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Objectives In evidence-based medicine, we base our conclusions on the effectiveness of interventions on the results of high-quality meta-analysis. If a new randomized controlled trial (RCT) is unlikely to change the pooled effect estimate, conducting the new trial is a waste of resources. We evaluated whether recommendations not to conduct further RCTs reduced the number of trials registered for two scenarios. Methods Analysis of registered trials on the World Health Organisation (WHO) International Clinical Trials Registry Platform (ICTRP). We regarded trial protocols relevant if they evaluated the effectiveness of (1) exercise for chronic low back pain (LBP) and (2) cognitive behavioural therapy (CBT) for chronic pain. We calculated absolute and relative numbers and change of registered trials in a pre-set time window before and after publication of the recommendations, both published in 2012. Results We found 1,574 trials registered in the WHO trial registry for exercise in LBP (459 before 2012; 1,115 after) and 5,037 trials on chronic pain (1,564 before 2012; 3,473 after). Before 2012, 13 trials on exercise for LBP (out of 459) fit the selection criteria, compared to 42 trials (out of 1,115) after, which represents a relative increase of 33%. Twelve trials (out of 1,564) regarding CBT for chronic pain, fit the selection criteria before 2012 and 18 trials (out of 3,473) after, representing a relative decrease of 32%. We found that visibility, media exposure and strength of the recommendation were related to a decrease in registered trials. Conclusions Recommendations not to conduct further RCTs might reduce the number of trials registered if these recommendations are strongly worded and combined with social media attention.
Learn More >Chronic pain is a major comorbidity of chronic inflammatory diseases. Here, we report that the cytokine IL-1β, which is abundantly produced during multiple sclerosis (MS), arthritis (RA), and osteoarthritis (OA) both in humans and in animal models, drives pain associated with these diseases. We found that the type 1 IL-1 receptor (IL-1R1) is highly expressed in the mouse and human by a subpopulation of TRPV1+ dorsal root ganglion neurons specialized in detecting painful stimuli, termed nociceptors. Strikingly, deletion of the Il1r1 gene specifically in TRPV1+ nociceptors prevented the development of mechanical allodynia without affecting clinical signs and disease progression in mice with experimental autoimmune encephalomyelitis and K/BxN serum transfer-induced RA. Conditional restoration of IL-1R1 expression in nociceptors of IL-1R1-knockout mice induced pain behavior but did not affect joint damage in monosodium iodoacetate-induced OA. Collectively, these data reveal that neuronal IL-1R1 signaling mediates pain, uncovering the potential benefit of anti-IL-1 therapies for pain management in patients with chronic inflammatory diseases.
Learn More >The use of exercise is a potential treatment option to modulate pain (exercise-induced hypoalgesia). The pain threshold (PT) response is a measure of pain sensitivity that may be a useful marker to assess the effect of physical exercise on pain modulation.
Learn More >Two factors related to the continuation of persistent pain are pain catastrophizing and illness perceptions. Pain neuroscience education is known to positively influence both in patients with persistent pain. As the integration of pain neuroscience education in monodisciplinary physiotherapy treatments is effective, integration in transdisciplinary cognitive-behavioral treatments seems recommendable. When doing so, the moderating effect of pain catastrophizing and perceptions on treatment results have to be examined, as these provide valuable information under which conditions treatment works. A bottom-up retrospective observational study evaluated the changes in clinical outcomes, and relationships between clinical outcomes and cognitive and emotional factors in patients with persistent pain. Multiple regression analysis, PROCESS macro, explored the moderating effects of pain catastrophizing on the relationship between illness perceptions and self-reported symptoms of central sensitization. In total, 78 patients were included in the study. A correlation between pretreatment scores and change scores in illness perceptions and self-reported symptoms of central sensitization following treatment were found (resp. R-sq 0.407, F(10,99) = 0.638, P = 0.000; R-sq 0.361, F(5, 54) = 0.609, P = 0.000; and R-sq 0.314, F(4,55) = 0.560, P = 0.00), however, moderation of pain catastrophizing scores on these correlations was not found. Even though an association between changes in pain catastrophizing and illness perceptions in patients with persistent pain was found, the direction or strength between the changes in illness perceptions and changes in self-reported symptoms of central sensitization was not influenced by pretreatment scores of pain catastrophizing.
Learn More >Pain permeates childhood and remains inadequately and/or inconsistently managed. Existing research and clinical practice guidelines have largely focused on factors influencing the immediate experience of pain. The need for and benefits of preparing children for future pain (e.g., painful procedures) has been well established. Despite being a robust predictor of future pain and distress, memories of past painful experiences remain overlooked in pediatric pain management. Just as autobiographical memories prepare us for the future, children's memories for past pain can be harnessed to prepare children for future painful experiences. Children's pain memories are malleable and can be reframed to be less distressing, thus reducing anticipatory distress and promoting self-efficacy. Parents are powerful agents of change in the context of pediatric pain and valuable historians of children's past painful experiences. They can alter children's pain memories to be less distressing simply by talking, or reminiscing, about past pain. This narrative review summarizes existing research on parent-child reminiscing in the context of acute and chronic pediatric pain and argues for incorporation of parent-child reminiscing elements into preparatory interventions for painful procedures.
Learn More >Peer support has found applications beyond the mental health field and is useful for managing several chronic disorders and supporting healthy lifestyle choices. Communication through telephone and the Internet allows for greater access to those who cannot meet in person. Adolescent chronic pain would seem ideally suited to benefit from online peer support groups. Research is lacking, however, to characterize benefit in terms of pain and function, despite a clear desire among adolescents for access to such programs. More rapid development of online applications is needed for peer support, and research into the associated outcomes will be necessary to optimally design such programs.
Learn More >Autism spectrum disorder is characterized by neurological, psychiatric and medical comorbidities-some conditions co-occur so frequently that comorbidity in autism is the rule rather than the exception. The most common autism co-occurring conditions are intellectual disability, language disorders, attention-deficit hyperactivity disorder, epilepsy, gastrointestinal problems, sleep disorders, anxiety, depression, obsessive-compulsive disorder, psychotic disorders, oppositional defiant disorder, and eating disorders. They are well known and studied. Migraine is the most common brain disease in the world, but surprisingly only a few studies investigate the comorbidity between autism and migraine. The aim of this narrative review is to explore the literature reports about the comorbidity between autism and migraine and to investigate the common neurotransmitter, immune, anatomical and genetic abnormalities at the base of these two conditions.
Learn More >The US opioid crisis and increasing prescription rates in Europe suggest inappropriate risk perceptions and behaviours of people who prescribe, take or advise on opioids: physicians, patients and pharmacists. Findings from cognitive and decision science in areas other than drug safety suggest that people's risk perception and behaviour can differ depending on whether they learnt about a risk through personal experience or description. xperiencing the isk of overutilising pioids among patients with chronic on-cancer pain in mbulatory care (ERONA) is the first-ever conducted trial that aims at investigating the effects of these two modes of learning on individuals' risk perception and behaviour in the long-term administration of WHO-III opioids in chronic non-cancer pain.
Learn More >Itch is a cardinal feature of pediatric disorders and can impair quality of life. However, few studies have addressed symptoms and impacts of itch in pediatric patients.
Learn More >Chronic pain often predicts the onset of psychological distress. Symptoms including anxiety and depression after pain chronification reportedly are caused by brain remodeling/recruitment of the limbic and reward/aversion circuitries. Pain is the primary precipitating factor that has caused opioid overprescribing and continued overuse of opioids leading to the current opioid epidemic. Yet experimental pain therapies often fail in clinical trials. Better understanding of underlying pathologies contributing to pain chronification is needed to address these chronic pain related issues. In the present study, a chronic neuropathic pain model persisting 10 weeks was studied. The model develops both anxiety- and pain-related behavioral measures to mimic clinical pain. The manganese-enhanced magnetic resonance imaging (MEMRI) utilized improved MRI signal contrast in brain regions with higher neuronal activity in the rodent chronic constriction trigeminal nerve injury (CCI-ION) model. T1-weighted MEMRI signal intensity was increased compared to controls in supraspinal regions of the anxiety and aversion circuitry, including anterior cingulate gyrus (ACC), amygdala, habenula, caudate, and dorsomedial periaqueductal gray (PAG). Despite continuing mechanical hypersensitivity, MEMRI T1 signal intensity as the neuronal activity measure, was not significantly different in thalamus and decreased in somatosensory cortex (S1BF) of CCI-ION rats compared to naïve controls. This is consistent with decreased fMRI BOLD signal intensity in thalamus and cortex of patients with longstanding trigeminal neuropathic pain reportedly associated with grey matter volume decrease in these regions. Significant increase in MEMRI T2 signal intensity in thalamus of CCI-ION animals was indication of tissue water content, cell dysfunction and/or reactive astrogliosis. Decreased T2 signal intensity in S1BF cortex of rats with CCI-ION was similar to findings of reduced T2 signals in clinical patients with chronic orofacial pain indicating prolonged astrocyte activation. These findings support use of MEMRI and chronic rodent models for preclinical studies and therapeutic trials to reveal brain sites activated only after neuropathic pain has persisted in timeframes relevant to clinical pain and to observe treatment effects not possible in short-term models which do not have evidence of anxiety-like behaviors. Potential improvement is predicted in the success rate of preclinical drug trials in future studies with this model.
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