Browse by Audience
Osteoarthritis (OA) manifests with chronic pain, motor impairment, and proprioceptive changes. However, the role of the brain in the disease is largely unknown. Here, we studied brain networks using the mathematical properties of graphs in a large sample of knee and hip OA (KOA, n = 91; HOA, n = 23) patients. We used a robust validation strategy by subdividing the KOA data into discovery and testing groups and tested the generalizability of our findings in HOA. Despite brain global topological properties being conserved in OA, we show there is a network wide pattern of reorganization that can be captured at the subject-level by a single measure, the hub disruption index. We localized reorganization patterns and uncovered a shift in the hierarchy of network hubs in OA: primary sensory and motor regions and parahippocampal gyrus behave as hubs and insular cortex loses its central placement. At an intermediate level of network structure, frontoparietal and cingulo-opercular modules showed preferential reorganization. We examined the association between network properties and clinical correlates: global disruption indices and isolated degree properties did not reflect clinical parameters; however, by modeling whole brain nodal degree properties, we identified a distributed set of regions that reliably predicted pain intensity in KOA and generalized to hip OA. Together, our findings reveal that while conserving global topological properties, brain network architecture reorganizes in OA, at both global and local scale. Network connectivity related to OA pain intensity is dissociated from the major hub disruptions, challenging the extent of dependence of OA pain on nociceptive signaling.
Learn More >The striking difference between men and women in headache prevalence is suggested to develop in adolescence. Although headaches are common and affect quality of life and daily functioning, the evidence needed to develop effective counselling and preventive approaches is still limited.Using data collected at age 11, 14, 17 and 20 years in the Dutch PIAMA birth cohort study (n=3064 with > 1 questionnaire), we assessed headache prevalence and incidence in girls and boys and explored associations with early life, environmental, lifestyle, health and psychosocial factors. Associations were analysed longitudinally with generalized linear mixed models and discrete time hazard models.From age 11 to 20, the prevalence of headache increased from 9.4% to 19.8% in girls and hardly changed in boys (7.6% to 6.1%). Headache commonly co-occurred with other unfavorable health and psychosocial conditions. 88% of the girls and 76% of boys with headache also reported at least one of the following at age 17: sleeping problems, asthma, hay fever, musculoskeletal complaints, fatigue, low mental health or worrying. Results suggest higher headache prevalence in adolescents following lower educational tracks, in those who skip breakfast >2 days per week and in boys exposed to tobacco smoke in infancy. In girls, sleeping problems and musculoskeletal complaints were associated with higher odds of incident headache and residential greenness with lower odds of incident headache.The high prevalence and strong female predominance of headache, already in adolescence and often with comorbidities deserve recognition by professionals in (preventive) health care settings and schools.
Learn More >Use of parenteral opioids is a major risk factor for postoperative nausea and vomiting. Conventional opioids bind to µ-opioid receptors (MOR), stimulate both the G-protein signaling (achieving analgesia); and the β-arrestin pathway (associated with opioid-related adverse effects). Oliceridine, a next-generation IV opioid, is a G-protein selective MOR agonist, with limited recruitment of β-arrestin. In two randomized, placebo- and morphine-controlled phase 3 studies of patients with moderate-to-severe acute pain following bunionectomy or abdominoplasty, oliceridine at demand doses of 0.1, 0.35, and 0.5 mg provided rapid and sustained analgesia vs. placebo with favorable gastrointestinal (GI) tolerability. In this exploratory analysis, we utilized a clinical endpoint assessing gastrointestinal tolerability, "complete GI response" defined as the proportion of patients with no vomiting and no use of rescue antiemetic to characterize the GI tolerability profile of oliceridine vs. morphine.
Learn More >The aim of the study was to investigate patient satisfaction amongst academic pain management centers and associated factors.
Learn More >Preclinical studies demonstrate that sleep disruption diminishes morphine analgesia and modulates reward processing. We sought to translate these preclinical findings to humans by examining whether sleep disruption alters morphine's analgesic and hedonic properties. We randomized 100 healthy adults to receive morphine versus placebo after two nights of undisturbed sleep (US) and two nights of forced awakening (FA) sleep disruption. Sleep conditions were counterbalanced, separated by a two-week washout. The morning after both sleep conditions, we tested cold pressor pain tolerance before and 40-min after double-blind injection of .08 mg/kg morphine or placebo. The primary outcome was the analgesia index, calculated as the change in cold pressor hand withdrawal latency (HWL) before and after drug injection. Secondary outcomes were ratings of feeling "high," drug "liking," and negative drug effects. We found a significant sleep condition by drug interaction on the analgesia index (95% CI - 0.57, - 0.001). After US, subjects receiving morphine demonstrated significantly longer HWL compared to placebo (95% CI 0.23, 0.65), but not after FA (95% CI - 0.05, 0.38). Morphine analgesia was diminished threefold under FA, relative to US. After FA, females (95% CI - 0.88, - 0.05), but not males (95% CI - 0.23, 0.72), reported decreased subjective "high" effects compared to US. After FA, females (95% CI 0.05, 0.27), but not males (95% CI - 0.10, 0.11), administered morphine reported increased negative drug effects compared to US. These data demonstrate that sleep disruption attenuates morphine analgesia in humans and suggest that sleep disturbed males may be at greatest risk for problematic opioid use.
Learn More >To examine the effect of sex on migraine trigger factors.
Learn More >Pharmacological treatment of cluster headache constitutes the core of clinical management, but evidence is sparse. We aimed to generate insight in the existing treatment and identify associations between clinical features and treatment response.
Learn More >Examine factors associated with post-procedure opioid receipt and persistent opioid use among opioid-naïve patients in a nationally representative sample SUMMARY BACKGROUND DATA:: We used panels 18-20 in the Medical Expenditures Panel Survey (MEPS) between the years 2013 to 2015. Respondents ages 18 and over with any self-reported procedure in the previous year with complete data on the outcome variables for the remainder of the two-year study period.
Learn More >Migraine is associated with an increased risk of ischemic stroke. The associations are stronger in migraine with aura than in migraine without aura, in women than in men, and in younger subjects. However, the mechanisms by which migraine might increase the risk of ischemic stroke are debated.
Learn More >Most migraine patients report neck pain as part of their migraine symptomatology, but it is unknown whether triggering neck pain would induce migraine attacks. Our aim was to assess the occurrence of headache and/or neck pain after an endurance test of the neck muscles among migraineurs and controls.
Learn More >