gms | German Medical Science

Introduction: Keratinocytes play an important role in the dialog between skin and cutaneous sensory neurons. Among others, they are an essential source of cutaneous nerve growth factor (NGF), a neurotrophin that contributes to persistent pain in inflammation and neuropathy.

Materials and methods: We studied the interaction of human keratinocytes (hKTs) and regenerating afferent nerve fibers by transplanting hKTs into a ligated and transected peripheral nerve.

Results: The hKTs self-assembled into a multi-laminar spheroid cellular structure resembling the corpus spinosum of epidermis. Axonal sprouts surrounded the structure although they were excluded from entry. Levels of NGF were elevated at the transplant site. Whole cell patch clamp recordings from primary afferent neurons whose cut axons were present near the transplanted hKTs displayed extreme hyperexcitability. These neurons generated high frequency trains of action potentials during step depolarization stimuli, and they sometimes showed afterdischarge. Many fired spontaneously at resting membrane potential. This spontaneous firing originated from subthreshold membrane potential oscillations. Animals with extreme hyperexcitability of their cut afferents exhibited profound pain behaviour.

Conclusion: The results demonstrate that afferent hyperexcitability results from contact between keratinocytes and injured and regenerating nerve fiber endings. The resulting impulse discharge may contribute to pain in neuropathy, post-surgical scars and burns.