A major role for the initiation of chronic pain in human was attributed to long-term sensitization of nociceptive afferents, especially the subclass of mechano-insensitive (“silent”) C-nociceptors. Using identical stimulation paradigms as in human microneurography, we recently demonstrated that pig and human C-fibers have comparable axonal and sensory properties. Thus, single nerve fiber recordings in pig provide a translational animal model to study mechanisms governing nociceptor excitability and its experimental modulation, in vivo. Our main focus is the axonal transformation site as pivotal integrator of signals from the periphery conveyed by various transduction molecules and the signal processing along the axon.

By employing single fiber extracellular recordings in anesthetized pigs, we aim to understand functional differences between classes of unmyelinated C-fibers concerning:

• physiological sensory and axonal response patterns
• excitability changes induced by inflammatory mediators (especially neurotrophins)
• contribution of axonal sensitization to the initiation and maintenance of long-lasting hyperalgesic states.