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BACKGROUND: A crisis in pain management persists, as does the epidemic of opioid overdose deaths, addiction, and diversion. Pain medicine is meeting these challenges by returning to its origins: the Bonica model of multidisciplinary pain care. The 2018 Academic Consortium White Paper detailed the historical context and magnitude of the pain crisis and the evidence base for nonpharmacologic strategies. More than 50% of chronic opioid use begins in the acute pain care setting. Acupuncture may be able to reduce this risk. OBJECTIVE: This article updates the evidence base for acupuncture therapy for acute pain with a review of systematic reviews and meta-analyses on postsurgical/perioperative pain with opioid sparing and acute nonsurgical/trauma pain, including acute pain in the emergency department. METHODS: To update reviews cited in the 2018 White Paper, electronic searches were conducted in PubMed, MEDLINE, CINAHL, and the Cochrane Central Register of Controlled Trials for acupuncture and acupuncture therapy and acute pain, surgery, peri-operative, trauma, emergency department, urgent care, review(s) , systematic review, meta-analysis, with additional manual review of titles, links, and reference lists. RESULTS: There are 22 systematic reviews, 17 with meta-analyses of acupuncture in acute pain settings, and a review for acute pain in the intensive care unit. There are additional studies of acupuncture in acute pain settings. CONCLUSION: The majority of reviews found acupuncture therapy to be an efficacious strategy for acute pain, with potential to avoid or reduce opioid reliance. Future multicenter trials are needed to clarify the dosage and generalizability of acupuncture for acute pain in the emergency department. With an extremely low risk profile, acupuncture therapy is an important strategy in comprehensive acute pain care.

Osteoarthritis (OA) is a progressive joint disease, that occurs frequently in the aging population and is a major cause of disability worldwide. Both glucosamine and chondroitin are biologically active molecules that are substrates for proteoglycan, an essential component of the cartilage matrix. Evidence supports the use of glucosamine and chondroitin as symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) with impact on OA symptoms and disease-modifying effects in the long term. Glucosamine and chondroitin are administered in exogenous form as a sulfate salt and multiple formulations of these agents are available, both as prescription-grade products and nutritional supplements. However, while all preparations may claim to deliver a therapeutic level of glucosamine or chondroitin not all are supported by clinical evidence. Only patented crystalline glucosamine sulfate (pCGS) is shown to deliver consistently high glucosamine bioavailability and plasma concentration in humans, which corresponds to demonstrated clinical efficacy. Similarly, clinical evidence supports only the pharmaceutical-grade chondroitin sulfate. The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) advocates, through careful consideration of the evidence base, that judicious choice of glucosamine and chondroitin formulation is essential to maximize clinical benefit, patient adherence and satisfaction with treatment. In future, the ESCEO recommends that complex molecules with biological activity such as pCGS may be treated as "biosimilars" akin to the European Medicines Agency guidance on biological medicinal products. It seems likely that for all other complex molecules classed as SYSADOAs, the recommendation to use only formulations clearly supported by the evidence-base should apply.

Aim: This study was aimed at investigating the availability and prescription of different medicinal variants of cannabis and their status in European countries., Methods: A -web-based survey was sent to all member societies of the -European Federation of Addiction Societies (EUFAS) in 2 waves during the summer of 2017. All 34 member societies in 19 different European countries were invited to participate., Results: We received 28 responses from 17 European countries. The cannabis extract nabiximol (Sativex®) is the most prevalent cannabis-based medicinal product marketed in Europe. Synthetic cannabinoids and standardized cannabis are less prevalent, and no country allows the growing of cannabis for personal medical use. The bringing of medical cannabis products from across borders to countries where the drug is not marketed is quite limited. The use of medical cannabis is restricted to some central medical conditions, but off-label use is prevalent in some countries., Conclusion: The use of medical cannabis in Europe seems to be restricted mostly to the use of the cannabis extract, nabiximol. There is only limited use of the cannabis plant as such for medical purposes, possibly indicating a different scenario in Europe as compared to the USA. Position Statement: EUFAS as an umbrella association of European addiction societies stresses the need for further studies on the efficacy of medical cannabis and warrants for possible dangers associated with the increasing popularity of medical cannabis. We need regulations at European level concerning registration and medical indications, development of uniform compounds and strength of products, and rules concerning sales and marketing., (© 2018 S. Karger AG, Basel.)

Purpose: Chronic low back pain is a leading cause of disability worldwide. A clinical model for its cause is lacking. Defining a cause based clinical model and a framework of understanding back pain in terms of peripheral structural and central functional pain is essential for optimal management., Materials and Methods: We describe the results of the largest published audit of 41 chronic low back pain patients, receiving outpatient sublingual ketamine therapy for defined central functional pain along with conventional peripheral structural pain management. Our clinical model assigns Movement Dysfunction as the primary cause for low back pain symptoms and restores it with Movement Therapy focused rehabilitation which is also defined. Patients were derived from a tertiary single neurosurgical specialist practice in Brisbane Australia over a three year period., Results: Severe pain and disability measurements more than halved and only 13% of patients ceased ketamine prematurely due to predominantly non-sinister side effects common to all pharmaceutical therapies. All other surveyed metrics of utility were highly favourable in this challenging cohort of chronic back pain patients biased to poor outcomes., Conclusions: Outpatient ketamine maintains high efficacy and safety used in conjunction with a unique clinical model that describes chronic low back pain.

Abstract: Many questions regarding the clinical management of people experiencing pain and related health policy decision-making may best be answered by pragmatic controlled trials. To generate clinically relevant and widely applicable findings, such trials aim to reproduce elements of routine clinical care or are embedded within clinical workflows. In contrast with traditional efficacy trials, pragmatic trials are intended to address a broader set of external validity questions critical for stakeholders (clinicians, healthcare leaders, policymakers, insurers, and patients) in considering the adoption and use of evidence-based treatments in daily clinical care. This article summarizes methodological considerations for pragmatic trials, mainly concerning methods of fundamental importance to the internal validity of trials. The relationship between these methods and common pragmatic trials methods and goals is considered, recognizing that the resulting trial designs are highly dependent on the specific research question under investigation. The basis of this statement was an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) systematic review of methods and a consensus meeting. The meeting was organized by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership. The consensus process was informed by expert presentations, panel and consensus discussions, and a preparatory systematic review. In the context of pragmatic trials of pain treatments, we present fundamental considerations for the planning phase of pragmatic trials, including the specification of trial objectives, the selection of adequate designs, and methods to enhance internal validity while maintaining the ability to answer pragmatic research questions., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Background: Basic data on migraine headache characteristics, including frequency and severity, headache-associated impairment, and the intake of pain killer medications, may be influenced by the recording manner of these data. Headache diary can be used for that purpose. This study was done to evaluate if the regular use of headache diary can make a difference for patients with chronic migraine or not. Methods: This study included the patients with chronic migraine with improper headache control, who were coming to neurology outpatient clinic and were asked to record their data using either paper or digital diary. Results: Fifty patients mainly from females were included in our study, showed better compliance and headache control by detection and management of their reported triggers. The most reported triggering factors were stress followed by sleep deprivation. Conclusions: Headache diary regular recording is helpful in better management of headache attacks regarding frequency, duration, and pain intensity in patients with chronic migraine. [ABSTRACT FROM AUTHOR]

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Author(s): Samir Jaber [sup.1], Giuseppe Citerio [sup.2] [sup.3], Daniel Talmor [sup.4] Author Affiliations: (1) grid.414352.5, Intensive Care Unit and Transplantation, Department of Anesthesia and Critical Care B (DAR B), Hôpital [...]

Opioid misuse is a widespread public health problem, and opioids are often prescribed in the dental environment. These recommendations provide alternatives to opioids to reduce or eliminate dental procedure–related acute pain. A multidisciplinary working group developed these clinical recommendations to specifically address procedure-related acute pain. These recommendations, which are based on published peer-reviewed research and guidelines, include therapies used before, during, and after dental procedures. When evidence is not definitive, the best practices, which are based on experts' consensus, are included. The recommendations are not intended to be exhaustive. These recommendations are a summary of the evidence and best practices for opioid alternatives to treat acute pain related to dental procedures. Dental providers should prioritize opioid stewardship when managing procedure-related pain with strategies such as thorough preprocedure pain assessment, minimally invasive techniques, preemptive analgesia, intraprocedure pain management, and appropriately selected postprocedure pharmacologic therapy. These recommendations are a concise resource for clinical providers. It is important to address patients' procedure-related pain, using nonopioids whenever possible. Alternatives are outlined, allowing providers to make informed decisions. [ABSTRACT FROM AUTHOR]

This discussion article examines narrative positioning related to pain management for people who use substances at the end of life. We explore how dominant narrative genres associated with biomedicine, such as 'restitution' and narratives common within the context of drug services such as 'recovery' can hinder effective pain management within this population. We argue that these discourses can marginalise the ethical self-identity of patients who use substances at the end of life. It can also trouble health and social care professionals in supporting patients and generating counter-narratives that challenge those often associated with substance use. Stigma is a common experience for this population with stereotyping as 'junkies' and associated with criminality. They are positioned as drug-seeking, and this requires more surveillance at the end of life when opioid therapy is potentially more available and authorised. This can make it challenging to generate 'companion' stories that are positive and maintain moral adequacy. Dominant biomedical narrative genres often prevent the recognition of the fractured stories that people using substances can often present with. This can lead to narrative silencing and to the under treatment of pain. The person's self-identity is invested in narratives of recovery, and opioid use symbolises their addicted past because for practitioners, this population is at clinical risk with the potential for drug seeking behaviours. Whilst not requiring formal ethical review this discussion paper was constructed in accordance with good scientific practice with the work of other researchers respected and cited appropriately. [ABSTRACT FROM AUTHOR]

The adulteration of whiskey with analgesics and sedation drugs has been a common practice to prevent hangover the following day and promote loss of consciousness. In both situations, the portable and low cost detection platforms are of paramount importance for forensic investigations. This report describes the use of electrochemical paper‐based analytical devices (ePADs) fabricated by pencil drawing for detecting metamizole, paracetamol and midazolam maleate in whiskey. Different types of paper substrates and graphite pencils were initially characterized with ferrocyanide. The best results were achieved using vegetal paper and Aquarelle/6B pencils. ePADs revealed a decrease in current signal indicating a short lifetime, thus limiting their use to disposable sensors. Despite the short lifetime, the graphite pencil ePADs revealed good electrochemical reproducibility (RSD=3.3 %). The forensic feasibility of the proposed ePADs was demonstrated through the analysis of metamizole and paracetamol in whiskey. The limit of detection (LOD) achieved for paracetamol and metamizole were 45 and 20 mg L−1, respectively. ePADs were also tested to detect midazolam maleate in whiskey. The signal recorded exhibited linear correlation in a wide concentration range (25–1000 mg L−1) and a LOD of ca. 5 mg L−1. Considering the disposability and operational simplicity, ePADs offer a good strategy for detecting adulterations in alcoholic beverages at the point‐of‐need. [ABSTRACT FROM AUTHOR]

Poor research reporting is a major contributing factor to low study reproducibility, financial and animal waste. The ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines were developed to improve reporting quality and many journals support these guidelines. The influence of this support is unknown. We hypothesized that papers published in journals supporting the ARRIVE guidelines would show improved reporting compared with those in non-supporting journals. In a retrospective, observational cohort study, papers from 5 ARRIVE supporting (SUPP) and 2 non-supporting (nonSUPP) journals, published before (2009) and 5 years after (2015) the ARRIVE guidelines, were selected. Adherence to the ARRIVE checklist of 20 items was independently evaluated by two reviewers and items assessed as fully, partially or not reported. Mean percentages of items reported were compared between journal types and years with an unequal variance t-test. Individual items and sub-items were compared with a chi-square test. From an initial cohort of 956, 236 papers were included: 120 from 2009 (SUPP; n = 52, nonSUPP; n = 68), 116 from 2015 (SUPP; n = 61, nonSUPP; n = 55). The percentage of fully reported items was similar between journal types in 2009 (SUPP: 55.3 ± 11.5% [SD]; nonSUPP: 51.8 ± 9.0%; p = 0.07, 95% CI of mean difference -0.3–7.3%) and 2015 (SUPP: 60.5 ± 11.2%; nonSUPP; 60.2 ± 10.0%; p = 0.89, 95%CI -3.6–4.2%). The small increase in fully reported items between years was similar for both journal types (p = 0.09, 95% CI -0.5–4.3%). No paper fully reported 100% of items on the ARRIVE checklist and measures associated with bias were poorly reported. These results suggest that journal support for the ARRIVE guidelines has not resulted in a meaningful improvement in reporting quality, contributing to ongoing waste in animal research. [ABSTRACT FROM AUTHOR]

Chronic pain is a complex condition that significantly impacts patients' quality of life and presents a substantial burden on healthcare systems. This paper reviews innovative approaches to chronic pain management, addressing existing pharmacological options and integrating therapies. In the context of emerging pharmacological treatments, including biologics and novel analgesics, targeted pain pathways are evaluated for their potential to provide more effective and reliable pain relief. Additionally, advancements in neuromodulation techniques, such as sleep-inducer rope provocation and Transcutaneous Electrical Nerve Stimulation (TENS), are explored for their role in modulating pain signals and reducing reliance on opioids. The integration of behavioral health sciences through mobile technology and wearable devices is examined for their ability to enhance patient self-management and facilitate real-time pain monitoring. Furthermore, this paper discusses the importance of combining various branches of care models that integrate medical, psychological, and physical therapy approaches to address the multifactorial nature of chronic pain. Case studies and objective challenges are reviewed to highlight the effectiveness and obstacles of these innovative approaches. By adopting a holistic and patient-centered perspective, this paper aims to provide a comprehensive understanding of future directions in chronic pain management, emphasizing the need for ongoing research and collaboration with healthcare professionals to improve patient outcomes and quality of life. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses articles in the issue on topics including mental health disorders, and opioid crisis.

The United States is facing a national opioid epidemic, and medical systems are in need of non-pharmacologic strategies that can be employed to decrease the public's opioid dependence. Acupuncture has emerged as a powerful, evidence-based, safe, cost-effective, and available treatment modality suitable to meeting this need. Acupuncture has been shown to be effective for the management of numerous types of pain conditions, and mechanisms of action for acupuncture have been described and are understandable from biomedical, physiologic perspectives. Further, acupuncture's cost-effectiveness can dramatically decrease health care expenditures, both from the standpoint of treating acute pain and through avoiding addiction to opioids that requires costly care, destroys quality of life, and can lead to fatal overdose. Numerous federal regulatory agencies have advised or mandated that healthcare systems and providers offer non-pharmacologic treatment options for pain. Acupuncture stands out as the most evidence-based, immediately available choice to fulfill these calls. Acupuncture can safely, easily, and cost-effectively be incorporated into hospital settings as diverse as the emergency department, labor and delivery suites, and neonatal intensive care units to treat a variety of commonly seen pain conditions. Acupuncture is already being successfully and meaningfully utilized by the Veterans Administration and various branches of the U.S. military, in some studies demonstrably decreasing the volume of opioids prescribed when included in care. [ABSTRACT FROM AUTHOR]

Purpose: Given the current and increasing awareness of the opioid crisis, this study aimed to characterise the types of analgesic prescription for conservatively managed renal colic., Methods: This was a retrospective cohort study of consecutive patients presenting to the Emergency Department (ED) in 2014-2019. Patients were included if they had radiographically confirmed obstructing calculus, managed conservatively without intervention, and were given a prescription for analgesia on discharge. Patient demographics were recorded and analysed. Opioid, non-opioid, and alpha-blocker medications were compared according to patient and disease parameters, and clinician training. Oral morphine equivalents (OMEs) were used to compare prescribed quantities. Subgroup analyses of stone size and location were performed., Results: Our analysis included 1761 patients with confirmed renal colic: median age of 50 years (16-96). Altogether, 88% of included patients were prescribed opioids on discharge, while only 68% were prescribed non-opioids (p < 0.001). Oxycodone immediate release was the most frequently prescribed analgesic. Logistic regression modelling controlling for patient and disease characteristics significantly predicted more non-opioid (p < 0.001) and alpha-blocker (p = 0.037) prescription with clinician training < 3 years. Linear regression modelling demonstrated that clinicians training < 3 years predicted lower OMEs per prescription compared to clinicians with ≥ 3 years of training (p = 0.001). Subgroup analyses supported similar predictions with training., Conclusions: Prescribing patterns are associated with different clinician experience levels. However, a substantial amount of opioids are still given overall on patient discharge regardless of the clinician experience. Educational interventions aimed at reducing the opioid prescription rate and quantities may be considered for clinicians of all training levels.

When tested in the acetic acid-induced writhing and formalin-induced paw-licking tests, the ethanol extract of Vernonia patula (VP) aerial parts showed significant antinociceptive activity. In neuropharmacological tests, it also significantly delayed the onset of sleep, increased the duration of sleeping time, and significantly reduced the locomotor activity and exploratory behaviour of mice. Five phenolic compounds, namely gallic acid, vanillic acid, caffeic acid, quercetin and kaempferol, were detected in VP following HPLC-DAD analysis. The presence of these phenolic compounds in VP provides some support for the observed antinociceptive and sedative effects. A computational study was performed to predict the binding affinity of gallic acid, vanillic acid, caffeic acid, quercetin and kaempferol towards the cannabinoid type 1 (CB1) receptor. Caffeic and vanillic acid showed the highest probable ligand efficiency indices towards the CB1 target. Vanillic acid displayed the best blood-brain barrier penetration prediction score. These findings provide some evidence for the traditional use of VP to treat pain., (© 2020 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.)

Objective. Understanding factors while selecting an analgesic and its usage pattern by Indian healthcare practitioners (HCPs). Methods. Questionnaire-based survey was conducted among six healthcare specialties. Results. Total 448 HCPs participated. Patient’s age (72.8%, 74.4%, 87.5%, and 78.9%) and duration of therapy (70.8%, 66.2%, 69.6%, and 73.6%) were main attributes for selecting an opioid according to general practitioners (GPs), dentists, consulting physicians (CPs), and surgeons, respectively. Patient’s age was important factor while selecting NSAID according to 77.60%, 66.91%, and 84.20% of GPs, dentists, surgeons, respectively. For mild pain, paracetamol was the choice according to 77%, 78.57% and 74% of GPs, CPs, and surgeons, respectively. For moderate pain, 77%, 87.50%, 68%, and 80.30% of GPs, CPs, surgeons and orthopedicians, respectively, preferred the use of paracetamol + tramadol combination. For moderate pain, NSAID + paracetamol and paracetamol+diclofenac were used by 68.94% and 47.73% of orthopedicians, respectively. Lack of pain clinic (38.8%) in city was commonly cited reason for not referring patients to pain clinics. Conclusion. Patient’s age, duration of therapy, comorbid conditions, frequency of dosing, and severity of pain are important parameters while selecting analgesics. Paracetamol and its combinations are commonly used for mild and moderate pain, respectively. Pain clinics currently have limited presence in India. [ABSTRACT FROM AUTHOR]

Chronic mechanical low back pain (cLBP) is a leading cause of disability and a major socio-economic burden internationally. The lifetime prevalence of non-specific LBP is approximately 84%, with the prevalence of cLBP at about 23%. Clinically available analgesic/adjuvant medications often provide inadequate pain relief in patients experiencing cLBP. Hence, the urgency for discovery of effective and better tolerated medications. Fourteen days after the induction of five shallow annular punctures (5X) in the lumbar intervertebral discs at L4/L5 and L5/L6 in male Sprague-Dawley rats, mechanical hyperalgesia was fully developed in the lumbar axial deep tissues at L4/L5 (primary) and L1 (secondary). Importantly, mechanical allodynia in the hindpaws was absent. From day 28, we assessed the face validity of our mild to moderate LBP-5X rat model using four clinically available analgesic/adjuvant drugs, namely gabapentin, morphine, meloxicam and amitriptyline relative to vehicle. Additionally, the anti-hyperalgesic effects of J-2156, a highly selective small molecule somatostatin type 4 receptor agonist was assessed. Single i.p. bolus doses of gabapentin and meloxicam at the highest doses tested (100 and 30 mg/kg, respectively) alleviated secondary hyperalgesia (L1) but not primary hyperalgesia (L4/5). Morphine at 1 mg/kg alleviated both primary and secondary hyperalgesia in these tissues, whereas amitriptyline at the doses tested, lacked efficacy. These findings attest to the face validity of our model. J-2156 at 10 and 30 mg/kg alleviated secondary hyperalgesia in the lumbar axial deep tissues at L1 with a non-significant trend for relief of primary hyperalgesia in the corresponding tissues at L4/L5 in these animals., (© 2020 John Wiley & Sons Australia, Ltd.)

Objective: To assess the effect of perioperative pregabalin on pain behavior in dogs after intervertebral disc surgery., Study Design: Prospective, randomized, controlled clinical trial with a blinded observer., Animals: Forty-six client-owned dogs undergoing intervertebral disc surgery., Methods: Dogs were randomly assigned to two groups, with the placebo group receiving opioids alone and the pregabalin group receiving opioids plus pregabalin. Opioid analgesia consisted of 0.6 mg/kg l-methadone given intravenously at anesthetic induction, followed by 0.2 mg/kg given at 8, 16, and 24 hours after extubation and fentanyl patches applied at the end of surgery. Pregabalin was given orally (4 mg/kg) 1 hour before anesthesia, followed by postoperative treatment three times per day (4 mg/kg) for 5 days. The outcome measures were the treatment-group differences in peri-incisional mechanical sensitivity and Glasgow Composite Measure Pain Scale (CMPS-SF) assessed during the first 5 postoperative days. Pregabalin serum concentrations were measured after 24, 72, and 120 hours., Results: Pregabalin reduced pain levels in the treatment group by a mean of 2.5 CMPS-SF units (95% confidence interval [CI] = -3.19 to -1.83, P < .001) compared with the control group during the study period. Pregabalin increased the mechanical nociceptive threshold by a mean of 6.89 N per day (95% CI = 1.87-11.92, P < .001) and of 7.52 N per day (95% CI = 2.29-12.77, P < .001) during the study period, depending on location. Mean levels of serum pregabalin were 5.1, 4.71, and 3.68 μg/mL at 24, 72, and 120 hours postoperatively, respectively., Conclusion: Postoperative signs of pain after surgical treatment of intervertebral disc herniation (IVDH) were reduced when dogs received perioperative pregabalin rather than opioids alone., Clinical Significance: Perioperative pregabalin reduces postoperative pain after surgical treatment of IVDH., (© 2020 The American College of Veterinary Surgeons.)

General Purpose: To provide information about the effectiveness of topical analgesic and local anesthetic agents for reducing pain associated with chronic leg ulcers., Target Audience: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care., Learning Objectives/outcomes: After participating in this educational activity, the participant will:1. Distinguish adverse reactions to topical analgesics and local anesthetic agents.2. Evaluate the effectiveness of topical analgesics and local anesthetic agents for pain associated with chronic leg ulcers.3. Identify substances used as topical analgesics and local anesthetic agents and the application of those agents., Abstract: To examine the evidence related to the effectiveness of topical analgesic and topical local anesthetic agents for reducing pain associated with chronic leg ulcers.A systematic search and review of the literature were undertaken using key search terms such as leg ulcers, topical anesthetics, topical analgesics, and pain. Six databases were electronically searched for articles published between January 1990 and August 2019.A total of 23 articles were identified that met the inclusion criteria. Data were extracted using content analysis. Most of the included studies were randomized controlled trials; however, the reported methodology for most of studies was poor, so the validity and reliability of the evidence are uncertain. Lidocaine/prilocaine cream, ibuprofen foam, and morphine gel were the most examined topical agents. Lidocaine/prilocaine cream significantly improved wound-related pain compared with all other studied agents. For topical analgesic agents, ibuprofen foam reduced chronic leg ulcer pain significantly, whereas morphine gel was ineffective.Lidocaine/prilocaine cream and ibuprofen foam are effective agents for reducing wound-related pain associated with chronic leg ulcers. Effective use of topical agents could reduce the need for systemic pain relief agents, mitigating potential adverse effects, while giving clinicians another treatment option to manage wound-related pain associated with chronic leg ulcers.

Aims: To explore recollections of pain and pain management during induced abortions., Design: Mixed-methods exploratory study in Sweden., Methods: A web-based survey was distributed between October 2017 - July 2018 via Swedish discussion boards and social media. Open-ended questions were asked about recollection of pain and pain management, followed by self-reported ratings. The survey was answered by 185 participants, responses were analysed with qualitative content analysis., Findings: Recollections of pain intensity illustrated considerable pain and a traumatic event, described in temporal aspects and likened to other painful conditions such as dysmenorrhoea and childbirth. Recollections of pain management illustrated experiences of insufficient treatment of pain and dissatisfaction with pain management, including inefficient treatment and lack of professional attendance. Psychological aspects and consequences illustrated that participants related psychological distress to physical pain, felt unprepared for the physical pain and emphasized the importance of psychological support. Those who experienced intense pain described long-term psychological consequences, including fear of childbirth., Conclusion: Physical pain and psychological distress can manifest as considerable challenges during induced abortion. Abortion-related pain is a multidimensional phenomenon involving physical and psychological components that needs to be rigorously treated. When physical pain is unsuccessfully treated, women may experience long-term psychological consequences after an abortion., Impact: The results illustrate the importance of holistic abortion care where the multidimensional components of abortion-related pain are considered. Patients need to be offered sufficient preparatory information about potential physical pain and psychological distress. This study indicates that there is room for improvement in pain management. Larger studies are needed., (© 2019 John Wiley & Sons Ltd.)

Background and Objective: Pain is a common symptom in patients who survive cancer and in those who live with progressive advanced disease. Evidence from meta-analyses suggests that pain remains poorly controlled for a large proportion of patients; barriers to good management include poor assessment of pain, inadequate support for patient self-management and late or inadequate access to strong opioid analgesia in those with advanced disease.Methods: The European Pain Federation (EFIC) established a Task Force in 2017 which convened a European group of experts, drawn from a diverse range of relevant clinical disciplines, to prepare a position paper on appropriate standards for the management of cancer-related pain. The expert panel reviewed the available literature and made recommendations using the GRADE system to combine quality of evidence with strength of recommendation. The panel took into account the desirable and undesirable effects of the management recommendation, including the cost and inconvenience of each when deciding the recommendation.Results and Conclusions: The 10 standards presented are aimed to improve cancer pain management and reduce variation in practice across Europe. The Task Force believes that adoption of these standards by all 37 countries will promote the quality of care of patients with cancer-related pain and reduce unnecessary suffering.Significance: Pain affects up to 40% of cancer survivors and affects at least 66% of patients with advanced progressive disease, many of whom experience poor pain control. These 10 standards are aimed to improve cancer pain management, promote the quality of care of patients and reduce variation across Europe. [ABSTRACT FROM AUTHOR]

An electrochemical sensor for paracetamol is described that consists of a glassy carbon electrode (GCE) that was modified with the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) doped with MnO 2 nanoflowers. The hydrothermally synthesized MnO 2 nanoflowers possess a large surface area and can be doped into PEDOT through electrochemical deposition to form a conducting polymer nanocomposite. The nanoflowers are shown to be uniformly distributed within the nanocomposite as revealed by elemental mapping analysis. The nanocomposite displays excellent catalytic activity toward the electrochemical oxidation of paracetamol. The modified GCE, best operated at a working potential of around 0.37 V (vs. SCE) has a linear response in 0.06 to 435 μM paracetamol concentration range and a very low limit of detection (31 nM at a signal-to-noise ratio of 3). The sensor exhibits excellent reproducibility and stability, and satisfying accuracy for paracetamol detection in pharmaceutical samples. Graphical abstract A highly sensitive electrochemical sensor capable of detecting paracetamol with a limit of detection down to 31 nM was developed based on MnO 2 nanoflowers doped conducting polymer PEDOT.

Abstract: Background: The use of non‐human primates (NHPs) in research remains a major societal concern with public expectations that appropriate anaesthetics and analgesics are used to minimize any pain or distress caused to animals undergoing invasive procedures. A literature review was conducted to examine the reporting of anaesthesia and analgesia methods used in non‐human primates undergoing surgical procedures, with recovery from anaesthesia. Methods: A total of 397 papers from peer‐review journals published between 2010 and 2015 were examined. Results: Only 25.9% of papers reported the analgesic regimen used, with carprofen and buprenorphine the 2 most widely used agents. Reporting of the anaesthetic regimens was included in 49.9% of papers. Ketamine and isoflurane were the most frequently used anaesthetic agents. Conclusions: Anaesthetic and analgesic regimens administered to NHPs remain poorly reported. This lack of detailed descriptions of protocols does little to reassure the public or regulatory authorities that appropriate high standards of perioperative care are employed. [ABSTRACT FROM AUTHOR]

Poorly controlled pain is a global public health issue. The personal, familial and societal costs are immeasurable. Only a minority of European patients have access to a comprehensive specialist pain clinic. More commonly the responsibility for chronic pain management and initiating opioid therapy rests with the primary care physician and other non-specialist opioid prescribers. There is much confusing and conflicting information available to non-specialist prescribers regarding opioid therapy and a great deal of unjustified fear is generated. Opioid therapy should only be initiated by competent clinicians as part of a multi-faceted treatment programme in circumstances where more simple measures have failed. Throughout, all patients must be kept under close clinical surveillance. As with any other medical therapy, if the treatment fails to yield the desired results and/or the patient is additionally burdened by an unacceptable level of adverse effects, the overall management strategy must be reviewed and revised. No responsible clinician will wish to pursue a failed treatment strategy or persist with an ineffective and burdensome treatment. In a considered attempt to empower and inform non-specialist opioid prescribers, EFIC convened a European group of experts, drawn from a diverse range of basic science and relevant clinical disciplines, to prepare a position paper on appropriate opioid use in chronic pain. The expert panel reviewed the available literature and harnessed the experience of many years of clinical practice to produce these series of recommendations. Its success will be judged on the extent to which it contributes to an improved pain management experience for chronic pain patients across Europe.Significance: This position paper provides expert recommendations for primary care physicians and other non- specialist healthcare professionals in Europe, particularly those who do not have ready access to specialists in pain medicine, on the safe and appropriate use of opioid medications as part of a multi-faceted approach to pain management, in properly selected and supervised patients. [ABSTRACT FROM AUTHOR]

Background: It is common practice for emergency physicians to give parenteral opioids for acute pain, however, some treating physicians have concerns that using parenteral opioids can lead to nausea and vomiting when used alone. Therefore, antiemetics are often given prophylactically with opioids for nausea and vomiting in the emergency department (ED). This systematic review evaluates the use of prophylactic antiemetics with parenteral opioids for the treatment of acute pain in the ED.Methods: A 10-year literature search using keywords was performed in PubMed for English-language human studies. Abstracts were screened to identify high-quality studies, which then underwent a more rigorous structured review. The recommendations are made based on the literature review.Results: Eight articles met criteria for structured review and citation in this article. These include one review article, two randomized controlled trials, three prospective observational trials, one retrospective study, and one pre- and post-intervention trial.Conclusions: Based on the literature review, routine use of prophylactic antiemetics are not indicated with administration of parenteral opioids for treatment of acute pain in the ED, as nausea and vomiting are infrequent side effects. The recent literature clearly demonstrates that there are potential undesirable side effects from the use of antiemetics when using opioids. However, one subgroup of patients, those with a known history of nausea and vomiting after opioid use or a history of travel sickness, may benefit from the use of prophylactic antiemetic when being treated with parenteral opioids. [ABSTRACT FROM AUTHOR]

Ethnopharmacological Relevance: In Brazilian popular medicine, Lippia alba leaves are used in teas to treat pain and inflammatory diseases., Aim of the Study: to evaluate the chemical composition, antinociceptive, and anti-inflammatory activities of Lippia alba essential oil and its major compound geraniol., Material and Methods: Lippia alba leaves were collected in Pará state, Brazil. The leaf essential oil was obtained using a modified Clevenger-type extractor. Then, the oil was analyzed by GC and GC-MS analyses. To evaluate the toxicity of LaEO and geraniol, the doses of 50, 300, and 2000 mg/kg were used in a mouse model. For antinociception tests, abdominal contortion, hot plate, and formalin tests were used; all groups were treated with LaEO and geraniol at doses of 25, 50, and 100 mg/kg; and to evaluate inflammation using the ear edema model., Results: The constituents identified in the highest content were oxygenated monoterpenes: geraniol (37.5%), geranial (6.7%) and neral (3.8%). The animals treated with LaEO and geraniol demonstrated atypical behaviors with aspects of lethargy and drowsiness, characteristics of animals in a state of sedation; the relative weights showed no significant difference compared to the controls. In the abdominal contortion test, LaEO at 25 mg/kg, 50 mg/kg doses, and 100 mg/kg reduced the number of contortions, representing a percentage reduction of 84.64%, 81.23%, and 66.21% respectively. In the hot plate test, LaEO and geraniol increased the latency time at doses of 25, 50, and 100 mg/kg in all test periods; there was no statistical difference between LaEO and geraniol. In the first phase of the formalin test, only doses of 25 mg/kg and 100 mg/kg of LaEO showed significant activity, reducing the latency time by 53.40% and 58.90%. LaEO at doses of 25 mg/kg and 100 mg/kg reduced the size of the edema, demonstrating an anti-inflammatory activity of 59.38% (25 mg/kg) and 50% (100 mg/kg)., Conclusion: Lippia alba essential oil and geraniol showed central/peripheral analgesic and anti-inflammatory potential and can be used as an alternative or complementary treatment to conventional drugs. More studies are needed to evaluate its action mechanisms and its analgesic effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: The bark of Canarium schweinfurthii is used in ethnomedicine for the treatment of diabetes, pain, malaria, fever and diarrhoea., Aim of the Study: The chemical phytoconstituents, antidiarrheal, anti-inflammatory and antinociceptive effects and safety profile of the aqueous extract of Canarium schweinfurthii bark (AECSB) were investigated., Materials and Methods: Gas chromatography-mass spectrometry (GC-MS) was used to analyse the phytochemical composition. In the acute toxicity test, AECSB were administered up to 2 g/kg by oral gavage. For the subacute toxicity test (28 days), rats in group 1 (control) received no AECSB, while rats in groups 2-4 were administered different doses of AECSB. Charcoal meal transit and castor oil-induced diarrhoea models were used to study the antidiarrheal effect, while egg albumin/carrageenan and acetic acid/tail immersion models were used for the anti-inflammatory and antinociceptive studies, respectively. With the exception of the acute toxicity experiment, AECSB was administered orally at doses of 200, 400 and 800 mg/kg., Results: Bioactive phytoconstituents identified include p-cymene, δ-terpinene, linalool and phytol. No adverse effects or mortality were observed in acute and subacute studies. Treatment with AECSB (28 days) had no significant effect on organ weight, biochemical, hematologic and histopathologic parameters compared to the control groups (p > 0.05). Comparable antidiarrheal and antinociceptive effects were observed in both AECSB- and standard drug-treated groups, while the 400 and 800 mg/kg AECSB-treated groups showed remarkable anti-inflammatory effects compared to the standard drug-treated and control groups (p < 0.05)., Conclusion: AECSB has antidiarrheal, antinociceptive and anti-inflammatory effects and can be safely used for therapeutic purposes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Piper methysticum G. Forst (Piperaceae) is traditionally consumed in Polynesian culture. The roots are used to produce an entheogenic drink and traditional medicine with sedative and anxiolytic properties. There is also evidence that it functions as a pain reliever. Kavalactones, its main active ingredients, exhibit psychoactive effects on the central nervous system. However, the active ingredients and pharmacological mechanisms underlying the analgesic effect of kavalactones are unclear., Aim of the Study: This study investigated the effects of kavain and yangonin on nociception, inflammatory hyperalgesia, and neuropathic mechanical allodynia at the spinal level., Materials and Methods: Male Sprague-Dawley rats were administered kavain and yangonin (27.14 and 19.36 nmol/rat) via intrathecal injection. Tail-flick tests were performed to evaluate the anti-nociceptive properties. The efficacy of kavain and yangonin on inflammatory hyperalgesia was examined using a plantar test in rats with carrageenan-induced paw inflammation. The von Frey test was used to assess mechanical allodynia induced by partial sciatic nerve ligation., Results: Intrathecal injection of yangonin demonstrated a relatively potent anti-nociceptive effect and attenuated carrageenan-induced hyperalgesia. These effects were completely reversed by the co-administration of PF 514273, a cannabinoid 1 (CB 1 ) receptor antagonist. However, yangonin did not affect mechanical allodynia at the spinal level. Kavain, another abundant kavalactone, did not affect nociception, hyperalgesia, or mechanical allodynia at the spinal level., Conclusions: Overall, our study demonstrated that yangonin exerts anti-nociception and anti-inflammatory hyperalgesia effects via CB 1 receptors at the spinal level. We identified a single kavalactone, yangonin, extracted from kava as a promising treatment for pain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Pain and inflammation are the most frequent reasons for which people seek medical care. Currently available analgesics against these conditions produce fatal adverse effects. NPK 500 capsules is an alternative herbal analgesic employed to treat dysmenorrhea, peptic ulcer and pain. NPK 500 is produced from Cassia sieberiana. A plant used in traditional medicine to treat pain and inflammation., Aim of the Study: This study reports the analysis, phytochemical characterization and mechanism of analgesic and anti-inflammatory activities of two NPK 500 capsules, called old and new NPK500 capsules (ONPK500 and NNPK500) respectively., Materials and Methods: Physicochemical, organoleptic, GC-MS and LC-MS methods were employed to analyze the NPK 500 capsules. Analgesic activity was evaluated using tail immersion, Randall-Selitto and acetic acid induced writing tests. Anti-inflammatory activity was evaluated using carrageenan-induced rat paw inflammation. Additionally, pro-inflammatory mediators such as prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase 1 and 2 (COX-2 and COX-1) were quantified in the sera of the rats using Enzyme Linked Immunosorbent Assay (ELISA) kits., Results: Thirteen major compounds were characterized in the NNPK 500 capsules via the GC-MS and LC-MS spectroscopies. Kaempferol was the major compound characterized in addition to physcion, β-sitosterol 3-O-β-D-glucopyranoside, betulinic acid and nine others. Physicochemical and organoleptic indices of the capsules were also derived for its authentication and quality control. Furthermore, NNPK 500 0.5-1.5 mg/kg p.o. produce significant (P < 0.5) analgesic activity (160-197%) higher than that of ONPK500 (109.8%) and Morphine (101%) in the tail immersion test. The analgesic activity of NNPK 500 0.5-1.5 mg/kg p.o. (171.0-258.3%) and ONPK 500 (179.5%) were also significant (P < 0.01) and higher than that of Aspirin (103.00%) in the Randall-Selitto test. Both capsules also demonstrated significant (P < 0.5) analgesic and anti-inflammatory activities in the acetic acid-induced writhing and carrageenan-indued paw edema tests respectively. The two NPK500 capsules also, significantly (P < 0.5) inhibited PGE2 and iNOS but not COX-2 and COX-1 in the carrageenan-indued paw edema test., Conclusion: These results show that NNPK 500 and ONPK 500 capsules possessed potent analgesic and anti-inflammatory activities via inhibition of PGE2 and iNOS as a result of their chemical constituents. NPK500 capsules thus, relief acute pain and inflammation without causing gastrointestinal, renal or hepatic injuries, since they did not inhibit COX-1., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The global increase in forcibly displaced populations highlights the importance of understanding their health needs. Chronic pain is prevalent among refugees, poses significant personal and public health challenges, and complicates their integration into new home countries. Understanding refugees' pain post-migration and how it is being managed is crucial for ensuring adequate and timely interventions and fostering health equity. This paper explores the associations between pain levels and the use of painkillers, healthcare services, and long-term impairment among Syrian refugees with chronic pain, one year after their resettlement in Norway., Methods: This cross-sectional study is based on survey data collected from 353 quota refugees in 2018-19, one year after resettlement in Norway. The primary outcomes were the use of painkillers, the use of healthcare services, and long-term impairment, according to reported chronic pain levels. Associations between these outcomes and chronic pain levels were studied using Poisson regression, adjusted by sociodemographic variables and trauma experience., Results: Of the 353 adults included, 52% were women, and the median age was 36 years. A total of 5% reported very mild/mild, 10% moderate, and 12% strong/very strong chronic pain over the last four weeks. Significant associations were found between all chronic pain levels and use of non-prescription painkillers (adjusted relative risks (aRR) (95% CI)); mild (3.1 (2.0-4.7)), moderate (1.8 (1.1-2.8)), strong (1.7 (1.1-2.6)), and prescription painkillers; mild (4.6 (2.2-9.5)), moderate (5.6 (3.2-10.0)), strong (6.7 (3.9-11.3)), compared to those without chronic pain. Use of emergency rooms, specialist care, and hospitalization were significantly associated with strong chronic pain, with aRR (95% CI) of 2.0 (1.2-3.5), 3.9 (2.1-7.0) and 2.4 (1.3-4.4), respectively. Long-term impairment was strongly associated with chronic pain across all pain levels; mild (8.6 (5.6-13.49)), moderate (6.7 (4.3-10.5)) and strong (6.6 (4.3-10.4))., Conclusion: Despite their young age, more than a quarter of the Syrian refugees in our study reported chronic pain one year after resettlement in Norway. High levels of pain were related to the use of medication, healthcare services, and long-term impairment. Understanding the dynamics of pain among refugees is crucial to ensure adequate and timely management., (© 2024. The Author(s).)

Cold atmospheric plasma (CAP) has been employed as a therapy against both acute and chronic skin lesions, contaminated or not, and has effects on angiogenesis and reepithelialization promoting healing. In this context, the present study aimed to evaluate the effects of a CAP jet associated with pharmacological treatment described by the 2015 AAHA/AAFP pain management guidelines and the 2022 WSAVA guidelines for the recognition, assessment, and treatment of pain, on the healing of chronic skin lesions caused by a pruritic reaction resulting from post-surgical neuropathic pain. To this end, a single CAP application was performed on a feline patient with a 6 months old recurrent contaminated cervical skin lesions along with administration of ketamine (10 µg/kg/min) following the prescription of prednisone (1 mg/kg, SID, 6 days), gabapentin (8 mg/kg, BID, 60 days) and amitriptyline (0.5 mg /kg, SID, 60 days). A single application of plasma associated with an NMDA antagonist, anti-inflammatory steroid, tricyclic antidepressant and gabapentinoid thus provided a significant improvement in the macroscopic appearance of the lesion within 10 days, and the owner reported the cessation of intense itching within the first four hours after treatment and a consequent improvement in the animal's quality of life. The medical treatment was finished almost a year since the writing of this paper, without clinical or reported recurrent signs of the condition. Therefore, we observed that single dose CAP application associated with ketamine, gabapentin, amitriptyline and prednisone leads to significant healing of chronically infected skin lesions resulting from post-surgical neuropathic pain., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

In the pursuit of new lead compounds with fewer side effects than opioids, the novel synthetic phytochemical core, 3,3-dibromoflavanone (3,3-DBF), has emerged as a promising candidate for pain management. Acute assays demonstrated dose-dependent central and peripheral antinociceptive activity of 3,3-DBF through the μ-opioid receptor. This study aimed to explore repeated administration effects of 3,3-DBF in mice and compare them with morphine. Mice were treated with 3,3-DBF (30 mg/kg), morphine (6 mg/kg), or vehicle for 10 days, alongside single-treatment groups. Unlike morphine, 3,3-DBF demonstrated antinociceptive effects in the hot plate test without inducing tolerance. Locomotor activity and motor coordination tests (evaluated through the inverted screen and rotarod tests) revealed no significant differences between the 3,3-DBF-treated and control groups. The gastrointestinal transit assay indicated that 3,3-DBF did not induce constipation, in contrast to morphine. Furthermore, withdrawal signs assessed with the Gellert-Holtzman scale were not comparable to morphine. Additionally, 3,3-DBF exhibited antidepressant-like activity, reducing immobility time in the forced swimming and tail suspension tests, akin to imipramine. In summary, 3,3-DBF demonstrated antinociceptive effects without inducing tolerance or dependence and exhibited antidepressant properties. These findings highlight the potential of 3,3-DBF as a promising therapeutic agent for pain management and its comorbidities, offering advantages over morphine by minimizing side effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Inflammatory arthritis leads to peripheral nerve sensitization, but the therapeutic effect is often unsatisfactory. Our preliminary studies have found that in mice with inflammatory arthritis, the use of ionotropic glutamate receptor antagonists can produce a good analgesic effect without altering foot swelling, suggesting that pain relief may be related to the improvement of neuropathic pain. However, the underlying mechanisms remain unclear. To further investigate the effects of neuropathic pain medications on inflammatory arthritis and the impact of the ionotropic glutamate receptor NR2B subunit (NR2B) on inflammatory arthritis, this study employed gabapentin (GBP) treatment on the inflammatory arthritis mouse model (the adjuvant induced arthritis, AIA), and we found a significant reduction in pain. Further studies revealed that in AIA, the expression levels of NR2B, TRPV1, pain-related molecules (substance P, PGE 2 ), inflammatory cytokines (IL-1, IL-6, TNF-α, and GM-CSF) and Ca 2+ were elevated in the foot and dorsal root ganglia (DRG). GBP treatment was able to influence the downregulation of the expression levels of NR2B, TRPV1, pain-related molecules, inflammatory cytokines and Ca 2+ . Mechanistic studies have shown that GBP treatment affects the downregulation of NR2B, and the downregulation of NR2B expression leads to the downregulation of TRPV1, pain-related molecules and inflammatory cytokines, thereby alleviating pain. These results suggest that in peripheral sensitization caused by AIA, GBP can play a role in improving pain, and NR2B may be a key target of peripheral nerve sensitization induced by inflammatory arthritis. GBP provides a theoretical basis for the clinical treatment of inflammatory arthritis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Herbs of the genus Juniperus (family Cupressaceae) have been commonly used in ancestral folk medicine known as "Al'Araar" for treatment of rheumatism, diabetes, inflammation, pain, and fever. Bioassay-guided isolation of bioactives from medicinal plants is recognized as a potential approach for the discovery of novel drug candidates. In particular, non-addictive painkillers are of special interest among herbal phytochemicals., Aim of the Study: The current study aimed to assess the safety of J. thurifera, J. phoenicea, and J. oxycedrus aqueous extracts in oral treatments; validating the traditionally reported anti-inflammatory and analgesic effects. Further phytochemical investigations, especially for the most bioactive species, may lead to isolation of bioactive metabolites responsible for such bioactivities supported with in vitro enzyme inhibition assays., Materials and Methods: Firstly, the acute toxicity study was investigated following the OECD Guidelines. Then, the antinociceptive, and anti-inflammatory bioactivities were evaluated based on chemical and mechanical trauma assays and investigated their underlying mechanisms. The most active J. thurifera n-butanol fraction was subjected to chromatographic studies for isolating the major anti-inflammatory metabolites. Moreover, several enzymatic inhibition assays (e.g., 5-lipoxygenase, protease, elastase, collagenase, and tyrosinase) were assessed for the crude extracts and isolated compounds., Results: The results showed that acute oral administration of the extracts (300-500 mg/kg, p. o.) inhibited both mechanically and chemically triggered inflammatory edema in mice (up to 70% in case of J. thurifera) with a dose-dependent antinociceptive (tail flick) and anti-inflammatory pain (formalin assay) activities. This effect was partially mediated by naloxone inhibition of the opioid receptor (2 mg/kg, i. p.). In addition, 3-methoxy gallic acid (1), quercetin (2), kaempferol (3), and ellagic acid (4) were successfully identified being involved most likely in J. thurifera extract bioactivities. Nevertheless, quercetin was found to be the most potent against 5-LOX, tyrosinase, and protease with IC 50 of 1.52 ± 0.01, 192.90 ± 6.20, and 399 ± 9.05 μM, respectively., Conclusion: J. thurifera extract with its major metabolites are prospective drug candidates for inflammatory pain supported with inhibition of inflammatory enzymes. Interestingly, antagonism of opioid and non-opioid receptors is potentially involved., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Syagrus coronata, a palm tree found in northeastern Brazil, popularly known as licuri, has socioeconomic importance for the production of vegetable oil rich in fatty acids with nutritional and pharmacological effects. Licuri oil is used in traditional medicine to treat inflammation, wound healing, mycosis, back discomfort, eye irritation, and other conditions., Aim of the Study: The study aimed to evaluate the antinociceptive, anti-inflammatory, and antipyretic effects of treatment with Syagrus coronata fixed oil (ScFO), as well as to determine the safety of use in mice., Materials and Methods: Initially, the chemical characterization was performed by gas chromatography-mass spectrometry. Acute single-dose oral toxicity was evaluated in mice at a dose of 2000 mg/kg. Antinociceptive activity was evaluated through abdominal writhing, formalin, and tail dipping tests, and the anti-inflammatory potential was evaluated through the model of acute inflammation of ear edema, peritonitis, and fever at concentrations of 25, 50, and 100 mg/kg from ScFO., Results: In the chemical analysis of ScFO, lauric (43.64%), caprylic (11.7%), and capric (7.2%) acids were detected as major. No mortality or behavioral abnormalities in the mice were evidenced over the 14 days of observation in the acute toxicity test. ScFO treatment decreased abdominal writhing by 27.07, 28.23, and 51.78% at 25, 50, and 100 mg/kg. ScFO demonstrated central and peripheral action in the formalin test, possibly via opioidergic and muscarinic systems. In the tail dipping test, ScFO showed action from the first hour after treatment at all concentrations. ScFO (100 mg/kg) reduced ear edema by 63.76% and leukocyte and neutrophil migration and IL-1β and TNF-α production in the peritonitis test., Conclusion: Mice treated with ScFO had a reduction in fever after 60 min at all concentrations regardless of dose. Therefore, the fixed oil of S. coronata has the potential for the development of new pharmaceutical formulations for the treatment of pain, inflammation, and fever., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Ethnopharmacological Relevance: Yuanhu Zhitong Prescription (YZP) is a well-known traditional Chinese medicine (TCM) formula for neuropathic pain (NP) therapy with a satisfying clinical efficacy. However, the underlying pharmacological mechanism and its compatibility principle remain unclear., Aim of the Study: This study aims to investigate the analgesic and compatibility mechanisms of YZP on neuropathic pain (NP) at the gene and biological process levels., Materials and Methods: The chronic constriction injury (CCI) rats were intragastrically administrated with extracts of YZP, YH and BZ separately, and then mechanical hypersensitivity were measured to evaluate the analgesic effects between YH and BZ before and after compatibility. Then, RNA-seq and bioinformatics analyses were performed to elucidate the potential mechanisms underlying YZP's analgesia and compatibility. Finally, the expression levels and significant differences of key genes were analyzed., Results: Behaviorally, both YZP and YH effectively alleviated mechanical allodynia in CCI rats, with YZP being superior to YH. In contrast, we did not observe an analgesic effect of BZ. Genetically, YZP, YH, and BZ reversed the expression levels of 52, 34, and 42 aberrant genes in the spinal cord of CCI rats, respectively. Mechanically, YZP was revealed to alleviate NP mainly by modulating the inflammatory response and neuropeptide signaling pathway, which are the dominant effective processes of YH. Interestingly, the effective targets of YZP were especially enriched in leukocyte activation and cytokine-mediated signaling pathways. Moreover, BZ was found to exert an adjunctive effect in enhancing the analgesic effect of YH by promoting skeletal muscle tissue regeneration and modulating calcium ion transport., Conclusions: YH, as the monarch drug, plays a dominant role in the analgesic effect of YZP that effectively relieves NP by inhibiting the spinal inflammation and neuropeptide signaling pathway. BZ, as the minister drug, not only synergistically enhances analgesic processes of YH but also helps to alleviate the accompanying symptoms of NP. Consequently, YZP exerted a more potent analgesic effect than YH and BZ alone. In conclusion, our findings offer new insights into understanding the pharmacological mechanism and compatibility principle of YZP, which may support its clinical application in NP therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Chronic pain is a common and challenging clinical problem that significantly impacts patients' quality of life. The sodium channel Nav1.8 plays a crucial role in the occurrence and development of chronic pain, making it one of the key targets for treating chronic pain. In this article, we combined virtual screening with cell membrane chromatography techniques to establish a novel method for rapid high-throughput screening of selective Nav1.8 inhibitors. Using this approach, we identified a small molecule compound 6, which not only demonstrated high affinity and inhibitory activity against Nav1.8 but also exhibited significant inhibitory effects on CFA-induced chronic inflammatory pain. Compared to the positive drug VX-150, compound 6 showed a more prolonged analgesic effect, making it a promising candidate as a Nav1.8 inhibitor with potential clinical applications. This discovery provides a new therapeutic option for the treatment of chronic pain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Artemisia annua L., known for antimalarial activity, has demonstrated evidence of anti-inflammatory potential. Previously our research group reported the anti-inflammatory and antinociceptive effect of a sesquiterpene lactone-enriched fraction (Lac-FR) obtained from plant, containing artemisinin and deoxyartemisinin. Both the isolated compounds and Lac-FR evaluated on experimental animal models, in the formalin test showed that deoxyartemisinin reduced both neurogenic pain (56.55 %) and inflammatory pain (45.43 %). These findings were superior to the effect of artemisinin (reduction of 28.66 % and 33.35 %, respectively). In the tail flick test, the antinociceptive effect reported as a percentage of the maximum possible effect (%MPE), deoxyartemisinin showed a lower antinociceptive effect (41.57 %) compared to morphine (75.94 %) in 0.5 h. After 1.5 h, the MPE of deoxyartemisinin (87.99 %) exceeded the effect of morphine (47.55 %), without reversal with naloxone. The MPE of artemisinin (23.3 %) observed after 2 h was lower than deoxiartemisinin, without reversal with the opioid antagonist. Lac-FR and artemisinin demonstrated reductions in ear edema of 43.37 % and 48.19 %, respectively, higher than the effect of deoxyartemisinin (33.64 %). Artemisinin reduced tumor necrosis factor alpha (TNF-α) (76.96 %) more selectively when compared to interleukin-1beta (IL-1β) (48.23 %) and interleukin-6 (IL-6) (44.49 %). Lac-FR showed greater selectivity in IL-6 reduction (56.49 %) in relationship to TNF-α (46.71 %) and IL-1β (45.12 %), whereas deoxyartemisinin selectively reduced TNF-α (37.37 %). The results of our study indicate that the lactones isolated did not have relationship with the opioid system. Deoxyartemisinin showed a higher antinociceptive potential than artemisinin. Whereas, artemisinin showed a higher reduction of inflammation and mediators, with a better anti-inflammatory activity outcome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Pain is a common public health problem and remains as an unmet medical need. Currently available analgesics usually have limited efficacy or are accompanied by many adverse side effects. To achieve satisfactory pain relief by multimodal analgesia, new combinations of nefopam and gabapentinoids (pregabalin/gabapentin) were designed and assessed in inflammatory, osteoarthritis and neuropathic pain. Isobolographic analysis was performed to analyze the interactions between nefopam and gabapentinoids in carrageenan-induced inflammatory pain, mono-iodoacetate-induced osteoarthritis pain and paclitaxel-induced peripheral neuropathic pain in mice. The anti-inflammatory effect and motor performance of monotherapy or their combinations were evaluated in the carrageenan-induced inflammatory responses and rotarod test, respectively. Nefopam (1, 3, 5, 10, 30 mg/kg, p.o.), pregabalin (3, 6, 12, 24 mg/kg, p.o.) or gabapentin (25, 50, 75, 100 mg/kg, p.o.) dose-dependently reversed mechanical allodynia in three pain models. Isobolographic analysis indicated that the combinations of nefopam and gabapentinoids exerted synergistic anti-nociceptive effects in inflammatory, osteoarthritis, and neuropathic pain mouse models, as evidenced by the experimental ED 50 (median effective dose) falling below the predicted additive line. Moreover, the combination of nefopam-pregabalin/gabapentin alleviated carrageenan-induced inflammation and edema, and also prevented gabapentinoids-related sedation or ataxia by lowering their effective doses. Collectively, the co-administration of nefopam and gabapentinoids showed synergistic analgesic effects and may result in improved therapeutic benefits for treating pain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Shentong Zhuyu Decoction (STZYD) is a traditional prescription for promoting the flow of Qi and Blood which is often used in the treatment of low back and leg pain clinicall with unclear mechanism. Neuropathic pain (NP) is caused by disease or injury affecting the somatosensory system. LncRNAs may play a key role in NP by regulating the expression of pain-related genes through binding mRNAs or miRNAs sponge mechanisms., Aim of the Study: To investigate the effect and potential mechanism of STZYD on neuropathic pain., Methods: Chronic constriction injury (CCI) rats, a commonly used animal model, were used in this study. The target of STZYD in NP was analyzed by network pharmacology, and the analgesic effect of STZYD in different doses (H-STZYD, M-STZYD, L-STZYD) on CCI rats was evaluated by Mechanical withdrawal thresholds (MWT) and thermal withdrawal latency (TWL). Meanwhile, RNA-seq assay was used to detect the changed mRNAs and lncRNAs in CCI rats after STZYD intervention. GO analysis, KEGG pathway analysis, and IPA analysis were used to find key target genes and pathways, verified by qPCR and Western Blot. The regulatory effect of lncRNAs on target genes was predicted by co-expression analysis and ceRNA network construction., Results: We found that STZYD can improve hyperalgesia in CCI rats, and H-STZYD has the best analgesic effect. The results of network pharmacological analysis showed that STZYD could play an analgesic role in CCI rats through the MAPK/ERK/c-FOS pathway. By mRNA-seq and lncRNA-seq, we found that STZYD could regulate the expression of Cnr1, Cacng5, Gucy1a3, Kitlg, Npy2r, and Grm8, and inhibited the phosphorylation level of ERK in the spinal cord of CCI rats. A total of 27 lncRNAs were associated with the target genes and 30 lncRNAs, 83 miRNAs and 5 mRNAs participated in the ceRNA network., Conclusion: STZYD has the effect of improving hyperalgesia in CCI rats through the MAPK/ERK/c-FOS pathway, which is related to the regulation of lncRNAs to Cnr1 and other key targets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: The natural anodyne Ligustilide (Lig), derived from Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort., has been traditionally employed for its analgesic properties in the treatment of dysmenorrhea and migraine, and rheumatoid arthritis pain. Despite the existing reports on the correlation between TRP channels and the analgesic effects of Lig, a comprehensive understanding of their underlying mechanisms of action remains elusive., Aim of the Study: The objective of this study is to elucidate the mechanism of action of Lig on the analgesic target TRPA1 channel., Methods: The therapeutic effect of Lig was evaluated in a rat acute soft tissue injury model. The analgesic target was identified through competitive inhibition of TRP channel agonists at the animal level, followed by Fluo-4/Ca 2+ imaging on live cells overexpressing TRP proteins. The potential target was verified through in-gel imaging, colocalization using a Lig-derived molecular probe, and a drug affinity response target stability assay. The binding site of Lig was identified through protein spectrometry and further analyzed using molecular docking, site-specific mutation, and multidisciplinary approaches., Results: The administration of Lig effectively ameliorated pain and attenuated oxidative stress and inflammatory responses in rats with soft tissue injuries. Moreover, the analgesic effects of Lig were specifically attributed to TRPA1. Mechanistic studies have revealed that Lig directly activates TRPA1 by interacting with the linker domain in the pre-S1 region of TRPA1. Through metabolic transformation, 6,7-epoxyligustilide (EM-Lig) forms a covalent bond with Cys703 of TRPA1 at high concentrations and prolonged exposure time. This irreversible binding prevents endogenous electrophilic products from entering the cysteine active center of ligand-binding pocket of TRPA1, thereby inhibiting Ca 2+ influx through the channel opening and ultimately relieving pain., Conclusions: Lig selectively modulates the TRPA1 channel in a bimodal manner via non-electrophilic/electrophilic metabolic conversion. The epoxidized metabolic intermediate EM-Lig exerts analgesic effects by irreversibly inhibiting the activation of TRPA1 on sensory neurons. These findings not only highlight the analgesic mechanism of Lig but also offer a novel nucleophilic attack site for the development of TRPA1 antagonists in the pre-S1 region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This research aims to investigate the possible antiallodynic and antihyperalgesic effects of pure vitexin and vitexin-loaded solid lipid nanoparticles (SLN) on neuropathic pain and the pathways mediating these effects. Chronic constriction nerve injury was induced in female rats, and the effects of vitexin at the doses of 5, 10, 20, 40 mg/kg were evaluated. Ketanserin, ondansetron, WAY-100635, yohimbine and bicuculin, which are antagonists of receptors on pain pathways. were used to examine the mechanisms of the effects of vitexin. Pure vitexin exhibited antiallodynic activity at all administered doses, whereas antihyperalgesic activity was not observed at 5 mg/kg vitexin dose. SLN formulation was prepared with 5 mg/kg vitexin, the lowest dose. Vitexin-loaded formulation significantly increased antiallodynic and antihyperalgesic effects. Ondansetron, WAY-100635, yohimbine, and bicuculine antagonized the antiallodynic and antihyperalgesic effects of vitexin. So, it was concluded that serotonin (5-hydroxtryptamine, 5-HT) receptor subtypes 5-HT3 and 5-HT1A, alpha-2 adrenergic, and γ-Aminobutyric acid type A (GABA-A) receptors are involved in the antiallodynic and antihyperalgesic activity of vitexin. In conclusion, vitexin and vitexin-loaded formulation have the potential for clinical use in neuropathic pain management, and different pain pathways contributed to this effect. And also, it is thought that vitexin-loaded SLN formulation is more effective than pure vitexin, which will provide an advantage in treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aims: The objective of this study was to demonstrate that sustained-release (SR) pregabalin is non-inferior to immediate-release (IR) pregabalin in attenuating diabetic peripheral neuropathic (DPN) pain along with patient satisfaction and compliance., Methods: This was an 8-week, randomized, active-controlled, open-label, phase 4 study. Eligible subjects who had been on IR pregabalin for 4 weeks were randomized to 1:1 ratio to either continue with twice-daily IR pregabalin (75 mg), or to switch to once-daily SR pregabalin (150 mg). Primary efficacy endpoint was the change in visual analogue scale (VAS) scores after 8 weeks of treatment compared to baseline in both SR and IR pregabalin groups., Results: Among 130 randomized subjects, 125 patients were included in full analysis set. For the change in VAS pain score, the least squares (LS) mean were -17.95 (SR pregabalin) and -18.74 (IR pregabalin) and the LS mean difference between both groups was 0.79, with the upper limit of the 95 % confidence interval [-5.99, 7.58] below the pre-specified non-inferiority margin of 9.2 mm., Conclusions: This study demonstrates that the new once-daily SR pregabalin formulation is not different to the twice-daily IR pregabalin in alleviating DPN pain, indicating its potential as a promising treatment for DPN pain with a comparable safety profile., Trial Registration: ClinicalTrials.gov, NCT05624853., Competing Interests: Declaration of competing interest The authors declare the following potential conflicts of interest with respect to the research, authorship, and publication of this paper: “ The authors declare no competing financial interest in the publication of our data.”, (Copyright © 2024 Elsevier Inc. All rights reserved.)

The cover picture illustrates the fabrication process of electrochemical paper‐based analytical devices (ePADs) fabricated by pencil drawing for detecting analgesics and sedation drugs in whiskey. Analgesics are commonly used to adulterate alcoholic beverages to prevent the hangover. On other hand, sedative drugs are occasionally added to alcoholic beverages to promote loss of consciousness, amnesia and hallucination in the victim. The ePADs fabricated with graphite pencil were successfully tested to detect metamizole, paracetamol and midazolam maleate, as model drugs, in whiskey samples. Due to the inherent portability, disposability, low cost, operational simplicity and speed, ePADs can emerge as an attractive strategy for point‐of‐need by crime scene or police agents. More details are discussed in the article by Anderson A. Dias, Thiago M. G. Cardoso, Cyro L. S. Chagas, Virgílio X. G. Oliveira, Rodrigo A. A. Munoz, Charles S. Henry, Mário H. P. Santana, Thiago R. L. C. Paixão and Wendell K. T. Coltro. DOI: 10.1002/elan.201800308 [ABSTRACT FROM AUTHOR]

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