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Local inflammation in the joint is considered to contribute to osteoarthritis (OA) progression. Here, we describe an immunomodulating nanoparticle for OA treatment. Intradermal injection of lipid nanoparticles (LNPs) loaded with type II collagen (Col II) and rapamycin (LNP-Col II-R) into OA mice effectively induced Col II-specific anti-inflammatory regulatory T cells, substantially increased anti-inflammatory cytokine expression, and reduced inflammatory immune cells and proinflammatory cytokine expression in the joints. Consequently, LNP-Col II-R injection inhibited chondrocyte apoptosis and cartilage matrix degradation and relieved pain, while injection of LNPs loaded with a control peptide and rapamycin did not induce these events. Adoptive transfer of CD4CD25 T cells isolated from LNP-Col II-R-injected mice suggested that T induced by LNP-Col II-R injection were likely responsible for the therapeutic effects. Collectively, this study suggests nanoparticle-mediated immunomodulation in the joint as a simple and effective treatment for OA.
Learn More >Due to its opioid and non-opioid mechanism of action, tapentadol is considered an atypical opioid with improved gastrointestinal tolerability versus traditional opioids. As for all opioid analgesics it is important to understand how to discontinue a treatment when it is not needed anymore. The aim of this article was to provide an overview of opioid therapy in non-cancer pain, with a specific focus on tapering of tapentadol in patients with chronic non-cancer pain, and suggestions on how to achieve tapering.
Learn More >We hypothesized that the high-dose opioid requirement in patients carrying the rs4680-GG variant in the COMT gene encoding catechol-O-methyltransferase would be greater for patients taking morphine than for those taking oxycodone, thus providing a much-needed biomarker to inform opioid selection for cancer pain.
Learn More >Recent studies showed that balanced opioid-free anesthesia is feasible and desirable in several surgical settings. However, in thoracic surgery, scientific evidence is still lacking. Thus, we conducted the first systematic review and meta-analysis of opioid-free anesthesia in this field.
Learn More >To assess the burden and consequences of migraine in Brazil in terms of health-related quality of life (HRQoL), work productivity and daily activities, and healthcare resource utilization (HRU).
Learn More >(1) Background: To assess the time trend in the prevalence of chronic neck pain (CNP), chronic low back pain (CLBP), and migraine or frequent headache (MFH) among people with diabetes in Spain from 2014 to 2020, this study identified sex differences and compared the prevalence of these pain sites between people with diabetes and age-sex-matched non-diabetic subjects. (2) Methods: The study design included a cross-sectional and a case-control study. The data were obtained from the European Health Interview Surveys for Spain conducted in 2014 and 2020. The presence of diabetes, CNP, CLBP, and MFH was self-reported. Study covariates included sociodemographic characteristics, comorbidities, lifestyles, and pain-related variables. (3) Results: Among people with diabetes, the prevalence of CNP, CLBP, and MFH did not improve from 2014 to 2020. Women with diabetes had a significantly higher prevalence of all the pain sites analyzed than men with diabetes. After matching by sex and age, the prevalence of CNP (26.0% vs. 21.1%; < 0.001), CLBP (31.2% vs. 25.0%; < 0.001), and MFH (7.7% vs. 6.5%; = 0.028) was higher for people with diabetes than for those without diabetes. Self-reported mental disease was independently associated with reporting the three pain sites analyzed in people with diabetes. (4) Conclusions: The prevalence of CNP, CLBP, and MFH has remained stable over time. Remarkable sex differences were found, with a higher prevalence among women than men with diabetes. Diabetes was associated with reporting in all the pain sites analyzed. Self-reported mental disease was associated with reporting CNP, CLBP, and MFH.
Learn More >Observational studies suggest that 25-hydroxy vitamin D (25(OH)D) concentration is inversely associated with pain. However, findings from intervention trials are inconsistent. We assessed the effect of vitamin D supplementation on pain using data from a large, double-blind, population-based, placebo-controlled trial (the D-Health Trial). 21,315 participants (aged 60-84 years) were randomly assigned to a monthly dose of 60,000 IU vitamin D3 or a matching placebo. Pain was measured using the 6-item Pain Impact Questionnaire (PIQ-6), administered 1, 2 and 5 years after enrollment. We used regression models (linear for continuous PIQ-6 score and log-binomial for binary categorizations of the score, namely 'some or more pain impact' and 'presence of any bodily pain') to estimate the effect of vitamin D on pain. We included 20,423 participants who completed ≥1 PIQ-6. In blood samples collected from 3943 randomly selected participants (∼800 per year) the mean (SD) 25(OH)D concentrations were 77 (SD 25) and 115 (SD 30) nmol/L in the placebo and vitamin D groups, respectively. Most (76%) participants were predicted to have 25(OH)D concentration >50 nmol/L at baseline. The mean PIQ-6 was similar in all surveys (∼50.4). The adjusted mean difference in PIQ-6 score (vitamin D cf placebo) was 0.02 (95% CI, -0.20 to 0.25). The proportion of participants with some or more pain impact and with presence of bodily pain was also similar between groups (both prevalence ratios 1.01, 95% CI 0.99 to 1.03). In conclusion, supplementation with 60,000 IU of vitamin D3 per month had negligible effect on bodily pain.
Learn More >Fibromyalgia (FM) is characterized by chronic and generalized musculoskeletal pain. There is currently no cure for FM, but alternative treatments are available. Among them, gradual strength training programs (ST) which on daily activities are a valid option to improve some of the pronounced symptoms of FM that affect quality of life, such as fatigue, pain, sleep quality, and physical function. However, there is a need for more information on optimal training programs to improve anxiety and fatigue symptoms.
Learn More >The TWIK-related spinal cord K channel (TRESK) is part of the two-pore domain K channel family (K), which are also called leak potassium channels. As indicated by the channel family name, TRESK conducts K ions along the concentration gradient in a nearly voltage-independent manner leading to lowered membrane potentials. Although functional and pharmacological similarities exist, TRESK shows low sequence identity with other K channels. Moreover, the channel possesses several unique features such as its sensitivity to intracellular Ca ions, that are not found in other K2P channels. High expression rates are found in immune-associated and neuronal cells, especially in sensory neurons of the dorsal root and trigeminal ganglia. As a consequence of the induced hyperpolarization, TRESK influences neuronal firing, the release of inflammatory mediators and the proliferation of distinct immune cells. Consequently, this channel might be a suitable target for pharmacological intervention in migraine, epilepsy, neuropathic pain or distinct immune diseases. In this review, we summarize the biochemical and biophysical properties of TRESK channels as well as their sensitivity to different known compounds. Furthermore, we give a structured overview about the physiological and pathophysiological impact of TRESK, that render the channel as an interesting target for specific drug development.
Learn More >Neuropathic pain (NP) is a chronic disease caused by damage to the peripheral or central nervous system. Connexin 43 (Cx43), the primary connexin expressed by astrocytes, has been reported to be significantly increased in NP. However, the roles and mechanisms of Cx43 in the development and maintenance of NP remain largely unknown, while microglia activation has been commonly regarded as a key factor of NP. In the present study, we found that Cx43 deletion significantly ameliorated spared nerve injury (SNI)-induced NP and suppressed SNI induced c-Fos expression in the spinal cord. Notably, Cx43 deletion led to much less SNI-induced microglia activation in the spinal cord. These results suggest that astrocyte Cx43 may play a significant role in regulating microglial activation and NP.
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