LAUSR

BACKGROUND Intradermal injection of 1 µg nerve growth factor (NGF) causes sustained nociceptor sensitization. Slowly depolarizing electrical current preferentially activates C-nociceptors. METHODS We explored the differential contribution of A-delta and C-nociceptors in NGF sensitized skin using slowly depolarizing transcutaneous electrical current stimuli, CO2 laser heat, mechanical impact, and A-fiber compression block. In 14 healthy volunteers pain rating was recorded on a numeric scale at days 1 - 14 after NGF treatment. Ratings during A- fiber conduction block were investigated at days 3 and 7 post NGF. RESULTS Pain ratings to electrical, CO2 heat and mechanical impact stimuli were enhanced (> 30%, p < 0.0005, ANOVA) at NGF-injection sites. Axon reflex erythema evoked by electrical stimulation was also larger at NGF-injection sites (p < 0.02, ANOVA). Diminution of pain during continuous (1 min) sinusoidal current stimulation at 4 Hz was less pronounced after NGF (p < 0.05, ANOVA). Pain ratings to electrical sinusoidal and mechanical impact stimuli during A-fiber conduction block were significantly elevated at the NGF sites compared to NaCl-treated skin (p < 0.05, ANOVA). CONCLUSIONS NGF-induced sensitization of human skin to electrical and mechanical stimuli is primarily driven by C-nociceptors with little contribution from A-delta fibers. Less pronounced accommodation during ongoing sinusoidal stimulation suggests that NGF could facilitate axonal spike generation and conduction in primary afferent nociceptors in humans. Further studies using this sinusoidal electrical stimulation profile to investigate patients with chronic inflammatory pain may allow localized assessment of skin C-nociceptors and their putative excitability changes under pathologic conditions.