Nociceptor sensitization to mechanical and thermal stimuli in pig skin in vivo

Primary hyperalgesia to mechanical and thermal stimuli are major clinical symptoms of inflammatory pain and can be induced experimentally by ultraviolet‐B (UV‐B) irradiation in humans. We set‐up a pig model in order to have more options for pharmacological intervention on primary hyperalgesia. Pig skin was irradiated with a dose one‐ to threefold higher than the minimum erythema dose (MED) and investigated for mechanical and heat responsiveness 24 and 48h post UV‐B treatment. C‐fiber activation upon mechanical and thermal stimulation was assessed indirectly by extent of the axon reflex erythema (flare) measured by laser Doppler imaging. Mechanical stimulation with von Frey filaments (100mN) induced flare responses in UV‐B treated skin at 24 and 48h, but no effect was measured in normal untreated skin. Increased mechanical stimulation (600mN) elicited a small flare response in normal skin in an area of 1.8cm² on average that was extending about 2.5cm² in the UV‐B irradiated sites. Thermal stimuli provoked in normal pig skin flare areas of approximately 2cm² (45°C, 10s) and 4.5cm² (47°C, 10s) which increased to about 3.5cm² (45°C) and 5.5cm² (47°C) following UV‐B irradiation at 24 and 48h. No significant differences of mechanically or thermally induced hypersensitivity were seen between 24 and 48h after irradiation. We conclude that UV‐B induced mechanical and heat sensitization of primary afferent nociceptors can be assessed in pig skin, providing a new human‐like model of primary hyperalgesia. Sensitization of primarily mechano‐insensitive (silent) nociceptors, which are underlying the flare response in humans, most probably contributes to the observation presented here.