Inflammation and pain in skin and deep tissues

doi:10.5278/VBN.PHD.MED.00015

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Inflammation and pain in skin and deep tissues

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.

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Abstract: Ultraviolet-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.

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Book Chapter•

Wall and Melzack's textbook of pain

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Joanna M Zakrzewska, Benjamin C. Lopez

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.

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Abstract: WALL AND MELZACK'S TEXTBOOK OF PAIN, revised under new editorial leadership, and with a host of new, multidisciplinary international contributors ...

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527 citations

Journal Article•DOI•

Increased content and transport of substance P and calcitonin gene-related peptide in sensory nerves innervating inflamed tissue: Evidence for a regulatory function of nerve growth factor in vivo

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Josef Donnerer, Rufina Schuligoi, Rainer Amann, Christoph Stein

01 May 1992-Neuropeptides

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.

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223 citations

Journal Article•DOI•

Core Topics in Pain.

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A Philip J. Lake

01 Apr 2007-Anesthesiology

19 citations

Journal Article•DOI•

Sensory defunctionalization induced by 8% topical capsaicin treatment in a model of ultraviolet-B-induced cutaneous hyperalgesia.

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Silvia Lo Vecchio¹, Hjalte Holm Andersen¹, Jesper Elberling², Lars Arendt-Nielsen¹•Institutions (2)

Aalborg University¹, Copenhagen University Hospital²

24 Jul 2021-Experimental Brain Research

TL;DR: In this article, the authors explored the contribution of capsaicin-sensitive nociceptors in the development of mechanical and heat hyperalgesia in humans following ultraviolet-B (UVB) irradiation.

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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.

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Journal Article•DOI•

A new human experimental pain model: the heat/capsaicin sensitization model.

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Karin L. Petersen¹, Michael C. Rowbotham•Institutions (1)

University of California, San Francisco¹

14 May 1999-Neuroreport

TL;DR: The heat/capsaicin sensitization model is a new human experimental pain model that synergistically combines non-invasive physical and chemical methods of nociceptor stimulation to produce stable and long-lasting hyperalgesia with a low potential for skin injury.

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Abstract: The heat/capsaicin sensitization model is a new human experimental pain model that synergistically combines non-invasive physical and chemical methods of nociceptor stimulation to produce stable and long-lasting hyperalgesia with a low potential for skin injury. In 10 healthy volunteers the forearm was stimulated with a 45 degrees C thermode for 5 min to produce an area of secondary hyperalgesia. Applying capsaicin cream for 30 min further expanded the area of secondary hyperalgesia. Periodically heating the treated skin with a previously non-painful temperature of 40 degrees C re-kindled the sensitization enough to maintain stable areas of secondary hyperalgesia for 4h. The evoked pain was moderate and well tolerated. The heat/capsaicin sensitization model should be well suited for studying pain mechanisms and testing new analgesics.

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183 citations

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

...It also has to be simple to perform, without any sign of spontaneous pain, and it must cause stable and reproducible primary and secondary hyperalgesia without inducing tissue or psychological damages (Petersen and Rowbotham 1999)....
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...A mild and non-painful heat stimulus of 40°C for 5 minutes was applied resulting in a reinforcement of the secondary hyperalgesic area for up to 4 h (Petersen and Rowbotham 1999)....
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Journal Article•DOI•

Pressure pain thresholds in different tissues in one body region. The influence of skin sensitivity in pressure algometry.

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Eva Kosek¹, Jan Ekholm, Per Hansson•Institutions (1)

Karolinska Institutet¹

01 Jun 1999-Scandinavian Journal of Rehabilitation Medicine

TL;DR: Under the given circumstances, skin pressure pain sensitivity was demonstrated to influence the PPT and EMLA cream increased PPTs compared to control sites in all examined areas.

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Abstract: This study aimed at determining whether there are differences in pressure pain sensitivity in different tissues in the same body region when systematically assessed, before and after skin hypoesthesia. Pressure pain thresholds (PPTs) were assessed bilaterally in 15 healthy females at the bony part of the epicondylus lateralis humeri, at the belly of m. extensor carpi ulnaris and at m. brachioradialis where the superficial radial nerve branches pass underneath ("muscle/nerve" site). Following a double blind design, a local anaesthetic cream (EMLA) or a control cream was applied to the skin and PPTs were reassessed. The PPT was significantly (p < 0.001) lower at the "muscle/nerve" site than at the bony and "pure" muscle sites. The PPTs over the bony and "pure" muscle sites did not differ. There was no significant difference when PPTs were compared before and after application of EMLA cream. However, PPTs after control cream were lower (p < 0.001) over all examined areas than those obtained prior to cream application. Thus, EMLA cream increased PPTs compared to control sites in all examined areas (p < 0.001). Under the given circumstances, skin pressure pain sensitivity was demonstrated to influence the PPT.

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182 citations

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

...This is in line wit h the findings reported by several studies where th e authors tried to eliminate the contribution of the skin to pressure stimulation by inducing cutaneous anaesthesia (Graven-Nielsen et al., 2004; Kosek et al., 1999; Laursen et al., 1997)....
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...This is in line with the findings reported by several studies where the authors tried to eliminate the contribution of the skin to pressure stimulation by inducing cutaneous anaesthesia (Graven-Nielsen et al., 2004; Kosek et al., 1999; Laursen et al., 1997)....
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Journal Article•DOI•

Bradykinin and Nerve Growth Factor Play Pivotal Roles in Muscular Mechanical Hyperalgesia after Exercise (Delayed-Onset Muscle Soreness)

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Shiori Murase¹, Etsuji Terazawa, Fernando Queme, Hiroki Ota, Teru Matsuda, Kenji Hirate, Yasuko Kozaki, Kimiaki Katanosaka, Toru Taguchi, Hisako Urai, Kazue Mizumura - Show less +7 more•Institutions (1)

Nagoya University¹

10 Mar 2010-The Journal of Neuroscience

TL;DR: It is shown that NGF upregulation through activation of B2 bradykinin receptors is essential (though not satisfactory) to mechanical hyperalgesia after exercise, and why lengthening contraction but not shortening contraction induces DOMS.

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Abstract: Unaccustomed strenuous exercise that includes lengthening contraction (LC) often causes delayed-onset muscle soreness (DOMS), a kind of muscular mechanical hyperalgesia. The substances that induce this phenomenon are largely unknown. Peculiarly, DOMS is not perceived during and shortly after exercise, but rather is first perceived after ∼1 d. Using B2 bradykinin receptor antagonist HOE 140, we show here that bradykinin released during exercise plays a pivotal role in triggering the process that leads to muscular mechanical hyperalgesia. HOE 140 completely suppressed the development of muscular mechanical hyperalgesia when injected before LC, but when injected 2 d after LC failed to reverse mechanical hyperalgesia that had already developed. B1 antagonist was ineffective, regardless of the timing of its injection. Upregulation of nerve growth factor (NGF) mRNA and protein occurred in exercised muscle over a comparable time course (12 h to 2 d after LC) for muscle mechanical hyperalgesia. Antibodies to NGF injected intramuscularly 2 d after exercise reversed muscle mechanical hyperalgesia. HOE 140 inhibited the upregulation of NGF. In contrast, shortening contraction or stretching induced neither mechanical hyperalgesia nor NGF upregulation. Bradykinin together with shortening contraction, but not bradykinin alone, reproduced lasting mechanical hyperalgesia. We also showed that rat NGF sensitized thin-fiber afferents to mechanical stimulation in the periphery after 10–20 min. Thus, NGF upregulation through activation of B2 bradykinin receptors is essential (though not satisfactory) to mechanical hyperalgesia after exercise. The present observations explain why DOMS occurs with a delay, and why lengthening contraction but not shortening contraction induces DOMS.

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165 citations

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

...Another important theory considers NGF as the key substance in mainta ini g DOMS induced by eccentric contraction (Murase et al., 2010)....
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...humans and animals (Cheung et al., 2003; Murase et al., 2010; Taguchi et al., 2005), and the research results reflect events seen in acute infla mm tion (Smith 1991)....
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...Since one of the most supported theories about DOMS indicates the NGF as one of the fundamental substance implicated in the development of muscle soreness induced by 8 DOMS (Murase et al., 2010), the cutaneous UVB-model was applied in combination with NGFinduced muscle soreness....
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...In experiments conducted in rats, Murase and co-workers demonstrated that intramuscular administration of anti-NGF antibody 6 h after eccentric contractions could block completely the induction of muscle mechanical hyper algesia (Murase et al., 2010)....
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...22 that may explain the delayed development of DOMS fo llowing eccentric contraction, which is in line with similar reports in humans (Murase et al., 2010)....
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Journal Article•DOI•

Stimulus features relevant to the perception of sharpness and mechanically evoked cutaneous pain.

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Joel D. Greenspan¹, Sandra L. B. McGillis¹•Institutions (1)

Syracuse University¹

01 Jan 1991-Somatosensory and Motor Research

TL;DR: Comparison of the perceptual thresholds with the thresholds for nociceptors determined in electrophysiological studies indicates that the sensation of nonpainful sharpness is likely to be mediated by nocicesptors, and considerably more than threshold activation of nocICEptors is necessary for normal pain perception.

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Abstract: Mechanical probes of various sizes and shapes were used to determine thresholds for the perception of pressure, sharpness, and pain on the human finger. As force increased, perception changed from dull pressure to sharp pressure to sharp pain. With the smallest probe (0.01 mm2), sharpness threshold was very close to pressure threshold. As probe size increased, sharpness and pain threshold expressed in terms of force) increased in proportion to probe circumference (not probe area), whereas pressure threshold increased relatively little. Pain and sharpness thresholds also increased as probe angle became obtuse. There was a statistically significant increase in both thresholds with a probe angle change of 15 degrees. Thus, both size and shape are necessary to describe a mechanical stimulus adequately, and pressure (force/area) is not a sufficient metric for pain studies. Thresholds varied at different skin sites on the finger. The dorsal surface had lower thresholds than the volar surface, but the difference between the two areas was not always statistically significant. The compliance of the skin (e.g., the amount of indentation produced by a given force) exhibited no relation to sharpness or pain threshold, whether considered within subjects at various skin sites, or across subjects at the same skin site. Comparison of the perceptual thresholds with the thresholds for nociceptors determined in electrophysiological studies indicates that the sensation of nonpainful sharpness is likely to be mediated by nociceptors. Furthermore, considerably more than threshold activation of nociceptors is necessary for normal pain perception.

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162 citations

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

...This is in line with the findings by other authors reporting increasing threshold with increasing probe size (Greenspan and McGillis 1991; Jensen et al., 1986)....
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Journal Article•DOI•

Experimental human pain models: a review of standardised methods for preclinical testing of analgesics.

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Camilla Staahl¹, Asbjørn Mohr Drewes¹•Institutions (1)

Aalborg University¹

01 Sep 2004-Basic & Clinical Pharmacology & Toxicology

TL;DR: A brief introduction to the methods used to evoke and assess pain in the skin, muscle and viscera is given and new methods using multimodal stimulation and activation of central pain mechanisms can to a higher degree mimic the clinical situation.

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Abstract: Treatment of pain is one of the major challenges in clinical medicine. However, it is often difficult to evaluate the effect of a treatment, as the many symptoms of the underlying diseases often confound this assessment. Furthermore, as the pain mechanisms in many diseases are poorly understood, the limited successful trial and error approach is most often used in the selection of analgesics. Hence, there is a need for new methods in the characterization and treatment of pain. Human experimental pain models offer the possibility to explore the pain system under controlled settings. The models can also be used to screen the analgesic profiles of drugs targeted to treat pain. This review gives a brief introduction to the methods used to evoke and assess pain in the skin, muscle and viscera. New methods using multimodal stimulation and activation of central pain mechanisms can to a higher degree mimic the clinical situation, and such methods are recommended in the future screening of analgesics. Examples of the use of experimental pain models in the testing of analgesics are given. With these models the therapeutic spectrum may be defined from a differentiated knowledge on the effect of drugs on the pain system. Such information may be used in the future guidelines for trials and clinical use of analgesics.

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153 citations

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

...This sensitization mimics the inflammatory condition and the decrease in pain thresholds present in some disorders involving the musculoskeletal system, making the models very useful from a clinical perspective (Mørk et al., 2003; Staahl and Drewes 2004)....
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...Capsaicin, the component of chili peppers, is one of the most used chemically-induced pain models and it causes a type of inflammation called neurogenic inflammation (Staahl and Drewes 2004)....
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...When the applied stimulation reaches a certain 27 pressure, the filament bends, allowing the activation of Aβ-fiber mediating touch sensation and the measurement of the allodynic area (Staahl and Drewes 2004)....
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...It is believed that both Aδ- and C-fibres are involved in the perception of the pain arising from pressure stimulation (Staahl and Drewes 2004)....
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...…DOMS does not induce pain at rest, typically present in musculoskeletal conditions such as fibromyalgia (Gracely et al., 2003), and has also the disadvantage of being difficult to control since this method involves numerous muscle groups within the investigated region (Staahl and Drewes 2004)....
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