Serotonin norepinephrine reuptake inhibitors in managing neuropathic pain following spinal and non-spinal surgery: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: While serotonin norepinephrine reuptake inhibitors (SNRIs) offer promise in managing Post-surgical neuropathic pain (PSNP), uncertainties remain. This study aims to evaluate the effectiveness and adverse events of SNRIs in managing PSNP. METHODS: Systematic searches of PubMed, Embase, and Cochrane databases up to January 1st 2023 identified randomized controlled trials (RCTs) comparing SNRIs to placebo for PSNP. The primary outcome measures were pain at rest and adverse events post-surgery. Subgroup analyses were conducted based on surgical type and specific SNRIs. RESULTS: A total of 19 RCTs, encompassing 1440 participants (719 in the SNRI group vs 721 in the placebo group), met the inclusion criteria and were included. The pooled results demonstrated that pain scores were significantly lower in patients treated with SNRIs at 2 hours (MD:-0.26; 95%CI: -0.47 to -0.04; p=0.02), 6 hours (MD:-0.68; 95%CI: -1.01 to -0.34; p<0.0001), 24 hours (MD:-0.54; 95%CI: -0.99 to -0.09; p=0.02), and 48 hours (MD:-0.66; 95%CI: -1.23 to -0.10; p=0.02) post-surgery. In terms of adverse events, dizziness (OR:2.53; 95%CI: 1.34-4.78; p=0.004) and dry mouth (OR:2.21; 95%CI: 1.25-3.92; p=0.007) were significantly higher in the SNRIs group. Subgroup analysis showed that SNRI was found to significantly lower the 24-hour pain score after spinal surgery (MD:-0.45; 95%CI: -0.84 to -0.05; p=0.03). Duloxetine (MD:-0.63; 95%CI: -1.15 to -0.11; p=0.02) had a significant effect in lowering the 24-hour pain score at rest compared to placebo, whereas venlafaxine did not. CONCLUSIONS: SNRIs yielded considerable pain score reductions across multiple post-surgical intervals, although accompanied by an increased incidence of dizziness and dry mouth.

Associations of Sociodemographic and Psychosocial Factors with Headache Symptom Among Indonesian Adolescents Based on the 5th Wave of the Indonesian Family Life Survey (IFLS-5).

BACKGROUND: Headaches are common among children and adolescents, with more than half of adolescents reporting headache symptom worldwide. The number of migraine sufferers among adolescents has increased dramatically in the past decade. Headache has negatively influenced children and has been linked with emotional and behavioral problems. STUDY DESIGN: A cross-sectional study. METHODS: This study was conducted using secondary data from the Indonesian Family Life Survey (IFLS) to evaluate the relationship between sociodemographic and psychosocial factors in Indonesian adolescents and headaches. We used data from the fifth wave of IFLS, which was conducted between September 2014 and April 2015. The figures represent roughly 83% of the Indonesian population. We investigated the possible relationship between sociodemographic and psychosocial factors in adolescents with headaches. RESULTS: A total of 3605 participants (1875 females and 1730 males) aged 15 to 19 years with headache symptom were included in the study. Headache was associated with sleep disturbances (OR 1.99; 95% CI: 1.72, 2.30), depression (OR 1.94; 95% CI: 1.65, 2.28), and female gender (OR 1.72; 95% CI: 1.50, 1.98). Other factors contributing to headaches include poor/moderate sleep quality (OR 1.25; 95% CI: 1.08, 1.45) and low income (OR 1.22; 95% CI: 1.01, 1.48). CONCLUSION: In Indonesian adolescents aged 15 to 19 with headaches, sleep disturbances were the dominant factor associated with headache occurrence. Other factors such as depression, female gender, low socioeconomic status (SES), and poor/moderate sleep quality showed a positive association with headaches but further large population-based studies with more refined variables are needed to elucidate this association.

Study of the Mechanisms and Therapeutic Approaches of Migraine in Women and Pregnancy: A Literature Review.

Headache is a significant and debilitating health problem, affecting more than half of the population worldwide. Migraine is a type of headache that is strongly associated with women and accounts for the high number of years lived with disability among women. The pathophysiology of migraine attacks may begin with a premonitory phase, followed by an aura phase and migraine headache. In women, many factors influence the prevalence of migraine, and sex hormone fluctuations around the menstruation cycle were believed to impact the pathogenesis of migraine. The International Classification of Headache Disorders, 3rd edition identifies menstrual migraine as pure menstrual migraine without aura and menstrually related migraine without aura. While migraine without aura (MwoA) was clearly associated with menstruation, migraine with aura (MwA) was generally unrelated to menstruation. Studies suggested that estrogen withdrawal is a trigger for MwoA, but high estrogen states are a trigger for MwA. During pregnancy, the increase in estrogen hypothetically prevents migraine attacks. There are several strategies for managing menstrual migraine, from acute/abortive, mini-preventive, and continuous preventive treatment. Managing migraine during pregnancy follows a similar strategy, but the drugs' safety profile should be considered.

Secretome as neuropathology-targeted intervention of Parkinson's disease.

Parkinson's disease (PD) is the second most common progressive neurodegenerative disease, characterized by apoptosis of dopaminergic neurons in substansia nigra pars compacta (SNpc) caused by ⍺-synuclein aggregation. The use of secretomes released by medicinal signaling cells (MSCs) is one the promising preventive approaches that target several mechanisms in the neuropathology of PD. Its components target the lack of neurotrophin factors, proteasome dysfunction, oxidative stress, mitochondrial dysfunction, and at last neuroinflammation via several pathways. The complex and obscure pathology of PD induce the difficulty of the search of potential preventive approach for this disease. We described the potential of secretome of MSC as the novel preventive approach for PD, especially by targeting the said major pathogenesis of PD.

Inhaled Levodopa (CVT-301) for the Treatment of Parkinson Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Purpose of Review: To investigate the efficacy and safety of CVT-301 in treating motor fluctuation in patients with Parkinson disease (PD). Recent Findings: This study demonstrated that the CVT-301 group had a higher proportion of patients achieving an ON state than the placebo group (odds ratio [OR] = 2.68; 95% confidence interval [CI]: 1.86-3.86; p < 0.00001). Moreover, CVT-301 had also shown to improve motor function by Unified Parkinson Disease Rating Scale part III score (standardized mean difference = 3.83; 95% CI: 2.44-5.23; p < 0.00001) and promote an overall improvement of PD by Patient Global Impression of Change self-rating (OR = 2.95; 95% CI: 1.78-4.9; p < 0.00001). The most common adverse events encountered were respiratory symptoms (OR = 12.18; 95% CI: 5.01-29.62; p < 0.00001) and nausea (OR = 3.95; 95% CI: 1.01-15.41; p = 0.05). Summary: CVT-301 had the potential to be an alternative or even a preferred treatment for motor fluctuation in patients with PD.

Vascular Endothelial Growth Factor 936 C/T Gene Polymorphism in Indonesian Subjects with Diabetic Polyneuropathy.

AIM: This study aimed to confirm the role of f VEGF gene 936 C/T polymorphism and Diabetic Polyneuropathy (DPN) in the Indonesian population as well as to investigate its relationship with VEGF-A level and the role of vascular risk factors. MATERIAL AND METHODS: This was a cross-sectional study involving 152 subjects. Clinical symptoms and signs of DPN were examined using DNE and DNS scoring followed by nerve conduction study. All subjects underwent anthropometric, clinical examination and laboratory procedures to obtain body mass index, HbA1C level, lipid profile, Polymorphism of +936 C/T VEGF gene (PCR-RFLP technique), and VEGF-A plasma level (ELISA). Statistical analysis using a t-test or Mann-Whitney was performed to assess continuous data and Chi-square for categorical data. Multivariate logistic regressions were also performed to determine the relationship between independent variables and DPN. RESULTS: Sixty-nine (45.4%) fulfilled the diagnostic criteria of DPN. There was a significant association between CT + TT genotype and DPN (OR 0.35 95%CI 0.16-0.79 p = 0.01). Multivariate logistic regression showed that plasma VEGF-A level (OR = 1.003; 95% CI = 1.000-1.007; p = 0.03), diabetes duration (OR = 1.108; 95% CI = 1.045-1.175; p = 0.001), and CT+TT genotype (OR = 0.347; 95%CI = 0.148-0.817; p = 0.013) were associated with DPN. Sub-group analysis on subjects with HbA1C level ≥7% showed that VEGF-A (OR = 1.011; 95%CI = (1.004-1.017; p = 0.03), diabetes duration (OR = 1.245; 95% CI = 1.117-1.388; p < 0.001), CT + TT genotype (OR = 0.259; 95%CI = 0.074-0.911p = 0.035), with an adition of HDL (OR = 0.916; 95% CI = 0.857-0.978; p = 0.009) were significant predictors of DPN while LDL (OR = 1.017; 95% CI = 1.000-1.035; p = 0.053) acted as modifying factor. CONCLUSION: It appeared that CT + TT genotype of VEGF +936 gene might act as a protecting factor for DPN while VEGF-A, diabetes duration, HDL, and LDL acted as risk factors especially on subjects with HbA1C level ≥ 7.