Browsing by Subject "Pain measurement"

Now showing 1 - 8 of 8
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    A Novel Perioperative Multidose Methadone-Based Multimodal Analgesic Strategy in Children Achieved Safe and Low Analgesic Blood Methadone Levels Enabling Opioid-Sparing Sustained Analgesia With Minimal Adverse Effects
    (Wolters Kluwer, 2021) Sadhasivam, Senthilkumar; Aruldhas, Blessed W.; Packiasabapathy, Senthil; Overholser, Brian R.; Zhang, Pengyue; Zang, Yong; Renschler, Janelle S.; Fitzgerald, Ryan E.; Quinney, Sara K.; Anesthesia, School of Medicine
    Background: Intraoperative methadone, a long-acting opioid, is increasingly used for postoperative analgesia, although the optimal methadone dosing strategy in children is still unknown. The use of a single large dose of intraoperative methadone is controversial due to inconsistent reductions in total opioid use in children and adverse effects. We recently demonstrated that small, repeated doses of methadone intraoperatively and postoperatively provided sustained analgesia and reduced opioid use without respiratory depression. The aim of this study was to characterize pharmacokinetics, efficacy, and safety of a multiple small-dose methadone strategy. Methods: Adolescents undergoing posterior spinal fusion (PSF) for idiopathic scoliosis or pectus excavatum (PE) repair received methadone intraoperatively (0.1 mg/kg, maximum 5 mg) and postoperatively every 12 hours for 3-5 doses in a multimodal analgesic protocol. Blood samples were collected up to 72 hours postoperatively and analyzed for R-methadone and S-methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidene (EDDP) metabolites, and alpha-1 acid glycoprotein (AAG), the primary methadone-binding protein. Peak and trough concentrations of enantiomers, total methadone, and AAG levels were correlated with clinical outcomes including pain scores, postoperative nausea and vomiting (PONV), respiratory depression, and QT interval prolongation. Results: The study population included 38 children (10.8-17.9 years): 25 PSF and 13 PE patients. Median total methadone peak plasma concentration was 24.7 (interquartile range [IQR], 19.2-40.8) ng/mL and the median trough was 4.09 (IQR, 2.74-6.4) ng/mL. AAG concentration almost doubled at 48 hours after surgery (median = 193.9, IQR = 86.3-279.5 µg/mL) from intraoperative levels (median = 87.4, IQR = 70.6-115.8 µg/mL; P < .001), and change of AAG from intraoperative period to 48 hours postoperatively correlated with R-EDDP (P < .001) levels, S-EDDP (P < .001) levels, and pain scores (P = .008). Median opioid usage was minimal, 0.66 (IQR, 0.59-0.75) mg/kg morphine equivalents/d. No respiratory depression (95% Wilson binomial confidence, 0-0.09) or clinically significant QT prolongation (median = 9, IQR = -10 to 28 milliseconds) occurred. PONV occurred in 12 patients and was correlated with morphine equivalent dose (P = .005). Conclusions: Novel multiple small perioperative methadone doses resulted in safe and lower blood methadone levels, <100 ng/mL, a threshold previously associated with respiratory depression. This methadone dosing in a multimodal regimen resulted in lower blood methadone analgesia concentrations than the historically described minimum analgesic concentrations of methadone from an era before multimodal postoperative analgesia without postoperative respiratory depression and prolonged corrected QT (QTc). Larger studies are needed to further study the safety and efficacy of this methadone dosing strategy.
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    Child pain-related injustice appraisals mediate the relationship between just-world beliefs and pain-related functioning
    (Wiley, 2021) Daenen, Frederick; McParland, Joanna; Baert, Fleur; Miller, Megan Marie; Hirsh, Adam Todd; Vervoort, Tine; Psychology, School of Science
    Background: Research among adult and paediatric samples suggests that pain-related injustice appraisals contribute to adverse pain-related functioning. However, a singular focus on pain-related injustice appraisals carries the risk of underestimating the role of broader concepts of justice. This study examined the unique roles of child pain-related injustice appraisals and just-world beliefs in understanding disability and physical, emotional, social and academic functioning, as well as the mediating role of injustice appraisals in the relationship between just-world beliefs and functioning. Methods: Participants comprised a school sample of 2,174 children (Study 1) and a clinical sample of 146 paediatric chronic pain patients (Study 2) who completed the Injustice Experience Questionnaire (IEQ), Personal and General Belief in a Just World scales (JWB-P/G), Functional Disability Inventory (FDI), Pain Catastrophizing Scale for Children (PCS-C) and Pediatric Quality of Life Inventory (PEDSQL). Results: For both samples, child pain-related injustice appraisals were associated with poorer functioning, after controlling for just-world beliefs, catastrophizing, pain intensity, age and sex. In the school sample, injustice appraisals mediated the associations of both personal and general just-world beliefs with functioning. In the clinical sample, injustice appraisals mediated the association of personal, but not general, just-world beliefs with all functioning scales. Conclusions: The current findings attest to the unique role of pain-related injustice appraisals in understanding child pain-related functioning and their explanatory value in understanding the relationship between fundamental just-world beliefs and child pain-related functioning. Significance: The present study adds to emerging literature on the adverse effects of child pain-related injustice appraisals in the context of pain, through showing that pain-related injustice appraisals are uniquely associated with pain-related functioning and mediate the relationship between just-world beliefs and pain-related functioning. These findings suggest that interventions may target pain-related injustice appraisals as a mechanism for change in children.
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    Disentangling trait versus state characteristics of the Pain Catastrophizing Scale and the PHQ-8 Depression Scale
    (Wiley, 2020-09) Dumenci, Levent; Kroenke, Kurt; Keefe, Francis J.; Ang, Dennis C.; Slover, James; Perera, Robert A.; Riddle, Daniel L.; Medicine, School of Medicine
    Background: Research on the role of trait versus state characteristics of a variety of measures among persons experiencing pain has been a focus for the past few decades. Studying the trait versus state nature of the Pain Catastrophizing Scale (PCS) and the Patient Health Questionnaire (PHQ-8) depression scale would be highly informative given both are commonly measured in pain populations and neither scale has been studied for trait/state contributions. Methods: The PHQ-8 and PCS were obtained on persons undergoing knee arthroplasty at baseline, 2-, 6- and 12-month post-surgery (N = 402). The multi-trait generalization of the latent trait-state model was used to partition trait and state variability in PCS and PHQ-8 item responses simultaneously. A set of variables were used to predict trait catastrophizing and trait depression. Results: For total scores, the latent traits and latent states explain 63.2% (trait = 43.2%; state = 20.0%) and 50.2% (trait = 29.4%; state = 20.8%) of the variability in PCS and PHQ-8, respectively. Patients with a high number of bodily pain sites, high levels of anxiety, young patients and African-American patients had high levels of trait catastrophizing and trait depression. The PCS and the PHQ-8 consist of both enduring trait and dynamic state characteristics, with trait characteristics dominating for both measures. Conclusion: Clinicians and researchers using these scales should not assume the obtained measurements solely reflect either trait- or state-based characteristics. Significance: Clinicians and researchers using the PCS or PHQ-8 scales are measuring both state and trait characteristics and not just trait- or state-based characteristics.
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    Experimental pain and auditory sensitivity in overactive bladder syndrome: a Symptoms of the Lower Urinary Tract Dysfunction Research Network (LURN) Study
    (Wolters Kluwer, 2022) Harte, Steven E.; Wiseman, Jon; Wang, Ying; Smith, Abigail R.; Yang, Claire C.; Helmuth, Margaret; Kreder, Karl; Kruger, Grant H.; Gillespie, Brenda W.; Amundsen, Cindy; Kirkali, Ziya; Lai, H. Henry; LURN Study Group; Anesthesia, School of Medicine
    Purpose: The objective of this study was to investigate the presence of nonbladder sensory abnormalities in participants with overactive bladder syndrome (OAB). Materials and methods: Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) study participants with OAB symptoms and controls were recruited from 6 U.S. tertiary referral centers. Quantitative sensory testing (QST) was performed to determine pressure pain sensitivity at the thumbnail bed and auditory sensitivity. Fixed and mixed effect multivariable linear regressions and Weibull models were used to compare QST responses between groups. Pearson correlations were used to assess the relationship between QST measures. Associations between QST and self-reported symptoms were explored with linear regression. Results: A total of 297 participants were analyzed (191 OAB, 106 controls; 76% white, 51% male). OAB cases were older than controls (57.4 vs 52.2 years, p=0.015). No significant differences in experimental thumbnail (nonbladder) pain or auditory sensitivity were detected between OAB cases and controls. Correlations between pressure and auditory derived metrics were weak to moderate overall for both groups, with some significantly stronger correlations for cases. Exploratory analyses indicated increased pressure pain and auditory sensitivity were modestly associated with greater self-reported bladder pain and pain interference with physical function. Conclusions: As a group, no significant differences between OAB cases and controls were observed in experimental nonbladder pain or auditory sensitivity during QST. Associations between QST outcomes and clinical pain raise the possibility of centrally mediated sensory amplification in some individuals with OAB.
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    Implementing a pragmatic clinical trial to tailor opioids for chronic pain on behalf of the IGNITE ADOPT PGx investigators
    (Wiley, 2024) Skaar, Todd C.; Myers, Rachel A.; Fillingim, Roger B.; Callaghan, John T.; Cicali, Emily; Eadon, Michael T.; Elwood, Erica N.; Ginsburg, Geoffrey S.; Lynch, Sheryl; Nguyen, Khoa A.; Obeng, Aniwaa Owusu; Park, Haesuk; Pratt, Victoria M.; Rosenman, Marc; Sadeghpour, Azita; Shuman, Saskia; Singh, Rajbir; Tillman, Emma M.; Volpi, Simona; Wiisanen, Kristin; Winterstein, Almut G.; Horowitz, Carol R.; Voora, Deepak; Orlando, Lori; Chakraborty, Hrishikesh; Van Driest, Sara; Peterson, Josh F.; Cavallari, Larisa A.; Johnson, Julie A.; Dexter, Paul R.; IGNITE Pragmatic Trials Network; Medicine, School of Medicine
    Chronic pain is a prevalent condition with enormous economic burden. Opioids such as tramadol, codeine, and hydrocodone are commonly used to treat chronic pain; these drugs are activated to more potent opioid receptor agonists by the hepatic CYP2D6 enzyme. Results from clinical studies and mechanistic understandings suggest that CYP2D6-guided therapy will improve pain control and reduce adverse drug events. However, CYP2D6 is rarely used in clinical practice due in part to the demand for additional clinical trial evidence. Thus, we designed the ADOPT-PGx (A Depression and Opioid Pragmatic Trial in Pharmacogenetics) chronic pain study, a multicenter, pragmatic, randomized controlled clinical trial, to assess the effect of CYP2D6 testing on pain management. The study enrolled 1048 participants who are taking or being considered for treatment with CYP2D6-impacted opioids for their chronic pain. Participants were randomized to receive immediate or delayed (by 6 months) genotyping of CYP2D6 with clinical decision support (CDS). CDS encouraged the providers to follow the CYP2D6-guided trial recommendations. The primary study outcome is the 3-month absolute change in the composite pain intensity score assessed using Patient-Reported Outcomes Measurement Information System (PROMIS) measures. Follow-up will be completed in July 2024. Herein, we describe the design of this trial along with challenges encountered during enrollment.
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    Increased spatial dimensions of repetitive heat and cold stimuli in older women
    (Wolters Kluwer, 2017-05) Naugle, Kelly M.; Cruz-Almeida, Yenisel; Fillingim, Roger B.; Staud, Roland; Riley, Joseph L., III; Kinesiology, School of Physical Education and Tourism Management
    Protocols of temporal summation (TS) of pain typically involve the delivery of brief repetitive noxious pulses of a constant intensity while measuring the perceived intensity of pain after each pulse. The size percept of noxious repetitive stimulation has been poorly characterized. Furthermore, no studies have investigated age differences in TS of cold pain. The current study examined TS of pain intensity and the perceived size of the painful area during repetitive noxious heat and cold pulses in healthy younger (n = 104) and older adults (n = 40). Trials of 10 brief repetitive noxious heat or cold pulses were delivered to the upper extremities. Participants rated the perceived size of the painful area or intensity of pain after each pulse. The magnitude of change for the size percept and intensity for pain were calculated for each trial. The results indicated that older adults experienced greater TS of the size percept of cold stimuli compared with younger adults. Additionally, older women experienced greater TS of the size percept of heat stimuli compared with older men and all younger participants. No overall age or sex differences were found in the TS of pain intensity for cold or heat trials. These results suggest dysfunctional modulation of the spatial percept of the painful stimuli by older adults, and in particular older women, during repetitive noxious thermal pulses.
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    Racial Disparities in Observers’ Attention to and Estimations of Others’ Pain
    (Wolters Kluwer, 2022) Kissi, Ama; Van Ryckeghem, Dimitri M.L; Mende-Siedlecki, Peter; Hirsh, Adam; Vervoort, Tine; Psychology, School of Science
    Research has demonstrated racial disparities in pain care such that Black patients often receive poorer pain care than White patients. Little is known about mechanisms accounting for the emergence of such disparities. The present study had 2 aims. First, we examined whether White observers' attentional processing of pain (using a visual search task [VST] indexing attentional engagement to and attentional disengagement from pain) and estimation of pain experience differed between White vs Black faces. Second, we examined whether these differences were moderated by (1) racially biased beliefs about pain experience and (2) the level of pain expressed by Black vs White faces. Participants consisted of 102 observers (87 females) who performed a VST assessing pain-related attention to White vs Black avatar pain faces. Participants also reported on racially biased beliefs about White vs Black individuals' pain experience and rated the pain intensities expressed by White and Black avatar faces. Results indicated facilitated attentional engagement towards Black (vs White) pain faces. Furthermore, observers who more strongly endorsed the belief that White individuals experience pain more easily than Black individuals had less difficulty disengaging from Black (vs White) pain faces. Regarding pain estimations, observers gave higher pain ratings to Black (vs White) faces expressing high pain and White (vs Black) faces expressing no pain. The current findings attest to the importance of future research into the role of observer attentional processing of sufferers' pain in understanding racial disparities in pain care. Theoretical and clinical implications are discussed, and future research directions are outlined.
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    Research approaches for evaluating opioid sparing in clinical trials of acute and chronic pain treatments: Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials recommendations
    (International Association for the Study of Pain, 2021) Gewandter, Jennifer S.; Smith, Shannon M.; Dworkin, Robert H.; Turk, Dennis C.; Gan, Tong Joo; Gilron, Ian; Hertz, Sharon; Katz, Nathaniel P.; Markman, John D.; Raja, Srinivasa N.; Rowbotham, Michael C.; Stacey, Brett R.; Strain, Eric C.; Ward, Denham S.; Farrar, John T.; Kroenke, Kurt; Rathmell, James P.; Rauck, Richard; Brown, Colville; Cowan, Penney; Edwards, Robert R.; Eisenach, James C.; Ferguson, McKenzie; Freeman, Roy; Gray, Roy; Giblin, Kathryn; Grol-Prokopczyk, Hanna; Haythornthwaite, Jennifer; Jamison, Robert N.; Martel, Marc; McNicol, Ewan; Oshinsky, Michael; Sandbrink, Friedhelm; Scholz, Joachim; Scranton, Richard; Simon, Lee S.; Steiner, Deborah; Verburg, Kenneth; Wasan, Ajay D.; Wentworth, Kerry; Medicine, School of Medicine
    Randomized clinical trials have demonstrated the efficacy of opioid analgesics for the treatment of acute and chronic pain conditions, and for some patients, these medications may be the only effective treatment available. Unfortunately, opioid analgesics are also associated with major risks (eg, opioid use disorder) and adverse outcomes (eg, respiratory depression and falls). The risks and adverse outcomes associated with opioid analgesics have prompted efforts to reduce their use in the treatment of both acute and chronic pain. This article presents Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus recommendations for the design of opioid-sparing clinical trials. The recommendations presented in this article are based on the following definition of an opioid-sparing intervention: any intervention that (1) prevents the initiation of treatment with opioid analgesics, (2) decreases the duration of such treatment, (3) reduces the total dosages of opioids that are prescribed for or used by patients, or (4) reduces opioid-related adverse outcomes (without increasing opioid dosages), all without causing an unacceptable increase in pain. These recommendations are based on the results of a background review, presentations and discussions at an IMMPACT consensus meeting, and iterative drafts of this article modified to accommodate input from the co-authors. We discuss opioid sparing definitions, study objectives, outcome measures, the assessment of opioid-related adverse events, incorporation of adequate pain control in trial design, interpretation of research findings, and future research priorities to inform opioid-sparing trial methods. The considerations and recommendations presented in this article are meant to help guide the design, conduct, analysis, and interpretation of future trials.