Search Results (695)

The impact of genetic variation in sickle cell patients plays a significant role in opioid therapy individual response and pain management. This review aims to provide a comprehensive overview of the importance of exploring genetic variability and its impact on pain management in patients with sickle cell disease. It also explores opioid therapy variability and opioid Safety. With respect to literature, the polymorphisms in the key metabolic enzymes CYP2D6, UGT2B7, and COMT, as well as variations in the OPRM1, are important modifiers of the pharmacokinetics and pharmacodynamics of opioids. Variations in the COMT gene can influence how the body manages certain brain chemicals and how pain is experienced, while changes in the OPRM1 gene can alter how well opioids bind to their receptors. They help determine how opioids are broken down in the body, how well they attach to pain receptors, and how pain is felt by someone with sickle cell disease. Patients with reduced-function and ultra-rapid CYP2D6 alleles have a modified metabolism of codeine and tramadol, which presents either a reduced analgesic response or a risk for increased toxicity. These observations support the case for the need for tailored opioid prescriptions in a population that is genetically diverse, as well as the risk of not having standardized pain measurement, and the absence of clinical implementation. There remains the risk of unrecognized pharmacogenomics, lack of data, and personalized opioid descriptions persist. Future research should focus on integrating genetic testing into clinical practice to optimize opioid selection, personalize medicine, minimize adverse effects, and ensure each patient receives treatment that is both effective and safe to enhance quality of life for individuals with sickle cell disease. Full article

Background/Objectives: Cancer pain affects 55–95% of patients with advanced malignancy, representing a complex syndrome involving nociceptive, neuropathic and nociplastic mechanisms. Despite therapeutic advances, two-thirds of patients with metastatic cancer experience inadequate pain control. This scoping review synthesizes recent advances in cancer pain pathophysiology and management, focusing on molecular and cellular mechanisms, emerging pharmacological, interventional and technological therapies and key evidence gaps to inform future precision-based pain management strategies. Methods: Following PRISMA-ScR methodology, we searched PubMed, Embase, Scopus, and Web of Science for studies published between January 2022 and September 2025. After screening 3412 records, 278 studies were included and analyzed across different domains: biological mechanisms, pharmacological management, interventional and neuromodulatory approaches, radiotherapy developments, and digital health innovations. Results: Recent mechanistic research reveals cancer pain arises from tumor–neuron–immune crosstalk, with malignant cells secreting neurotrophic factors that promote axonal sprouting and nociceptor sensitization. Genetic polymorphisms and epigenetic modifications contribute to inter-individual pain variability. Management strategies are evolving toward multimodal precision medicine: NSAIDs and opioids remain foundational, complemented by adjuvant agents and interventional procedures including nerve blocks, intrathecal delivery, and neuromodulation (spinal cord and dorsal root ganglion stimulation). Stereotactic body radiotherapy demonstrates superior analgesic durability versus conventional approaches. Digital health innovations, such as mobile applications, remote monitoring, wearables, and AI-enabled predictive models, enable continuous assessment and personalized treatment optimization. Conclusions: Cancer pain management is transitioning toward mechanism-based precision medicine integrating biological insights, advanced interventional techniques, and digital technologies. However, implementation challenges persist, including limited randomized trials for interventional approaches, the incomplete external validation of AI tools, and digital health equity concerns. Future research must prioritize prospective controlled studies and equitable integration into routine care. Full article

Postoperative pain management in pediatric patients remains a significant challenge despite improvements in perioperative care. Regional anesthesia techniques applied as part of multimodal analgesia strategies offer the potential to reduce opioid use, accelerate recovery, and minimize side effects such as respiratory depression, nausea, and delayed mobilization. This review examines the clinical applications, advantages, and limitations of regional anesthesia blocks in the context of common pediatric surgical procedures—appendectomy, inguinal hernia repair, circumcision, cholecystectomy, and pyloromyotomy. We provide procedural comparisons in terms of analgesic efficacy, opioid-sparing effects and suitability for ambulatory surgery. In conclusion, regional anesthesia techniques have significant potential to improve postoperative outcomes in pediatric patients. However, block selection should be individualized, considering the type of surgical procedure, patient characteristics, and operator experience. Increasing applicability and routinely implementing ultrasound-guided procedures will encourage the safer and more effective use of these techniques in pediatric anesthesia. Full article

Codeine, an opioid analgesic present in many over-the-counter (OTC) formulations, is frequently misused through non-medical extraction techniques such as cold water extraction (CWE). These practices carry substantial risks, including incomplete removal of hepatotoxic co-formulants, contamination, and highly unpredictable dosing. We report a fatal case of a 29-year-old man who ingested codeine extracted from Antidol^® tablets in combination with energy drinks and psychotropic medications. Post-mortem LC–MS/MS analysis revealed the presence of codeine (0.66 µg/mL), morphine (0.02 µg/mL), hydroxyzine (2.52 µg/mL), alprazolam (0.15 µg/mL), paracetamol (30.64 µg/mL), and additional substances in blood samples. Concentrations of codeine and hydroxyzine exceeded therapeutic ranges and were consistent with values reported in fatal intoxications, confirming a poly-drug poisoning. This case highlights the danger associated with non-medical codeine use, particularly when combined with central nervous system (CNS) depressants, and underscores the need for stricter regulation of OTC codeine-containing products as well as improved public awareness of the risks associated with domestic extraction methods. Full article

A wound has been defined as a disruption of tissue integrity. Pain, bleeding, and the risk of infection are inherent features of wounds, while chronic wounds are often accompanied by serous exudate. Pain associated with chronic wounds is usually underestimated and inadequately addressed in routine clinical care, despite being considered by patients as one of the most burdensome factors affecting their quality of life. Traditionally, management of wound-related pain has relied primarily on systemic analgesics, commonly administered orally. However, recently, there has been accumulated interest in the potential of topical analgesics. Unfortunately, both systemic and local administrations of conventional analgesics (e.g., NSAIDs, opioids) might carry risks of adverse effects, including delayed wound healing and systemic absorption. In this review, we summarize current research on the use of local analgesia for painful wounds and explore the potential of topically applied peptides with analgesic activity as a promising alternative to conventional pain management strategies. We also discuss recent innovations in the development of therapeutic peptides, including those with anti-inflammatory and regenerative activities, which might further enhance outcomes in the wound healing process. Finally, we address challenges associated with topical peptide delivery across compromised skin barriers and examine strategies to overcome these limitations, while outlining future directions for formulation and clinical application of peptide-based wound therapies. Full article

Background: Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) for clavicle fracture pain management carry significant adverse effect and allergic reaction risks. This study assessed ultrasound-guided nerve block (USNB) efficacy for acute clavicle fracture pain in emergency department (ED) patients, providing an alternative to NSAIDs and opioids with fewer adverse effects. Methods: This retrospective, single-center observational study was conducted in accordance with Methods of Medical Record Review Studies in Emergency Medicine Research guidelines. Adult patients (≥20 years) who presented to the ED with traumatic clavicle fractures between 1 January 2015 and 30 November 2023 were included. Of the 343 eligible patients, 12 received ultrasound-guided nerve blocks (USNB) and 331 received standard care. To improve exchangeability, 1:10 matching with replacement was performed according to patients’ characteristics, such as age, sex, initial pain score, and comorbidities. The primary outcome was pain relief, assessed via the pain intensity difference (PID) on the Numerical Rating Scale within 360 min post-intervention. Meaningful pain relief was defined as a PID ≥ 4. Secondary outcomes included rescue opioid use, ED length of stay, hospital length of stay, and USNB-associated complications, such as vascular puncture, nerve injury, or local anesthetic systemic toxicity. Data were analyzed using time-course, time-to-event (time to meaningful pain relief), and linear regression analyses. Results: A total of 12 patients in the USNB group and 85 matched patients in the standard care group were analyzed after baseline characteristics matching with replacement. Compared to standard care, USNB was associated with significantly greater pain relief (p < 0.001). In the time-to-event analysis, USNB led to a 3.41-fold faster achievement of meaningful pain relief compared with that achieved with standard care (HR = 3.41; 95% CI, 1.47–7.90; p = 0.004). No significant differences were observed between groups in rescue opioid use, ED length of stay, or hospital length of stay. No USNB-associated complication developed in the USNB group. Conclusions: In patients with traumatic clavicle fractures, USNB provides more rapid and sustained pain relief than standard analgesic care in the ED, without increasing the ED length of stay. Large prospective studies are needed to confirm these findings. Full article

Background: Depression and diabetic neuropathy (DN) commonly complicate diabetes and impair glycemic control and quality of life. Ketamine and its S-enantiomer, esketamine, provide rapid antidepressant and analgesic effects, yet diabetes-related pathophysiology and co-therapies may modify exposure, response, and safety. Methods: We conducted a scoping review following PRISMA-ScR. MEDLINE/PubMed, CINAHL, and APA PsycInfo were searched (January 2020–31 May 2025). Eligible human and animal studies evaluated ketamine, esketamine, or norketamine in the context of diabetes (type 1 [T1DM], type 2 [T2DM], gestational [GDM]), or DN, and reported psychiatric, analgesic, metabolic, or mechanistic outcomes. Two reviewers independently screened and charted data; no formal risk-of-bias assessment was performed. Results: Eleven studies met inclusion criteria: four human case reports/series (three T1DM, one T2DM), one randomized trial in GDM, two narrative reviews of topical ketamine for DN, and four preclinical rodent studies using streptozotocin- or diet-induced diabetes models. Short-term improvements were reported for treatment-resistant depression and neuropathic pain, including opioid-sparing postoperative analgesia in GDM. Glycemic effects varied across settings, with both hyperglycemia and hypoglycemia reported. Mechanistic and clinical drug–drug and drug-disease interactions (particularly involving metformin, GLP-1 receptor agonists, SGLT2 inhibitors, and CYP3A4/CYP2B6 modulators) remain insufficiently studied. We outline a forward-looking population pharmacokinetic (popPK) and pharmacokinetic-pharmacodynamic (PK-PD) research agenda, including priority covariates (eGFR, hepatic function, inflammatory status, HbA1c, genotype, co-medications) and sparse-sampling windows for future model-informed precision dosing. Conclusions: Current evidence supports cautious, selective use of ketamine for refractory depression and DN within multidisciplinary diabetes care. Purpose-built popPK/PK-PD studies in both human and preclinical diabetic models cohorts are needed to quantify variability, define drug–disease–drug interactions and glycemic risk, and inform individualized dosing strategies. Full article

Chronic pain and sleep disturbances are frequently associated and profoundly affect the quality of life, creating intertwined physical, emotional, and social challenges. This narrative review synthesizes current evidence on the molecular mechanisms and pharmacological influences underlying this bidirectional relationship. Elevated pro-inflammatory cytokines (IL-1β, IL-6, IL-10, TNF-α), neurodegenerative markers (tau, β-amyloid 42), metabolic hormones, and fasting glucose have been consistently associated with both objective and subjective sleep impairments in chronic pain conditions. Pharmacological agents such as melatonin and opioids exhibit heterogeneous effects on neurophysiological pathways, reflecting differences in mechanisms of action and their modulation of biological processes. Rather than offering therapeutic recommendations, this review aims to clarify how these mediators and drugs shape the complex interplay between pain and sleep. Overall, the evidence suggests that persistent dysregulation of inflammatory, neurodegenerative, and metabolic pathways may drive the reciprocal and detrimental interaction between chronic pain and sleep disturbances, highlighting opportunities for targeted research and integrated clinical strategies. Full article

Knee osteoarthritis (OA) affects around 37% of U.S. adults over 60, with over 25% experience depressive symptoms (DSs), linked to worse pain and outcomes. Yet their impact on analgesic use and recovery remains unclear. This study aimed to assess if DSs influence analgesic use and functional outcomes in knee OA. Using data from the Osteoarthritis Initiative (n = 3680), we used a Machine Learning (ML)-based Gradient Boosting Machine (GBM) model to perform propensity score matching, matching patients with knee OA and DSs (n = 487) to those without DSs (n = 487). Outcomes at baseline, 1 and 2 years included analgesic use, function (WOMAC), quality of life (KOOS-QoL), and physical health (SF-12 PCS). Regression and timepoint models compared follow-up with baseline. DSs alone were not associated with greater opioid use up to Year 2 (OR = 0.89, 95% CI: 0.45–1.73; p = 0.73). Among patients with DSs, SF-12 PCS improvement was less likely at Year 1, while decline was more likely up to Year 2. DSs in OA were linked to poorer physical health, but often greater functional gains than those in OA without DSs, with no difference in opioid use. These findings highlight the need for multidisciplinary strategies, addressing both pain and psychosocial wellbeing. Full article

Introduction: Opioids are the most commonly used analgesic drugs for acute and chronic severe pain and are metabolized in the liver via cytochrome P450 (CYP) enzymes and UDP-glucuronosyltransferases (UGTs). Methods: A narrative review of the literature was conducted by searching the PubMed database up to December 2025, with English as the only language restriction. Relevant studies were identified using the keywords “opioids,” “pharmacogenetic,” “cytochrome mutations,” and “interactions.” Results: Polymorphisms in CYP2D6 and CYP3A4 genes can affect the pharmacokinetics, clinical effect, and safety of opioids. Furthermore, enzyme induction and inhibition by concomitant drugs or compounds (herbal products or food) are sources of variability factors in drug response that may be predictable. Conclusions: This review article summarizes current evidence on the role of pharmacogenetics and opioid-related interactions, offering a framework to better understand interindividual variability in opioid response and to inform future multimodal approaches. Full article

Background and Objectives: Effective pain control after laparoscopic colorectal surgery is crucial for Enhanced Recovery After Surgery (ERAS) protocols. The transversus abdominis plane block (TAPB) provides somatic analgesia but lacks visceral coverage. The quadratus lumborum block (QLB) has emerged as an alternative, potentially offering both somatic and visceral blockade, but its superiority is debated. This systematic review and meta-analysis aimed to compare the analgesic efficacy of QLB versus TAPB in this setting. Materials and Methods: A comprehensive search of PubMed, Scopus, CENTRAL, and Web of Science was conducted for randomized controlled trials (RCTs) up to November 2025. Primary outcomes were 24 h postoperative and intraoperative opioid consumption. Secondary outcomes included pain scores, length of hospital stay (LoS), surgery duration, and adverse events. Standardized mean differences (SMD) and risk ratios (RR) were pooled. Results: Five RCTs involving 520 patients were included. No significant difference was found in 24 h postoperative opioid consumption (SMD: −1.62, 95% CI [−3.45, 0.20]; p = 0.08) or intraoperative opioid consumption (SMD: 0.38, 95% CI [−0.36, 1.12]; p = 0.31). QLB provided better, transient pain relief at rest at 12 h (SMD: −0.30, 95% CI [−0.52, −0.07]; p = 0.01) and during movement at 6 h (SMD: −0.20, 95% CI [−0.49, −0.09]; p = 0.01). No other time points for pain showed significant differences. QLB was associated with a shorter surgery duration (MD: −5.61 min, 95% CI [−10.38, −0.85]; p = 0.02), but not LoS (p = 0.53) or rates of PONV (p = 0.24) or dizziness (p = 0.32). Conclusions: With uncertain evidence, QLB and TAPB showed no significant difference in opioid consumption. QLB demonstrated a statistically significant but transient early analgesic advantage. This heterogeneity may be due to different QLB techniques, warranting further investigation. Full article

Background and Objectives: Surgical stress during robotic-assisted radical prostatectomy (RARP) elicits a measurable systemic inflammatory response despite the minimally invasive approach. Intravenous lidocaine has been increasingly investigated for its potential anti-inflammatory, analgesic, and immunomodulatory benefits, but evidence in robotic urologic oncology remains limited. This study aimed to evaluate whether intraoperative lidocaine infusion attenuates postoperative inflammation, improves analgesic outcomes, and accelerates early recovery following RARP. Materials and Methods: This prospective non-randomized observational study included 80 patients undergoing elective RARP, divided into a Lidocaine Group (n = 40) receiving an intraoperative bolus and continuous infusion, and a Control Group (n = 40) receiving standard anesthesia without lidocaine. Serum IL-6, TNF-α, CRP, and fibrinogen were measured at baseline, end of surgery, and 24 h postoperatively. Postoperative pain scores, opioid consumption, gastrointestinal recovery, ambulation, and length of stay were recorded. Statistical analyses included repeated-measures ANOVA, correlation testing, and between-group comparisons. Results: Baseline characteristics were similar between groups. At 24 h postoperatively, lidocaine administration was associated with a significantly attenuated inflammatory response, with lower levels of IL-6 (45.7 ± 10.8 vs. 68.9 ± 12.6 pg/mL, p < 0.01) and TNF-α (20.5 ± 5.1 vs. 27.2 ± 6.4 pg/mL, p < 0.01) compared with controls. Patients receiving lidocaine reported lower postoperative pain scores and required significantly less opioid analgesia, with a total 24 h consumption of 8.9 ± 3.4 vs. 14.8 ± 5.2 mg morphine milligram equivalents (p < 0.001). Lidocaine was also associated with faster recovery, including earlier oral intake and a shorter length of hospital stay (2.9 ± 0.7 vs. 3.6 ± 0.9 days, p = 0.003). No lidocaine-related adverse events were observed. Conclusions: In this prospective observational study, intraoperative intravenous lidocaine was associated with attenuated early postoperative inflammation, improved analgesic outcomes, and enhanced early recovery following RARP. These findings support the potential role of intravenous lidocaine as a safe adjunct in multimodal perioperative management; however, given the non-randomized observational design, causal inferences should be interpreted with caution. Further randomized controlled trials are warranted to confirm causality and to validate long-term clinical and mechanistic effects. Potential residual confounding inherent to the observational design should be considered when interpreting these findings. Full article

Pain is a dominant symptom in acute pancreatitis, yet high-level evidence guiding optimal analgesic management in acute pancreatitis has been limited. Emerging evidence suggests a role of non-steroidal anti-inflammatory drugs, including cyclooxygenase-2 inhibitors, and opioids in the management of pain in acute pancreatitis patients. Based on a narrative review of the current literature, we provide an overview of available evidence, give an update on recent studies, and propose a treatment algorithm for pain management in acute pancreatitis, considering pharmacological and non-pharmacological modalities, patient comorbidities, and disease severity. Existing studies are generally limited by small sample sizes, heterogeneity in outcomes, unidimensional pain assessments, and a lack of understanding for the pathophysiology of pain in acute pancreatitis. Future trials should focus on multicentre collaboration, comprehensive pain evaluation, adequate sample sizes, and understanding the complex molecular mechanisms of acute pancreatitis pain. Full article

Background/Objectives: Target-controlled infusion (TCI) with remifentanil or sufentanil provides stable and effective anesthesia. This randomized prospective trial investigated the comparative efficacy of TCI using sufentanil versus remifentanil on postoperative analgesia and recovery profiles in patients after laparoscopic subtotal gastrectomy under remimazolam-based total intravenous anesthesia (TIVA). Methods: Sixty-six patients who underwent laparoscopic subtotal gastrectomy were randomly allocated to receive either TCI-based sufentanil or remifentanil in TIVA with remimazolam. The primary endpoint was the cumulative fentanyl consumption within 24 h after surgery. The secondary outcomes were pain intensity at rest and during activity, and recovery parameters including time to extubation, length of post-anesthesia care unit (PACU) stay, and quality of recovery (QoR-40) on postoperative day 1 (POD1). Results: The cumulative fentanyl consumption over the 24 h postoperative period was similar between the two groups. However, compared with the remifentanil group, the sufentanil group required significantly less fentanyl during the immediate postoperative period (0–0.5 h) (p < 0.001) and exhibited lower pain scores both at rest and during activity during the first postoperative hour (p < 0.001). Although the Sedation-Agitation Scale score at PACU admission was significantly lower in the sufentanil group (p < 0.001), the overall recovery profiles, including time to extubation, PACU stay, and QoR-40 scores on POD 1, were comparable between the groups. Conclusions: TCI-based sufentanil and remifentanil in TIVA with remimazolam showed similar overall analgesic efficacies and recovery outcomes after laparoscopic subtotal gastrectomy. Both opioid strategies are effective for postoperative pain management, with a slight advantage in immediate postoperative pain control for sufentanil. Full article

Introduction: During pharmaceutical care, community pharmacists play a crucial role by carrying out interventions aimed at preventing, detecting, and resolving drug-related problems (DRPs) and negative outcomes associated with medication (NOM), simultaneously enhancing patients’ knowledge about their treatments. The chronic use of Benzodiazepines (BZDs) is known to be associated with risks such as tolerance, dependence, and cognitive impairment. Furthermore, the combined use of BZDs with other medications or alcohol may expose patients to significant drug interactions. Objectives: This study aimed to characterize and describe the clinical profile of patients using BZDs, to evaluate the extent of polypharmacy and potential drug interactions, to investigate their level of knowledge regarding BZD treatment, and ultimately, to propose evidence-based interventions from the community pharmacy to contribute to improving patient safety and minimizing risks associated with BZD use. Method: A cross-sectional, descriptive study was conducted in a single community pharmacy in Gran Canaria (Canary Islands, Spain). The study population comprised 125 adult patients with active BZD prescriptions. Data collection was performed through pharmacist–patient structured interviews using a questionnaire that included sociodemographic, clinical, and BZD knowledge variables. Results: Lormetazepam and alprazolam were the BZDs most frequently prescribed and dispensed. Potential drug interactions with other medications were detected in 38.4% of BZD users. Notably, 61.5% of patients using BZDs also reported the concurrent use of opioid analgesics, with tramadol being the most common opioid (48.1% of BZD users were also treated with tramadol). Statistically significant differences were observed between patients with and without BZD and other drug interactions in several adverse outcome variables, including the risk of falls (p = 0.003), cognitive impairment (p = 0.047), and urinary incontinence (p = 0.016). Existing BZD dependence is detected in 25% and 22.1% of cases, respectively. Patients’ knowledge of their BZD treatment revealed critical gaps, which are identified as a challenge and a clear opportunity for intervention through pharmaceutical care services. Conclusions: The findings underscore the essential and proactive role of community pharmacists in identifying and managing drug interactions, as well as in supporting deprescribing strategies through collaborative and interprofessional care models. Full article