Axonal hyperexcitability after combined NGF sensitization and UV-B inflammation in humans

BackgroundBoth nerve growth factor (NGF) and ultraviolet-B (UV-B) irradiation sensitize nociceptive nerve endings and increase axonal excitability of nociceptors. Combining NGF and UV-B treatment is supra-additive for sensory sensitization and even caused spontaneous pain in about 70% of the subjects. MethodsUV-B irradiation was performed at day 21 after intradermal NGF injection in 13 volunteers. Pain thresholds, electrically induced axon reflex erythema and pain (1.5-fold pain threshold, 5-100Hz) was analysed at days 22, 24, 28, 35, 49 and 70 and correlated to hyperalgesia and spontaneous pain. ResultsElectrical pain threshold after combined NGF/UVB was reduced below single treatment at 24h but not at 72h post-UV-B irradiation. At the NGF/UV-B site, electrical pain was enhanced at all frequencies compared with single NGF and UV-B sites at 24 and 72h with pain ratings exceeding control values about twofold to threefold [657 vs. 25 +/- 8 visual analogue scale (VAS) (24h) and 55 +/- 9 vs. 22 +/- 5 VAS (72h)]. Hyperalgesia to electrical stimulation correlated with hyperalgesia to pinprick (Spearman r=0.44; p<0.001, Bonferroni corr.) and supra-threshold heat (Spearman r=0.55; p<0.001) stimulation at 24h only. Electrical pain thresholds at the NGF/UV-B site weakly correlated to spontaneous pain levels (Spearman r=0.3; p=0.025, without Bonferroni correction). In contrast, electrically induced pain or axon reflex erythema did not correlate to spontaneous pain levels. ConclusionsThe combination of NGF and UV-B increases axonal excitability that contributes to hyperalgesia and might also facilitate ongoing spontaneous pain.