Ultraviolet-B-induced mechanical hyperalgesia: A role for peripheral sensitisation

Ultraviolet (UV) induced cutaneous inflammation is emerging as a model of pain with a novel sensory phenotype. A UVB dose of 1000 mJ/cm2 produces a highly significant thermal and mechanical hypersensitivity. Here we examined the properties and mechanisms of such hyperalgesia in rats. Significantly, the mechanical hyperalgesia (with ∼60% change in withdrawal thresholds) was restricted to the lesion site with no changes in mechanical threshold in adjacent non-irradiated skin (i.e. no secondary hypersensitivity), suggesting a peripheral mechanism. Consistent with this, we found that primary mechanical hypersensitivity showed no significant changes after intrathecal treatment with 10 μg of the NMDA-receptor antagonist MK-801. Using an in vitro skin-nerve preparation, in the presence and absence of UVB-inflammation, suprathreshold responses to skin displacement stimuli of 6-768 μm of 103 peripheral nociceptors were recorded. At the peak of UVB-induced hyperalgesia we observed that mechanical response properties of Aδ-nociceptors recorded from UVB-inflamed skin (n = 19) were significantly diminished, by ∼50%, compared to those recorded from naïve skin (n = 13). The mechanical response properties of heat-sensitive C-nociceptors were unchanged while their heat responses were significantly increased, by ∼75%, in UVB-inflamed (n = 26) compared to naïve skin (n = 12). Heat-insensitive C-nociceptors, however, demonstrated significantly enhanced (by ∼60%) response properties to mechanical stimulation in UVB-inflamed (n = 21) compared to naïve skin (n = 12). Notably alteration in mechanical responses of Aδ- and heat-insensitive C-nociceptors were particular to stronger stimuli. Spontaneous activity was not induced by this dose of UVB. We conclude that UVB-induced mechanical hyperalgesia may be explained by a net shift in peripheral nociceptor response properties.