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Roger B Fillingim - One of the best experts on this subject based on the ideXlab platform.
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oprm1 oprk1 and comt genetic polymorphisms associated with opioid effects on Experimental Pain a randomized double blind placebo controlled study
Pharmacogenomics Journal, 2020Co-Authors: Margaret R Wallace, Roland Staud, Roger B FillingimAbstract:Genetic polymorphisms have been shown to affect opioid requirement for Pain relief. However, true genetic effect is often difficult to assess due to underlying Pain conditions and placebo effects. The goal of this study was to understand how common polymorphisms affect opioid effects while controlling for these factors. A randomized, double-blind, placebo-controlled study was implemented to assess how opioid effects are modulated by COMT (rs6269, rs4633, rs4848, rs4680), OPRM1 (A118G), and OPRK1 (rs1051660, rs702764, rs16918875). One hundred and eight healthy subjects underwent Experimental Pain testing before and after morphine, butorphanol, and placebo (saline). Association analysis was performed between polymorphisms/haplotypes and opioid response, while correcting for race, gender, placebo effects, and multiple comparisons. Pressure Pain was significantly associated with rs6269 and rs4633 following butorphanol. The AA genotype of rs4680 or A_T_C_A/ A_T_C_A (rs6269_rs4633_ rs4818_rs4680) diplotype of COMT, combined with the AG genotype of OPRM1 A118G, showed significantly increased pressure Pain threshold from butorphanol. Opioid effects on pressure, ischemic, heat Pain, and side effects were nominally associated with several SNPs and haplotypes. Effects were often present in one opioid but not the other. This indicates that these polymorphisms affect Pain relief from opioids, and that their effects are opioid and Pain modality specific.
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Racial/ethnic differences in Experimental Pain sensitivity and associated factors – Cardiovascular responsiveness and psychological status
2019Co-Authors: Hee Jun Kim, Roger B Fillingim, Joel D Greenspan, Cynthia L Renn, Meg Johantgen, Richard Ohrbach, William Maixner, Shijun Zhu, Susan G DorseyAbstract:This study evaluated the contributions of psychological status and cardiovascular responsiveness to racial/ethnic differences in Experimental Pain sensitivity. The baseline measures of 3,159 healthy individuals—non-Hispanic white (NHW): 1,637, African-American (AA): 1,012, Asian: 299, and Hispanic: 211—from the OPPERA prospective cohort study were used. Cardiovascular responsiveness measures and psychological status were included in structural equation modeling based mediation analyses. Pain catastrophizing was a significant mediator for the associations between race/ethnicity and heat Pain tolerance, heat Pain ratings, heat Pain aftersensations, mechanical cutaneous Pain ratings and aftersensations, and mechanical cutaneous Pain temporal summation for both Asians and AAs compared to NHWs. HR/MAP index showed a significant inconsistent (mitigating) mediating effect on the association between race/ethnicity (AAs vs. NHWs) and heat Pain tolerance. Similarly, coping inconsistently mediated the association between race/ethnicity and mechanical cutaneous Pain temporal summation in both AAs and Asians, compared to NHWs. The factor encompassing depression, anxiety, and stress was a significant mediator for the associations between race/ethnicity (Asians vs. NHWs) and heat Pain aftersensations. Thus, while Pain catastrophizing mediated racial/ethnic differences in many of the QST measures, the psychological and cardiovascular mediators were distinctly restrictive, signifying multiple independent mechanisms in racial/ethnic differences in Pain.
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bayesian analysis of the effect of transcranial direct current stimulation on Experimental Pain sensitivity in older adults with knee osteoarthritis randomized sham controlled pilot clinical study
Journal of Pain Research, 2018Co-Authors: Hyochol Ahn, Robert Suchting, Adam J Woods, Hongyu Miao, Charles E Green, Raymond Y Cho, Eunyoung Choi, Roger B FillingimAbstract:Purpose Previous studies have indicated that transcranial direct current stimulation (tDCS) with the anode over the motor cortex and the cathode over the contralateral supraorbital region is effective in reducing clinical Pain in patients with chronic Pain, but these studies have not focused on Experimental Pain sensitivity. Therefore, the aim of this study was to examine the effect of tDCS on Experimental Pain sensitivity in older adults with knee osteoarthritis (OA). Patients and methods Forty community-dwelling participants aged 50-70 years with knee OA Pain were randomly assigned to receive five daily sessions of 2 mA tDCS for 20 minutes (n = 20) or sham tDCS (n = 20) using a parallel group design. A multimodal quantitative sensory testing battery was completed, including heat Pain, pressure Pain threshold (PPT), punctate mechanical Pain, and conditioned Pain modulation (CPM). Results The active tDCS group showed greater increases in heat Pain thresholds and tolerances, PPTs, and CPM, and reductions in punctate Pain. In addition, beneficial changes in Experimental Pain measures were associated with reductions in clinical Pain. Future studies are needed to extend these findings to better understand the underlying mechanisms of tDCS as well as to optimize treatment parameters including number and duration of stimulation sessions. Conclusion Our findings demonstrate that tDCS reduces Experimental Pain sensitivity, and these beneficial changes in Experimental Pain measures were associated with reductions in clinical Pain.
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The Relationship between Acculturation and Experimental Pain Sensitivity in Asian Americans with Knee Osteoarthritis
Hindawi Limited, 2018Co-Authors: Hyochol Ahn, Hongyu Miao, Setor K. Sorkpor, Miyong Kim, Chengxue Zhong, Jing Wang, Debra Lyon, Roger B FillingimAbstract:Multiple studies in healthy populations and clinical samples have shown that ethnic minorities have greater Pain sensitivity than their majority counterparts. Acculturation is speculated to be one of the sociocultural factors contributing to Pain sensitivity since cultural beliefs and practices can influence the way patients perceive and respond to Pain. However, the relationship of acculturation to Pain sensitivity in minority populations remains poorly understood. Therefore, in this cross-sectional study, we examined the relationship between acculturation and Experimental Pain sensitivity in 50 Asian Americans residing in North Central Florida with knee osteoarthritis Pain. The Suinn-Lew Asian Self Identity Acculturation Scale was used to assess acculturation, and multimodal quantitative sensory testing was performed to measure Experimental sensitivity, including heat Pain tolerance, pressure Pain threshold, and punctate mechanical Pain. Descriptive and regression analyses were performed. Participants’ mean age was 55.7 years, and about half of this sample were Korean American (56%). The participants had lived in the United States for 21 years on average. Regression analyses indicated that lower acculturation to American culture may contribute to greater Experimental Pain sensitivity. Asian Americans who were more acculturated to the American culture had higher heat Pain tolerance (beta = 0.61, P=0.01), higher pressure Pain threshold (beta = 0.59, P=0.02), and lower ratings of punctate mechanical Pain (beta = −0.70, P
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Experimental Pain phenotype profiles in a racially and ethnically diverse sample of healthy adults
Pain Medicine, 2013Co-Authors: Yenisel Cruzalmeida, Joseph L Riley, Roger B FillingimAbstract:Objective To examine patterns of interindividual variability in Experimental Pain responses emerging from multiple Experimental Pain measures in a racially/ethnically diverse sample of healthy adults and to examine the association between the derived phenotype profiles with demographic, psychological, and health-related measures. Methods Two hundred and ninety-one participants underwent heat, cold, pressure, and ischemic Pain assessments, and completed several psychological and health-related assessments. The Experimental Pain measures were subjected to a principal component analysis and factor scores were used to compute Pain Sensitivity Index scores. The scores were subsequently submitted to a cluster analysis to identify patterns of Pain sensitivity across Experimental Pain modalities. Results The sample was equally composed of non-Hispanic whites, African Americans, and Hispanic whites. Sensitivity scores were computed for heat Pain, pressure Pain, cold Pain, ischemic Pain, and temporal summation of heat Pain. Five distinct clusters were characterized by high heat Pain sensitivity, low ischemic Pain sensitivity, low cold Pain sensitivity, low pressure Pain sensitivity, and high temporal summation. Cluster membership was significantly different by sex as well as somatic reactivity and catastrophizing, although cluster differences were most pronounced between the heat Pain-sensitive individuals vs the cold Pain-insensitive individuals. Conclusions Our findings highlight the importance of phenotyping individuals to account for interindividual differences in Pain responses. Our findings also replicate previously reported Pain phenotypes, which are not solely related to demographic, psychosocial, or health-related factors in our healthy participants. Future studies designed to elucidate the biological underpinnings of Pain sensitivity profiles would be of substantial value.
Asbjørn Mohr Drewes - One of the best experts on this subject based on the ideXlab platform.
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genetic influences of oprm1 oprd1 and comt on morphine analgesia in a multi modal multi tissue human Experimental Pain model
Basic & Clinical Pharmacology & Toxicology, 2017Co-Authors: Anne Estrup Olesen, Lona L. Christrup, Asbjørn Mohr Drewes, Hiroe Sato, Lecia Moller NielsenAbstract:Human studies on Experimentally induced Pain are of value to elucidate the genetic influence on morphine analgesia under controlled conditions. The aim of this study was to investigate whether genetic variants of mu-, kappa- and delta-opioid receptor genes (OPRM1, OPRK1 and OPRD1) and catechol-O-methyltransferase gene (COMT) are associated with the morphine analgesia. The study was a randomized, double-blind, two-way, crossover, single-dose study conducted in 40 healthy participants, where morphine was compared with placebo. Pain was induced by contact heat, muscle pressure, bone pressure, rectal stimulations (mechanical, electrical and thermal) and cold pressor test (immersion of the hand into ice water). Sixteen genetic polymorphisms of four candidate genes were explored. Variability in morphine analgesia to contact heat stimulation was associated with COMT rs4680 (p = 0.04), and rectal thermal stimulation was associated with OPRM1 rs9479757 (p = 0.03). Moreover, in males, variability in morphine analgesia to rectal thermal stimulation was associated with OPRD1 polymorphisms: rs2234918 (p = 0.01) and rs533123 (p = 0.046). The study was explorative and hypothesis-generating due to the relatively small study size. However, results suggest that genetic variants in the COMT and OPRM1 irrespective of gender, and OPRD1 in males may contribute to the variability in morphine analgesia in Experimental Pain models.
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objective markers of the analgesic response to morphine in Experimental Pain research
Journal of Pharmacological and Toxicological Methods, 2015Co-Authors: Anne Brokjaer, Anne Estrup Olesen, Lona L. Christrup, Mads Kreilgaard, Carina Graversen, Mikkel Gram, Albert Dahan, Asbjørn Mohr DrewesAbstract:Abstract Introduction In Experimental Pain research the effect of opioids is normally assessed by verbal subjective response to analgesia. However, as many confounders in Pain assessment exist, objective bed-side assessment of the effect is highly warranted. Therefore, we aimed to assess the effect of morphine on three objective pharmacodynamic markers (pupil diameter, prolactin concentration and resting electroencephalography (EEG)) and compare the changes from placebo with subjective analgesia on Experimental muscle Pain for convergent validation. Methods Fifteen healthy male participants received placebo or 30 mg rectal morphine at two separate sessions. At baseline and several time points after drug administration, the central effects of morphine were assessed by Experimental muscle Pain, pupil diameter, prolactin concentration and resting EEG. Results Morphine increased tolerance to muscle Pain, together with significant reductions in pupil diameter and increase in prolactin concentration (all P P P = 0.001). The effect of morphine on EEG was seen as a decrease in the relative theta (4–7.5 Hz) activity ( P = 0.03), but was not significant until 120 min after dosing and did not correlate to the increase in tolerated muscle pressure (r = –0.1, P = 0.43). Discussion Prolactin concentration and pupil diameter showed similar temporal development, had good dynamic ranges and were sensitive to morphine. Thus, both measures proved to be sensitive measures of morphine effects. EEG may give additive information on the brain's response to Pain, however more advanced analysis may be necessary. We therefore recommend using pupil diameter in studies where a simple and reliable objective measure of the morphine-induced central activation is needed.
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human Experimental Pain models for assessing the therapeutic efficacy of analgesic drugs
Pharmacological Reviews, 2012Co-Authors: Anne Estrup Olesen, Camilla Staahl, Trine Andresen, Asbjørn Mohr DrewesAbstract:Pain models in animals have shown low predictivity for analgesic efficacy in humans, and clinical studies are often very confounded, blurring the evaluation. Human Experimental Pain models may therefore help to evaluate mechanisms and effect of analgesics and bridge findings from basic studies to the clinic. The present review outlines the concept and limitations of human Experimental Pain models and addresses analgesic efficacy in healthy volunteers and patients. Experimental models to evoke Pain and hyperalgesia are available for most tissues. In healthy volunteers, the effect of acetaminophen is difficult to detect unless neurophysiological methods are used, whereas the effect of nonsteroidal anti-inflammatory drugs could be detected in most models. Anticonvulsants and antidepressants are sensitive in several models, particularly in models inducing hyperalgesia. For opioids, tonic Pain with high intensity is attenuated more than short-lasting Pain and nonPainful sensations. Fewer studies were performed in patients. In general, the sensitivity to analgesics is better in patients than in healthy volunteers, but the lower number of studies may bias the results. Experimental models have variable reliability, and validity shall be interpreted with caution. Models including deep, tonic Pain and hyperalgesia are better to predict the effects of analgesics. Assessment with neurophysiologic methods and imaging is valuable as a supplement to psychophysical methods and can increase sensitivity. The models need to be designed with careful consideration of pharmacological mechanisms and pharmacokinetics of analgesics. Knowledge obtained from this review can help design Experimental Pain studies for new compounds entering phase I and II clinical trials.
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assessing analgesic actions of opioids by Experimental Pain models in healthy volunteers an updated review
British Journal of Clinical Pharmacology, 2009Co-Authors: Lars Arendtnielsen, Anne Estrup Olesen, Asbjørn Mohr Drewes, Camilla Staahl, Trine AndresenAbstract:AIM Experimental Pain models may help to evaluate the mechanisms of action of analgesics and target the clinical indications for their use. This review addresses how the efficacy of opioids can be assessed in human volunteers using Experimental Pain models. The drawback with the different study designs is also discussed.
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is the Pain in chronic pancreatitis of neuropathic origin support from eeg studies during Experimental Pain
World Journal of Gastroenterology, 2008Co-Authors: Asbjørn Mohr Drewes, Georg Dimcevski, Maciej Gratkowski, Saber A K Sami, Peter Funchjensen, Lars ArendtnielsenAbstract:Is the Pain in chronic pancreatitis of neuropathic origin? Support from EEG studies during Experimental Pain
Lars Arendtnielsen - One of the best experts on this subject based on the ideXlab platform.
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p46 s rp11 819c21 1 and znrd1 as long non coding rna changes following Experimental Pain correlate with laser evoked potential habituation
Clinical Neurophysiology, 2019Co-Authors: Catello Vollono, Lars Arendtnielsen, Costanza Pazzaglia, Luca Padua, Rocco Giordano, Massimo Santoro, Enrica Di Sipio, Massimiliano ValerianiAbstract:Background Long non-coding RNAs (lncRNAs) are a group of non-coding RNAs acting as regulators of gene expression, through interaction with histones or through interaction with complementary DNA sequences, implicated in various human diseases such as cancer, cardiovascular diseases, autoimmune and neurodegenerative disorders and have been reported to be involved in the modulation of neuropathic Pain. We recorded Laser Evoked Potentials (LEPs) in order to study: (1) lncRNAs modifications in Experimental Pain model; (2) correlation between the lncRNA changes and objective measure of Pain perception. Material and methods LEPs were recorded in 11 healthy subjects after hand and perioral region stimulation. Three consecutive series were recorded for each stimulation site in order to investigate the habituation. Blood samples were collected immediately before LEP recording (baseline) and after 30-min (post-Pain). We screened 84 lncRNAs, involved in autoimmunity and inflammatory response. Results We identified 2 lncRNAs up-regulated at the post-Pain time: RP11-819C21.1 (fold change = 8.2; p = 0.038) and ZNRD1 antisense RNA 1 non-protein coding (ZNRD1-AS) (fold change = 6.3; p = 0.037). The up-regulation of both lncRNAs showed a significant positive correlation with the LEP habituation to perioral region stimulation (p = 0.04 and p = 0.01, respectively). Conclusions This is the first study showing lncRNA changes in a Pain Experimental model. RP11-819C21.1 and ZNRD1-AS shows as direct target miR-19a and miR19b, a class of microRNAs involved in modulation of multiple potassium channel α-subunits. lncRNAs could be involved in the pathophysiology of Painful diseases characterized by reduced habituation to Pain.
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415 effect of the benzodiazepine clobazam in chronic low back Pain and Experimental Pain modalities a randomized placebo controlled crossover study
The Journal of Pain, 2016Co-Authors: Jurg Schliessbach, Lars Arendtnielsen, Pascal Henri Vuilleumier, Andreas Siegenthaler, Lukas Butikofer, Andreas Limacher, Peter Juni, H Zeilhofer, Michele CuratoloAbstract:GABAergic compounds enhance endogenous inhibitory control within the central nervous system and are therefore potentially useful in human Pain conditions. Clobazam is an agonist at the benzodiazepine-binding site of GABA-A receptors. We investigated its effect on low back Pain and Experimental Pain modalities in chronic low back Pain. Forty-nine patients with chronic low back Pain received a single oral dose of clobazam 20 mg and the active placebo tolterodine 1 mg in a double-blinded cross-over fashion. Pain intensity (0-10) (primary endpoint) was measured in the supine and sitting position. Nine Experimental Pain modalities of pressure, electrical and thermal Pain, including conditioned Pain modulation, were applied at body sites distant to the low back. All assessments were made during 2 hours after drug intake. Pain intensity in the supine position was significantly lower after clobazam compared to placebo (60 minutes: 2.9 vs. 3.5, p=0.008; 90 minutes: 2.7 vs. 3.3, p=0.024; 120 minutes: 2.4 vs. 3.1, p=0.005). Pain intensity in the sitting position was not significantly different between the groups. No effect on Experimental Pain tests was observed. The results are suggestive for an analgesic effect of clobazam in low back Pain. The lack of effect in the sitting position suggests that GABAergic modulation may be less effective during mechanical strain of injured structures that may occur in the sitting position; the effect in the supine position suggests that GABAergic modulation is more effective at rest, when central sensitization processes may predominate over peripheral nociception. The lack of effect on Experimental Pain modalities suggests that GABAergic compounds may not be effective on non-sensitized neural pathways that are not functionally connected to the site of injury. The finding of the present study encourages pharmacologic research on GABAergic compounds that are devoid of tolerance and sedation. Funded by the Swiss National Science Foundation.
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evaluation of anti hyperalgesic and analgesic effects of two benzodiazepines in human Experimental Pain a randomized placebo controlled study
PLOS ONE, 2013Co-Authors: Pascal Henri Vuilleumier, Lars Arendtnielsen, Marie Besson, Jules Alexandre Desmeules, Michele CuratoloAbstract:Background and Aims Compounds that act on GABA-receptors produce anti-hyperalgesia in animal models, but little is known on their effects in humans. The aim of this study was to explore the potential usefulness of GABA-agonism for the control of Pain in humans. Two agonists at the benzodiazepine-binding site of GABAA-receptors (clobazam and clonazepam) were studied using multiple Experimental Pain tests. Positive results would support further investigation of GABA agonism for the control of clinical Pain.
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factor analysis of responses to thermal electrical and mechanical Painful stimuli supports the importance of multi modal Pain assessment
Pain, 2011Co-Authors: Alban Y Neziri, Lars Arendtnielsen, Michele Curatolo, Eveline Nuesch, Pasquale Scaramozzino, Ole Kaeseler Andersen, Peter JuniAbstract:During the last decade, a multi-modal approach has been established in human Experimental Pain research for assessing Pain thresholds and responses to various Experimental Pain modalities. Studies have concluded that differences in responses to Pain stimuli are mainly related to variation between individuals rather than variation in response to different stimulus modalities. In a factor analysis of 272 consecutive volunteers (137 men and 135 women) who underwent tests with different Experimental Pain modalities, it was determined whether responses to different Pain modalities represent distinct individual uncorrelated dimensions of Pain perception. Volunteers underwent single Painful electrical stimulation, repeated Painful electrical stimulation (temporal summation), test for reflex receptive field, pressure Pain stimulation, heat Pain stimulation, cold Pain stimulation, and a cold pressor test (ice water test). Five distinct factors were found representing responses to 5 distinct Experimental Pain modalities: pressure, heat, cold, electrical stimulation, and reflex-receptive fields. Each of the factors explained approximately 8% to 35% of the observed variance, and the 5 factors cumulatively explained 94% of the variance. The correlation between the 5 factors was near null (median ρ=0.00, range -0.03 to 0.05), with 95% confidence intervals for pairwise correlations between 2 factors excluding any relevant correlation. Results were almost similar for analyses stratified according to gender and age. Responses to different Experimental Pain modalities represent different specific dimensions and should be assessed in combination in future pharmacological and clinical studies to represent the complexity of nociception and Pain experience.
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assessing analgesic actions of opioids by Experimental Pain models in healthy volunteers an updated review
British Journal of Clinical Pharmacology, 2009Co-Authors: Lars Arendtnielsen, Anne Estrup Olesen, Asbjørn Mohr Drewes, Camilla Staahl, Trine AndresenAbstract:AIM Experimental Pain models may help to evaluate the mechanisms of action of analgesics and target the clinical indications for their use. This review addresses how the efficacy of opioids can be assessed in human volunteers using Experimental Pain models. The drawback with the different study designs is also discussed.
Anne Estrup Olesen - One of the best experts on this subject based on the ideXlab platform.
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genetic influences of oprm1 oprd1 and comt on morphine analgesia in a multi modal multi tissue human Experimental Pain model
Basic & Clinical Pharmacology & Toxicology, 2017Co-Authors: Anne Estrup Olesen, Lona L. Christrup, Asbjørn Mohr Drewes, Hiroe Sato, Lecia Moller NielsenAbstract:Human studies on Experimentally induced Pain are of value to elucidate the genetic influence on morphine analgesia under controlled conditions. The aim of this study was to investigate whether genetic variants of mu-, kappa- and delta-opioid receptor genes (OPRM1, OPRK1 and OPRD1) and catechol-O-methyltransferase gene (COMT) are associated with the morphine analgesia. The study was a randomized, double-blind, two-way, crossover, single-dose study conducted in 40 healthy participants, where morphine was compared with placebo. Pain was induced by contact heat, muscle pressure, bone pressure, rectal stimulations (mechanical, electrical and thermal) and cold pressor test (immersion of the hand into ice water). Sixteen genetic polymorphisms of four candidate genes were explored. Variability in morphine analgesia to contact heat stimulation was associated with COMT rs4680 (p = 0.04), and rectal thermal stimulation was associated with OPRM1 rs9479757 (p = 0.03). Moreover, in males, variability in morphine analgesia to rectal thermal stimulation was associated with OPRD1 polymorphisms: rs2234918 (p = 0.01) and rs533123 (p = 0.046). The study was explorative and hypothesis-generating due to the relatively small study size. However, results suggest that genetic variants in the COMT and OPRM1 irrespective of gender, and OPRD1 in males may contribute to the variability in morphine analgesia in Experimental Pain models.
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the genetic influences on oxycodone response characteristics in human Experimental Pain
Fundamental & Clinical Pharmacology, 2015Co-Authors: Anne Estrup Olesen, Camilla Staahl, Hiroe Sato, Lecia Moller Nielsen, Joanne Droney, S GrettonAbstract:Human Experimental Pain studies are of value to study basic Pain mechanisms under controlled conditions. The aim of this study was to investigate whether genetic variation across selected mu-, kappa- and delta-opioid receptor genes (OPRM1, OPRK1and OPRD1, respectively) influenced analgesic response to oxycodone in healthy volunteers. Experimental multimodal, multitissue Pain data from previously published studies carried out in Caucasian volunteers were used. Data on thermal skin Pain tolerance threshold (PTT) (n = 37), muscle pressure PTT (n = 31), mechanical visceral PTT (n = 43) and thermal visceral PTT (n = 41) were included. Genetic associations with Pain outcomes were explored. Nineteen opioid receptor genetic polymorphisms were included in this study. Variability in oxycodone response to skin heat was associated with OPRM1 single-nucleotide polymorphisms (SNPs) rs589046 (P < 0.0001) and rs563649 (P < 0.0001). Variability in oxycodone response to visceral pressure was associated with four OPRM1 SNPs: rs589046 (P = 0.015), rs1799971 (P = 0.045), rs9479757 (P = 0.009) and rs533586 (P = 0.046). OPRM1 SNPs were not associated with oxycodone visceral heat threshold, however, one OPRD1 rs419335 reached significance (P = 0.015). Another OPRD1 SNP rs2234918 (P = 0.041) was associated with muscle pressure. There were no associations with OPRK1 SNPs and oxycodone response for any of the Pain modalities. Associations were found between analgesic effects of oxycodone and OPRM1 and OPRD1 SNPs; therefore, variation in opioid receptor genes may partly explain responder characteristics to oxycodone.
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objective markers of the analgesic response to morphine in Experimental Pain research
Journal of Pharmacological and Toxicological Methods, 2015Co-Authors: Anne Brokjaer, Anne Estrup Olesen, Lona L. Christrup, Mads Kreilgaard, Carina Graversen, Mikkel Gram, Albert Dahan, Asbjørn Mohr DrewesAbstract:Abstract Introduction In Experimental Pain research the effect of opioids is normally assessed by verbal subjective response to analgesia. However, as many confounders in Pain assessment exist, objective bed-side assessment of the effect is highly warranted. Therefore, we aimed to assess the effect of morphine on three objective pharmacodynamic markers (pupil diameter, prolactin concentration and resting electroencephalography (EEG)) and compare the changes from placebo with subjective analgesia on Experimental muscle Pain for convergent validation. Methods Fifteen healthy male participants received placebo or 30 mg rectal morphine at two separate sessions. At baseline and several time points after drug administration, the central effects of morphine were assessed by Experimental muscle Pain, pupil diameter, prolactin concentration and resting EEG. Results Morphine increased tolerance to muscle Pain, together with significant reductions in pupil diameter and increase in prolactin concentration (all P P P = 0.001). The effect of morphine on EEG was seen as a decrease in the relative theta (4–7.5 Hz) activity ( P = 0.03), but was not significant until 120 min after dosing and did not correlate to the increase in tolerated muscle pressure (r = –0.1, P = 0.43). Discussion Prolactin concentration and pupil diameter showed similar temporal development, had good dynamic ranges and were sensitive to morphine. Thus, both measures proved to be sensitive measures of morphine effects. EEG may give additive information on the brain's response to Pain, however more advanced analysis may be necessary. We therefore recommend using pupil diameter in studies where a simple and reliable objective measure of the morphine-induced central activation is needed.
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human Experimental Pain models for assessing the therapeutic efficacy of analgesic drugs
Pharmacological Reviews, 2012Co-Authors: Anne Estrup Olesen, Camilla Staahl, Trine Andresen, Asbjørn Mohr DrewesAbstract:Pain models in animals have shown low predictivity for analgesic efficacy in humans, and clinical studies are often very confounded, blurring the evaluation. Human Experimental Pain models may therefore help to evaluate mechanisms and effect of analgesics and bridge findings from basic studies to the clinic. The present review outlines the concept and limitations of human Experimental Pain models and addresses analgesic efficacy in healthy volunteers and patients. Experimental models to evoke Pain and hyperalgesia are available for most tissues. In healthy volunteers, the effect of acetaminophen is difficult to detect unless neurophysiological methods are used, whereas the effect of nonsteroidal anti-inflammatory drugs could be detected in most models. Anticonvulsants and antidepressants are sensitive in several models, particularly in models inducing hyperalgesia. For opioids, tonic Pain with high intensity is attenuated more than short-lasting Pain and nonPainful sensations. Fewer studies were performed in patients. In general, the sensitivity to analgesics is better in patients than in healthy volunteers, but the lower number of studies may bias the results. Experimental models have variable reliability, and validity shall be interpreted with caution. Models including deep, tonic Pain and hyperalgesia are better to predict the effects of analgesics. Assessment with neurophysiologic methods and imaging is valuable as a supplement to psychophysical methods and can increase sensitivity. The models need to be designed with careful consideration of pharmacological mechanisms and pharmacokinetics of analgesics. Knowledge obtained from this review can help design Experimental Pain studies for new compounds entering phase I and II clinical trials.
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assessing analgesic actions of opioids by Experimental Pain models in healthy volunteers an updated review
British Journal of Clinical Pharmacology, 2009Co-Authors: Lars Arendtnielsen, Anne Estrup Olesen, Asbjørn Mohr Drewes, Camilla Staahl, Trine AndresenAbstract:AIM Experimental Pain models may help to evaluate the mechanisms of action of analgesics and target the clinical indications for their use. This review addresses how the efficacy of opioids can be assessed in human volunteers using Experimental Pain models. The drawback with the different study designs is also discussed.
C Campbell - One of the best experts on this subject based on the ideXlab platform.
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changes in Pain catastrophizing predict later changes in fibromyalgia clinical and Experimental Pain report cross lagged panel analyses of dispositional and situational catastrophizing
Arthritis Research & Therapy, 2012Co-Authors: C Campbell, Robert R Edwards, Mpepera Simango, Vani A Mathur, L Mccauley, S Bounds, Lora Conn, Kevin R FontaineAbstract:Fibromyalgia (FM), characterized by wide-spread diffuse Pain and sensory abnormalities, is associated with elevated indices of distress and Pain-related catastrophizing compared to both Pain-free samples and those with chronic Pain conditions. Catastrophizing is a pervasive negative mental set, and is a strong predictor of negative Pain-related outcomes such as clinical Pain intensity, and physical disability. Situational catastrophizing, measured in the context of Experimentally-induced Pain, is strongly related to enhanced Pain sensitivity, a core aspect of the pathophysiology of fibromyalgia. However, little is known regarding the temporal course of the association between catastrophizing and Pain-related "outcomes". Most studies involve only static assessments of Pain and catastrophizing at a single time point, which provides little insight into the direction of the observed associations. We sought to investigate the temporal relationships between catastrophizing and indices of both clinical Pain (substudy 1) and Experimentally-induced Pain (substudy 2) in a larger randomized controlled longitudinal trial. Fifty-seven patients with FM completed catastrophizing, depression, and Pain questionnaires as well as laboratory cold pressor Pain testing at baseline, post-intervention and three month follow-up during a lifestyle physical activity study. Cross-lagged panel analyses were used to address these temporal relationships. In substudy 1, analyses revealed that pre-to-post changes in dispositional catastrophizing ratings prospectively accounted for unique variance in subsequent post-to-follow-up changes in clinical Pain ratings (p = 0.005), while pre-to-post changes in Pain ratings did not account for unique variance in post-to-follow-up changes in catastrophizing ratings. An identical pattern was observed Experimentally in substudy 2, with pre-to-post changes in situational catastrophizing ratings prospectively accounting for unique variance in subsequent post-to-follow-up changes in Experimental Pain ratings (p = 0.014), while pre-to-post changes in Pain ratings did not account for unique variance in post-to-follow-up changes in catastrophizing ratings. Specifically, initial alterations in catastrophizing were associated with subsequent alterations in clinical and Experimentally induced Pain. Controlling for levels of depression did not affect the results. These findings provide empirical evidence that catastrophizing processes might precede and contribute to subsequent alterations in the Pain experience for FM patients. clinicaltrials.gov: NCT00383084 .
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ethnicity interacts with the oprm1 gene in Experimental Pain sensitivity
Pain, 2012Co-Authors: B Hastie, C Campbell, Joseph L Riley, D Herrera, Lee M Kaplan, Kathrina Virtusio, Jeffrey S Mogil, Margaret R Wallace, Roger B FillingimAbstract:Abstract Robust interindividual variation in Pain sensitivity has been observed, and recent evidence suggests that some of the variability may be genetically mediated. Our previous data revealed significantly higher pressure Pain thresholds among individuals possessing the minor G allele of the A118G SNP of the mu-opioid receptor gene (OPRM1) compared with those with 2 consensus alleles. Moreover, ethnic differences in Pain sensitivity have been widely reported. Yet, little is known about the potential interactive associations of ethnicity and genotype with Pain perception. This study aimed to identify ethnic differences in OPRM1 allelic associations with Experimental Pain responses. A total of 247 healthy young adults from three ethnic groups (81 African Americans; 79 non-white Hispanics; and 87 non-Hispanic whites) underwent multiple Experimental Pain modalities (thermal, pressure, ischemic, cold pressor). Few African Americans (7.4%) expressed the rare allele of OPRM1 compared to non-Hispanic whites and Hispanics (28.7% vs. 27.8%, respectively). Across the entire sample, OPRM1 genotype did not significantly affect Pain sensitivity. However, analysis in each ethnic group separately revealed significant genotype effects for most Pain modalities among non-Hispanic-whites (P
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ethnic identity predicts Experimental Pain sensitivity in african americans and hispanics
Pain, 2007Co-Authors: B Rahimwilliams, C Campbell, Joseph L Riley, B Hastie, D Herrera, Roger B FillingimAbstract:The aim of this study was to examine Experimental Pain sensitivity in three ethnic groups, African Americans, Hispanic Americans and non-Hispanic White Americans, and to determine whether ethnic identity is differentially associated with Pain sensitivity across ethnic groups. Participants included sixty-three African American, sixty-one Hispanic and eighty-two non-Hispanic white participants who were assessed using three Experimental Pain measures: thermal, cold-pressor and ischemic. Participants' ethnic identity was assessed using the Multi-group Ethnic Identity Measure (MEIM). Ethnic group differences in Pain responses were observed, with African American and Hispanic subjects showing lower cold and heat Pain tolerances than non-Hispanic White Americans. In addition, Pain range (i.e. tolerance-threshold) was computed for heat, cold and ischemic Pain, and the two minority groups again had lower values compared to non-Hispanic White Americans. Ethnic identity was associated with Pain range only for African American and Hispanic groups. Statistically controlling for ethnic identity rendered some of the group differences in Pain range non-significant. These findings indicate that ethnic identity is associated with Pain sensitivity in ethnic minority groups, and may partially mediate group differences in Pain perception. The results of the present investigation provide evidence of ethnic group differences in responses to Experimental Pain across multiple noxious stimuli, with both minority groups exhibiting greater sensitivity to laboratory evoked Pain compared to non-Hispanic White Americans.
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cluster analysis of multiple Experimental Pain modalities
Pain, 2005Co-Authors: B Hastie, Roland Staud, Michael E Robinson, C Campbell, Joseph L Riley, Roger B Fillingim, Toni L GloverAbstract:Identifying individual differences in Pain is an important topic; however, little is known regarding patterns of responses across various Experimental Pain modalities. This study evaluated subgroups emerging from multiple Experimental Pain measures. One hundred and eighty-eight individuals (59.0% female) completed several psychological instruments and underwent ischemic, pressure, and thermal Pain assessments. Thirteen separate Pain measures were obtained by using three Experimental Pain modalities with several parameters tested within each modality. The Pain ratings and scores were submitted to factor analysis that identified four Pain factors from which Pain Sensitivity Index (PSI) scores were computed: heat Pain (HP), pressure Pain (PP), ischemic Pain (IP), and temporal summation of heat Pain (TS). Cluster analyses of PSI scores revealed four distinct clusters. The first cluster demonstrated high overall Pain sensitivity, the second cluster revealed high TS, the third cluster showed particular insensitivity to IP and low sensitivity across Pain modalities except PP, and the fourth cluster demonstrated low sensitivity to PP. Significant correlations were found between psychological measures and Index scores and those differed by sex. Cluster membership was associated with demographic variables of ethnicity and sex as well as specific psychosocial variables, although cluster differences were only partially explained by such factors. These analyses revealed that groups respond differently across varied Pain stimuli, and this was not related solely to demographic or psychosocial factors. These findings highlight the need for future investigation to identify patterns of responses across different Pain modalities in order to more accurately characterize individual differences in responses to Experimental Pain.
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morphine responses and Experimental Pain sex differences in side effects and cardiovascular responses but not analgesia
The Journal of Pain, 2005Co-Authors: Donald D Price, C Campbell, Roger B Fillingim, B Hastie, Toni L Glover, Timothy J Ness, Roland StaudAbstract:Abstract Sex differences in analgesic responses to μ opioid agonists have been reported, although the direction of these differences varies across studies. To further characterize sex differences in responses to μ opioids, the analgesic effects of intravenous morphine (0.08 mg/kg) were determined in healthy women (n = 61) and men (n = 39) by using 3 Experimental Pain models, heat Pain, pressure Pain, and ischemic Pain. Each Pain procedure was conducted before and after double-blind administration of both morphine and saline, which occurred on separate days in counterbalanced order. Although morphine produced significant analgesic effects for all Pain stimuli, no significant sex differences in morphine analgesia emerged. However, morphine attenuated cardiovascular reactivity to the ischemic Pain task in men but not women, and women reported significantly more drug-related adverse effects than men. These findings are in contrast with some recent clinical and Experimental results suggesting more robust analgesic response to μ opioids among women compared to men, although the data indicate that sex differences in non-analgesic effects of morphine were present. These results suggest that sex differences in responses to morphine might depend on the Pain model and/or drug dose as well as the specific end point assessed. Perspective This study examines morphine responses in women and men by using laboratory Pain measures. The results indicate no sex differences in analgesia, but women reported greater side effects, and morphine attenuated cardiovascular responses more strongly among men than women. These results add to the literature regarding sex differences in response to opioids.
