Patterns of activity-dependent conduction velocity changes differentiate classes of unmyelinated mechano-insensitive afferents including cold nociceptors, in pig and in human

Activity-dependent slowing of conduction velocity (ADS) differs between classes of human nociceptors. These differences likely reflect particular expression and use-dependent slow inactivation of axonal ion channels and other mechanisms governing axonal excitability. In this study, we compared ADS of porcine and human cutaneous C-fibers. Extracellular recordings were performed from peripheral nerves, using teased fiber technique in pigs and microneurography in humans. We assessed electrically-induced conduction changes and responsiveness to natural stimuli. In both species, the group of mechano-insensitive C-fibers showed the largest conduction slowing (∼30%) upon electrical stimulation (2 Hz for 3 min). In addition, we found mechano-insensitive cold nociceptors in pig that slowed only minimally (<10% at 2 Hz), and a similar slowing pattern was found in some human C-fibers. Mechano-sensitive afferents showed an intermediate conduction slowing upon 2 Hz stimulation (pig: 14%, human 23%), whereas sympathetic efferent fibers in pig and human slowed only minimally (5% and 9%, respectively). In fiber classes with more pronounced slowing, conduction latencies recovered slower; i.e. mechano-insensitive afferents recovered the slowest, followed by mechano-sensitive afferents whereas cold nociceptors and sympathetic efferents recovered the fastest. We conclude that mechano-insensitive C-fiber nociceptors can be differentiated by their characteristic pattern of ADS which are alike in pig and human. Notably, cold nociceptors with a distinct ADS pattern were first detected in pig. Our results therefore suggest that the pig is a suitable model to study nociceptor class-specific changes of ADS.