Our understanding of how peripheral damage-sensing neurons (nociceptors) respond to noxious stimuli is fundamental to the development of effective analgesics. To date, numerous studies have presented diverging hypotheses on how nociceptors encode modality-specific stimuli, including labelled-line, intensity dependence or pattern theory. In this short review, we appraise data from electrophysiological, behavioural, imaging and molecular expression studies from the last 60 years, in order to obtain a coherent view of modality-specific sensing in peripheral sensory neurons. We propose a mechanistic explanation for the broad range of values obtained for the incidence of polymodal nociceptors that reconciles apparently contradictory data.
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