Functional signatures of human somatosensory C fibers by microneurography

Microneurography allows the recording of single C-fiber action potentials of a peripheral nerve innervating the skin in the awake, conscious human. The method is highly relevant to assess and understand the function of human peripheral nociceptors and correlate nociceptor discharges to human sensation. Given the current translational gap between preclinical and clinical research, in-depth understanding of human nerve fiber physiology becomes increasingly important. In this review, we bring together the current knowledge of afferent C-fiber types described to date and describe by which assays their function can be determined, how they react to the applied stimuli, and how this leads to the current classification(s) used in the field. We provide novel synthesis of C-fiber functions and discuss potential links between specific fiber characteristics and their physiology. The review aims to provide an in-depth overview of existing microneurography data of human dermal C fibers, which may serve as basis for efforts to bridge the gap between functional and structural studies in pain research. The knowledge presented here may help to establish a link between the functional microneurography findings in humans and other basic science research methods such as RNA sequencing techniques. This is a prerequisite for translational studies of the somatosensory system to identify biomarkers or develop well-targeted treatment for pain and itch in human.