Translational Pain Research: From Mouse to Man (Frontiers in Neuroscience)


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The study, published in Frontiers in Behavioral Neuroscience , was conducted with mouse models of preterm birth. Sensory stimulation was applied from before the injury occurred until the final stages of infancy, a period in preterm infants equivalent to being born at seven months until two years. The manipulation consisted in tactile and propioceptive stroking and massaging of the mice three times within an eight-minute period, twice a day. The results revealed that this intervention had a notable neurological protection on both genders throughout their lives, but researchers highlight that the effects were especially positive among males.

The neurological protection in both genders was correlated to the improvement of functional capacities, reflexes, and an improvement in memory results. The research also analysed for the first time the impact of perinatal hypoxic and ischemic brain injuries, demonstrating that although the same degree of neuropathological severity exists, the damage affects each gender's functional, neurological, cognitive and emotional capacities differently depending on the stage of life and task undertaken.

Male mice showed to have infantile hyperactivity, which normalises as they became adults. In contrast, the anxiety and emotional traits of these injuries lasted throughout their lives.

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Both genders showed poorer learning processes at short and long terms, but there was more damage to memory among the males," explains Aida Muntsant, PhD student at the INc-UAB and first author of the paper. Materials provided by Universitat Autonoma de Barcelona. Together, these studies have demonstrated that by understanding mechanisms underlying UVB hyperalgesia and sensory changes during inflammation, new therapeutic approaches to treat inflammatory pain states in general can be developed.

Further to the targets above discussed, new exciting strategies could be developed by the identification of cellular mechanisms triggered by pain, as discussed below. Therefore, this model may allow us to identify novel mediators of sensitization that are important in the UVR and other pain states.

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A large number of upregulated transcripts were identified by the group, among them a variety of interleukins, chemokines, and cyclooxygenase and iNOS that were consistent between humans and rats Notably, a dramatic upregulation of CXCL5 expression was observed at the peak of inflammation Moreover, the authors demonstrated that injection of CXCL5 is proalgesic, producing a reduction of mechanical pain threshold, similar to UVB irradiation Most importantly, the study showed that blockade of CXCL5 postirradiation, using a neutralizing antibody, reduces the mechanical pain threshold, as well as the levels of the immune response at the site Recently, a further investigative study not only reproduced the data in the human skin, but also suggested that fibroblasts might be involved in triggering the expression and secretion of CXCL5 at the skin, ultimately boosting UV response Given these findings, a step forward toward the validation of these targets is crucial, so they could meaningfully represent a plausible treatment for inflammatory hyperalgesia.

One group used the same principle of UVB inflammation but with the intent of identifying lipid mediators By comparing tissue from skin, DRG's and spinal dorsal horn, the study identified almost 20 different lipids isoforms that were upregulated upon UVB irradiation, nearly all in peripheral tissues and almost none at DRG and spinal cord levels By comparing skin samples of patients and rodents exposed to UVB, the authors presented a remarkable level of similarity across the different species, identifying changes on over common genes Most of the changes in expression were found in the skin, as previously reported Unsurprisingly, many of the genes upregulated were related to inflammation The group also looked at molecular changes at the DRGs and identified 39 genes differentially regulated There is a considerable need to develop new classes of analgesic drugs , , , and as a result, there have been many efforts to bring new drugs to the clinic.

Unfortunately, these efforts have, to date, had only limited success in terms of new drug registrations. One of the blocks to drug development in this area has been translation from preclinical studies to humans. There are probably multiple contributory factors, but one in particular has been a concern over some of the models of persistent pain used in the preclinical studies.

The model produces a localized inflammatory response in an accessible tissue.

Ultraviolet Radiation on the Skin: A Painful Experience? - Europe PMC Article - Europe PMC

Most importantly, the UVR model of inflammation can be elicited both in humans and laboratory animals, apparently with consistent features in these species. This last feature, which is not shared by many of the preclinical models used, allows for a much greater confidence in translation. As the model can be induced easily in humans, it can also be used in phase I studies and potentially provide an early indication of efficacy. We are grateful to the Wellcome Trust for their support of some of our work presented here. Europe PMC requires Javascript to function effectively.

Translational Neurosciences Focus Program / Forschungszentrum Translationale Neurowissenschaften

Recent Activity. Discomfort and sensory changes caused by skin sunburn are the main common features experienced by many of us, a phenomena triggered by the combination of long and short wavelengths radiation UVA and UVB, respectively. UVR, particularly UVB, produces a controllable and sterile inflammation that causes a robust dose-dependent hypersensitivity with minimal confounding effects. The snippet could not be located in the article text.

Translational Pain Research: From Mouse to Man

This may be because the snippet appears in a figure legend, contains special characters or spans different sections of the article. CNS Neurosci Ther. Published online Aug PMID: Douglas M. Lopes 1 and Stephen B.

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McMahon 1. Stephen B. Corresponding author. This article has been cited by other articles in PMC.

Summary Excessive exposure of skin to ultraviolet radiation UVR has dramatic clinical effects in humans, and it is a significant public health concern. Introduction Excessive exposure of the skin to ultraviolet radiation UVR is a common occurrence in tropical and even temperate latitudes. Open in a separate window. Figure 1. Table 1 Summary of pharmacological interventions that have been tested in UVB models. Second application prolonged the beneficial effects of the drug. Adverse effects were reported.

Conclusions There is a considerable need to develop new classes of analgesic drugs , , , and as a result, there have been many efforts to bring new drugs to the clinic. Conflict of Interest The authors declare no conflict of interest. Acknowledgment We are grateful to the Wellcome Trust for their support of some of our work presented here. References 1. Severe burn injury in Europe: A systematic review of the incidence, etiology, morbidity, and mortality.

Crit Care ; 14 :R Burns ; 22 — Prevalence of sunburn, sun protection, and indoor tanning behaviors among Americans: Review from national surveys and case studies of 3 states. Eur J Cancer ; 37 — Protection of children against sunburn: A survey of parental practice in Leicester. Br J Dermatol ; — Summer sunburn and sun exposure among US youths ages 11 to National prevalence and associated factors. Pediatrics ; 1 Pt 1 — Solar Ultraviolet Radiation: Global burden of disease from solar ultraviolet radiation. Environmental Burden of Disease Series, No.


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Hoffmann RT, Schmelz M. Eur J Pain ; 3 — Histologic changes associated with ultraviolet A—induced erythema in normal human skin.

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J Am Acad Dermatol ; 9 — Willis I, Cylus L. UVA erythema in skin: Is it a sunburn? J Invest Dermatol ; 68 — Warin AP. The ultraviolet erythemas in man. Br J Dermatol ; 98 — Effects of antihyperalgesic drugs on experimentally induced hyperalgesia in man. Pain ; 76 — J Invest Dermatol ; — Light, including ultraviolet.

J Autoimmun ; 34 :J—J Young AR. Acute effects of UVR on human eyes and skin. Prog Biophys Mol Biol ; 92 — Diffey BL. Sources and measurement of ultraviolet radiation. Methods ; 28 :4— Pain ; — Ultraviolet light induced injury: Immunological and inflammatory effects.

Immunol Cell Biol ; 79 — Toxicology ; — Matsumura Y, Ananthaswamy HN. Toxic effects of ultraviolet radiation on the skin. Toxicol Appl Pharmacol ; — J Invest Dermatol ; S—41S. Eur J Pain ; 13 — Spatial sensory organization and body representation in pain perception. Curr Biol ; 23 :R—R Schmelz M. Neuronal sensitivity of the skin. Eur J Dermatol. Todd AJ. Neuronal circuitry for pain processing in the dorsal horn. Nat Rev Neurosci ; 11 — Perceptual changes accompanying controlled preferential blocking of A and C fibre responses in intact human skin nerves.

Exp Brain Res ; 16 — Photoaging: Mechanisms and repair.


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      Translational Pain Research: From Mouse to Man (Frontiers in Neuroscience) Translational Pain Research: From Mouse to Man (Frontiers in Neuroscience)
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      Translational Pain Research: From Mouse to Man (Frontiers in Neuroscience) Translational Pain Research: From Mouse to Man (Frontiers in Neuroscience)
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