PMID- 18571954 OWN - NLM STAT- MEDLINE DCOM- 20090626 LR - 20181201 IS - 1532-2149 (Electronic) IS - 1090-3801 (Linking) VI - 13 IP - 4 DP - 2009 Apr TI - Facilitated neurotrophin release in sensitized human skin. PG - 399-405 LID - 10.1016/j.ejpain.2008.05.005 [doi] AB - 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. FAU - Paterson, Sarah AU - Paterson S AD - Unilever R&D Laboratory Port Sunlight, Bebington, Wirral, United Kingdom. FAU - Schmelz, Martin AU - Schmelz M FAU - McGlone, Francis AU - McGlone F FAU - Turner, Graham AU - Turner G FAU - Rukwied, Roman AU - Rukwied R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080620 PL - England TA - Eur J Pain JT - European journal of pain (London, England) JID - 9801774 RN - 0 (Biomarkers) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Inflammation Mediators) RN - 0 (Nerve Growth Factors) RN - 2968PHW8QP (Citric Acid) RN - 9061-61-4 (Nerve Growth Factor) SB - IM MH - Adult MH - Biomarkers/analysis/metabolism MH - Brain-Derived Neurotrophic Factor/metabolism MH - Citric Acid/pharmacology MH - Dermatitis/*metabolism/physiopathology MH - Erythema/metabolism/physiopathology MH - Female MH - Humans MH - Hyperalgesia/*metabolism/physiopathology MH - Inflammation Mediators/pharmacology MH - Microdialysis MH - Middle Aged MH - Nerve Growth Factor/metabolism MH - Nerve Growth Factors/*metabolism MH - Pain Measurement MH - Pain Threshold/physiology MH - Sensory Receptor Cells/*metabolism MH - Skin/innervation/*metabolism/physiopathology MH - Up-Regulation/physiology EDAT- 2008/06/24 09:00 MHDA- 2009/06/27 09:00 CRDT- 2008/06/24 09:00 PHST- 2008/01/16 00:00 [received] PHST- 2008/04/25 00:00 [revised] PHST- 2008/05/11 00:00 [accepted] PHST- 2008/06/24 09:00 [pubmed] PHST- 2009/06/27 09:00 [medline] PHST- 2008/06/24 09:00 [entrez] AID - S1090-3801(08)00110-9 [pii] AID - 10.1016/j.ejpain.2008.05.005 [doi] PST - ppublish SO - Eur J Pain. 2009 Apr;13(4):399-405. doi: 10.1016/j.ejpain.2008.05.005. Epub 2008 Jun 20.