Heat-rekindling in UVB-irradiated Skin Above NGF-sensitized Muscle: Experimental Models of Prolonged Mechanical Hypersensitivity

Experimental models of prolonged pain hypersensitivity in humans are desirable for screening novel analgesic compounds. In this study, heat stimuli were applied in ultraviolet-B (UVB)-irradiated skin and in the UVB-irradiated skin combined with nerve growth factor (NGF)-injected muscle to investigate 1) whether the evoked mechanical hypersensitivity by UVB irradiation would be prolonged or enhanced following heat rekindling, and 2) whether the combination between cutaneous and muscle hypersensitivity may influence the rekindling effects. Skin sensitization was induced in 25 volunteers by UVB irradiation in areas above the upper-trapezius muscle, low-back or forearm. Muscle sensitization was induced in the low back by bilateral injections of NGF. The area of cutaneous hyperalgesia was evaluated 3 days after the irradiation by mechanical pin-prick stimulation whereas the areas of allodynia were evaluated 1, 2 and 3 days after irradiation by von Frey hair assessments. Cutaneous heat stimulation (40°C for 5 min) was performed on the 3(rd) day to investigate its effect on the areas of cutaneous allodynia and hyperalgesia. Findings revealed that 1) allodynia and hyperalgesia developed following UVB irradiation, 2) heat stimulation of the UVB-irradiated skin enlarged both hyperalgesic and allodynic areas (P < 0.01), and 3) muscle sensitization did not influence the effect of UVB on allodynia or the response to heat rekindling. These data suggest that heat rekindling applied to an UVB-sensitized skin can maintain or facilitate allodynia and hyperalgesia for a longer period offering a suitable model for testing analgesic compounds when sufficient duration of time is needed for investigation of drug efficacy.