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DOI

Inflammation and pain in skin and deep tissues

01 Jan 2015-

TL;DR: Evaluate the change in sensitivity after inflammation inside and outside the irradiated skin and investigate the existence of a mechanism of cumulative effects between cutaneous and deep-tissue hyperalgesia and allodynia induced by UVB irradiation after application of heat stimuli and sensitization of deep tissues.

AbstractUltraviolet-B irradiation model has been used for many years as a translational model since it is well known to induce cutaneous inflammatory pain in both animals and humans. The aim of this study project was to evaluate time course and sensory changes induced by UVB and in particular: 1) evaluate the change in sensitivity after inflammation inside and outside the irradiated skin, 2) investigate the existence of a mechanism of cumulative effects between cutaneous and deep-tissue hyperalgesia, 3) investigate the effect on mechanical hyperalgesia and allodynia induced by UVB irradiation after application of heat stimuli and sensitization of deep tissues.

Topics: Hyperalgesia (59%), Allodynia (57%)

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Citations
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Book Chapter
01 Jan 2006
TL;DR: The Wall and Melzack's Textbook of Pain is revised under new editorial leadership, and with a host of new, multidisciplinary international contributors.
Abstract: WALL AND MELZACK'S TEXTBOOK OF PAIN, revised under new editorial leadership, and with a host of new, multidisciplinary international contributors ...

502 citations


Journal ArticleDOI
TL;DR: Findings point towards a regulatory function for nerve growth factor in vivo in the stimulation of sensory neuropeptide synthesis during prolonged inflammatory processes.
Abstract: The responses of sensory neuropeptides during unilateral, Freund's adjuvant-induced, paw inflammation in the rat were examined. After five days of inflammation, the substance P and calcitonin gene-related peptide content in the sciatic nerve supplying the inflamed paw were increased by 60-75% when compared with the contralateral side. At this time-point, there was also a 30-40% increase in the substance P and calcitonin gene-related peptide content of the dorsal root ganglia (L4-L6), and a 40% increase in the calcitonin gene-related peptide content of the L4-L6 segments of the dorsal spinal cord on the inflammation side. In the dorsal root ganglia, calcitonin gene-related peptide content was also increased as early as 12 h and 48 h after induction of paw inflammation. On day 5 of inflammation, the axonal transport of both sensory neuropeptides towards the inflamed paw, as determined after sciatic nerve ligation, was also markedly increased as compared with the control side. Despite this increased transport, the amount of substance P and calcitonin gene-related peptide present in the inflamed paw itself was either reduced or remained unchanged from day 1 through to day 5 of inflammation pointing towards reduced storage and increased release of the peptides in the inflamed tissue. Nerve growth factor content was markedly increased in the sciatic nerve of the inflamed paw with a peak of +136% at time-point 24 h after induction of inflammation. When rats were systemically treated with anti-nerve growth factor serum, the increase in neuropeptide content in the sciatic nerve of the inflamed paw (day 5) was prevented. On the other hand, local injections of nerve growth factor for 5 days into a noninflamed paw were able to induce an increase in substance P and calcitonin gene-related peptide content in the supplying sciatic nerve. These findings point towards a regulatory function for nerve growth factor in vivo in the stimulation of sensory neuropeptide synthesis during prolonged inflammatory processes.

221 citations


Journal ArticleDOI

18 citations


Journal ArticleDOI
Abstract: Subpopulations of primary nociceptors (C- and Aδ-fibers), express the TRPV1 receptor for heat and capsaicin. During cutaneous inflammation, these afferents may become sensitized, leading to primary hyperalgesia. It is known that TRPV1+ nociceptors are involved in heat hyperalgesia; however, their involvement in mechanical hyperalgesia is unclear. This study explored the contribution of capsaicin-sensitive nociceptors in the development of mechanical and heat hyperalgesia in humans following ultraviolet-B (UVB) irradiation. Skin areas in 18 healthy volunteers were randomized to treatment with 8% capsaicin/vehicle patches for 24 h. After patches removal, one capsaicin-treated area and one vehicle area were irradiated with 2xMED (minimal erythema dose) of UVB. 1, 3 and 7 days post-UVB exposure, tests were performed to evaluate the development of UVB-induced cutaneous hyperalgesia: thermal detection and pain thresholds, pain sensitivity to supra-threshold heat stimuli, mechanical pain threshold and sensitivity, touch pleasantness, trans-epidermal water loss (TEWL), inflammatory response, pigmentation and micro-vascular reactivity. Capsaicin pre-treatment, in the UVB-irradiated area (Capsaicin + UVB area), increased heat pain thresholds (P 0.2). No effects of capsaicin were reported on touch pleasantness (P = 1), TEWL (P = 0.31), inflammatory response and pigmentation (P > 0.3) or micro-vascular reactivity (P > 0.8) in response to the UVB irradiation. 8% capsaicin ablation predominantly defunctionalizes TRPV1+-expressing cutaneous nociceptors responsible for heat pain transduction, suggesting that sensitization of these fibers is required for development of heat hyperalgesia following cutaneous UVB-induced inflammation but they are likely only partially necessary for the establishment of robust primary mechanical hyperalgesia.

References
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Journal ArticleDOI
16 Oct 2009-Cell
TL;DR: Genetic, electrophysiological, and pharmacological studies are elucidating the molecular mechanisms that underlie detection, coding, and modulation of noxious stimuli that generate pain.
Abstract: The nervous system detects and interprets a wide range of thermal and mechanical stimuli, as well as environmental and endogenous chemical irritants. When intense, these stimuli generate acute pain, and in the setting of persistent injury, both peripheral and central nervous system components of the pain transmission pathway exhibit tremendous plasticity, enhancing pain signals and producing hypersensitivity. When plasticity facilitates protective reflexes, it can be beneficial, but when the changes persist, a chronic pain condition may result. Genetic, electrophysiological, and pharmacological studies are elucidating the molecular mechanisms that underlie detection, coding, and modulation of noxious stimuli that generate pain.

2,904 citations


"Inflammation and pain in skin and d..." refers background in this paper

  • ...Pain comprises a complex experience involving not only the transduction of noxious stimuli but also cognitive and emotional aspects of the stimuli when it is processed in higher cortical areas in the brain (Basbaum et al., 2009)....

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  • ...directly on the nociceptors by interacting with ion channels or specific receptors located on the surface of the sensory nerve endings innervating th e area (Basbaum et al., 2009; Julius and Basbaum 2001)....

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  • ...Pa in comprises a complex experience involving not only the transduction of noxious stimuli but al so cognitive and emotional aspects of the stimuli when it is processed in higher cortical areas in th e brain (Basbaum et al., 2009)....

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  • ...Alteration of the pain path induces hyper responsiveness or hypersensitivity (Basbaum et al., 2009)....

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  • ...Inflammatory pain and inflammation are mediated by release of inflammatory mediators, called also “inflammatory soup”, from damaged cells that increase the sensitivity of nociceptors to noxious thermal or mechanical stimuli (Basbaum et al., 2009; Holdcroft and Jaggar 2005; Huang et al., 2006)....

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Journal ArticleDOI
13 Sep 2001-Nature
TL;DR: Efforts to determine how primary sensory neurons detect pain-producing stimuli of a thermal, mechanical or chemical nature have revealed new signalling mechanisms and brought us closer to understanding the molecular events that facilitate transitions from acute to persistent pain.
Abstract: The sensation of pain alerts us to real or impending injury and triggers appropriate protective responses. Unfortunately, pain often outlives its usefulness as a warning system and instead becomes chronic and debilitating. This transition to a chronic phase involves changes within the spinal cord and brain, but there is also remarkable modulation where pain messages are initiated - at the level of the primary sensory neuron. Efforts to determine how these neurons detect pain-producing stimuli of a thermal, mechanical or chemical nature have revealed new signalling mechanisms and brought us closer to understanding the molecular events that facilitate transitions from acute to persistent pain.

2,272 citations


"Inflammation and pain in skin and d..." refers background in this paper

  • ...Among these inflammatory mediators, some substances lik protons, ATP and serotonin can act directly on the nociceptors by interacting with ion channels or specific receptors located on the surface of the sensory nerve endings innervating the area (Basbaum et al., 2009; Julius and Basbaum 2001)....

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  • ...Other mediators, such as bradykinin a d NGF, act by binding to metabotropic receptors and membrane receptors that work through a secondary messenger (Julius and Basbaum 2001)....

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  • ...These neurons then, transmit pain messages to specific parts of the brain, such us thalamus, reticular formation, and cerebral cortex (Julius and Basbaum 2001)....

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Journal ArticleDOI
TL;DR: Current slow-acting antirheumatic drugs have limited efficacy and many side effects and do not improve the long-term prognosis of rheumatoid arthritis.
Abstract: Rheumatoid arthritis is a common chronic inflammatory and destructive arthropathy that cannot be cured and that has substantial personal, social, and economic costs. The long-term prognosis is poor: 80 percent of affected patients are disabled after 20 years,1 and life expectancy is reduced by an average of 3 to 18 years.2 The medical cost of rheumatoid arthritis averages $5,919 per case per year in the United States3 and approximately £2,600 per case per year in the United Kingdom.4 Current slow-acting antirheumatic drugs have limited efficacy and many side effects. Moreover, they do not improve the long-term prognosis of rheumatoid arthritis. . . .

2,072 citations


"Inflammation and pain in skin and d..." refers background in this paper

  • ...…clinical conditions are characterized by the presence of inflammatory reaction, including rheumatoid arthritis, a common chronic inflammatory disorder involving the synovial membrane and the joints (Choy and Panayi 2001) and fibromyalgia, a disorder of generalized musculoskeletal pain (Wolfe 1991)....

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Journal ArticleDOI
01 Dec 1983-Nature
TL;DR: An animal model is developed where changes occur in the threshold and responsiveness of the flexor reflex following peripheral injury that are analogous to the sensory changes found in man, and shows that it in part arises from changes in the activity of the spinal cord.
Abstract: Noxious skin stimuli which are sufficiently intense to produce tissue injury, characteristically generate prolonged post-stimulus sensory disturbances that include continuing pain, an increased sensitivity to noxious stimuli and pain following innocuous stimuli. This could result from either a reduction in the thresholds of skin nociceptors (sensitization)1,2 or an increase in the excitability of the central nervous system so that normal inputs now evoke exaggerated responses3,4. Because sensitization of peripheral receptors occurs following injury5–7, a peripheral mechanism is widely held to be responsible for post-injury hypersensitivity. To investigate this I have now developed an animal model where changes occur in the threshold and responsiveness of the flexor reflex following peripheral injury that are analogous to the sensory changes found in man. Electrophysiological analysis of the injury-induced increase in excitability of the flexion reflex shows that it in part arises from changes in the activity of the spinal cord. The long-term consequences of noxious stimuli result, therefore, from central as well as from peripheral changes.

1,955 citations


"Inflammation and pain in skin and d..." refers background in this paper

  • ...The process of nociception refers to the recognition of a noxious stimulus from a nociceptor and its transmission to the brain through peripheral and central neurons (Holdcroft and Jaggar 2005; Kidd and Urban 2001; Woolf 1983)....

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Journal ArticleDOI
TL;DR: Exercise is the most effective means of alleviating pain during DOMS, however the analgesic effect is also temporary, and athletes who must train on a daily basis should be encouraged to reduce the intensity and duration of exercise for 1–2 days following intense DOMS-inducing exercise.
Abstract: Delayed onset muscle soreness (DOMS) is a familiar experience for the elite or novice athlete. Symptoms can range from muscle tenderness to severe debilitating pain. The mechanisms, treatment strategies, and impact on athletic performance remain uncertain, despite the high incidence of DOMS. DOMS is most prevalent at the beginning of the sporting season when athletes are returning to training following a period of reduced activity. DOMS is also common when athletes are first introduced to certain types of activities regardless of the time of year. Eccentric activities induce micro-injury at a greater frequency and severity than other types of muscle actions. The intensity and duration of exercise are also important factors in DOMS onset. Up to six hypothesised theories have been proposed for the mechanism of DOMS, namely: lactic acid, muscle spasm, connective tissue damage, muscle damage, inflammation and the enzyme efflux theories. However, an integration of two or more theories is likely to explain muscle soreness. DOMS can affect athletic performance by causing a reduction in joint range of motion, shock attenuation and peak torque. Alterations in muscle sequencing and recruitment patterns may also occur, causing unaccustomed stress to be placed on muscle ligaments and tendons. These compensatory mechanisms may increase the risk of further injury if a premature return to sport is attempted. A number of treatment strategies have been introduced to help alleviate the severity of DOMS and to restore the maximal function of the muscles as rapidly as possible. Nonsteroidal anti-inflammatory drugs have demonstrated dosage-dependent effects that may also be influenced by the time of administration. Similarly, massage has shown varying results that may be attributed to the time of massage application and the type of massage technique used. Cryotherapy, stretching, homeopathy, ultrasound and electrical current modalities have demonstrated no effect on the alleviation of muscle soreness or other DOMS symptoms. Exercise is the most effective means of alleviating pain during DOMS, however the analgesic effect is also temporary. Athletes who must train on a daily basis should be encouraged to reduce the intensity and duration of exercise for 1–2 days following intense DOMS-inducing exercise. Alternatively, exercises targeting less affected body parts should be encouraged in order to allow the most affected muscle groups to recover. Eccentric exercises or novel activities should be introduced progressively over a period of 1 or 2 weeks at the beginning of, or during, the sporting season in order to reduce the level of physical impairment and/or training disruption. There are still many unanswered questions relating to DOMS, and many potential areas for future research.

1,027 citations


"Inflammation and pain in skin and d..." refers result in this paper

  • ...DOMS has been investigated in both humans and animals (Cheung et al., 2003; Murase et al., 2010; Taguchi et al., 2005), and the research results reflect events seen in acute inflamm tion (Smith 1991)....

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