Rejected

Traumatic brain injury (TBI) represents an important public health problem and is followed by neuroinflammation and neurological dysfunctions. It has been suggested that brain trauma is often associated to deep behavioral alterations and chronic pain-like syndrome. Despite inducing minimal brain damage, mild TBI (mTBI) leads to persistent behavioral changes, including anxiety, depression, social interaction impairment, and aggressiveness. The clinical management of these symptoms is still unsatisfactory and new pharmacological treatments are needed, especially for the aggressiveness and depression. In a mouse model of mTBI, we investigated the effect of 2-Pentadecyl-2-Oxazoline (PEA-OXA), a natural compound, that is a secondary metabolite, found in green and roasted coffee beans, on both the pain perception, and neuropsychiatric dysfunctions. We found that the compound acts as a α2 adrenergic antagonist and this mechanism is here described for the first time. Mild TBI mice, starting from 14-d post-trauma, developed anxious and aggressive behavior, whilst depressive-like behavior and impaired social interactions were observed from the 60th d onward. PEA-OXA normalized all the behavioral changes investigated. We also investigated the memory impairments through Morris Water Maze (MWM) test. Both sham and mTBI mice treated with PEA-OXA showed amelioration in the reversal task of the MWM. Nevertheless, the main symptom of the long-term mTBI is represented by the depressive-like behavior, which was completely reversed by PEA-OXA repeated administration. In humans, mTBI-induced depression precedes the appearance of dementias and is characterized by a massive deficit of GABAergic transmission in the cortices. We found that PEA-OXA normalized the GABA changes in the prefrontal cortex. In order to prove the α2-mediated effect of the PEA-OXA we have performed open field test in naïve animals by microinjecting into the medial prefrontal cortex the dexomedetomidine, a selective α2 agonist with or without PEA-OXA co-injection. We found that PEA-OXA antagonized the α2 agonist effect on the locomotor activity. Moreover, PEA-OXA microinjection into the medial prefrontal cortex induced an enhancement of dopamine release. Collectively, these data suggest that this natural compound, through its multi-target activity is able to: i) ameliorate behavioral alterations (i.e. depression), ii) selectively normalize cortical GABA levels, iii) rescue the impaired neuronal activity in the prefrontal cortex.

Over the past two decades, there has been a sharp rise in the use of prescription opioids. In several countries, most notably the United States, opioid-related harm has been deemed a public health crisis. As surgeons are among the most prolific prescribers of opioids, growing attention is now being paid to the role that opioids play in surgical care. While opioids may sometimes be necessary to provide patients with adequate relief from acute pain after major surgery, the impact of opioids on the quality and safety of surgical care calls for greater scrutiny. This narrative review summarizes the available evidence on rates of persistent postsurgical opioid use and highlights the need to target known risk factors for persistent postoperative use before patients present for surgery. We draw attention to the mounting evidence that preoperative opioid exposure places patients at risk of persistent postoperative use, while also contributing to an increased risk of several other adverse clinical outcomes. By discussing the prevalence of excess opioid prescribing following surgery and highlighting significant variations in prescribing practices between countries, we note that there is a pressing need to optimize postoperative prescribing practices. Guided by the available evidence, we call for specific actions to be taken to address important research gaps and alleviate the harms associated with opioid use among surgical patients.

Even though the type, extent and reasons for self-medication practice (SMP) vary, globally self-medication (SM) is rising to relieve burdens on health services. However, inappropriate SMP results in economic wastes, damage of vital organs, incorrect therapy selection, risk of adverse drug reactions and development of antimicrobial-resistant pathogens. These consequences have severe implications including legal, ethical and quality of health-care delivery. Temporal increment and high prevalence of SM among health professionals is also a major bottleneck for Ethiopia. Hence, the study aimed to assess the SM among health-care professionals (HCPs) in selected governmental hospitals of Western Ethiopia.

Studies have proven that improving patients' acceptance of chronic pain could be an effective therapy for alleviating pain and other symptoms. Our objectives were to investigate the correlation between chronic pain acceptance and clinical variables in ankylosing spondylitis (AS), and the prediction role of chronic pain acceptance for biologics treatment. First, 167 AS patients were recruited to complete a series of questionnaires, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Chronic Pain Acceptance Questionnaire (CPAQ), Hospital Anxiety and Depression Scale (HADS), and Tampa Scale for Kinesiophobia (TSK). Bivariate correlation analysis was utilized to investigate the correlation between pain acceptance and clinical variables. Based on the level of chronic pain acceptance and serum C-reactive protein (CRP), patients were separated into four subgroups. Then, another 68 patients initiating anti-tumor necrosis factor (TNF) treatment were recruited to complete the questionnaires at baseline (T0) and 3 months after treatment (T3). The changes in clinical variables and treatment response were compared between multiple subgroups. Chronic pain acceptance had strong correlations with anxiety, depression and fear of movement, and moderate correlations with BASFI and pain intensity. Both activity engagement (AE) and pain willingness (PW) had significant correlations with pain intensity, BASFI and psychological status. In addition, AE had a significant correlation with disease duration, while PW had a significant correlation with ASDAS-CRP. Subgroup analysis showed that patients with low chronic pain acceptance and high levels of serum CRP had the highest BASDAI. Among patients initiating anti-TNF treatment, those with high pain acceptance and high levels of serum CRP achieved the most obvious reduction in BASDAI after 3 months treatment. Pain acceptance is a new tool to assess pain in AS which may also reflect physical and psychological status. Clinicians should identify high-risk patients with low chronic pain acceptance and high levels of serum CRP, and give psychological and pharmacological intervention promptly. Moreover, the combination of baseline chronic pain acceptance and serum CRP level could be used to predict the treatment response in AS patients initiating biologics treatment.

Venom-derived peptides display diverse biological and pharmacological activities that make them useful in a wide range of applications in medicine and pharmaceutical biotechnology. They have potential to treat various health problems such as diabetes mellitus, hypertension, chronic pain and others. Despite the high potential for new drug development, a number of limitations have been reported for these compounds, including chemical instability, poor oral absorption, short half-life and toxicity, which complicate the process of converting venom peptides into therapeutic agents. One possibility to overcome these disadvantages is to encapsulate these molecules into nanocarriers. Up to date, some venom-derived peptides have been loaded into different types of nanomaterials and promising results have achieved. The present work reports examples of these peptides and the types of nanocarriers used. Based on this review, information can be taken to select the best conditions and materials to encapsulate biologically active venom-derived peptides for pharmaceutical application.

Chronic neck pain (NP) attributed to myofascial pain syndrome is one of the particularly common skeletal muscle disorder associated with the hyperirritable zone in the taut band of muscle. Trigger points (TPs) are the physical interpretation of the myofascial pain syndrome. In the United States, 30%-85% of pain patients have been affected by myofascial TPs. To reveal preliminary evidence on the clinical efficacy of ischemic compression therapy, dry cupping, and their combination on improving the TPs' pressure pain threshold (PPT), neck range of motion (NROM), and neck disability index (NDI) in patients with TPs and nonspecific NP. Besides, assess the feasibility of conducting a randomized clinical trial (RCT). A randomized pilot study was conducted on 24 patients with TPs and nonspecific NP. Patients were randomly assigned to three groups: the cupping group, the ischemic compression group, and the combination therapy group. PPT, NROM, and NDI were assessed before and after 4 weeks of treatment. The results showed a statistically significant improvement in NDI, PPT, and NROM compared with values before the treatment ( < 0.05) in all groups. Although no significant difference was detected between ischemic compression (IC) and dry cupping, the combination approach showed significantly higher and faster improvement ( < 0.05). It is feasible to conduct a main RCT. Both IC and dry cupping may hold promise in treating TPs; a combination of the two therapies may provide superior improving rate.

The objective of this systematic review was to assess the analgesic efficacy of duloxetine (DLX) for fibromyalgia (FM) and find which dosage between 60mg/d DLX and 120mg/d DLX was more suitable for clinical application. A systematic search through multiple databases (Cochrane Central Register of Controlled Trials (CENTRAL), ProQuest, Pubmed) was conducted from 2000 until March 7, 2019. All steps were performed by two or more independent reviewers. A meta-analysis was performed to report the effects of DLX on pain reduction and its accompanied adverse events. This meta-analysis, including 7 studies with totaling 2642 FM patients, demonstrated that DLX could produce greater pain relief in FM than placebo (standardized mean difference (SMD) -0.26; 95% confidence interval (CI) -0.37 to -0.16). The Risk Ratio (RR) of at least 30% pain relief was 1.31(95%CI 1.19 to 1.44); The RR of at least 50% pain relief was 1.46 (95% CI 1.28 to 1.67). However, the adverse events were more common in patients with DLX than the ones with placebo (RR 1.17, 95%CI 1.12 to 1.23). The subgroup analyses of withdrawal effects demonstrated that 120mg/d DLX had a higher incidence (RR 0.96, 95% CI 0.80 to 1.15) than 60mg/d DLX (RR 0.77, 95% CI 0.63 to 0.93). In general, DLX was a great choice for pain relief in FM. Moreover, 60mg/d DLX produced less withdrawal effects than 120mg/d DLX. Highlight Fibromyalgia(FM) is a chronic condition of unknown etiology, characterized by widespread pain and often associated with other symptoms. Duloxetine (DLX), a serotonin-norepinephrine (noradrenaline) reuptake inhibitor(SNRI), is used to treat FM in many countries. DLX can produce greater pain relief in FM than placebo. DLX can bring about more adverse events than placebo. 60mg/d DLX produce less withdrawal than 120mg/d DLX for FM patients.

Persistent postural perceptual dizziness (PPPD) is a clinical condition characterized by unsteadiness present on most days for a period of at least 3 months. The aim of our work was to assess vestibular function, the role of anxiety, and possible interactions between visual and vestibular systems in patients with PPPD.

To estimate the maximum tolerated dose (MTD) and/or identify the recommended Phase II dose (RP2D) for combined INC280 and buparlisib in patients with recurrent glioblastoma with homozygous phosphatase and tensin homolog (PTEN) deletion, mutation or protein loss.