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The introduction of new drug classes for chronic migraine, such as monoclonal antibodies for calcitonin-gene-related peptide or its receptor (CGRPr), or antagonists of the same CGRP, have opened a new scenario in a selected population of individuals with migraine, and those presenting with chronic form of migraine in association with medication overuse. Medication overuse is now considered a complication of chronic migraine and, in fact, the treatment with CGRP(r)-MAbs of chronic migraine with medication overuse results in a clinical improvement of chronic migraine itself, accompanied by a parallel and obvious reduction in the intake of specific and non-specific acute migraine drugs. Education on the correct use of these drugs will be an essential tool to reduce the disability and costs of people suffering from CM complicated by MO, considering the long-term safety of the new therapies targeting the CGRP pathways. Only in this way can medication overuse risk can be reduced at its nadir in the scenario of chronicity of migraines.

Rheumatoid arthritis (RA) is a chronic systemic disease of connective tissue with periods of exacerbation and remission. Fatigue is excessive strain throughout the body that is disproportionate or unrelated to an activity or lifestyle. Fatigue is an integral part of RA in most patients. The study aimed to assess the level of fatigue in RA patients and establish the relationship between fatigue and demographic and clinical factors. The study group consisted of 128 RA patients according to European League Against Rheumatism (EULAR) criteria. The Functional Assessment of Chronic Illness Therapy-Fatigue and -Medical Outcomes Study Short Form 36 (SF-36) vitality scores were used to assess the severity of fatigue symptoms. The analyzed variables were gender, age, disease duration, education, marital status, place of residence, work and residence status, pharmacological treatment, pain, morning stiffness, hemoglobin, C-reactive protein (CRP), rheumatoid factor (RF), compression soreness, Richie Articular Index, and DAS28 disease activity. The examined patients experience chronic fatigue-the mean value on the FACIT-F scale was 24.1 ± 9.1 points and on the SF-36 Vitality score was 14.2 ± 1.8 points. There is a relationship between the level of fatigue and pain, long-lasting morning stiffness, active disease, increased soreness of joints, and low hemoglobin values. When analyzing the symptom of fatigue, each patient should be approached individually, using the existing questionnaires or asking key questions to recognize the situation. The presence of fatigue symptoms should be considered during therapy and patient care by searching for and eliminating additional, intensifying stimuli and increasing its level.

Balneotherapy may be a relevant treatment for chronic low back pain (LBP) in individuals > 60 years old. This pilot study aimed to determine the effectiveness of balneotherapy for chronic LBP in people > 60 years old and to determine profiles of responders with trajectory model analysis. This was a pilot prospective open cohort study, with repeated measurements using validated questionnaires; participants were their own controls. The primary endpoint was the proportion of participants with a change in pain intensity between the start of treatment and 3 months after treatment assessed with a numeric scale (NS) from 0 to 100 mm, with an effect size (ES) > 0.5. The assessments involved questionnaires that were self-administered on days (D) 1 and 21 and at months 3 and 6. The secondary objective was to determine the profile of responders to balneotherapy. We included 78 patients (69.2% women), mean age 68.3 ± 5.3 years. The mean pain score on the NS was 48.8 ± 19.9 at D1 and 39.1 ± 20.5 at 3 months ( < 0.001). The ES was 0.47 [95% confidence interval [CI] 0.25 to 0.69] for the whole sample; 36% (28/78) had an ES > 0.5; 23% (18/78) had a moderate ES (0 to 0.5); and 41% (32/78) had an ES of zero (14/78) or < 0 (18/78), corresponding to increased pain intensity. The pain trajectory model showed that the change in pain between D1 and D21 for trajectory A (larger reduction in pain intensity) was -50% [95% CI -60 to -27], and for trajectory B (smaller reduction in pain intensity), it was -13% [-33 to 0] ( < 0.001). Between Day 1 and month 3, the change for trajectory A was -33% [-54; 0] and for trajectory B was -13% [-40 to 0] ( = 0.14). Finally, between D1 and month 6, the change for trajectory A was -50% [-60 to 0] and for trajectory B was -6% [-33 to 17] ( = 0.007). The patients in trajectory A reported performing more physical activity than those in trajectory B ( = 0.04). They were also less disabled, with a mean Oswestry Disability Index of 40.4 versus 45.7 for those in trajectory A and B, respectively, ( = 0.03) and had a higher total Arthritis Self-Efficacy Scale score. This real-life study of the effectiveness of balneotherapy on chronic LBP identified distinct pain trajectories and predictive variables for responders. These criteria could be used in decision-making regarding the prescription of balneotherapy, to ensure personalized management of chronic LBP.

Preclinical data point to the contribution of transient receptor potential ankyrin 1 (TRPA1) channels to the complex mechanisms underlying migraine pain. TRPA1 channels are expressed in primary sensory neurons, as well as in glial cells, and they can be activated/sensitized by inflammatory mediators. The aim of this study was to investigate the relationship between TRPA1 channels and glial activation in the modulation of trigeminal hyperalgesia in preclinical models of migraine based on acute and chronic nitroglycerin challenges. Rats were treated with ADM_12 (TRPA1 antagonist) and then underwent an orofacial formalin test to assess trigeminal hyperalgesia. mRNA levels of pro- and anti-inflammatory cytokines, calcitonin gene-related peptide (CGRP) and glia cell activation were evaluated in the Medulla oblongata and in the trigeminal ganglia. In the nitroglycerin-treated rats, ADM_12 showed an antihyperalgesic effect in both acute and chronic models, and it counteracted the changes in CGRP and cytokine gene expression. In the acute nitroglycerin model, ADM_12 reduced nitroglycerin-induced increase in microglial and astroglial activation in trigeminal nucleus caudalis area. In the chronic model, we detected a nitroglycerin-induced activation of satellite glial cells in the trigeminal ganglia that was inhibited by ADM_12. These findings show that TRPA1 antagonism reverts experimentally induced hyperalgesia in acute and chronic models of migraine and prevents multiple changes in inflammatory pathways by modulating glial activation.

Inflammatory arthritis is a severe joint disease that causes long-lasting pain that reduces a patient's quality of life. Several commercial medicines have been used to reduce the inflammation in arthritis. However, they have side effects that affect other organs and increase the infection rate in the patient. Therefore, searching for alternative medicines from natural herbs to use as a substitute for chemical drugs and reduce the side effects of drugs has become the focus of investigation. DC., known as andaliman, is an endemic spice that originates from Tapanuli, North Sumatera (Indonesia). Our previous study confirmed that andaliman exerts anti-inflammatory and xanthin oxidase enzymatic inhibitory activities. Unfortunately, there are no in vivo studies on the efficacy of andaliman in reducing inflammation in arthritis. This research aimed to produce an andaliman extract rich in essential oils, to formulate andaliman extract in a nanoemulsion product, and to test their anti-arthritic and anti-inflammatory effects on suppressing the gene expression of inflammatory arthritis in vivo. Several steps were used to conduct this experiment, including andaliman extraction, bioactive compound identification, nanoandaliman formulation, in vivo inflammatory arthritis mice modeling using complete Freund's adjuvant (CFA), and gene expression quantification using quantitative PCR (qPCR). Andaliman extract and nanoandaliman effectively reduced arthritic scores in CFA-induced arthritic mice. Both treatments also demonstrated anti-inflammatory potential via blocking several arthritic inflammatory gene expressions from cartilage tissue and brain in CFA-induced mice. Nanoandaliman at low dose (25 mg/kg bw) exerted a higher suppressive effect against the gene expression of and compared to that of andaliman extract. At high dose (100 mg/kg bw), andaliman extract effectively inhibited the expression of and genes in arthritic mice. These data suggest that nanoandaliman may be an alternative, natural anti-arthritic and anti-inflammatory candidate for the management of inflammatory arthritis.

Acute and chronic pain are two completely distinct universes […].

Sex workers are a highly underprivileged population which is present all around the world. Sex work is associated with negative social stigma which affects all aspects of the sex workers' lives including healthcare, service providers and police. The stigma may result in increased stress, mental health problems, feelings of isolation and social exclusion. In the present study, 36 sex workers (SW) and 304 subjects from the general population in Israel (GP) were evaluated for the presence of bruxism and Temporomandibular disorders (TMD), with the use of Diagnostic Criteria for Temporomandibular Disorders (DC/TMD- Axis I). When compared to the general population, sex workers presented larger maximal assisted mouth opening and higher prevalence of the following TMD diagnoses: Disc displacement with reduction, Myalgia, Myofascial pain with referral, Arthralgia (left and right) and Headache attributed to TMD. The odds of sex workers suffering from one of these diagnoses were twice to five times higher than those of the general population. The study shows that health problems of sex workers go beyond venereal diseases, HIV and mental disorders which are commonly studied. Oral health, TMD and oral parafunctions are some of the additional health issues that should be addressed and explored in this population.

Although current evidence supports the use of dry needling for improving some clinical outcomes in people with neck pain, no previous research explored the effects of dry needling on the central processing of pain and autonomic nervous system in this population. Therefore, this clinical trial aimed to compare the effects of real and sham dry needling on autonomic nervous system function, pain processing as well as clinical and psychological variables in patients with chronic nonspecific neck pain. A double-blinded randomized clinical trial including 60 patients with neck pain was conducted. Patients were randomized to the real needling ( = 30) or sham needling ( = 30) group. Skin conductance (SC), pressure pain thresholds (PPTs), temporal summation (TS), conditioned pain modulation (CPM) as well as pain intensity, related-disability, catastrophism, and kinesiophobia levels were assessed by an assessor blinded to the allocation intervention. The results did not find significant group * time interactions for most outcomes, except for the global percentage of change of SC values (mean: F = 35.90, < 0.001, ηp2 = 0.459; minimum: F = 33.99, = 0.839, ηp2 = 0.371; maximum: F = 24.71, < 0.001, ηp2 = 0.037) and PPTs at C5-C6 joint in the same side of needling (F = 9.982; = 0.003; = 0.147), in favor of the dry needling group. Although the proportion of subjects experiencing moderate to large self-perceived improvement after the intervention was significantly higher (X2 = 8.297; = 0.004) within the dry needling group ( = 18, 60%) than in the sham needling group ( = 7, 23.3%), both groups experienced similar improvements in clinical and psychological variables. Our results suggested that dry needling applied to patients with chronic nonspecific neck pain produced an immediate decrease in mechanical hyperalgesia at local sites and produced an increase in skin conductance as compared with sham needling. No changes in central pain processing were observed. A single session of sham or real dry needling was similarly effective for decreasing related disability, pain intensity, catastrophism, and kinesiophobia levels. Further studies are needed to better understand the clinical implications of autonomic nervous system activation on central sensitization and pain processing in the long-term after the application of dry needling.

Lower back pain commonly arises from intervertebral disc (IVD) failure, often caused by deteriorating annulus fibrosus (AF) and/or nucleus pulposus (NP) tissue. High socioeconomic cost, quality of life issues, and unsatisfactory surgical options motivate the rapid development of non-invasive, regenerative repair strategies for lower back pain. This study aims to evaluate the AF regenerative capacity of injectable matrix repair strategy in ex vivo porcine organ culturing using collagen type-I and polycaprolactone nanofibers (PNCOL) with encapsulated fibroblast cells. Upon 14 days organ culturing, the porcine IVDs were assessed using gross optical imaging, magnetic resonance imaging (MRI), histological analysis, and Reverse Transcriptase quantitative PCR (RT-qPCR) to determine the regenerative capabilities of the PNCOL matrix at the AF injury. PNCOL-treated AF defects demonstrated a full recovery with increased gene expressions of AF extracellular matrix markers, including Collagen-I, Aggrecan, Scleraxis, and Tenascin, along with anti-inflammatory markers such as CD206 and IL10. The PNCOL treatment effectively regenerates the AF tissue at the injury site contributing to decreased herniation risk and improved surgical outcomes, thus providing effective non-invasive strategies for treating IVD injuries.

Among cardiovascular diseases, hypertension is one of the main risk factors predisposing to fatal complications. Oxidative stress and chronic inflammation have been identified as potentially responsible for the development of endothelial damage and vascular stiffness, two of the primum movens of hypertension and cardiovascular diseases. Based on these data, we conducted an open-label randomized study, first, to evaluate the endothelial damage and vascular stiffness in hypertense patients; second, to test the effect of supplementation with a physiological antioxidant (melatonin 1 mg/day for 1 year) in patients with essential hypertension vs. hypertensive controls. Twenty-three patients of either gender were enrolled and randomized 1:1 in two groups (control and supplemented group). The plasmatic total antioxidant capacity (as a marker of oxidative stress), blood pressure, arterial stiffness, and peripheral endothelial function were evaluated at the beginning of the study and after 1 year in both groups. Our results showed that arterial stiffness improved significantly ( = 0.022) in supplemented patients. The endothelial function increased too, even if not significantly ( = 0.688), after 1 year of melatonin administration. Moreover, the supplemented group showed a significative reduction in TAC levels ( = 0.041) correlated with the improvement of arterial stiffness. These data suggest that melatonin may play an important role in reducing the serum levels of TAC and, consequently, in improving arterial stiffness.