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Many studies suggest a strong familial component to fibromyalgia (FM). However, these studies have nearly all been confined to individuals with "primary" FM, i.e. FM without any other accompanying disorder. The current 2011-16 criteria for diagnosing FM construct a score using a combination of the number of painful body sites and the severity of somatic symptoms (FM-score). We estimated the genetic heritability of FM-score across sex and age groups to identify subgroups of individuals with greater heritability, which may help in the design of future genetic studies.
Learn More >Patellofemoral pain (PFP) is a common complaint among young sports active adolescents. This study evaluated the longitudinal changes in pronociceptive and antinociceptive mechanisms in young adolescents with PFP, their impact on prognosis, and responsiveness to treatment. Adolescents (N = 151, aged 10-14 years) diagnosed with PFP were compared with age-matched controls (N = 50) and subsequently tracked while participating in an intervention focussed on activity modification. They underwent quantitative sensory testing at baseline (preintervention), 4 weeks (during initial treatment), and 12 weeks (after treatment). Pressure pain thresholds (PPTs) were recorded on the knee, shin, and elbow. Temporal summation of pain (TSP) was assessed by the increase in pain intensity during 10 repeated cuff pressure pain stimulations on the leg. Conditioned pain modulation (CPM) was defined as change in cuff pain thresholds on one leg, during painful cuff conditioning on the contralateral leg. At baseline, adolescents with PFP had decreased PPTs at the knee, shin, and elbow (P < 0.001) as well as more facilitated TSP (P < 0.05) compared with controls. For CPM at baseline, controls displayed an increase in cuff pain thresholds during conditioning (P < 0.05), while those with PFP did not. More facilitated baseline TSP was associated with less improvements in pain intensity during the intervention (P < 0.01). Pressure pain thresholds increased at both follow-ups (P < 0.001), and the increased PPTs were associated with decreases in pain intensity (r = 0.316; P < 0.001). Overall, TSP remained facilitated at follow-ups, and there was no change in CPM. This is the first study to demonstrate a pronociceptive mechanism as a prognostic factor in young adolescents with PFP.
Learn More >Context and objective Opioids have heterogeneous side effects including a well-known effect of sedation; however, the opposing effect of stimulation, or somatic activation, has been largely ignored or overlooked. The objective of this study is to determine the prevalence of opioid-induced somatic activation (OISA). Methods We conducted a retrospective chart review of 189 patients seen by a single clinical psychiatrist/pain specialist. During the initial encounter, the clinician took a standardized history of every opioid currently or previously taken by the patients, and enquired if the patients had experienced a somatically activating or sedating effect per opioid. Results Patients recalled an average exposure to 5.1 opioids (SD: 1.9). Ninety-one patients (48.1%; mean: 1.6) reported somatic activation, while 118 (62.4%; mean: 1.7) reported sedation from at least one opioid. Fifty-eight patients (30.7%) identified at least one opioid as activating, and another as sedating. The distribution of OISA did not significantly differ by gender, race, primary pain diagnosis, or depression. The distribution of OISA by oxycodone significantly differed compared to morphine sulfate (27.3% vs 8.9%; p: 0.005), while sedation did not (29.0% vs 24.3%; p: 0.46). Conclusions In this study, we quantified the previously unstudied phenomenon of OISA. This phenomenon appears dependent on opioid type with some opioids, such as oxycodone, appearing more likely to have this effect. Given current concerns about the risks of opioids in high-risk populations, future studies are needed to study this phenomenon to arrive at an accurate determination of the potential risks and benefits of OISA.
Learn More >Current patient-reported outcome measures for itch are limited and may not capture its full impact on health-related quality of life (HRQOL). We sought to develop, calibrate and validate banks of questions assessing the HRQOL impact of itch as part of Patient-Reported Outcomes Measurement Information System® (PROMIS®). A systematic process of literature review, content-expert review, qualitative research, testing in a sample of 600 adults, classical test theory methods, and item response theory (IRT) analyses were applied. Exploratory and confirmatory factor analyses were followed by item response theory (IRT) model and item fit analyses. Four itch-related item banks were developed: (1) general concerns, (2) mood and sleep, (3) clothing and physical activity, and (4) scratching behavior. IRT and expert content review narrowed the item banks to 25, 18, 15 and 5 items, respectively. Validity of the item banks was supported by good convergent and discriminant validity with itch intensity, internal consistency and no significant floor or ceiling effects. In conclusion, the PROMIS Itch Questionnaire (PIQ) banks have excellent measurement properties and efficiently and comprehensively assess the burden of itch.
Learn More >Ubrogepant is a novel, oral calcitonin gene-related peptide (CGRP) receptor antagonist intended for the acute treatment of migraine attacks. Ubrogepant has a chemical structure distinct from previous small-molecule CGRP receptor antagonists that were associated with elevated serum alanine aminotransferase (ALT) in clinical trials. Here, we report overall and hepatic safety data from two placebo-controlled phase I trials of ubrogepant, spray-dried oral compressed tablet (SD-OCT) in healthy male volunteers. Trial A was a pharmacokinetic (PK) trial of single (100-400 mg) and multiple (40-400 mg) ascending doses. Trial B was a dedicated hepatic safety trial assessing daily use of ubrogepant 150 mg for 28 days. Serum ALT (as hepatotoxicity biomarker) and PK data are reported. Ubrogepant was well-tolerated in both trials, with a low incidence of adverse events that did not differ greatly from placebo. Changes in mean ALT levels were minimal and similar to placebo. Over 28 days of treatment, the mean percentage change in ALT from baseline was < 5% at all time points. No participant in either trial demonstrated ALT ≥ 3× upper limit of normal at any time. Ubrogepant SD-OCT demonstrated linear PK appropriate for acute treatment of migraine, with rapid uptake (time of maximum plasma concentration (t ): 2-3 hours) and no accumulation with daily use. Overall, there was no evidence of ubrogepant-associated hepatotoxicity with daily doses up to 400 mg for 10 days or with daily ubrogepant 150 mg for 28 days. Supratherapeutic dosing is a useful strategy for characterizing hepatic safety in early drug development.
Learn More >Buprenorphine is a Schedule III analgesic that is recommended as the firstline long-acting opioid for the treatment of chronic pain due to its ceiling effect on respiratory depression, adverse effect profile, and analgesic efficacy. However, prescription drug coverage policies commonly require that patients try and fail multiple Schedule II conventional opioids before approval of on-label use of buprenorphine for chronic pain.
Learn More >There is an unmet medical need for pruritus associated with chronic kidney disease, a distressing complication characterized by generalized and persistent itch affecting 20% to 40% of patients undergoing hemodialysis. Here we report the results of a phase 2 trial evaluating the efficacy and safety of a novel peripherally restricted kappa opioid receptor agonist, difelikefalin, in adult patients undergoing hemodialysis with pruritus.
Learn More >Although opioids can be effective medications in certain situations, they are associated with harms, including opioid use disorder and overdose. Studies have revealed unexplained prescribing variation and prescribing mismatched with patient-reported pain for many indications.
Learn More >There is evidence regarding the presence of alterations in both the stress response and the endogenous pain modulation systems of people with fibromyalgia (FM). However, research on pain modulation under induced stress on FM patients is scarce and contradictory. The present study analyzes stress-induced changes in pain and intolerance thresholds among FM patients, examining the possible existence of differences linked to PTSD comorbidity and gaining insights into the role of cardiovascular reactivity. Eighteen women diagnosed with FM and comorbid PTSD (FM + PTSD), 18 women diagnosed with FM and no PTSD (FM-PTSD), and 38 healthy women (HC) were exposed to the Social Stress Test task. Pressure pain thresholds and intolerance thresholds were measured before and during stress induction, and after a recovery period, while systolic blood pressure and heart rate were simultaneously recorded. Overall, while pain thresholds decreased during stress and recovery for HC, no significant changes were observed for women with FM. The intolerance threshold decreased for HC during stress, but was maintained at basal level during recovery. FM-PTSD women exhibited a delayed response, with a drop at recovery. For FM + PTSD, tolerance levels remained unchanged. In addition, cardiovascular reactivity did not seem to explain these results. This performance of the pain modulation system seems to follow the same pattern of hypoactive responsiveness under stressors that has previously been observed in FM patients on the autonomic and neuroendocrine axes. Such a hypoactive pattern may involve a non-adaptive response that may contribute to the development and maintenance of chronic pain.
Learn More >retrospective population-based cohort analysis.
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