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Mechanical sensitization, increased axonal excitability and spontaneous activity in C-nociceptors following UVB irradiation in pig skin.
Pain 2021 January 13
ABSTRACT: UVB irradiation induces hyperalgesia in human and animal pain models. We investigated mechanical sensitization, increase in axonal excitability and spontaneous activity in different C-nociceptor classes following UVB in pig skin. We focused on units with receptive fields covering both irradiated and non-irradiated skin allowing intra-individual comparisons. 35 pigs were irradiated in a chessboard pattern and extracellular single-fibre recordings were obtained 10-28 h later (152 fibers). Units from the contralateral hindlimb served as control (n=112). Irradiated and non-irradiated parts of the same innervation territory were compared in 36 neurons: low threshold C-touch fibers (n=10) and sympathetic efferents (n=2) were unchanged, but lower mechanical thresholds and higher discharge frequency at threshold were found in mechanosensitive nociceptors (n=12). Half of them could be activated with non-noxious brush stimuli in the sunburn. 4 of 12 mechano-insensitive nociceptors were found sensitized to mechanical stimulation in the irradiated part of the receptive field. Activity dependent slowing of conduction was reduced in the irradiated and in the non-irradiated skin as compared to the control leg whereas increased ability to follow high stimulation frequencies was restricted to the sunburn (108.5 ± 37 Hz UVB vs. 6.3 ± 1 Hz control). Spontaneous activity was more frequent in the sunburn (72/152 vs. 31/112). Mechanical sensitization of primary nociceptors and higher maximum following frequency are suggested to contribute to primary hyperalgesia, whereas spontaneous activity of silent nociceptors might offer a mechanistic link contributing to ongoing pain and facilitated induction of spinal sensitization.
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