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Migraine is a prevalent primary headache disorder and is usually considered as benign. However, structural and functional changes in the brain of individuals with migraine have been reported. High frequency of white matter abnormalities, silent infarct-like lesions, and volumetric changes in both gray and white matter in individuals with migraine compared to controls have been demonstrated. Functional magnetic resonance imaging (MRI) studies found altered connectivity in both the interictal and ictal phase of migraine. MR spectroscopy and positron emission tomography studies suggest abnormal energy metabolism and mitochondrial dysfunction, as well as other metabolic changes in individuals with migraine. In this review, we provide a brief overview of neuroimaging studies that have helped us to characterize some of these changes and discuss their limitations, including small sample sizes and poorly defined control groups. A better understanding of alterations in the brains of patients with migraine could help not only in the diagnosis but may potentially lead to the optimization of a targeted anti-migraine therapy.
Learn More >We aimed to examine 1) the relationship between multifocal pain and clinical characteristics, including demographics, pain outcomes, somatic symptoms, health-related quality of life, depression, and anxiety, and 2) whether multifocal pain was independently associated with treatment response.
Learn More >Clinimetric cross-sectional cohort study in adults with paraplegic spinal cord injury (SCI) and neuropathic pain (NP).
Learn More >Epidemiology of chronic pain in children and adolescents: a protocol for a systematic review update.
Chronic pain, defined as persistent or recurring pain or pain lasting longer than 3 months, is a common childhood problem and can profoundly impact children's physical, psychological and social functioning. The last comprehensive systematic review estimating the prevalence of chronic pain in children and adolescents was published in 2011. Since then, the literature on paediatric chronic pain has grown substantially. This manuscript outlines a protocol for an updated systematic review to provide updated estimates of the prevalence of various forms of chronic pain in children and adolescence. The review will also examine the relationship between sociodemographic and psychosocial factors related to chronic pain prevalence.
Learn More >Erenumab is a monoclonal antibody against calcitonin gene-related peptide receptors, which showed efficacy in migraine attack prevention. The aims of the present pilot study were to i) evaluate the effect of single dose of Erenumab 70 mg on laser evoked potentials from trigeminal and brachial stimulation in a cohort of migraine patients; ii) correlate the neurophysiological changes with clinical outcome after 3 months' treatment.
Learn More >Functional dyspepsia (FD) is associated with both chronic gastrointestinal distress and anxiety and depression. Here, we hypothesized that aberrant gastric signals, transmitted by the vagus nerve, may alter key brain regions modulating affective and pain behavior. Using a previously validated rat model of FD characterized by gastric hypersensitivity, depression- and anxiety-like behavior, we found that vagal activity in response to gastric distention was increased in FD rats. The FD phenotype was associated with gastric mast cell hyperplasia and increased expression of corticotrophin-releasing factor (CRF) and decreased brain-derived neurotrophic factor in the central amygdala. Subdiaphragmatic vagotomy reversed these changes and restored affective behavior to that of controls. Vagotomy partially attenuated pain responses to gastric distention, which may be mediated by central reflexes in the periaqueductal gray, as determined by local injection of lidocaine. Ketotifen, a mast cell stabilizer, reduced vagal hypersensitivity, normalized affective behavior and attenuated gastric hyperalgesia. In conclusion, vagal activity, partially driven by gastric mast cells, induces long-lasting changes in CRF signaling in the amygdala that may be responsible for enhanced pain and anxiety- and depression-like behaviors. Together, these results support a "bottom-up" pathway involving the gut-brain axis in the pathogenesis of both gastric pain and psychiatric co-morbidity in FD.
Learn More >Painful stimuli evoke a mixture of sensations, negative emotions and behaviors. These myriad effects are thought to be produced by parallel ascending circuits working in combination. Here we describe a pathway from spinal cord to brain for ongoing pain. Activation of a subset of spinal neurons expressing Tacr1 evokes a full repertoire of somatotopically-directed pain-related behaviors in the absence of noxious input. Tacr1 projection neurons (expressing NKR1) target a tiny cluster of neurons in the superior lateral parabrachial nucleus (PBN-SL). We showed that these neurons, which also express Tacr1 (PBN-SL), are responsive to sustained but not acute noxious stimuli. Activation of PBN-SL neurons alone did not trigger pain responses but instead served to dramatically heighten nocifensive behaviors and suppress itch. Remarkably, mice with silenced PBN-SL neurons ignored long-lasting noxious stimuli. Together, these data reveal new details about this spinoparabrachial pathway and its key role in the sensation of ongoing pain.
Learn More >: The prevalence of inadequate treatments for chronic pain has necessitated the search for biological factors that influence the transition to chronicity. : Antecubital blood was drawn from those who experienced acute, noncatastrophic musculoskeletal trauma. Follow-up occurred at 1, 3, 6, and 12 months with the primary outcome being Brief Pain Inventory (BPI) Functional Interference scores. Eight markers were chosen for latent profile analysis: brain-derived neurotrophic factor (BDNF); transforming growth factor-beta 1 (TGF-β1); C-reactive protein (CRP); tumor necrosis factor-alpha (TNF-α); interleukins (ILs) 1-beta, 6, and 10; and the stress hormone cortisol. : Mean age of the 106 participants was 44.6 years and 58.5% were female. The final model indicated a three-class solution that could be adequately described by three of the eight markers: class 1 = low concentration of all markers (33.9% of the sample), class 2 = average concentration of all markers (47.7%), and class 3 = high concentration of BDNF and TGF-β1 (18.3%). BPI Pain Interference scores captured at both inception and 6-month follow-up were compared across the three groups. Mean scores were significantly higher in class 3 for the BPI Interference subscale at inception (27.0 [SD 16.4] vs. 35.8 [SD 17.3], = 0.05) and at 6-month follow-up (2.2 [SD 4.8] vs. 7.3 [SD 10.7], = 0.03) compared to those of the other two classes. : Although recovered populations are not significantly different in BDNF and TGF-β1 levels, those who experience persisting disability are more likely to have moderate to high levels in serum.
Learn More >Clinicians have an increasing number of evidence-based interventions to treat pain in youth. Mediation analysis offers a way of investigating how interventions work, by examining the extent to which an intermediate variable, or mediator, explains the effect of an intervention. This systematic review examined studies that used mediation analysis to investigate mechanisms of interventions on pain-relevant outcomes for youth (3-18 years) with acute or chronic pain, and provides recommendations for future mediation research in this field. We searched five electronic databases for clinical trials or observational longitudinal studies that included a comparison group and conducted mediation analyses of interventions on youth and assessed pain outcomes. We found six studies ( = 635), which included a total of 53 mediation models examining how interventions affect pain-relevant outcomes for youth. Five studies were secondary analyses of randomized controlled trials of psychological interventions for chronic pain; one was a longitudinal observational study of morphine for acute pain. The pain conditions studied were irritable bowel syndrome, functional abdominal pain, juvenile fibromyalgia, mixed chronic pain, and post-operative pain. Fourteen putative mediators were tested, of which three partially mediated treatment effect; seven did not significantly mediate treatment effect and four had mixed results. Methodological and reporting limitations were common. There are substantial gaps in the field with respect to investigating, and therefore understanding, how paediatric interventions work.
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