title: Ultraviolet-B-induced mechanical hyperalgesia: A role for peripheral sensitisation.
abstract: Ultraviolet (UV) induced cutaneous inflammation is emerging as a model of pain with a novel sensory phenotype. A UVB dose of 1000mJ/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 approximately 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 10microg 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 6-768microm of 103 peripheral nociceptors were recorded. At the peak of UVB-induced hyperalgesia we observed that mechanical response properties of Adelta-nociceptors recorded from UVB-inflamed skin (n=19) were significantly diminished, by approximately 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 approximately 75%, in UVB-inflamed (n=26) compared to naïve skin (n=12). Heat-insensitive C-nociceptors, however, demonstrated significantly enhanced (by approximately 60%) response properties to mechanical stimulation in UVB-inflamed (n=21) compared to naïve skin (n=12). Notably alteration in mechanical responses of Adelta- 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.
authors.affiliation: Neurorestoration Group, The Wolfson Centre for Age Related Disease, King's College London, The Wolfson Wing, Hodgkin Building, Guy's Campus, London Bridge, London SE1 1UL, UK King's College London, Division of Genetics & Molecular Medicine, Tower Wing, Guy's Hospital, London SE1 9RT, UK Molecular Physiology of Somatic Sensation, Dept. of Neuroscience, Max-Delbrück Center for Molecular Medicine, Robert Rössle Str. 10, Berlin-Buch D-13122, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bishop
authors.forename: Fabien
authors.initials: F
authors.lastname: Marchand
authors.forename: Antony R
authors.initials: AR
authors.lastname: Young
authors.forename: Gary R
authors.initials: GR
authors.lastname: Lewin
authors.forename: Stephen B
authors.initials: SB
authors.lastname: McMahon
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004594:Electrophysiology; D006930:Hyperalgesia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009619:Nociceptors / Q000502:physiology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000473:pathology; D014466:Ultraviolet Rays
chemical_list: D016291:Dizocilpine Maleate