The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform
P D Drummond - One of the best experts on this subject based on the ideXlab platform.
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Sensory changes in the forehead of patients with complex regional Pain syndrome
Pain, 2006Co-Authors: P D Drummond, Philip M. FinchAbstract:The aim of this study was to investigate involvement of central mechanisms in complex regional Pain syndrome (CRPS). In particular, we wished to determine whether hyperalgesia extends ipsilaterally from the affected limb to the forehead. The Heat-Pain Threshold, pressure-Pain Threshold, and ratings of cold and sharpness were investigated on each side of the forehead and in the affected and unaffected limbs of 38 patients with features of CRPS. In addition, touch Thresholds were investigated in the limbs. The pressure-Pain Threshold was lower on the ipsilateral forehead than contralaterally, consistent with the presence of static mechanical hyperalgesia. Although the Heat-Pain Threshold and ratings of sharpness and cold did not differ between the two sides of the forehead in the group as a whole, the sharpness of pinprick sensations in the affected limb was mirrored by similar sensations in the ipsilateral forehead. Conversely, diminished sensitivity to light touch in the affected limb was associated with diminished sensitivity to sharpness, cold and Heat-Pain in the ipsilateral forehead. These findings suggest that central nociceptive processing is disrupted in CRPS, possibly due to disturbances in the thalamus or higher cortical centres.
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Enhancement of thermal hyperalgesia by alpha-adrenoceptors in capsaicin-treated skin.
Journal of the autonomic nervous system, 1998Co-Authors: P D DrummondAbstract:This study aimed to investigate whether the endogenous release of noradrenaline would influence hyperalgesia to Heat in skin sensitized by the topical application of 0.6% capsaicin. To release endogenous stores of noradrenaline, tyramine was introduced transcutaneously by iontophoresis into the volar aspect of the forearm of 19 healthy subjects. The Heat Pain Threshold fell from 43.7 +/- 3.8 degrees C to 41.3 +/- 4.0 degrees C after the iontophoresis of tyramine in capsaicin-treated skin (P < 0.001), but did not change significantly after tyramine iontophoresis in untreated skin. The Heat Pain Threshold decreased by 0.5 +/- 2.2 degrees C after the iontophoresis of saline, indicating that nonspecific factors did not fully account for the hyperalgesic effect of tyramine. Iontophoresis of the alpha-adrenergic antagonist, phenoxybenzamine, after the capsaicin treatment blocked the hyperalgesic effect of tyramine, suggesting that thermal hyperalgesia was mediated by alpha-adrenoceptors. However, iontophoresis of phenoxybenzamine before the capsaicin treatment was ineffective. These findings suggest that release of endogenous stores of noradrenaline increases sensitivity to Heat in skin sensitized by capsaicin. In addition, neurogenic inflammation appears to increase access to the receptors that facilitate thermal hyperalgesia.
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Enhancement of thermal hyperalgesia by α-adrenoceptors in capsaicin-treated skin
Journal of The Autonomic Nervous System, 1998Co-Authors: P D DrummondAbstract:This study aimed to investigate whether the endogenous release of noradrenaline would influence hyperalgesia to Heat in skin sensitized by the topical application of 0.6% capsaicin. To release endogenous stores of noradrenaline, tyramine was introduced transcutaneously by iontophoresis into the volar aspect of the forearm of 19 healthy subjects. The Heat Pain Threshold fell from 43.7 ± 3.8°C to 41.3 ± 4.0°C after the iontophoresis of tyramine in capsaicin-treated skin (P < 0.001), but did not change significantly after tyramine iontophoresis in untreated skin. The Heat Pain Threshold decreased by 0.5 ± 2.2°C after the iontophoresis of saline, indicating that nonspecific factors did not fully account for the hyperalgesic effect of tyramine. Iontophoresis of the α-adrenergic antagonist, phenoxybenzamine, after the capsaicin treatment blocked the hyperalgesic effect of tyramine, suggesting that thermal hyperalgesia was mediated by α-adrenoceptors. However, iontophoresis of phenoxybenzamine before the capsaicin treatment was ineffective. These findings suggest that release of endogenous stores of noradrenaline increases sensitivity to Heat in skin sensitized by capsaicin. In addition, neurogenic inflammation appears to increase access to the receptors that facilitate thermal hyperalgesia.
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The effect of noradrenaline, angiotensin II and vasopressin on blood flow and sensitivity to Heat in capsaicin-treated skin
Clinical Autonomic Research, 1998Co-Authors: P D DrummondAbstract:The effect of iontophoretically applied noradrenaline, angiotensin II and vasopressin on blood flow and sensitivity to Heat was investigated in the capsaicin-treated forearms of 52 healthy volunteers. Non-specific effects of a 4-min saline iontophoresis were investigated in another 19 subjects. Pretreatment with phentolamine inhibited vasoconstriction and thermal hyperalgesia to noradrenaline, indicating that α-adrenoceptors mediated these responses. The intensity of thermal hyperalgesia differed significantly across the following treatments: saline (Heat Pain Threshold 1.1°C lower than at control sites), angiotensin II (3.4°C), noradrenaline (6.4°C), and vasopressin (9.0°C). Decreases in skin blood flow were significantly greater after the iontophoresis of noradrenaline (65% reduction from baseline) and vasopressin (68%) than after the iontophoresis of angiotensin II (45%). In contrast to the other two drugs, angiotensin II induced thermal hyperalgesia in proportion to the intensity of vasoconstriction. The findings suggest that iontophoretic currents induce minor non-specific thermal hyperalgesia. Angiotensin II appears to increase sensitivity to Heat by an ischaemic mechanism, whereas an additional non-vascular influence contributes to thermal hyperalgesia induced by noradrenalinge and vasopressin. These mechanisms could contribute to hyperalgesia in chronic inflammatory or neuropathic Pain syndromes. Clin Auton Res 8:87–93 © 1998 Lippincott-Raven Publishers
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Independent effects of ischaemia and noradrenaline on thermal hyperalgesia in capsaicin-treated skin
Pain, 1996Co-Authors: P D DrummondAbstract:Noradrenaline increases thermal hyperalgesia in skin previously sensitized by capsaicin. The aim of the present study was to determine whether a vasoconstrictor ischaemic effect of noradrenaline increases thermal hyperalgesia. Heat Pain Thresholds were measured in the capsaicin-treated and untreated skin on the forearms of 13 normal volunteers. The iontophoresis of noradrenaline induced thermal hyperalgesia in untreated skin (mean Heat Pain Threshold at the noradrenaline site 42.2 +/- 4.2 degrees C compared with 47.3 +/- 3.5 degrees C at control sites, P < 0.001), and increased thermal hyperalgesia in capsaicin-treated skin (mean Heat Pain Threshold at the noradrenaline site 38.6 +/- 2.1 degrees C compared with 45.7 +/- 5.6 degrees C at control sites, P < 0.001). Heat Pain Thresholds did not change during venous congestion, induced by applying a cuff pressure of 60 mmHg to the upper arm. Increasing the cuff pressure to 200 mmHg decreased the Heat Pain Threshold by 2.4 +/- 2.3 degrees C at control sites in the capsaicin-treated skin (P < 0.01); nevertheless, thermal hyperalgesia was greater at the noradrenaline site than at control sites during arterial occlusion, both in capsaicin-treated and untreated skin (in the capsaicin-treated skin, mean Heat Pain Threshold during arterial occlusion 38.1 +/- 3.3 degrees C at the noradrenaline site compared with 43.4 +/- 6.5 degrees C at control sites, P < 0.001; in the untreated skin, mean Heat Pain Threshold at the noradrenaline site 44.3 +/- 3.6 degrees C compared with 47.9 +/- 3.1 degrees C at control sites, P < 0.001). Thermal hyperalgesia subsided in control sites in the capsaicin-treated skin after cuff pressure was released, but persisted at sites of noradrenaline iontophoresis (in the capsaicin-treated skin, mean Heat Pain Threshold during reactive hyperaemia 45.2 +/- 5.1 degrees C at the noradrenaline site compared with 49.3 +/- 6.0 degrees C at control sites, P < 0.01; in the untreated skin, mean Heat Pain Threshold at the noradrenaline site 46.5 +/- 3.3 degrees C compared with 48.8 +/- 3.0 degrees C at control sites, P < 0.001). Arterial occlusion could increase thermal hyperalgesia in capsaicin-treated skin by preventing the dispersal of nociceptive substances peripherally or through central summation of nociceptive signals. The hyperalgesic effect of noradrenaline is greater than the hyperalgesic effect of ischaemia, suggesting that some mechanism in addition to vasoconstriction contributes to the nociceptive effect of noradrenaline.
Norihiro Suzuki - One of the best experts on this subject based on the ideXlab platform.
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Functional interactions between transient receptor potential M8 and transient receptor potential V1 in the trigeminal system: Relevance to migraine pathophysiology.
Cephalalgia, 2017Co-Authors: Yohei Kayama, Mamoru Shibata, Tsubasa Takizawa, Keiji Ibata, Toshihiko Shimizu, Taeko Ebine, Haruki Toriumi, Michisuke Yuzaki, Norihiro SuzukiAbstract:Background Recent genome-wide association studies have identified transient receptor potential M8 ( TRPM8) as a migraine susceptibility gene. TRPM8 is a nonselective cation channel that mediates cool perception. However, its precise role in migraine pathophysiology is elusive. Transient receptor potential V1 (TRPV1) is a nonselective cation channel activated by noxious Heat. Both TRPM8 and TRPV1 are expressed in trigeminal ganglion (TG) neurons. Methods We investigated the functional roles of TRPM8 and TRPV1 in a meningeal inflammation-based migraine model by measuring the effects of facial TRPM8 activation on thermal allodynia and assessing receptor coexpression changes in TG neurons. We performed retrograde tracer labeling to identify TG neurons innervating the face and dura. Results We found that pharmacological TRPM8 activation reversed the meningeal inflammation-induced lowering of the facial Heat Pain Threshold, an effect abolished by genetic ablation of TRPM8. No significant changes in the Heat Pain Threshold were seen in sham-operated animals. Meningeal inflammation caused dynamic alterations in TRPM8/TRPV1 coexpression patterns in TG neurons, and colocalization was most pronounced when the ameliorating effect of TRPM8 activation on thermal allodynia was maximal. Our tracer assay disclosed the presence of dura-innervating TG neurons sending collaterals to the face. Approximately half of them were TRPV1-positive. We also demonstrated functional inhibition of TRPV1 by TRPM8 in a cell-based assay using c-Jun N-terminal kinase phosphorylation as a surrogate marker. Conclusions Our findings provide a plausible mechanism to explain how facial TRPM8 activation can relieve migraine by suppressing TRPV1 activity. Facial TRPM8 appears to be a promising therapeutic target for migraine.
Nanna B. Finnerup - One of the best experts on this subject based on the ideXlab platform.
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Difference in perception of Heat and the thermal grill illusion (TGI) in relation to the expression of the serotonin transporter and the effect of cutaneous capsaicin sensitization on the TGI
Scandinavian Journal of Pain, 2014Co-Authors: E.l. Schaldemose, Cathrine Baastrup, E. Horjales, Ditte Demontis, Peter Svensson, Nanna B. FinnerupAbstract:AbstractAimsThe aims of this study are to investigate the differences in (1) Heat Pain Threshold, (2) Pain and temperature perception of the TGI and (3) the sensation of capsaicin between subjects with high and low expression of the serotonin transporter (5-HTT). In addition the effects of capsaicin sensitization on the thermal grill illusion are studied.MethodsA total of 80 healthy subjects are selected on the basis of their tri-allelic 5-HTTLPR genotype. Threshold for Heat Pain is examined and Pain and unpleasantness of cutaneous capsaicin application are rated on visual analog scales (VAS). The sensory dimensions of the TGI (before and after capsaicin) is determined i.e. description of temperature (burning hot, hot, neutral, cold or freezing cold) and potential Pain and intensity of cold and warmth are rated on respective VAS-scales.ResultsThe study is ongoing. We expect that the low expression group has a higher Heat Pain Threshold and rates the TGI and capsaicin less Painful. The capsaicin sensitization lowers the Heat Pain Threshold and increases the cold Pain Threshold. Therefore we hypothesize a lower rating of the TGI, determined as a lower Heat VAS-score.ConclusionsNo conclusions yet. Preliminary results from the study will be presented at the SASP14.
Ruth Defrin - One of the best experts on this subject based on the ideXlab platform.
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Spatial resolution of the Pain system: a proximal-to-distal gradient of sensitivity revealed with psychophysical testing
Experimental Brain Research, 2012Co-Authors: Irit Weissman-fogel, Nurit Brayer-zwi, Ruth DefrinAbstract:The spatial resolution of the Pain system has not been studied in depth, and results are contradictory regarding the gradient of spatial resolution. Microneurographic recordings have revealed smaller receptive fields and higher density of nociceptors in more distal than proximal leg regions, whereas histological studies report higher density of C-fibers in more proximal than distal body regions. Due to this controversy, we conducted various psychophysical tests in order to examine the nociceptive spatial resolution and its gradient. Heat-Pain Threshold (HPT), perceived Pain intensity, spatial summation (SS) of Pain, two-point discrimination (2PD) of Pain, and Pain localization were measured in four body regions: upper back, thigh, lower leg, and foot. The highest HPT was demonstrated in the lower leg as compared with more proximal regions ( P
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Quantitative somatosensory testing of warm and Heat-Pain Thresholds: the effect of body region and testing method.
The Clinical journal of pain, 2006Co-Authors: Ruth Defrin, Merav Shachal-shiffer, Mischel Hadgadg, Chava PeretzAbstract:OBJECTIVES To study whether the sensitivity to noxious and innocuous Heat varies across the body. METHODS Heat-Pain Threshold and warm sensation Threshold were measured in 20 patients, using the Method of Limits (MLI) and the Method of Levels (MLE) in 5 regions: the chest, forearm, mid thigh, and the dorsal surface of the hand and foot. RESULTS With the Method of Limits, Heat-Pain Threshold increased gradually from the lowest level in the chest (mean 42 degrees C) to peak level in the foot (44.5 degrees C, P < 0.001). With the Method of Levels, Heat-Pain Threshold did not differ between body regions. Warm sensation Thresholds measured with both Method of Limits and the Method of Levels was higher in the chest (36.2 degrees C) and foot (36.8 degrees C) compared to the other regions (mean of 35.3 degrees C, P < 0.01). The correlation between Heat-Pain Threshold and warm sensation Threshold was low to moderate, depending on the tested region. Differences in Heat-Pain Threshold and warm sensation Threshold between the methods were highest in the legs and smallest in the chest. The correlation between the Method of Limits and Method of Levels was moderate for Heat-Pain Threshold (0.57) and good for warm sensation Threshold (0.71). DISCUSSION The sensitivity to noxious Heat is uniform across the body when measured with a reaction-time-free method (Method of Levels), but is greater in proximal than in distal regions, when measured with a reaction-time-dependent method (Method of Limits). Regardless of measuring method, the sensitivity to innocuous Heat is not uniform across the body. It is concluded that the Method of Levels is preferred when Heat-Pain Threshold is to be compared between body regions. For Heat-Pain Threshold, within-patient comparisons can be made between each pair of regions tested. However, for warm sensation Threshold, within-patient comparisons should be conducted between contralateral symmetrical regions.
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Spatial summation of Heat Pain: a reassessment.
Pain, 1996Co-Authors: Ruth Defrin, Gideon UrcaAbstract:Abstract Heat Pain Threshold is commonly considered to be an ‘absolute’ value, which is not dependent on the area stimulated. In contrast, supraThreshold Heat Pain sensation has been shown to be highly dependent on the area stimulated, with considerable spatial summation demonstrated both within and between dermatomes. The present study sought to reevaluate two major issues: (a) Whether nociceptive Thresholds are, indeed, independent of stimulation area. (b) Whether the spatial summation of supraThreshold Heat Pain sensation is independent of Threshold changes. Using noxious Heat we evaluated nociceptive Thresholds and perceived Pain intensity for contact areas of 0.25, 2.25, 6.25 and 15.36 cm 2 . Our results show that considerable spatial summation of Heat Pain Thresholds is obtained and an apparent spatial summation of perceived intensity can also be observed. However, these apparent changes in perceived Pain intensity can be accounted for completely by the changes in noxious Heat Thresholds. Furthermore, when using a stimulus configuration in which stimulation area was increased without changing nociceptive Threshold, no spatial summation of perceived Pain intensity was seen. Our results suggest that the spatial summation of perceived Heat Pain intensity can be attributed to reduced Heat Pain Threshold. Furthermore, our findings stress the importance of determining Pain Thresholds in studies examining the psychophysics of supraThreshold noxious stimuli.
Yohei Kayama - One of the best experts on this subject based on the ideXlab platform.
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Functional interactions between transient receptor potential M8 and transient receptor potential V1 in the trigeminal system: Relevance to migraine pathophysiology.
Cephalalgia, 2017Co-Authors: Yohei Kayama, Mamoru Shibata, Tsubasa Takizawa, Keiji Ibata, Toshihiko Shimizu, Taeko Ebine, Haruki Toriumi, Michisuke Yuzaki, Norihiro SuzukiAbstract:Background Recent genome-wide association studies have identified transient receptor potential M8 ( TRPM8) as a migraine susceptibility gene. TRPM8 is a nonselective cation channel that mediates cool perception. However, its precise role in migraine pathophysiology is elusive. Transient receptor potential V1 (TRPV1) is a nonselective cation channel activated by noxious Heat. Both TRPM8 and TRPV1 are expressed in trigeminal ganglion (TG) neurons. Methods We investigated the functional roles of TRPM8 and TRPV1 in a meningeal inflammation-based migraine model by measuring the effects of facial TRPM8 activation on thermal allodynia and assessing receptor coexpression changes in TG neurons. We performed retrograde tracer labeling to identify TG neurons innervating the face and dura. Results We found that pharmacological TRPM8 activation reversed the meningeal inflammation-induced lowering of the facial Heat Pain Threshold, an effect abolished by genetic ablation of TRPM8. No significant changes in the Heat Pain Threshold were seen in sham-operated animals. Meningeal inflammation caused dynamic alterations in TRPM8/TRPV1 coexpression patterns in TG neurons, and colocalization was most pronounced when the ameliorating effect of TRPM8 activation on thermal allodynia was maximal. Our tracer assay disclosed the presence of dura-innervating TG neurons sending collaterals to the face. Approximately half of them were TRPV1-positive. We also demonstrated functional inhibition of TRPV1 by TRPM8 in a cell-based assay using c-Jun N-terminal kinase phosphorylation as a surrogate marker. Conclusions Our findings provide a plausible mechanism to explain how facial TRPM8 activation can relieve migraine by suppressing TRPV1 activity. Facial TRPM8 appears to be a promising therapeutic target for migraine.
