Facilitated neurotrophin release in sensitized human skin

The neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) play a pivotal role in the generation and maintenance of hyperalgesia. In the present study we analyzed NGF and BDNF levels in human skin of the upper arm and axilla skin sites by dermal microdialysis and multiplexed assay. Skin sensitization and inflammatory responses were evoked experimentally by repetitive shaving of one axilla provoking local erythema and reduced heat pain thresholds. Acute excitation of skin nociceptors was performed by perfusion of the microdialysis catheters with citric acid pH 3. At baseline, neurotrophin concentrations did not differ significantly between the investigated skin sites. On average, NGF concentration was 5.8 fg/microug protein/ml sample volume and BDNF concentration was 87.5 fg/microg/ml. Citric acid perfusion marginally increased NGF levels to 7.3 fg/microg/ml on average in the upper arm and control axilla. Similarly, BDNF values increased at these control skin sites to about 122 fg/microg/ml following proton stimulation. In contrast, perfusion of the inflamed axilla with citric acid significantly enhanced the release of both NGF and BDNF. On average, NGF levels were analyzed at 14.6 fg/microg/ml and BDNF values at 202 fg/microg/ml. These data demonstrate enhanced level of neurotrophin release in inflamed human skin in vivo which might well contribute to peripheral sensitization. Analyses of neurotrophic factors by dermal microdialysis are useful endogenous markers to further explore their role in neuronal sensitization processes in human.