to spinal and cerebral structures are discussed in the order of their spatio-temporal activation sequence - as far as these are known. Already from the basis of the different receptor subtypes found on the thinly or unmyelinated nerve fibers in the periphery, the predominant principle of polymodality is demonstrated. Different input to the dorsal horn of the spinal cord by different nerve fiber populations to superficial and deep layers is explained, ascending tracts as well as descending systems capable of either facilitating or inhibiting the upstream flow of nociceptive information, together with their known transmitters. Finally, thalamic relay nuclei for sensory and nociceptive signals, as well as subcortical and cortical projection targets are discussed. To complete the current view of the nociceptive system, information from molecular biology and anatomic tracing studies as well as data from functional electrophysiologic cell recordings in animals and imaging studies in humans are assembled.