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


METHODS
UV-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, 5-100 Hz) was analysed at days 22, 24, 28, 35, 49 and 70 and correlated to hyperalgesia and spontaneous pain.


RESULTS
Electrical pain threshold after combined NGF/UVB was reduced below single treatment at 24 h but not at 72 h 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 72 h with pain ratings exceeding control values about twofold to threefold [65 ± 7 vs. 25 ± 8 visual analogue scale (VAS) (24 h) and 55 ± 9 vs. 22 ± 5 VAS (72 h)]. 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 24 h 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.


CONCLUSIONS
The combination of NGF and UV-B increases axonal excitability that contributes to hyperalgesia and might also facilitate ongoing spontaneous pain.
B
B
Rukwied
B
B
Weinkauf
M
M
Main
O
O
Obreja
M
M
Schmelz
D000328:Adult; D001369:Axons / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D059333:Central Nervous System Sensitization / Q000187:drug effects; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000209:etiology*; D007249:Inflammation / Q000209:etiology; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000008:administration & dosage / Q000494:pharmacology*; D010147:Pain Measurement / Q000295:instrumentation / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D012867:Skin / Q000187:drug effects / Q000503:physiopathology / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects
D020932:Nerve Growth Factor