Journal ArticleDOI
Characterisation of ultraviolet-B-induced inflammation as a model of hyperalgesia in the rat.
Thomas Bishop,David W. Hewson,Ping K. Yip,M S Fahey,David Dawbarn,Antony R. Young,Stephen B. McMahon +6 more
Reads0
Chats0
TLDR
It is concluded that UVB inflammation produces a dose‐dependent hyperalgesic state sensitive to established analgesics, which suggests thatUVB inflammation in the rat may represent a useful translational tool in the study of pain and the testing of analgesic agents.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 48 h 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.read more
Citations
More filters
Journal ArticleDOI
Antagonism of Nerve Growth Factor-TrkA Signaling and the Relief of Pain
TL;DR: Mechanisms by which NGF activation of its cognate receptor, tropomyosin-related kinase A receptor, regulates a host of ion channels, receptors, and signaling molecules to enhance acute and chronic pain are outlined.
Journal ArticleDOI
Sensory and signaling mechanisms of bradykinin, eicosanoids, platelet-activating factor, and nitric oxide in peripheral nociceptors
TL;DR: This review aims to give an account of the excitatory and sensitizing actions of inflammatory mediators including bradykinin, prostaglandins, thromboxanes, leukotrienes, platelet-activating factor, and nitric oxide on nociceptive primary afferent neurons.
Journal ArticleDOI
UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling.
Carlene Moore,Ferda Cevikbas,H. Amalia Pasolli,Yong Chen,Wei Kong,Cordula Kempkes,Puja K. Parekh,Suk Hee Lee,Nelly-Ange T. Kontchou,Iwei Yeh,Nan Marie Jokerst,Elaine Fuchs,Martin Steinhoff,Wolfgang Liedtke +13 more
TL;DR: The calcium-permeable TRPV4 ion channel in skin epithelial cells is identified as critical for translating the UVB stimulus into intracellular signals and also into signals from epithelial skin cell to sensory nerve cell that innervates the skin, causing pain.
Journal ArticleDOI
Targeting nerve growth factor in pain: what is the therapeutic potential?
TL;DR: Current options being explored include the development of humanized monoclonal antibodies to NGF or its tyrosine kinase receptor TrkA, and the sequestration of NGF using TrkAd5, a soluble receptor protein that binds NGF with picomolar affinity.
Journal ArticleDOI
Recognition and Alleviation of Pain in Laboratory Animals
TL;DR: A broad range of pharmacological and non-pharmacological strategies to prevent or treat pain is described in depth and the important issue of humane endpoints is central to any strategy dedicated to reduce or avoid unnecessary pain and distress, without compromising the scientific validity of the studies.
References
More filters
Journal ArticleDOI
The similarity of action spectra for thymine dimers in human epidermis and erythema suggests that DNA is the chromophore for erythema
Antony R. Young,Caroline A Chadwick,Graham I. Harrison,Osamu Nikaido,J Ramsden,Christopher S Potten +5 more
TL;DR: Data indicate that solar UVB (approximately 295-320 nm) is more damaging to basal cells than predicted from transmission data obtained from human epidermis ex vivo, and spectral comparisons suggest that DNA is a major chromophore for erythema in the 280-340 nm region.
Journal ArticleDOI
Mechanical and heat sensitization of cutaneous nociceptors after peripheral inflammation in the rat.
David Andrew,Joel D. Greenspan +1 more
TL;DR: The mechanical hyperalgesia caused by peripheral inflammation could be explained by nociceptor sensitization, and central mechanisms cannot be completely ruled out as contributing to such hyperalGESia, although their role may be much smaller than previously envisaged.
Journal ArticleDOI
Neutralization of endogenous NGF prevents the sensitization of nociceptors supplying inflamed skin.
TL;DR: NGF is a crucial component for the sensitization of primary afferent nociceptors associated with tissue inflammation and displayed essentially normal response properties, although the inflammation as evidenced by tissue oedema developed normally.
Journal Article
Peripheral opioid analgesia
Journal ArticleDOI
Opiates suppress carrageenan-induced edema and hyperthermia at doses that inhibit hyperalgesia.
TL;DR: The results indicate that opiates exert a moderate, though significant, reduction in the vascular signs of inflammation in addition to their reduction of hyperalgesia.