Characterisation of ultraviolet-B-induced inflammation as a model of hyperalgesia in the rat

Abstract

In humans, the acute inflammatory reaction caused by ultraviolet (UV) radiation is well studied and the sensory changes that are found have been used as a model of cutaneous hyperalgesia. Similar paradigms are now emerging as rodent models of inflammatory pain. Using a narrowband UVB source, we irradiated the plantar surface of rat hind paws. This produced the classical feature of inflammation, erythema, and a significant dose-dependent reduction in both thermal and mechanical paw withdrawal thresholds. These sensory changes peaked 48h after irradiation. At this time there is a graded facilitation of noxious heat evoked (but not basal) c-fos-like immunoreactivity in the L4/5 segments of the spinal cord. We also studied the effects of established analgesic compounds on the UVB-induced hyperalgesia. Systemic as well as topical application of ibuprofen significantly reduced both thermal and mechanical hyperalgesia. Systemic morphine produced a dose-dependent and naloxone sensitive reversal of sensory changes. Similarly, the peripherally restricted opioid loperamide also had a dose-dependent anti-hyperalgesic effect, again reversed by naloxone methiodide. Sequestration of NGF, starting at the time of UVB irradiation, significantly reduced sensory changes. We conclude that UVB inflammation produces a dose-dependent hyperalgesic state sensitive to established analgesics. This suggests that UVB inflammation in the rat may represent a useful translational tool in the study of pain and the testing of analgesic agents.

ROS-mediated activation of Drosophila larval nociceptor neurons by UVC irradiation

“…In support of this idea, a low dose of UV (slightly above 20 mJ/cm 2 ) is sufficient to kill Drosophila larvae [30]. This is far below the dose of 250–1000 mJ/cm 2 which merely sensitizes the sensory neurons in rats [47]. This finding is consistent with an increased susceptibility of insects and other small animals with simple integument system to the devastating effects of UVR.…”

UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling

“…To elucidate mechanisms, we used a mouse sunburn model and induced a state of lowered sensory thresholds associated with tissue injury caused by UV radiation (8)(9)(10). UV-sunburn-evoked lowering of sensory thresholds shares major hallmarks of pathological pain, a valuable feature of this model.…”

Corneal Sensory Nerve Activity in an Experimental Model of UV Keratitis

“…41 Furthermore, the higher incidence of ongoing firing and augmented responsiveness of polymodal nociceptors, combined with the reduced threshold of mechanonociceptors, also explains the presence of mechanical and chemical hyperalgesia observed 24 hours after UV exposure. 39,42 There is ample evidence of epithelial damage by UV radiation, with the generation of reactive oxygen species and oxidative stress 43,44 that are detrimental to corneal epithelial cells and may lead ultimately to apoptosis. Proinflammatory molecules, such as interleukins, cytokines, matrix metalloproteinases, nuclear factor-jB, or nitric oxide, are locally released in the cornea 12,45-50 accompanied by a significant elevation of interleukins and TNF-a concentrations in tears.…”