Heterogeneity in primary nociceptive neurons: from molecules to pathology

Pain sensation (nociception) is an alarm system aiming to signal the presence of potentially or actually harmful stimuli. In our hazard-rich environment, pain initiates the necessary reactions to prevent or limit tissue damage in response to noxious inputs playing therefore a crucial survival role. Specialized noxious stimuli detectors, called primary nociceptive neurons or nociceptors transduce and convey pain information to the central nervous system. Unlike other sensory systems, pain sensation could be evoked by a vast range of external or internal stimuli. Nearly any of the environmental stimuli could be potentially noxious depending on their nature and/or intensity and/or duration. Early studies at the beginning of the 20th century identified a discrete number of nociceptive neuronal types according to their electrophysiological responses or their degree of myelination. However, the advent of molecular biology techniques revealed an extraordinary diversity among nociceptors. Such heterogeneity likely reflects the evolutionary adaptation required to respond to an extremely variety of circumstances.