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The University of Washington instituted a policy requiring all credentialed clinicians who prescribe opioids to complete a one-time education activity about safe and responsible opioid prescribing. A scenario-based, interactive online learning module was developed for opioid management of acute pain in hospitalized adults. This study examined the impact of the education module on learners' knowledge, perceived competence, and use of guideline-adherent practices.
Learn More >Pediatric patients with chronic musculoskeletal conditions such as idiopathic scoliosis awaiting surgical correction can experience pain that interferes with their daily functioning. Reports of this interference are commonly gathered from patients through the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference Scale and through parent-proxy scores. However, the child and parent/caregiver reports vary. In order to provide appropriate treatment for young patients with pain, the nature of the discrepancies and under which circumstances the reports differ needs to be understood. This report offers new information on the level of concordance among parent and child report of pain interference within this patient population, and which parent and child characteristics may influence concordance rates.
Learn More >Remifentanil is commonly used clinically for perioperative pain relief, but it may induce postoperative hyperalgesia. Low doses of ketamine have remained a common choice in clinical practice, but the mechanisms of ketamine have not yet been fully elucidated. In this study, we examined the possible effects of ketamine on calcium/calmodulin-dependent protein kinase II α (CaMKIIα) and N-methyl-d-aspartate receptor (NMDAR) subunit NR2B in a mouse model of remifentanil-induced postoperative hyperalgesia (RIPH) in the primary somatosensory cerebral cortex (SI) region. The paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were used to assess mechanical allodynia and thermal hyperalgesia, respectively, before and after intraoperative remifentanil administration. Before surgery, mice received intrathecal injections of the following drugs: ketamine, NMDA, BayK8644 (CaMKII activator), and KN93 (CaMKII inhibitor). Immunofluorescence was performed to determine the anatomical location and expression of activated CaMKIIα, phosphorylated CaMKIIα (p-CaMKIIα). Additionally, western blotting was performed to assess p-CaMKIIα and NMDAR expression levels in the SI region. Remifentanil decreased the PWMT and PWTL at 0.5 h, 2 h, and 5 h and increased p-CaMKIIα expression in the SI region. Ketamine increased the PWMT and PWTL and reversed the p-CaMKIIα upregulation. Both BayK8644 and NMDA reversed the effect of ketamine, decreased the PWMT and PWTL, and upregulated p-CaMKIIα expression. In contrast, KN93 enhanced the effect of ketamine by reducing hyperalgesia and downregulating p-CaMKIIα expression. These results suggested that ketamine reversed RIPH by inhibiting the phosphorylation of CaMKIIα and the NMDA receptor in the SI region in mice.
Learn More >Since 2016, 35 of 50 U.S. states have passed opioid-limiting laws. The impact on postoperative opioid prescribing and secondary outcomes following ACDF remains unknown.
Learn More >The aims of this study review were to: systematically identify the current evidence base of randomised controlled trials (RCTs) of spinal cord stimulation (SCS) placebo (or 'sham') trials for neuropathic pain and (2) to undertake a meta-analysis to investigate the effectiveness of SCS when compared with a placebo comparator arm. Electronic databases were searched from inception until January 2019 for RCTs of SCS using a placebo/sham control. Searches identified eight eligible placebo-controlled randomised trials of SCS for neuropathic pain. Meta-analysis shows a statistically significant reduction in pain intensity during the active stimulation treatment periods compared to the control treatment periods; pooled mean difference -1.15 (95% confidence interval -1.75 to -0.55, p=0.001) on a 10-point scale. Exploratory study level subgroup analysis suggests a larger treatment effect in RCTs using a placebo control (defined as studies where the device was inactive and at least one of the study procedures was different between the arms) than a sham control (defined as all study procedures being equal between arms including SCS device behaviour). Our findings demonstrate limited evidence that SCS is effective in reducing pain intensity when compared to a placebo intervention. Our analyses suggest that the magnitude of treatment effect varies across trials and, in part, depends on the quality of patient blinding and minimisation of carryover effects. Improved reporting and further methodological research is needed into placebo and blinding approaches in SCS trials. Furthermore, we introduce a differentiation between placebo and sham concepts that may be generalisable to trials evaluating surgical or medical procedures.
Learn More >Sinusoidal current stimuli preferentially activate C-nociceptors. Sodium channel isoforms NaV1.7 and NaV1.8 have been implicated in this. Sympathetic efferent neurons lack NaV1.8 and were explored upon sinusoidal activation.
Learn More >The recent availability of paraesthesia/sensation free spinal cord stimulation (SCS) modalities allow the design of clinical trials of SCS using placebo/sham controls and blinding of patients, clinicians, and researchers. The aims of this study were to: 1) systematically review the current evidence base of randomized controlled trials (RCTs) of SCS placebo/sham trials and 2) to undertake a methodological critique of their methods. Based on this critique, we developed a checklist for the design and reporting of future RCTs of SCS.
Learn More >Breast cancer is one of the most commonly diagnosed cancers among women, and since the prognosis of breast cancer has substantially improved in past decades, complications of management are becoming increasingly apparent. Persistent pain lasting greater than 3 months after breast cancer surgery is unfortunately a common complication affecting approximately 30% of patients after tumour resection. Persistent breast cancer pain has neuropathic features and is typically mild-to-moderate in intensity, with approximately 10% suffering from severe pain. There is an increasing need to prevent persistent pain through the use of transitional pain programmes and perioperative interventions, and to identify novel treatment modalities to reduce suffering in those who unfortunately develop persistent pain. This review serves to provide an overview on persistent pain after breast cancer surgery, its pathophysiology, and current management strategies.
Learn More >Central post-stroke pain (CPSP) can occur after stroke in the somatosensory pathway that includes the posterolateral region of the thalamus. Tactile allodynia, in which innocuous tactile stimuli are perceived as painful, is common in patients with CPSP. Previous brain imaging studies have reported plastic changes in brain activity in patients with tactile allodynia after stroke, but a causal relationship between such changes and the symptoms has not been established. We recently developed a non-human primate (macaque) model of CPSP based on thalamic lesions, in which the animals show behavioral changes consistent with the occurrence of tactile allodynia. Here we performed functional magnetic resonance imaging under propofol anesthesia to investigate the changes in brain activation associated with the allodynia in this CPSP model. Before the lesion, innocuous tactile stimuli significantly activated the contralateral sensorimotor cortex. When behavioral changes were observed after the thalamic lesion, equivalent stimuli significantly activated pain-related brain areas, including the posterior insular cortex (PIC), secondary somatosensory cortex (SII), anterior cingulate cortex (ACC), and amygdala. Moreover, when either PIC/SII or ACC was pharmacologically inactivated, the signs of tactile allodynia were dampened. Our results show that increased cortical activity plays a role in CPSP-induced allodynia.
Learn More >The individual and social burdens associated with chronic pain have been escalating globally. Accurate pain measurement facilitates early diagnosis, disease progression monitoring and therapeutic efficacy evaluation, thus is a key for the management of chronic pain. Although the "golden standards" of pain measurement are self-reported scales in clinical practice, the reliability of these subjective methods could be easily affected by patients' physiological and psychological status, as well as the assessors' predispositions. Therefore, objective pain assessment has attracted substantial attention recently. Previous studies of functional magnetic resonance imaging (fMRI) revealed that certain cortices and subcortical areas are commonly activated in subjects suffering from pain. Dynamic pain connectome analysis also found various alterations of neural network connectivity that are correlated with the severity of clinical pain symptoms. Electroencephalograph (EEG) demonstrated suppressed spontaneous oscillations during pain experience. Spectral power and coherence analysis of EEG also identified signatures of different types of chronic pain. Furthermore, fMRI and EEG can visualize objective brain activities modulated by analgesics in a mechanism-based way, thus bridge the gaps between animal studies and clinical trials. Using fMRI and EEG, researchers are able to predict therapeutic efficacy and identify personalized optimal first-line regimens. In the future, the emergence of magnetic resonance spectroscopy and cell labelling in MRI would encourage the investigation on metabolic and cellular pain biomarkers. The incorporation of machine learning algorithms with neuroimaging or behavior analysis could further enhance the specificity and accuracy of objective pain assessments.
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