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Opioid-related deaths continue to increase in North America, an epidemic that was initiated by high rates of opioid prescribing. We designed a multifaceted, theory-informed Opioid Self-Assessment (OSA) package, to increase adherence to the Canadian Opioid Guideline among family physicians. This study aimed to assess changes in Canadian family physicians' knowledge and practices after completing the OSA package.
Slow deep breathing (SDB) is commonly employed in the management of pain, but the underlying mechanisms remain equivocal. This study sought to investigate effects of instructed breathing patterns on experimental heat pain and to explore possible mechanisms of action. In a within-subject experimental design, healthy volunteers (n = 48) performed four breathing patterns: 1) unpaced breathing (UB), 2) paced breathing at the participant's spontaneous breathing frequency (PB), 3) SDB at six breaths per minute with a high inspiration/expiration ratio (SDB-H), and 4) SDB at six breaths per minute with a low inspiration/expiration ratio (SDB-L). During presentation of each breathing pattern, participants received painful heat stimuli of three different temperatures and rated each stimulus on pain intensity. Respiration, heart rate, and blood pressure were recorded. Compared to UB, participants reported less intense pain during each of the three instructed breathing patterns. Among the instructed breathing patterns, pain did not differ between PB and SDB-H, and SDB-L attenuated pain more than the PB and SDB-H patterns. The latter effect was paralleled by greater blood pressure variability and baroreflex effectiveness index during SDB-L. Cardiovascular changes did not mediate the observed effects of breathing patterns on pain. Perspective: SDB is more efficacious to attenuate pain when breathing is paced at a slow rhythm with an expiration that is long relative to inspiration, but the underlying mechanisms remain to be elucidated.
To characterize phenotypes of a novel CACNA1A mutation causing familial hemiplegic migraine type 1.
Nausea and vomiting are often associated with opioid analgesia in cancer patients; however, only a subset of patients develop such side effects. Here, we tested the hypothesis that the occurrence of nausea and vomiting is modulated by the genetic background of the patients. Whole exome sequencing of DNA pools from patients with either low (n = 937) or high (n = 557) nausea and vomiting intensity, recruited in the European Pharmacogenetic Opioid Study, revealed a preliminary association of 53 polymorphisms. PCR-based genotyping of 45 of these polymorphisms in the individual patients of the same series confirmed the association for six SNPs in AIM1L, CLCC1, MUC16, PDE3A, POM121L2, and ZNF165 genes. Genotyping of the same 45 polymorphisms in 264 patients of the Italian CERP study, also treated with opioids for cancer pain, instead confirmed the association for two SNPs in ZNF568 and PDE3A genes. Only one SNP, rs12305038 in PDE3A, was confirmed in both series, although with opposite effects of the minor allele on the investigated phenotype. Overall, our findings suggest that genetic factors are indeed associated with nausea and vomiting in opioid-treated cancer patients, but the role of individual polymorphisms may be weak.
To investigate the functional connectivity (FC) in nonacute sciatica and the neuronal correlation of acupuncture analgesia.
Ketamine has recently emerged as a promising therapeutic alternative for abortive migraine therapy, likely secondary to N-methyl-d-aspartate antagonism. Most reports examine adults and the intravenous route. Fewer utilize intranasal administration or pediatric populations. Given the limited evidence for intranasal ketamine in pediatric migraine populations, we retrospectively reviewed our experience to further characterize safety and efficacy of intranasal ketamine in this population.
The evolution of peripheral and central changes following a peripheral nerve injury imply the onset of afferent signals that affect the brain. Changes to inflammatory processes may contribute to peripheral and central alterations such as altered psychological state and are not well characterized in humans. We focused on four elements that change peripheral and central nervous systems following ankle injury in 24 adolescent patients and 12 age-sex matched controls. Findings include (a) Changes in tibial, fibular, and sciatic nerve divisions consistent with neurodegeneration; (b) Changes within the primary motor and somatosensory areas as well as higher order brain regions implicated in pain processing; (c) Increased expression of fear of pain and pain reporting; and (d) Significant changes in cytokine profiles relating to neuroinflammatory signaling pathways. Findings address how changes resulting from peripheral nerve injury may develop into chronic neuropathic pain through changes in the peripheral and central nervous system.
Dorsal root ganglion (DRG) neurons detect sensory inputs and are crucial for pain processing. They are often studied in vitro as dissociated cell cultures with the assumption that this reasonably represents in vivo conditions. However, to the best of our knowledge, no study has directly compared genome-wide transcriptomes of DRG tissue in vivo versus in vitro or between laboratories and culturing protocols. Comparing RNA sequencing-based transcriptomes of native to cultured (4 days in vitro) human or mouse DRG, we found that the overall expression levels of many ion channels and G-protein-coupled receptors specifically expressed in neurons are markedly lower although still expressed in culture. This suggests that most pharmacological targets expressed in vivo are present under the condition of dissociated cell culture, but with changes in expression levels. The reduced relative expression for neuronal genes in human DRG cultures is likely accounted for by increased expression of genes in fibroblast-like and other proliferating cells, consistent with their mitotic status in these cultures. We found that the expression of a subset of genes typically expressed in neurons increased in human and mouse DRG cultures relative to the intact ganglion, including genes associated with nerve injury or inflammation in preclinical models such as BDNF, MMP9, GAL, and ATF3. We also found a striking upregulation of a number of inflammation-associated genes in DRG cultures, although many were different between mouse and human. Our findings suggest an injury-like phenotype in DRG cultures that has important implications for the use of this model system for pain drug discovery.
Fibromyalgia (FM), the most frequently encountered cause of widespread musculoskeletal pain, affects an estimated 2% of the general Italian population. However, it is not a homogeneous clinical entity, and a number of interacting factors can influence patient prognosis and the outcomes of standardised treatment programmes. Registries are a source of high-quality data for clinical research, but relating this information to individual patients is technically challenging. The aim of this article is to describe the structure and objectives of the first Italian Fibromyalgia Registry (IFR), a new web-based registry of patients with FM.
Research in adult populations indicates that several sociodemographic and environmental variables increase risk for pain and poor outcomes. There is little research exploring the impact of household income, health insurance coverage, barriers to health care, neighborhood and school safety, violence experienced, and neighborhood isolation on pediatric chronic pain. Data from the Add Health Study, a longitudinal examination of a nationally-representative adolescent sample were analyzed. The relationships between demographic variables, risk factors, chronic pain, and long-term health outcomes were examined. Adolescents with chronic pain had lower income, more health care barriers, greater safety concerns, and experienced more violence compared to those without pain. In a model together, female sex, White race/ethnicity, and greater health care barriers, safety concerns, and violence exposure conferred significant risk for chronic pain. Additional analyses revealed nuances in the strength of risk factors between racial/ethnic groups. Systemic health care barriers were significantly associated with chronic pain and may delay symptom alleviation and return to functioning. Considering access to care is necessary in prevention efforts. Among adolescents with chronic pain, greater safety concerns predicted poor mental health outcomes, particularly for White females. The cumulative stress of environmental concerns, such as safety, and managing chronic pain may worsen functioning. PERSPECTIVE: Adolescents with chronic pain had lower income, and more health care barriers, safety concerns, and violence exposure compared to those without chronic pain. Access to care is a significant problem in youth with chronic pain. The relationships between race/ethnicity, risk factors, and health outcomes is complex and requires additional research.