Articles: function.
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The perception of pain and ability to cope with it varies widely amongst people, which in part could be due to the presence of inhibitory (antinociceptive) or facilitatory (pronociceptive) effects in conditioned pain modulation (CPM). This study examined whether individual differences in CPM reflect functional connectivity (FC) strengths within nodes of the descending antinociceptive pathway (DAP). A heat-based CPM paradigm and resting-state functional magnetic resonance imaging (rs-fMRI) were used to test the hypothesis that an individual's capacity to exhibit inhibitory CPM (changes in test stimuli [TS] pain due to a conditioning stimulus [CS]) reflects FC of the subgenual anterior cingulate cortex (sgACC), periaqueductal gray (PAG), and rostral ventromedial medulla (RVM). ⋯ Furthermore, only the Antinociceptive subgroup exhibited a correlation of both left and right sgACC-RVM FC (medium effect sizes) with CPM effect magnitude. Women, compared with men were more likely to be categorized as pronociceptive. These data support the proposition that FC of the DAP reflects or contributes to inhibitory CPM.
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Traumatic orthopedic injuries are common and frequently associated with persistent pain, disability, and emotional distress. Risk factors of persistent pain and disability include pain catastrophizing and pain anxiety, though most interventions for orthopedic injuries are primarily biomedical (eg, surgeries, pharmacology, physiotherapy/exercise). The Toolkit for Optimal Recovery (TOR) is a brief, live video mind-body program designed to directly target pain catastrophizing and anxiety in patients with recent traumatic orthopedic injury to prevent persistent disability. ⋯ A multiple mediation analysis using multilevel structural equation modeling (MSEM) demonstrated that pain catastrophizing (b = -5.22, SE = 3.02, Bootstrapped 95% CIs = -0.04, -12.37) and pain anxiety (b = -8.45, SE = 3.59, Bootstrapped 95% CIs = -0.04, -12.37) each significantly mediated improvement in physical function. Overall, findings elucidate the mechanistic role of TOR's primary treatment targets (ie, reductions in pain catastrophizing and anxiety) in improving physical function. Findings highlight the importance of targeting pain catastrophizing and pain anxiety early after orthopedic injury through psychosocial interventions such as TOR.
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To examine recent changes in the birth prevalence of cerebral palsy in Australia; to examine the functional mobility of children with cerebral palsy by residential remoteness. ⋯ The birth prevalence of cerebral palsy declined markedly in Australia during 1995-2016, reflecting the effects of advances in maternal and perinatal care. Our findings highlight the need to provide equitable, culturally safe access to antenatal services for women, and to health and disability services for people with cerebral palsy, across Australia.
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Danon disease is a rare, X-linked, monogenic cardiomyopathy caused by mutations in the lysosomal-associated membrane 2 gene (LAMP2), which encodes the LAMP2 protein. In male patients, the predominant phenotype is progressive cardiac hypertrophy, cardiac dysfunction, and early death. There are no directed therapies for the disease. ⋯ A single infusion of RP-A501 appeared to be safe and was associated with cardiac LAMP2 expression and evidence of clinical improvement over a period of 24 to 54 months. (Funded by Rocket Pharmaceuticals; ClinicalTrials.gov number, NCT03882437.).
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Voltage-gated potassium channel subfamily q member 4 (Kcnq4) is predominantly expressed by hair cells and auditory neurons and regulates the neuronal excitability in the auditory pathway. Although it is further detected in myelinated large-diameter dorsal root ganglia (DRG) neurons in the periphery, the expression and function of Kcnq4 channel in nociceptors remains unknown. ⋯ Moreover, genetic ablation of Kcnq4 in Trpv1-positive neurons exacerbates both acute and chronic itch behavior in mice. Taken together, our results uncover a functional role of Trpv1-lineage neuron-expressing Kcnq4 channel in the modulation of itch-specific neuronal excitation in the periphery.