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The aim of the study was to investigate patient satisfaction amongst academic pain management centers and associated factors.
Learn More >Preclinical studies demonstrate that sleep disruption diminishes morphine analgesia and modulates reward processing. We sought to translate these preclinical findings to humans by examining whether sleep disruption alters morphine's analgesic and hedonic properties. We randomized 100 healthy adults to receive morphine versus placebo after two nights of undisturbed sleep (US) and two nights of forced awakening (FA) sleep disruption. Sleep conditions were counterbalanced, separated by a two-week washout. The morning after both sleep conditions, we tested cold pressor pain tolerance before and 40-min after double-blind injection of .08 mg/kg morphine or placebo. The primary outcome was the analgesia index, calculated as the change in cold pressor hand withdrawal latency (HWL) before and after drug injection. Secondary outcomes were ratings of feeling "high," drug "liking," and negative drug effects. We found a significant sleep condition by drug interaction on the analgesia index (95% CI - 0.57, - 0.001). After US, subjects receiving morphine demonstrated significantly longer HWL compared to placebo (95% CI 0.23, 0.65), but not after FA (95% CI - 0.05, 0.38). Morphine analgesia was diminished threefold under FA, relative to US. After FA, females (95% CI - 0.88, - 0.05), but not males (95% CI - 0.23, 0.72), reported decreased subjective "high" effects compared to US. After FA, females (95% CI 0.05, 0.27), but not males (95% CI - 0.10, 0.11), administered morphine reported increased negative drug effects compared to US. These data demonstrate that sleep disruption attenuates morphine analgesia in humans and suggest that sleep disturbed males may be at greatest risk for problematic opioid use.
Learn More >To examine the effect of sex on clinical response to triptans and to determine whether these differences are related to pharmacokinetics of triptans in men and women, we performed a systematic review and meta-analysis.
Learn More >In 2006, humans with a congenital insensitivity to pain (CIP) were found to lack functional Na 1.7 channels. In the 15 years since there has been a rush to develop selective Na 1.7 inhibitors with the goal of producing broadly effective analgesics without the problems of addiction and tolerance associated with opioids. Pharmacologically, this mission has been highly successful, leading to a number of highly potent and selective inhibitors of Na 1.7.However,there are very few examples where these inhibitors have yielded effective analgesia in preclinical pain models or human clinical trials. In this review we summarisethe role of Na 1.7 in nociception, its history as a therapeutic target, and the quest to develop potent inhibitors of this channel. Finally, we discuss possible reasons why the pain-free state seen in humans with CIP has been so elusive to recapitulate pharmacologically.
Learn More >Introduction Cluster headache [CH] is a severely disabling trigeminal autonomic cephalalgia [TAC]. Approximately 1 in 1,000 adults are affected by CH. Calcitonin gene related peptide [CGRP] is an important mediator in the pathophysiology of CH. Galcanezumab is a monoclonal antibody with an affinity for the CGRP peptide, FDA approved for prevention of episodic CH. Areas covered Search words queried were 'cluster headache', 'cluster headache and CGRP', 'cluster headache and galcanezumab'. Over 99 articles in Pubmed and prescribing information for galcanezumab was reviewed. Some of the data pertaining to CH trials with fremanezumab were reviewed using clinical trials.org. Expert opinion Galcanezumab has shown benefit in decreasing weekly frequency of CH attacks across week 1 through week 3 in patients with CH; 8.7 attacks in the galcanezumab group, as compared with 5.2 in the placebo group (95% confidence interval, 0.2 to 6.7; P = 0.04). It has a favorable risk benefit ratio. The prevention of CH with CGRP inhibition represents a novel advance for a condition with a significant unmet need. The negative trial results of galcanezumab for chronic cluster headache [CCH] may be due to the refractory nature and sheds light on the critical need to investigate the underlying biology and therapeutic options.
Learn More >Pain experience can change the central processing of nociceptive inputs, resulting in persistent allodynia and hyperalgesia. However, the underlying circuit mechanisms remain underexplored. Here, we focus on pain-induced remodeling of the projection from the mediodorsal thalamus (MD) to anterior cingulate cortex (ACC), a projection that relays spinal nociceptive input for central processing. Using optogenetics combined with slice electrophysiology, we detected in male mice that 7 days of chronic constriction injury (CCI; achieved by loose ligation of the sciatic nerve) generated AMPA receptor (AMPAR)-silent glutamatergic synapses within the contralateral MD-to-ACC projection. AMPAR-silent synapses are typically GluN2B-enriched nascent glutamatergic synapses that mediate the initial formation of neural circuits during early development. During development, some silent synapses mature and become 'unsilenced' by recruiting and stabilizing AMPARs, consolidating and strengthening the newly formed circuits. Consistent with these synaptogenic features, pain-induced generation of silent synapses was accompanied by increased densities of immature dendritic spines in ACC neurons and increased synaptic weight of GluN2B-containing NMDA receptors (NMDARs) in the MD-to-ACC projection. After prolonged (∼30 days) CCI, injury-generated silent synapses declined to low levels, which likely resulted from a synaptic maturation process that strengthens AMPAR-mediated MD-to-ACC transmission. Consistent with this hypothesis, viral-mediated knockdown of GluN2B in ACC neurons, which prevented pain-induced generation of silent synapses and silent synapse-mediated strengthening of MD-to-ACC projection after prolonged CCI, prevented the development of allodynia. Taken together, our results depict a silent synapse-mediated mechanism through which key supraspinal neural circuits that regulate pain sensitivity are remodeled to induce allodynia and hyperalgesia.
Learn More >A small number of studies have supported the efficacy of open-label placebos (OLPs) in reducing pain. However, research comparing the effectiveness of OLPs with deceptive placebos (DPs) is limited, and the relative impact on pain tolerance versus intensity are not yet understood. This study therefore, examined the effectiveness of a nasal placebo administered openly and deceptively on pain intensity and tolerance during a cold pressor test (CPT).
Learn More >Examine factors associated with post-procedure opioid receipt and persistent opioid use among opioid-naïve patients in a nationally representative sample SUMMARY BACKGROUND DATA:: We used panels 18-20 in the Medical Expenditures Panel Survey (MEPS) between the years 2013 to 2015. Respondents ages 18 and over with any self-reported procedure in the previous year with complete data on the outcome variables for the remainder of the two-year study period.
Learn More >In the last decade, machine learning has been widely used in different fields, especially because of its capacity to work with complex data. With the support of machine learning techniques, different studies have been using data-driven approaches to better understand some syndromes like mild cognitive impairment, Alzheimer's disease, schizophrenia, and chronic pain. Chronic pain is a complex disease that can recurrently be misdiagnosed due to its comorbidities with other syndromes with which it shares symptoms. Within that context, several studies have been suggesting different machine learning algorithms to classify or predict chronic pain conditions. Those algorithms were fed with a diversity of data types, from self-report data based on questionnaires to the most advanced brain imaging techniques. In this study, we assessed the sensitivity of different algorithms and datasets classifying chronic pain syndromes. Together with this assessment, we highlighted important methodological steps that should be taken into account when an experiment using machine learning is conducted. The best results were obtained by ensemble-based algorithms and the dataset containing the greatest diversity of information, resulting in area under the receiver operating curve (AUC) values of around 0.85. In addition, the performance of the algorithms is strongly related to the hyper-parameters. Thus, a good strategy for hyper-parameter optimization should be used to extract the most from the algorithm. These findings support the notion that machine learning can be a powerful tool to better understand chronic pain conditions.
Learn More >The pathophysiology of headaches associated with rhinosinusitis is poorly known. Since the generation of headaches is thought to be linked to the activation of intracranial afferents, we used an animal model to characterise spinal trigeminal neurons with nociceptive input from the dura mater and paranasal sinuses.
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