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Abstract Background Children under the age of 3 years have been diagnosed with complex regional pain syndrome (CRPS). They were found to be functionally disadvantaged and psychologically distressed in relation to children with other painful conditions. Case presentation An 18-month-old baby girl was referred to the pain clinic with a history of severe right lower limb pain that had begun 2 months earlier. The parents were unable to recall any trauma before the painful situation. Pain and allodynia were severe and extended from the toes to the gluteus area. She was low weight for her age (6700 g). The patient was on the maximum doses of gabapentin and amitriptyline accepted for her body weight and did not have the possibility to start rehabilitation due to severe pain and allodynia. After discussing the risks and potential benefits of a planned lumbar sympathetic block (LSB), the parents approved the interventional procedure. This is the first case report describing the LSB technique at such a young age. Method A lumbar sympathetic block was carried on at the third lumbar vertebral level, fluoroscopy-guided, and under general anesthesia (GA) initiated with ketamine iv. A 4-cm needle was introduced using a tunneled vision approach in an oblique view at the L3 level until adequate depth was confirmed in the lateral position. Safety considerations were taken in relation to the radiation dose and all drugs injected with dose adjustment to her body weight. The block was successful (the skin temperature increased by 2.8 °C) and was uneventful. Pain and allodynia were completely alleviated in the recovery room. At the follow-up after 3 and 8 weeks, the parents reported an 80% improvement in pain and allodynia, a 70% improvement in sleep, a weight gain of 900 g, and that she had started rehabilitation. Conclusions Lumbar sympathetic blocks can be considered at a very young age to treat CRPS if other non-invasive measures fail.

Abstract Background & aims Chronic migraine poses a global health burden, particularly affecting young women, and has substantial societal implications. This study aimed to assess the efficacy of Greater Occipital Nerve Block (GONB) in individuals with chronic migraine, focusing on the impact of local anesthetics compared with placebo. Methods A meta-analysis and systematic review were conducted following the PRISMA principles and Cochrane Collaboration methods. Eligible studies included case-control, cohort, and randomized control trials in adults with chronic migraine, adhering to the International Classification of Headache Disorders, third edition (ICHD3). Primary efficacy outcomes included headache frequency, duration, and intensity along with safety assessments. Results Literature searches across multiple databases yielded eight studies for qualitative analysis, with five included in the final quantitative analysis. A remarkable reduction in headache intensity and frequency during the first and second months of treatment with GONB using local anesthetics compared to placebo has been reported. The incidence of adverse events did not differ significantly between the intervention and placebo groups. Conclusion The analysis emphasized the safety and efficacy of GONB, albeit with a cautious interpretation due to the limited number of studies and relatively small sample size. This study advocates for further research exploring various drugs, frequencies, and treatment plans to enhance the robustness and applicability of GONB for chronic migraine management.

Our immune system acts to protect us in times of stress and traumatic injury. As part of the immune response, the body produces various cytokines, which mediate or modulate immune functions. Such cytokines include tumor necrosis factor (TNF) and interleukin 6 (IL-6) and IL-17. These cytokines can also act on the nervous system to influence pain perception. TNF-α triggers an inflammatory response and two forms of programmed cell death, apoptosis and necroptosis, depending on the pathological state. For individuals with chronic conditions relating to immune deficiency, the actions of these cytokines can present as chronic pain states, significantly altering quality of life. One attractive potential solution for treating this immune linked pain is by altering signaling pathways of pain-enhancing cytokines. Infliximab and etanercept are TNF inhibitors that are currently on the market for use in the treatment of chronic pain. Secukinumab and tocilizumab serve as IL inhibitors, utilized for a similar purpose. These novel immunotherapies have shown efficacy in numerous clinical studies with acceptable side effect profiles. In this review, we summarize the pharmacological profiles of these drugs and discuss their usage in treating chronic pain.

Abstract Introduction Dorsal root ganglion pulsed radiofrequency (DRG-PRF) is frequently used for the treatment of chronic lumbar radicular pain with good outcomes in terms of pain management. Transforaminal epidural steroid injection (TFESI) is often administered immediately after DRG-PRF to increase the anti-inflammatory effects, but support for the synergic mechanism is lacking in the literature. The aim of this study was to investigate the potential role of TFESI immediately after DRG-PRF and its possible role on pain intensity and patient disability. Methods A database of patients who underwent DRG-PRF with or without TFESI immediately after DRG-PRF was retrospectively analysed; propensity score matching was applied to the analysis to reduce possible bias. Pain intensity (numerical rating scale [NRS]) and Oswestry disability index (ODI) were recorded pre-operatively and at the 1- and 3-month follow-up in the two groups of patients. Results A total of 252 patients were included in this retrospective analysis, 126 patients in the DRG-PRF + TFESI group and 126 patients in the DRG-PRF group after propensity score matching. Both groups displayed a significant reduction in pain intensity (NRS score reduction; p

Spine pain (SP) is the most common musculoskeletal disorder that causes transitional forms of motor disability. Considering its affordability and safety, manipulative therapy (MT) stands as one of the primary therapeutic approaches for SP and the related dysfunctional consequences. However, it is still difficult to assess and quantify the results of this treatment since there is a lack of objective evaluation tools in the available scientific literature. Thus, the purpose of this comprehensive review is to summarize the main outcomes used to evaluate the effectiveness of spine manipulations, focusing on their strengths and weaknesses. An extensive review of the PubMed, Cochrane, and Embase databases was performed to identify the literature of the last ten years regarding MT and the related assessment tools. A total of 12 studies met the inclusion criteria. The analyzed literature indicates that a wide range of outcome measures have been used to assess the effectiveness of spine MT. Pain is the main aspect to be investigated but it remains difficult to elucidate since it is strongly linked to various dimensions such as self-perception and psychological aspects. Therefore, it seems necessary to include new tools for evaluating the effects of spine MT, with the aim of exploiting new technologies and taking into consideration the SP biomechanical and biopsychosocial aspects.

Abstract Background One million individuals in the USA die from acute myocardial infarction (MI), which currently affects 3 million people globally. The available data about the early and late outcomes of both biodegradable polymer drug-eluting stents (BP-DES) and durable polymer drug-eluting stents exhibit inconsistency. We performed a meta-analysis comparing the safety and efficacy of BP-DES with DP-DES. Methods PubMed, Google Scholar, EMBASE, Cochrane, Ovid Medline, and Clinical Trials.gov databases were used to find out studies comparing BP-DES to DP-DES. All the analyses used the random-effects model. Results A total of 18 studies were incorporated in this meta-analysis that involved 28,874 patients, out of which 11,997 received the BP Stent, and the rest of 16,578 received the DP stent. Thorough analyses revealed that the risk of all-cause death was significantly higher in the BP-DES group (5.4% vs 2.7%) (RR 1.22, p 0.02) for two years or less than two-year follow-up. For studies with more than two years of follow-up, all-cause death was 9.07% (599/6603) in BP-DES and 9.47% (531/5602) in the DP-DES group but failed to achieve statistically significant levels (RR 0.97, p 0.58). Conclusions The study revealed no clinically significant (P value was > 0.05) differences in all-cause death, cardiac death, target lesion revascularization (TLR), late stent thrombosis, device-oriented composite endpoint/target lesion failure (DOCE/TLF), myocardial infarction (MI), target vessel MI, target vessel revascularization (TVR), target vessel infarction (TVI) between BP-DES and DP-DES for more than two years of follow-up. Additionally, all-cause death was only outcomes which found to have a statistically significant difference for less than two years of follow-up, while remaining were statistically non-significant.

Abstract Introduction Dexketoprofen/tramadol 25/75 mg (DKP/TRAM) is a fixed-dose combination of a cyclooxygenase inhibitor and opioid receptor agonist. To better understand the efficacy and safety of DKP/TRAM in the treatment of moderate to severe acute lower back pain (LBP) with or without radiculopathy, we carried out a large explorative phase IV international, multicenter, prospective, randomized, double-blind, parallel group, placebo-controlled study (DANTE). Methods A total of 538 patients with or without a history of LBP and experiencing acute LPB of moderate to severe intensity [Numerical Rating Scale-Pain Intensity (NRS-PI) score > 5] were randomized 4:4:1:1 to DKP/TRAM 25/75 mg every 8 h (n = 211), tramadol (TRAM) 100 mg (n = 207), placebo-matched DKP/TRAM (n = 59), or placebo-matched TRAM (n = 61). Results The proportion of patients achieving the primary endpoint, defined as the time to first achieve NRS-PI score

Abstract Since the COVID-19 pandemic, healthcare systems are facing extraordinary challenges. Our approaches to medicine have changed and created a whole new generation of people who have chronic pain. Various medical services were postponed. The pandemic significantly impacted the bio-psychosocial model of pain and the management of chronic pain. These new challenges affected millions of patients worldwide, with more burden on patients with chronic pain. Telemedicine and digital health rather than traditional office visits have become essential tools for communications, resulting in an unmatched surge in telehealth adoption. This new approach facilitated the remote treatment and follow-up of patients who have difficulty to access the healthcare services, particularly patients with chronic pain and those who were receiving regular controlled medications. An extensive computer search was conducted, during the period (from January 2014 to March 2024), and included literature from PubMed, Scopus, MEDLINE, and Google scholar. According to preset inclusion and exclusion criteria, a total of 38 articles have been included in this review article. This literature review focuses on the innovation of telemedicine and digital health in pain management, especially in the context of the challenges posed by the COVID-19 pandemic. The manuscript provides a comprehensive overview of telemedicine and digital communications, their evolution, and their significance in healthcare. It also emphasizes the benefits, challenges, limitations, and the ethical concerns of telemedicine in pain management after the COVID-19 pandemic. Furthermore, the document explores the different modes of the telecommunications and discusses the future directions of the digital health technology.

Abstract One of the most common musculoskeletal disorders, osteoarthritis (OA), causes worldwide disability, morbidity, and poor quality of life by degenerating articular cartilage, modifying subchondral bone, and inflaming synovial membranes. OA pathogenesis pathways must be understood to generate new preventative and disease-modifying therapies. In recent years, it has been acknowledged that gut microbiota (GM) can significantly contribute to the development of OA. Dysbiosis of GM can disrupt the “symphony” between the host and the GM, leading to a host immunological response that activates the “gut–joint” axis, ultimately worsening OA. This narrative review summarizes research supporting the “gut–joint axis” hypothesis, focusing on the interactions between GM and the immune system in its two main components, innate and adaptive immunity. Furthermore, the pathophysiological sequence of events that link GM imbalance to OA and OA-related pain is broken down and further investigated. We also suggest that diet and prebiotics, probiotics, nutraceuticals, exercise, and fecal microbiota transplantation could improve OA management and represent a new potential therapeutic tool in the light of the scarce panorama of disease-modifying osteoarthritis drugs (DMOADs). Future research is needed to elucidate these complex interactions, prioritizing how a particular change in GM, i.e., a rise or a drop of a specific bacterial strain, correlates with a certain OA subset to pinpoint the associated signaling pathway that leads to OA.

Abstract Background Propofol has been the gold standard for anesthesia induction and maintenance due to its rapid onset and favorable pharmacokinetic properties. However, the search for alternative agents with improved safety and efficacy has led to the emergence of ciprofol (HSK3486), a structural analog of propofol. This systematic review and meta-analysis aim to comprehensively assess the safety and efficacy of ciprofol compared to propofol for anesthesia induction and maintenance in adult patients undergoing surgical procedures. Methods This study included only double-arm RCTs in which participants were aged eighteen or older undergoing surgery. For the statistical analysis of the extracted data, we employed RevMan 5.4.1. Results Ciprofol demonstrated a promising trend of higher anesthesiologists’ satisfaction during the induction phase (MD 0.14, 95%, CI − 0.28 to 0.56, p = 0.51), whereas Propofol was favored during maintenance. Propofol also exhibited advantages with a shorter time to successful anesthesia induction (MD 0.08 min, 95% CI 0.00 to 0.15, p = 0.04), and quicker attainment of full alertness (MD 0.11 min, 95% CI − 1.29 to 1.52, p = 0.87), suggesting its efficiency in clinical practice. Importantly, there were no significant disparities in the success rate of anesthesia. Conclusion Both ciprofol and propofol demonstrate comparable efficacy and safety for anesthesia induction and maintenance in adult patients undergoing surgery. While propofol provides a faster onset of induction, ciprofol exhibits advantages in terms of pain management. Clinicians should consider these findings when selecting anesthetic agents, and tailoring choices to individual patient needs and clinical scenarios.

Abstract Pain is a significant health issue, and pain assessment is essential for proper diagnosis, follow-up, and effective management of pain. The conventional methods of pain assessment often suffer from subjectivity and variability. The main issue is to understand better how people experience pain. In recent years, artificial intelligence (AI) has been playing a growing role in improving clinical diagnosis and decision-making. The application of AI offers promising opportunities to improve the accuracy and efficiency of pain assessment. This review article provides an overview of the current state of AI in pain assessment and explores its potential for improving accuracy, efficiency, and personalized care. By examining the existing literature, research gaps, and future directions, this article aims to guide further advancements in the field of pain management. An online database search was conducted via multiple websites to identify the relevant articles. The inclusion criteria were English articles published between January 2014 and January 2024). Articles that were available as full text clinical trials, observational studies, review articles, systemic reviews, and meta-analyses were included in this review. The exclusion criteria were articles that were not in the English language, not available as free full text, those involving pediatric patients, case reports, and editorials. A total of (47) articles were included in this review. In conclusion, the application of AI in pain management could present promising solutions for pain assessment. AI can potentially increase the accuracy, precision, and efficiency of objective pain assessment.

Sacroiliitis is the inflammation of the sacroiliac joint, the largest axial joint in the human body, contributing to 25% of lower back pain cases. It can be detected using various imaging techniques like radiography, MRI, and CT scans. Treatments range from conservative methods to invasive procedures. Recent advancements in artificial intelligence offer precise detection of this condition through imaging. Treatment options range from physical therapy and medications to invasive methods like joint injections and surgery. Future management looks promising with advanced imaging, regenerative medicine, and biologic therapies, especially for conditions like ankylosing spondylitis. We conducted a review on sacroiliitis using imaging data from sources like PubMed and Scopus. Only English studies focusing on sacroiliitis’s radiological aspects were included. The findings were organized and presented narratively.

Abstract Neuropathic pain (NP) is a chronic pain disorder arising from somatosensory nervous system impairment. Extensive evidence supports the notion that the gut microbiota (GM) is crucial in maintaining human health by performing vital tasks. At the same time, its disruption has been linked to the emergence and advancement of an expanding range of disorders, including NP, in which GM could play a role in its pathophysiology. The crosstalk between the nervous system and GM happens through immune mediators, metabolites, and nervous structures and involves both central and peripheral nervous systems. This literature review aims to thoroughly investigate the function of modulating GM in the treatment of NP. It will achieve this by integrating existing knowledge, identifying underlying mechanisms, and evaluating the possible clinical consequences of exploiting the gut–brain axis. We will cover the main therapeutic applications of the described GM-modulators, such as probiotics, faecal microbiota transplantation, dietary supplements and emotional support, to the main kinds of NP in which any evidence, even if only pre-clinical, has been unravelled in recent years. The explored NP areas include chemotherapy-induced peripheral neuropathy, diabetic neuropathy, trauma-induced neuropathic pain, trigeminal neuralgia, postherpetic neuralgia and low back pain.

Abstract Chronic nonmalignant pain is recognized as a complex, dynamic, phenomenological interplay between biological, psychological, and social factors that are individual to the person suffering from it. Therefore, its management and treatment ought to entail the individual’s biopsychosocial aspects that are often addressed by collaborative, inter/multidisciplinary multimodal care, as there is no biologic treatment. In an effort to enhance inter/multidisciplinary multimodal care, a narrative review of arts therapy as a mind–body intervention and its efficacy in chronic pain populations has been conducted. Changes in emotional and physical symptoms, especially pain intensity, during arts therapy sessions have also been discussed in in the context of attention distraction strategy. Arts therapy (visual art, music, dance/movement therapy, etc.) have been investigated to summarize relevant findings and to highlight further potential benefits, limitations, and future directions in this area. We reviewed 16 studies of different design, and the majority reported beneficial effects of art therapy in patients’ management of chronic pain and improvement in pain, mood, stress, and quality of life. However, the results are inconsistent and unclear. It was discovered that there is a limited amount of high-quality research available on the implications of arts therapy in chronic nonmalignant pain management. Due to the reported limitations, low effectiveness, and inconclusive findings of arts therapy in the studies conducted so far, further research with improved methodological standards is required.

AbstractBackground The emergence of genetically-modified human proteins and glucagon-like peptide-1 (GLP-1) receptor agonists have presented a promising strategy for effectively managing diabetes. Due to the scarcity of clinical trials focusing on the safety and efficacy of semaglutide as an adjunctive treatment for patients with type 2 diabetes who had inadequate glycemic control with metformin, we conducted a systematic review and meta-analysis. This was necessary to fill the gap and provide a comprehensive assessment of semaglutide compared to sitagliptin, a commonly prescribed DPP-4 inhibitor, in this patient population.Methods A comprehensive and systematic search was carried out on reputable databases including PubMed, the Cochrane Library, and Elsevier’s ScienceDirect to identify relevant studies that compared the efficacy of once-weekly Semaglutide with once-daily Sitagliptin in individuals diagnosed with type 2 diabetes mellitus. The analysis of the gathered data was performed utilizing the random-effects model, which considers both within-study and between-study variations.Results The meta-analysis incorporated three randomized controlled trials (RCTs), encompassing 2401 participants, with a balanced distribution across the treatment groups. The primary focus of the study revolved around evaluating changes in HbA1C, blood pressure, pulse rate, body weight, waist circumference, and BMI. The findings revealed that once-weekly Semaglutide showed substantially improved HbA1C (WMD: −0.98; 95% CI: −1.28, −0.69, p-value: < 0.0001; I2: 100%), systolic (WMD: −3.73; 95% CI: −5.42, −2.04, p-value:

Background: Hyperbaric oxygen therapy (HBOT) has been reported as an emerging treatment regimen for fibromyalgia syndrome (FMS), with a paucity of solid evidence. Accordingly, a systematic review and meta-analysis were performed to address the effectiveness of HBOT on FMS. Methods: We searched the Cochrane Database, EMBASE, Medline, PubMed, Clinicaltrials.gov, and PsycINFO, and the reference sections of original studies and systematic reviews from inception to May 2022. Randomized controlled trials (RCTs) on the treatment of FMS with HBOT were included. Outcome measures included pain, Fibromyalgia Impact Questionnaire (FIQ), Tender Points Count (TPC), and side effects. Results: Four RCTs, with 163 participants, were included for analysis. Pooled results showed that HBOT could benefit FMS with significant improvement at the end of treatment, including FIQ (SMD = −1.57, 95% CI −2.34 to −0.80) and TPC (SMD = −2.50, 95% CI −3.96 to −1.05). However, there was no significant effect on pain (SMD = −1.68, 95% CI, −4.47 to 1.11). Meanwhile, HBOT significantly increased the incidence of side effects (RR = 24.97, 95% CI 3.75 to 166.47). Conclusions: Collectively, emerging evidence from RCTs indicates that HBOT can benefit FMS patients in FIQ and TPC throughout the observation time phrases. Although HBOT has some side effects, it does not cause serious adverse consequences.

Abstract Introduction A modified Delphi strategy was implemented for obtaining recommendations that could be useful in the management of percutaneous radiofrequency treatment of lumbar facet joint syndrome, as the literature on the argument was poor in quality. Methods An Italian research team conducted a comprehensive literature search, defined the investigation topics (diagnosis, treatment, and outcome evaluation), and developed an explorative semi-structured questionnaire. They also selected the members of the panel. After an online meeting with the participants, the board developed a structured questionnaire of 15 closed statements (round 1). A five-point Likert scale was used and the cut-off for consensus was established at a minimum of 70% of the number of respondents (level of agreement ≥ 4, agree or strongly agree). The statements without consensus were rephrased (round 2). Results Forty-one clinicians were included in the panel and responded in both rounds. After the first round, consensus (≥ 70%) was obtained in 9 out of 15 statements. In the second round, only one out of six statements reached the threshold. The lack of consensus was observed for statements concerning the use of imaging for a diagnosis [54%, median 4, interquartile range (IQR) 3–5], number of diagnostic blocks (37%, median 4, IQR 2–4), bilateral denervation (59%, median 4, IQR 2–4), technique and number of lesions (66%, median 4, IQR 3–5), and strategy after denervation failure (68%, median 4, IQR 3–4). Conclusion Results of the Delphi investigations suggest that there is a need to define standardized protocols to address this clinical problem. This step is essential for designing high-quality studies and filling current gaps in scientific evidence.

Abstract Chronic low back pain is often due to L5S1 instability resulting in facet joint syndrome. Patients suffering from low back pain may also have a gait pattern characterized by a reduced speed and a shorter, asymmetrical step in order to reduce pain. This case is of a patient with L5S1 instability that occurred after L1 to L5 lumbar stabilization who was treated with radiofrequency (RF) denervation of the medial branch of L5S1 bilaterally. RF ablation outcome was tested by comparing its impact on pain, function, quality of life, and on gait pattern, before and 1 month after the procedure. To objectify the impact of a good pain control on gait, a video recording was performed (see Video 1).

Palmitoylethanolamide (PEA) emerged over the years as a promising approach in the management of chronic pain. Despite the fact that the efficacy of micron-size PEA formulations appears to be time-dependent, the optimal timing has not yet been elucidated. This systematic review and meta-analysis aim to estimate the possible advantage of an extended treatment in the relief of chronic pain. The literature search was conducted consulting scientific databases, to identify clinical trials in which micron-size PEA was administered for at least 60 days, and pain assessed by the Visual Analogue Scale (VAS) or Numeric Rating Scale (NRS). Nine studies matched the required criteria, for a total of 742 patients involved. The meta-analysis showed a statistically and clinically significant pain intensity reduction after 60 days of micron-size PEA supplementation, compared to 30 days (1.36 points, p < 0.01). The secondary analysis revealed a weighted NRS/VAS score decrease of 2.08 points within the first month of treatment. These two obtained scores corresponded to a 35.1% pain intensity reduction within the first month, followed by a further 35.4% during the second month. Overall, these results confirm the clinically relevant and time-depended pain-relieving effect of micron-size PEA and therefore the advantage of an extended treatment, especially in patient with incomplete pain management.

Abstract Acute low back pain (LBP) stands as a leading cause of activity limitation and work absenteeism, and its associated healthcare expenditures are expected to become substantial when acute LBP develops into a chronic and even refractory condition. Therefore, early intervention is crucial to prevent progression to chronic pain, for which the management is particularly challenging and the most effective pharmacological therapy is still controversial. Current guideline treatment recommendations vary and are mostly driven by expertise with opinion differing across different interventions. Thus, it is difficult to formulate evidence-based guidance when the relatively few randomized clinical trials have explored the diagnosis and management of LBP while employing different selection criteria, statistical analyses, and outcome measurements. This narrative review aims to provide a critical appraisal of current acute LBP management by discussing the unmet needs and areas of improvement from bench-to-bedside, and proposes multimodal analgesia as the way forward to attain an effective and prolonged pain relief and functional recovery in patients with acute LBP.

Purpose of Review: Notalgia paresthetica (NP) is a chronic cutaneous neuropathy primarily characterized by localized pruritus and associated dysesthesias, including sensations of pain, numbness, and tingling. The sensory neuropathy characteristic of NP is thought to result from spinal nerve entrapment caused by degenerative changes in the spine or musculoskeletal compression. This review summarizes the current medical literature with a focus on the past five years regarding NP, its pathophysiology, presentation, and current treatment options. Recent Findings: Though treatments exist with varying efficacy, to date, there exists no definitive treatment for NP. Treatment options for NP are varied and range from topical and oral agents to interventional procedures and physical therapy. Of the treatments evaluated, topical capsaicin remains the most efficacious treatment for NP. Conclusions: The lack of established treatment guidelines makes treating NP complicated as it dramatically affects patients’ quality of life. Further research with larger sample sizes is needed to evaluate better the most effective treatment and dosing regimen for patients afflicted with NP.

The diagnosis of chronic neuropathic pain requires a laborious process and can be a very long journey for the patients, one that can be characterized as an “odyssey.” Our aim was to describe the “diagnostic odyssey” associated with chronic neuropathic pain in the Greek context. Specialized clinicians working at dedicated chronic pain and palliative care centers were asked to participate in a survey regarding the diagnostic process in Greece. In total, 44 respondents provided information on the organization of their centers, the diagnostic process, and the perceived obstacles involved in the diagnosis of chronic neuropathic pain. Most respondents reported that their centers were not fully or efficiently organized and believed that additional specialized healthcare personnel should be employed. Raising public awareness about the existence of such centers was also considered key. The two main obstacles in reaching a diagnosis were the difficulty non-experts had in recognizing chronic neuropathic pain and the lack of acknowledgement that chronic neuropathic pain is a condition that needs to be addressed. When considering these responses in light of the extended socioeconomic burden associated with chronic neuropathic pain, efforts should be made to limit the “diagnostic odyssey” of chronic neuropathic pain in Greece. The aim of this study is to explore the experience of patients with chronic neuropathic pain in Greece from the viewpoint of pain specialists. A better organization of pain and palliative care centers, facilitation of communication with previously treating clinicians, increased personnel, utilization of a chronic pain registry, and guidelines development can aid in this venture. Keypoints: The diagnosis of chronic neuropathic pain in Greece is a laborious and time-consuming process that needs to be refined; Greek clinicians believe that their centers were not fully or efficiently organized and think that additional specialized healthcare personnel should be employed; Patient comorbidities and retards in visiting a clinic at the onset of symptoms delay the diagnosis of neuropathic pain and may complicate subsequent care; The diagnostic delay has been reported as three years between the onset of symptoms and seeking general medical help and another nine years before a referral to a pain specialist; Neuropathic pain is associated with patient distress and socioeconomic burdens, and diagnostic delays prolong the condition, may allow it to worsen, and utilize valuable healthcare resources without providing effective solutions.

Wheelchair basketball (WB) involves sports gestures that expose the shoulder to high biomechanical stress and frequently lead to shoulder pain (SP). Due to their physical peculiarities and sporting performance, these athletes require specific rehabilitation programs that are as fast, personalized and effective as possible. However, there are few studies specifically dedicated to these purposes. Surface electromyography (sEMG) seems a promising tool for better customization and achieving more targeted rehabilitation results. The aim of this study was to evaluate the usefulness of sEMG to monitor SP rehabilitation outcomes in WB players. Thirty-three athletes were enrolled in this non-randomized clinical study and divided into two groups. Both groups underwent a shoulder rehabilitation protocol, but only the experimental group was monitored in real time with sEMG on the shoulders. At enrollment (T0), at the end of 4 weeks of the rehabilitation program (T1), and 8 weeks after T1 (T2), the following outcome measures were collected: Wheelchair User’s Shoulder Pain Index (WUSPI), 20 m straight line test, shoulder abduction range of motion (ROM). There was a statistically significant difference for WUSPI and ROM scores in the comparison between groups (p < 0.001), and for all outcomes in the comparison between times and in the interaction between time and group (p < 0.001). Therefore, the experimental group showed a better improvement at all detection times compared to the control group. sEMG seems a useful tool for improving the monitoring of SP rehabilitation outcomes in WB players. This monitoring speeds up and improves the rehabilitative results, limiting the risk of sport abandonment and increasing the possibility for people with disabilities to quickly return to practice physical activity.

Abstract Introduction Chronic pain is a distressing condition that should be treated in specialized pain clinics. Pain clinics offer a holistic, evidence-based approach, including pharmacological, complementary, and invasive treatments. This study aimed to provide preliminary information regarding chronic pain treatments and identify reasons for accessing an important hub-spoke pain clinic network. Methods A retrospective multicenter cross-sectional study was carried out. A total of 1606 patients’ records were included. Patients were selected from the 26 pain clinics of a single region in Italy. Univariate and multivariate logistic regression models were used. Results Multivariate models showed that the use of opioids were considered effective for severe or moderate pain [odds ratio (OR) 0.41; 95% 0.33–0.51], while the use of invasive treatments (OR 2.45; 95% 1.95–3.06) and the use of complementary therapy (OR 1.87; 95% 1.38–2.51) were associated with severe or moderate pain. Overall, age, sex, nonsteroidal anti-inflammatory drugs (NSAID) use, a combination of NSAIDs, complementary therapies, and a combination of opioids and invasive treatments did not seem to be significantly associated with the nature of pain. Multivariate models confirmed that clinical parameters such as the nature of pain, multi-diagnosis, more than one site of pain, treatments, and general practitioner, but not the severity of pain and use of invasive treatments, had an impact on the choice of a pain clinic. Conclusion Opioids are useful in managing moderate or severe chronic pain. Multimodal approaches are used for the management of chronic pain. Moreover, it is not clear how patients are addressed to access different pain clinics (spoke versus hub) networks. More widespread adoption is needed for an interdisciplinary approach to managing chronic pain and adopting guideline recommendations, and rigorous research is required to provide more substantial evidence and support clinical practice.

Fibromyalgia is a complex and often misunderstood chronic pain disorder. It is characterized by widespread musculoskeletal pain, fatigue, and heightened sensitivity, and has evolved in diagnostic criteria and understanding over the years. Initially met with skepticism, fibromyalgia is now recognized as a global health concern affecting millions of people, with a prevalence transcending demographic boundaries. The clinical features and diagnosis of fibromyalgia encompass a range of symptoms beyond pain, including sleep disturbances and cognitive difficulties. This study emphasizes the importance of a comprehensive evaluation for accurate diagnosis, considering the shift from tender point reliance to a more holistic approach. Etiology and pathophysiology involve genetic predisposition, neurotransmitter dysregulation, central sensitization, and immune system involvement. Risk factors such as gender, age, family history, and comorbid conditions contribute to susceptibility. The impact on quality of life is profound, affecting physical and social aspects, often accompanied by mood disorders. Management approaches include pharmacological interventions, non-pharmacological therapies, lifestyle modifications, and alternative treatments. This study also delves into emerging research, exploring advances in neurobiological understanding, brain imaging, genetic markers, glutamate modulation, cannabinoids, gut microbiome, and digital health tools for fibromyalgia management. Overall, this study provides a nuanced and up-to-date overview of the complexities surrounding fibromyalgia, aiming to enhance understanding and support for individuals grappling with this challenging condition.

Recently, MDPI has acquired a new journal, Clinics and Practice, and started its development [...]

The present investigation summarizes relevant symptoms, differential diagnosis, imaging, and treatment options of Eagle Syndrome. A comprehensive literature review of peer-reviewed literature was employed utilizing most relevant databases. The diagnoses of Eagle Syndrome have recently increased because of increased awareness of physicians of Eagle Syndrome and the earlier identification of the cardinal symptoms of the disease. The most important symptoms are dysphagia in the setting of cervical neck pain, but there is a wide variety of symptomatology that make Eagle Syndrome a challenge to recognize and diagnose clinically. CT scan continues to be the standard of care for diagnosing Eagle Syndrome and CT Angiography has an important role in aiding diagnosis as well. Medical treatment options include steroids, antidepressants, and anticonvulsants however not all cases of Eagle Syndrome can be managed medically. Surgical approaches are varied but typically are either extraoral or transoral. This report aims to update providers on the important diagnostic criteria of Eagle Syndrome and how physicians can develop a treatment plan that addresses all the symptoms of patients with Eagle Syndrome because it can be treated safely and appropriately.

# Purpose of Review Seizures are a hyperexcitable, and hypersynchronous imbalance between excitatory and inhibitory factors (E/I imbalance) in neurotransmission, and epilepsy is the recurrent manifestation of seizures within a reasonable time frame and without being attributable to a reversible cause. Brivaracetam is a derivative of the antiepileptic agent, levetiracetam, that is used as adjuvant therapy for focal onset seizures. It was approved by the FDA in 2016 and has shown promising results with minimal adverse effect reactions in clinical trials. # Recent Findings Brivaracetam has been used in multiple clinical trials at various dosages in adults that have partial-onset seizures refractory to conventional treatment. A meta-analysis in 2016 showed that brivaracetam as adjunctive therapy was statically significant in its reduction of adults with drug-refractory seizure frequency.^1^ The most commonly reported adverse effects that patients who were taking brivaracetam experienced were somnolence, headache, and dizziness. Further studies are necessary to conclude long term efficacy and safety profile of brivaracetam. # Conclusion The treatment of epilepsy with pharmacologic agents is a difficult task due to balancing the efficacy of the drug with the side effect profile that will allow for the best quality of life for the patient. There are approximately 30 antiepileptic agents for clinicians to choose from. Brivaracetam is a novel antiepileptic agent that was approved for use by the FDA in 2016 and is showing promising results as monotherapy and adjunctive therapy in individuals with drug-refractory focal seizures while minimizing adverse drug reactions.

Migraine is a common form of primary headache, affecting up to 1 in every 6 Americans. The pathophysiology is an intricate interplay of genetic factors and environmental influence and is still being elucidated in ongoing studies. The trigeminovascular system is now known to have a significant role in the initiation of migraines, including the release of pain mediators such as CGRP and substance P. Traditional treatment of migraine is usually divided into acute and preventive treatment. Acute therapy includes non-specific therapy, such as NSAIDs and other analgesics, which may provide relief in mild to moderate migraines. 5-HT1 agonists may provide relief in severe migraine, but are not universally effective and carry a significant side-effect profile with frequent redosing requirement. Prophylactic therapy may reduce the occurrence of acute migraine attacks in selected patients, but does not completely eliminate it. More recently, CGRP antagonism has been studied and shown to be effective in both abortion and prevention of migraine. Novel medications, targeting CGRP, divide into CGRP antibodies and receptor antagonists (gepants). Rimegepant, a second-generation gepant, has shown efficacy in several clinical trials in treating acute migraine. Ongoing trials are also evaluating its role in migraine prophylaxis, and results are promising. It is also generally safer for use than existing options, does not appear to increase the chance of developing chronic migraines, and carries a very tolerable side effects profile. It is a part of a growing arsenal in migraine treatment, and may present the silver bullet for treatment of this disease.

An intranasal formulation of midazolam, Nayzilam, has been FDA-approved to treat intermittent, stereotypic episodes of frequent seizure activity. Nayzilam is easy to administer and can quickly treat seizures that occur outside of the hospital. The intra-nasal route of administration allows non-medical personal to administer the drug which makes it more accessible and user-friendly in the event of a seizure. Many studies have indicated quick cessation of seizures with Nayzilam compared to rectal diazepam, which has been the standard of care treatment. Nayzilam has been proven to be safe and effective for acute seizures in children, deeming it a revolutionary alternative in times where intravenous administration is not possible.

Buprenorphine, a novel long-acting analgesic, was developed with the intention of two purposes: analgesia and opioid use disorder. Regarding its pharmacodynamics, it is a partial agonist at mu receptors, an inverse agonist at kappa receptors, and an antagonist at delta receptors. For the purpose of analgesia, three formulations of buprenorphine were developed: IV/IM injectable formulation (Buprenex®), transdermal patch formulation (Butrans®), and buccal film formulation (Belbuca®). Related to opioid dependence, the formulations developed were subcutaneous extended release (Sublocade®), subdermal implant (Probuphine®), and sublingual tablets (Subutex®). Lastly, in order to avoid misuse of buprenorphine for opioid dependence, two combination formulations paired with naloxone were developed: film formulation (Suboxone®) and tablet formulation (Zubsolv®). In this review, we present details of each formulation along with their similarities and differences between each other and clinical considerations.

Multiple sclerosis (MS) is a prevalent neurologic autoimmune disorder affecting two million people worldwide. Symptoms include gait abnormalities, perception and sensory losses, cranial nerve pathologies, pain, cognitive dysfunction, and emotional aberrancies. Traditional therapy includes corticosteroids for the suppression of relapses and injectable interferons. Recently, several modern therapies—including antibody therapy and oral agents—were approved as disease-modifying agents. Monomethyl fumarate (MMF, Bafiertam) is a recent addition to the arsenal available in the fight against MS and appears to be well-tolerated, safe, and effective. In this paper, we review the evidence available regarding the use of monomethyl fumarate (Bafiertam) in the treatment of relapsing-remitting MS.

Multiple myeloma (MM) is a hematologic malignancy characterized by excessive clonal proliferation of plasma cells. The treatment of multiple myeloma presents a variety of unique challenges due to the complex molecular pathophysiology and incurable status of the disease at this time. Given that MM is the second most common blood cancer with a characteristic and unavoidable relapse/refractory state during the course of the disease, the development of new therapeutic modalities is crucial. Belantamab mafodotin (belamaf, GSK2857916) is a first-in-class therapeutic, indicated for patients who have previously attempted four other treatments, including an anti-CD38 monoclonal antibody, a proteosome inhibitor, and an immunomodulatory agent. In November 2017, the FDA designated belamaf as a breakthrough therapy for heavily pretreated patients with relapsed/refractory multiple myeloma. In August 2020, the FDA granted accelerated approval as a monotherapy for relapsed or treatment-refractory multiple myeloma. The drug was also approved in the EU for this indication in late August 2020. Of note, belamaf is associated with the following adverse events: decreased platelets, corneal disease, decreased or blurred vision, anemia, infusion-related reactions, pyrexia, and fetal risk, among others. Further studies are necessary to evaluate efficacy in comparison to other standard treatment modalities and as future drugs in this class are developed.

A migraine is a clinical diagnosis with a presentation of one or more severe unilateral or bilateral headache(s) often preceded by an aura and typically accompanied by nausea, vomiting, photophobia, and/or phonophobia. This neurological disease is often debilitating and greatly affects the quality of life of those it inflicts. In fact, a recent study conducted by the Global Burden of Disease and published in The Lancet Neurology revealed that migraines ranked second to only back pain as the most disabling disease. Triggers for migraines have ranged from female sex, low socioeconomic status, and diet to loud noises, sleep hygiene, and stress. Along with its clinical presentation, laboratory tests and imaging help rule out other potential causes of the headache and lead to a diagnosis of migraine. Migraines are typically divided into three phases: prodromal, headache, and postdrome. The pathophysiology of each phase remains under investigation, with differing theories regarding their pathways. Existing therapies are abortive therapies for acute migraines or preventative therapies. Abortive therapy consists of NSAIDs and triptans. Preventative therapies include tricyclic antidepressants, calcium channel blockers, beta-blockers, and anticonvulsants. In this review, we focus on the role of NSAIDs and the COX-2 inhibitor, celecoxib oral solution, for the abortive treatment of acute migraines.

Abstract Introduction Chronic pain (CP) is a complex multidimensional experience severely affecting individuals’ quality of life. Multiple cognitive, affective, emotional, and interpersonal factors play a major role in CP. Furthermore, the psychological, social, and physical circumstances leading to CP show high inter-individual variability, thus making it difficult to identify core syndrome characteristics. In a biopsychosocial perspective, we aim at identifying a pattern of psycho-physical impairments that can reliably discriminate between CP individuals and healthy controls (HC) with high accuracy and estimated generalizability using machine learning. Methods A total of 118 CP and 86 HC were recruited. All individuals were administered several scales assessing quality of life, physical and mental health, personal functioning, anxiety, depression, beliefs about medical treatments, and cognitive ability. These features were trained to separate CP from HC using support vector classification and repeated nested cross-validation. Results Our psycho-physical classifier was able to discriminate CP from HC with 86.5% balanced accuracy and significance (p = 0.0001). The most reliable features characterizing CP were anxiety and depression scores, and belief of harm from prolonged pharmacological treatments; for HP, the most reliable features were physical and occupational functioning, and vitality levels. Conclusion Our findings suggest that, using psychological and physical assessments, it is possible to classify CP from HC with high reliability and estimated generalizability via (i) a pattern of psychological symptoms and cognitive beliefs characteristic of CP, and (ii) a pattern of intact physical functioning characteristic of HC. We think that our algorithm enables novel insights into potential individualized targets for CP-related early intervention programs.

Abstract Introduction Despite the essential utility of opioids for the clinical management of pain, opioid-induced constipation (OIC) remains an important obstacle in clinical practice. In patients, OIC hinders treatment compliance and has negative effects on quality of life. From a clinician perspective, the diagnosis and management of OIC are hampered by the absence of a clear, universal diagnostic definition across disciplines and a lack of standardization in OIC treatment and assessment. Methods A multidisciplinary panel of physician experts who treat OIC was assembled to identify a list of ten corrective actions—five “things to do” and five “things not to do”—for the diagnosis and management of OIC, utilizing the Choosing Wisely methodology. Results The final list of corrective actions to improve the diagnosis and clinical management of OIC emphasized a need for: (i) better physician and patient education regarding OIC; (ii) systematic use of diagnostically validated approaches to OIC diagnosis and assessment (i.e., Rome IV criteria and Bristol Stool Scale, respectively) across various medical contexts; and (iii) awareness about appropriate, evidence-based treatments for OIC including available peripheral mu-opioid receptor antagonists (PAMORAs). Conclusions Physicians who prescribe long-term opioids should be forthcoming with patients about the possibility of OIC and be adequately versed in the most recent guideline recommendations for its management.

Abstract Concern about the appropriate role of nonsteroidal anti-inflammatory drugs (NSAIDs) in COVID-19 speculate that NSAIDs, in particular ibuprofen, may upregulate the entry point for the virus, the angiotensin-converting enzyme (ACE) 2 receptors and increase susceptibility to the virus or worsen symptoms in existing disease. Adverse outcomes with COVID-19 have been linked to cytokine storm but the most effective way to address exaggerated inflammatory response is complex and unclear. The Expert Working Group on the Commission of Human Medicines in the UK and other organizations have stated that there is insufficient evidence to establish a link between ibuprofen and susceptibility to or exacerbation of COVID-19. NSAID use must also be categorized by whether the drugs are relatively low-dose over-the-counter oral products taken occasionally versus higher-dose or parenteral NSAIDs. Even if evidence emerged arguing for or against NSAIDs in this setting, it is unclear if this evidence would apply to all NSAIDs at all doses in all dosing regimens. Paracetamol (acetaminophen) has been proposed as an alternative to NSAIDs but there are issues with liver toxicity at high doses. There are clearly COVID-19 cases where NSAIDs should not be used, but there is no strong evidence that NSAIDs must be avoided in all patients with COVID-19; clinicians must weigh these choices on an individual basis.

Abstract Cocoa has been reported to have medicinal properties. It contains a wide range of phytochemicals, including polyphenols, which have been shown to exert anti-inflammatory and antioxidant actions, and also to have a positive effect on pain. Other components of cocoa might be able to positively influence pain perception through various mechanisms. Despite encouraging results from preclinical studies, there is a lack of evidence of antinociceptive effects of cocoa from clinical trials in humans. Further research is needed to better identify the active principles in cocoa, to understand the underlying mechanisms of action, and to establish efficacy in humans.

Abstract Introduction In cancer-related pain refractory to systemic opioids, intrathecal (IT) administration of morphine can be a useful strategy. In clinical practice, IT morphine is usually combined with other drugs with different mechanisms of action, in order to obtain a synergistic analgesic effect. However, the discussion on efficacy and safety of IT combination therapy is still ongoing. The aim of this observational study was to report the effects of an IT combination of low doses of ziconotide, morphine, and levobupivacaine in end-stage cancer refractory pain. Methods Sixty adult patients, 21 females and 39 males, were enrolled to an IT device implant. The mean visual analogue scale of pain intensity (VASPI) score was 88 ± 20 mm. All patients started with a triple combination therapy: the initial IT dose of morphine was calculated for each patient based on the equivalent daily dose of morphine; an oral/IT ratio of 400/1 was used. For ziconotide, a standard slow titration schedule was started at 1.2 μg/day and the initial dose of levobupivacaine was 3 mg/day. Results The initial IT mean doses of morphine, ziconotide, and levobupivacaine were 0.8 ± 0.3 mg/day, 1.2 mcg/day and 3 mg/day, respectively. At day 2, a significant reduction in VASPI score was registered (49 ± 17, p

Abstract Pain management is challenging for both clinicians and patients. In fact, pain patients are frequently undertreated or even completely untreated. Optimal treatment is based on targeting the underlying mechanisms of pain and tailoring the management modality for each patient using a personalized approach. This narrative review deals with pain conditions that have a complex underlying mechanism and need an individualized and frequently multifactorial approach to pain management. The research is based on previously conducted studies, and does not contain any studies with human participants or animals performed by any of the authors. This is not an exhaustive review of the current evidence. However, it provides the clinician with a perspective on pain therapy targeting the underlying pain mechanism(s). When dealing with complex pain conditions, the prudent physician benefits from having a deep knowledge of various underlying pain mechanisms in order to provide a plan for optimal pharmacological pain relief to patients.

Abstract Introduction Chronic low back pain (LBP) caused by intervertebral disc herniation was reported in the 2010 Global Burden of Disease study to be the main reason for years lived with disability. It causes significant personal, social, and economic burdens. Many of those who suffer from LBP find conventional medical treatments to be unsatisfactory for treating their pain, so they are increasingly resorting to complementary and alternative medicine (CAM) therapies. Given that the population is aging, there is an urgent need to characterize the combinations of complementary therapies that yield the best outcomes and treatments, even for prolonged periods. This observational study aimed to evaluate the effect of ultramicronized palmitoylethanolamide (umPEA) + CAM (daily functional rehabilitation + decontracting massage) therapies on chronic pain in patients suffering from multiple herniated discs in the lumbar spine. Methods Eligible patients received 600 mg of umPEA twice a day in combination with a daily functional rehabilitation session according to the McKenzie Method of Mechanical Diagnosis and Therapy plus a decontracting massage for 20 consecutive days, followed by 600 mg of umPEA once a day for 40 days in addition to standard therapy. Results The results showed that the average pain intensity score, evaluated via the Numeric Rating Scale, progressively decreased during the study period, reaching a value that was not clinically relevant at the end of the observation period. Pain relief was paralleled by improvements in the physical and mental components of quality of life as evaluated with the SF-36 questionnaire as well as in disability for low back pain as evaluated with the Oswestry Disability Questionnaire. Collectively, the results demonstrate that umPEA in combination with CAM therapies could be an important strategy for combating LBP. Conclusions The multiple action of PEA in combination with CAM therapies may represent the multitarget approach needed to tackle the as-yet unsolved problem of chronic pain resistant to conventional therapies.

A clinical conundrum can occur when a patient with active opioid use disorder (OUD) or at elevated risk for the condition presents with cancer and related painful symptoms. Despite earlier beliefs that cancer patients were relatively unaffected by opioid misuse, it appears that cancer patients have similar risks as the general population for OUD but are more likely to need and take opioids. Treating such patients requires an individualized approach, informed consent, and a shared decision-making model. Tools exist to help stratify patients for risk of OUD. While improved clinician education in pain control is needed, patients too need to be better informed about the risks and benefits of opioids. Patients may fear pain more than OUD, but opioids are not always the most effective pain reliever for a given patient and some patients do not tolerate or want to take opioids. The association of OUD with mental health disorders (dual diagnosis) can also complicate delivery of care as patients with mental health issues may be less adherent to treatment and may use opioids for “chemical coping” as much as for pain control.

# Background Chronic pain significantly worsens the quality of life. Unlike neuropathic, musculoskeletal, postoperative pain, and cancer pain, chronic primary pain cannot be explained by an underlying disease or condition, making its treatment arduous. # Objectives This manuscript intends to provide a comprehensive review of the use of ketamine as a treatment option for specific chronic pain conditions. # Study Design A review article. # Setting A review of the literature. # Methods A search was done on PubMed for relevant articles. # Results A comprehensive review of the current understanding of chronic pain and the treatment of specific chronic pain conditions with ketamine. # Limitations Literature is scarce regarding the use of ketamine for the treatment of chronic pain. # Conclusion First-line treatment for many chronic pain conditions includes NSAIDs, antidepressants, anticonvulsants, and opioids. However, these treatment methods are unsuccessful in a subset of patients. Ketamine has been explored in randomized controlled trials (RCTs) as an alternative treatment option, and it has been demonstrated to improve pain symptoms, patient satisfaction, and quality of life. Conditions highlighted in this review include neuropathic pain, fibromyalgia, complex regional pain syndrome (CRPS), phantom limb pain (PLP), cancer pain, and post-thoracotomy pain syndrome. This review will discuss conditions, such as neuropathic pain, fibromyalgia, complex regional pain syndrome, and more and ketamine’s efficacy and its supplementary benefits in the chronic pain patient population. As the opioid crisis in the United States continues to persist, this review aims to understand better multimodal analgesia, which can improve how chronic pain is managed.

Benzodiazepines are one of the most commonly used medications in the field of anesthesia. They offer excellent anxiolytic and amnestic properties ideal for the perioperative period when patient anxiety is understandably heightened. Remimazolam has presented a favorable alternative to some of the common intravenous anesthetic agents used given its fast onset of action, high safety profile, and reasonably short duration of action. The drugs within the four classes of benzodiazepines, 2-keto-benzodiazepines, 3-hydroxy-benzodiazepines, triazolo-benzodiazepines, and 7-nitro-benzodiazepines provide varying degrees of anxiolysis, sedation, and amnesia. This is provided by the benzodiazepine molecule binding and causing a conformational change to the chloride ion channel to cause hyperpolarization and thus inhibition of the central nervous system. Each type of benzodiazepine has a preferred role within the realm of medicine. For instance, diazepam is used for the treatment of seizures and anxiety. Midazolam’s anxiolytic and anterograde amnestic properties are taking advantage of during the perioperative period. Lorazepam is beneficial for anxiety and status epilepticus. Remimazolam, currently in phase II and III clinical trials, has demonstrated a very short during of action and low context-sensitive half-time, allowing for its rapid removal even during a prolonged infusion. Much of its properties may be credited to being a soft drug, meaning it is a metabolically active drug that is rapidly inactivated in the body. This provides anesthesiologists and other practitioners administering it with a more predictable sedative. These properties have the potential to push it towards becoming the drug of choice for premedication during the perioperative period and sedation in the ICU. Furthermore, remimazolam does not seem to rely on any specific organ to be metabolized. The drug's ester moiety makes it a substrate for non-specific tissue esterase enzymes, meaning its metabolism and elimination are not impaired in patients with hepatic and/or renal disease. Its addictive potential closely resembles that of its parent compound, midazolam. Reports of its adverse reactions include headache and somnolence after an involuntary movement during infusion. Benzodiazepines are a great adjunct to anesthetic care. Remimazolam’s safety profile, pharmacokinetics, pharmacodynamics, and potential practical use make it quite favorable in this regard. It has the potential to equip anesthesiologists and other medical practitioners with a more predictable medication that has a good safety profile. However, further large clinical trials will provide us with a better understanding of the advantages and disadvantages of remimazolam.

Abstract With the rising concerns about long-term opioid use, particularly in patients with chronic noncancer pain, more and more patients are being considered for decreased doses or discontinuation of opioid therapy. This is a challenging clinical situation for both patient and clinician and should be presented in a shared decision-making model so that the patient understands the risks of opioid therapy and how the therapy will be discontinued. The patient should be aware of the long-range plan and its milestones. It is imperative that alternate pain control treatments be made available to the patient early, and that the patient never feels abandoned by the healthcare team. There can be many barriers in shared decision-making and multiple discussions between patient and provider may be required. Opioid use should not be decreased sharply or discontinued abruptly, but should be gradually decremented in a process known as tapering. Tapering should be systematic and planned in advance with the patient knowing the steps. Slow tapers (over months) are more comfortable for the patients but may not always be appropriate. There is guidance for planning the taper and the patient should be closely monitored throughout this process. If withdrawal symptoms occur, they can be managed, for example, with lofexidine. Patients should get full support as they explore new pain control options. For patients who have opioid use disorder, addiction counseling may be appropriate. Navigating opioid discontinuation can be slow work, but optimal results occur when the healthcare team works together and respectfully with the patient.

Abstract The presence of pain in elderly persons with cognitive decline is often neglected, under-reported, underestimated, misdiagnosed and not adequately treated, with consequences that have a strong impact on health, independence in activities of daily living and quality of life. There is no empirical evidence that people with dementia experience less pain; therefore, in patients with severe cognitive impairment the progression of cognitive decline dramatically affects the ability to verbalize the presence of pain. Self-assessment scales are considered the “gold standard” for pain assessment, but the presence of cognitive impairment is likely to reduce the reliability of these measures. Treatment of pain in elderly with cognitive decline or dementia is based on non-pharmacological and pharmacological strategies. Pharmacological treatment should consider physiological changes, high comorbidity and drug interactions that occur frequently in the elderly. This narrative review aims to describe current knowledge, methods of detection and treatment approaches for chronic pain in elderly persons with cognitive deficits.