Search Results (288)

Objective: Morphine is a widely used analgesic for severe pain, but tolerance is a major challenge in long-term pain management. This study examined the potential of Daflon^® to enhance morphine’s pain-relieving effects and to reduce tolerance in a rat model with neuropathic pain induced by partial sciatic nerve transection (PSNT). Methods: Male Wistar rats were divided into five groups: (1) Sham + Saline, (2) PSNT + Saline, (3) PSNT + morphine, (4) PSNT + Daflon, and (5) PSNT + morphine + Daflon. Morphine tolerance was induced through continuous intrathecal infusion (15 µg/µL/h, i.t.) for 7 days, starting on day 7 post-PSNT, while Daflon was administered orally (50 mg/kg/day, oral) for 7 days. Pain relief was assessed using tail-flick and paw withdrawal on days 1, 4, and 7 after osmotic pump implantation. Spinal cords were collected for immunohistochemistry to analyze glial expression, and serum biomarkers (TNF-α, IL-1β, IL-6, and IL-10) were measured to evaluate neuroinflammation. Results: The results showed that oral Daflon significantly enhanced morphine’s analgesic effects, evidenced by improved pain thresholds in all behavioral tests. Moreover, Daflon reduced morphine tolerance. Mechanistically, Daflon upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and activated heme oxygenase-1 (HO-1), reducing oxidative stress and modulating neuroinflammation through glial regulation. Combining morphine and Daflon reduces pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and enhances anti-inflammatory IL-10 serum level, showing a synergistic effect in managing neuropathic pain with greater efficacy and lower drug dependence. Histology and immunohistochemistry evaluations further confirmed that morphine and Daflon co-treatment substantially reduced mononuclear cell infiltration, astrocyte activation (as indicated by GFAP expression), and microglial activation (as indicated by Iba-1 expression) compared to single treatment. Conclusions: Our findings suggest that dual therapy synergistically targets both oxidative stress and inflammatory pathways, leading to stronger neuroprotection and pain relief. Importantly, the combination approach may allow for lower opioid dosages, minimizing the risks of opioid-related side effects. Overall, morphine and Daflon co-administration offers a promising and safer strategy for managing neuropathic pain and preserving spinal cord integrity. Full article

Recent advances in intraoperative nociception monitoring, such as the Surgical pleth index (SPI, GE Healthcare, Helsinki, Finland), may help optimize opioid use. Obese patients are particularly susceptible to opioid-related side effects, making this approach of interest in bariatric surgery. In this randomized pilot study, we investigated whether SPI-guided fentanyl administration would influence intraoperative opioid use and postoperative pain. We enrolled 49 patients undergoing laparoscopic gastric sleeve surgery under sevoflurane-based general anesthesia with multimodal perioperative analgesia, randomized to conventional fentanyl dosing at the anesthetist’s discretion (n = 25) or SPI-guided dosing (n = 24). The primary endpoint was intraoperative fentanyl consumption. Secondary outcomes included time to extubation, hemodynamic events, pain scores in the first 90 min postoperatively and rescue analgesia. Fentanyl use did not differ significantly between groups (SPI: 400 ± 101 mcg vs. control: 450 ± 56 mcg, p = 0.100). Extubation was faster with SPI guidance (8.1 ± 1.6 vs. 9.6 ± 1.3 min, p < 0.001). Hemodynamic events and rescue analgesia were less frequent in the SPI group, though not statistically significant. Pain scores were comparable, and no opioid-related adverse effects occurred. In our study, SPI-guided opioid administration did not reduce overall intraoperative fentanyl requirements compared with conventional practice but was associated with a modestly shorter time to extubation. Full article

Background/Objectives: Diabetic neuropathy (DN) is a prevalent complication of diabetes mellitus, affecting up to 50% of long-term patients and causing significant pain, reduced quality of life, and healthcare burden. Conventional treatments, including anticonvulsants, antidepressants, and opioids, offer limited efficacy and are associated with adverse effects. Emerging evidence suggests that cannabis, acting via the endocannabinoid system, may provide analgesic and neuroprotective benefits. This study evaluates the long-term effects of inhaled cannabis as adjunctive therapy for refractory painful DN. Inhaled cannabis exhibits rapid onset pharmacokinetics (within minutes, lasting 2–4 h) due to pulmonary absorption, targeting CB1 and CB2 receptors to modulate pain and inflammation. Methods: In this prospective, observational study, 52 patients with confirmed painful DN, unresponsive to at least three prior analgesics plus non-pharmacological interventions, were recruited from a single clinic. Following a 1-month washout, patients initiated inhaled medical-grade cannabis (20% THC, <1% CBD), titrated individually. Assessments occurred at baseline and annually for 5 years, including the Brief Pain Inventory (BPI) for pain severity and interference; the degree of pain relief; Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) score; HbA1c; and medication usage. Statistical analyses used repeated-measures ANOVA, Kruskal–Wallis tests, Welch’s t-tests, and Pearson’s correlations via Analyze-it for Excel. Results: Of 52 patients (mean age 45.3 ± 17.8 years; 71.2% male; diabetes duration 23.3 ± 17.8 years), 50 completed follow-up visits. Significant reductions occurred in BPI pain severity (9.0 ± 0.8 to 2.0 ± 0.7, p < 0.001), interference (7.5 ± 1.7 to 2.2 ± 0.9, p < 0.001), LANSS score (19.4 ± 3.8 to 10.2 ± 6.4, p < 0.001), and HbA1c (9.77% ± 1.50 to 7.79% ± 1.51, p < 0.001). Analgesic use decreased markedly (e.g., morphine equivalents: 66.8 ± 49.2 mg to 4.5 ± 9.6 mg). Cannabis dose correlated positively with pain relief (r = 0.74, p < 0.001) and negatively with narcotic use (r = −0.43, p < 0.001) and pain interference (r = −0.43, p < 0.001). No serious adverse events were reported; mild side effects (e.g., dry mouth or euphoria) occurred in 15.4% of patients. Conclusions: Inhaled cannabis showed sustained pain relief, improved glycemic control, and opioid-sparing effects in refractory DN over 5 years, with a favorable safety profile. These findings are associative due to the observational design, and randomized controlled trials (RCTs) are needed to confirm efficacy and determine optimal usage, addressing limitations such as single-center bias and small sample size (n = 52). Future studies incorporating biomarker analysis (e.g., endocannabinoid levels) could elucidate mechanisms and enhance precision in cannabis therapy. Full article

Pediatric hip surgeries are associated with moderate to high levels of pain, which, in severe cases can lead to opioid prescription and use. There is a growing focus on reducing post-operative pain in these patients to decrease the need for opioids, as well as increase early mobilization for recovery. Conventional methods of pain relief using opioids can have unwanted negative impacts on pediatric patients such as respiratory depression, nausea, confusion, and the concerning possibility for the development of dependence. Likewise, traditional methods of anesthesia, like the lumbar epidural block, can have unwanted systemic side effects, such as hypotension, urinary retention, arrhythmias, and spinal abscesses. These complications can lead to longer hospital stays and delayed recovery. This review analyzes the efficacy of a newer regional anesthesia technique, the pericapsular nerve group (PENG) block, in comparison to the lumbar epidural block. This technique utilizes precision-based anesthesia to selectively block the articular branches to the hip joint while avoiding the main trunks of the femoral and obturator nerves. Additionally, with the utilization of high-resolution ultrasound to guide the blocks, providers can increasingly count on proper insertion and predictable anesthetic spread. The result is a motor-sparing blockade that shows promise in allowing earlier mobilization and better functional recovery times after pediatric hip surgeries. Full article

Introduction: The management of peri-operative pain significantly impacts the post-operative recovery following kidney transplant. For decades, regional blocks have been utilized for post-operative pain management following abdominal surgery. The data on the routine use of regional blocks peri-operatively during kidney transplants are limited. We aim to review our current clinical practice of peri-operative use of regional blocks during kidney transplants and management of peri-operative pain up to 24 h. Methods: A consecutive series of 100 patients who underwent kidney transplant was reviewed. All demographic data including patient’s age, gender, race, and body mass index were collected. Pre-transplant co-morbidities were summarized for all patients and included the American Society of Anesthesiologists (ASA) score. Patients were divided into two groups based on whether they received a transversus abdominis plane (TAP) block. Group A consisted of patients who received an ultrasound-guided TAP block, while Group B included patients who did not receive any form of TAP block. The intra-operative and post-operative use of analgesia was recorded for up to 24 h post kidney transplant. All peri-operative complications were reviewed. The chi-square test and Fisher’s exact test was used to compare symptoms (nausea, vomiting, and pruritus) between the two groups. Similarly, the use of analgesia was also compared. Results: A total of 100 patients were identified and equally distributed between the two groups [Group A = 50 (TAP block), Group B = 50 (non-TAP block)]. There was a statistically significant reduction in the use of intraoperative fentanyl (p = 0.04) in Group A. There was no difference in the post-operative use of hydromorphone (p = 0.665), oxycodone (p = 0.75), and acetaminophen (p = 0.64) up to 24 h after the kidney transplant procedure. There was no difference between post-operative nausea (p = 0.766), vomiting (p = 0.436), and pruritus. There were no complications recorded secondary to the use of regional blocks in Group A. Conclusions: The use of regional anesthesia in kidney transplant recipients is a safe approach without complications. The study concluded that regional blocks decrease the use of intra-operative opioids. However, there was no difference in the use of post-operative requirements for analgesia or side effects up to 24 h after kidney transplant. Full article

Individuals with severe mental illness face a substantially higher risk of suicide compared with the general population, with drug overdose representing one of the most common and potentially lethal methods. This narrative review explores toxidromes frequently encountered in psychiatric populations, such as opioid, anticholinergic, and serotonergic toxicity, highlighting the clinical presentation in intentional overdose. Emphasis is placed on clinical recognition, antidote-based treatment, and systems-level strategies for the prevention of lethal overdose. We conducted a comprehensive literature search of PubMed, Google Scholar, and Web of Science for English-language articles using combinations of the following keywords: mental disorders; persons with psychiatric disorders; drug overdose; poisoning; serotonin syndrome; neuroleptic malignant syndrome; anticholinergic agents/poisoning; cholinergic antagonists/poisoning; psychotropic drugs/adverse effects; substance-related disorders; drug-related side effects and adverse reactions; polypharmacy; suicide, attempted; emergency service, hospital. By embedding toxidrome awareness into routine emergency and psychiatric practice, we aim to expedite treatment and improve patient outcomes. Full article

Background: Effective pain control is key to recovery after esophagectomy. Methadone may enhance analgesia and reduce opioid needs. Its role in thoracic surgery is not well defined. Methods: This single-center retrospective cohort study included 206 patients who underwent esophagectomy from 2017 to 2023. A total of 66 received intraoperative methadone, and 140 served as controls. The primary outcome was cumulative postoperative opioid use in morphine milligram equivalents (MMEs) at 12, 24, 36, 48, and 72 h. Secondary outcomes included pain scores, time to first opioid, and opioid-related side effects. Results: Demographics were similar between groups. Intraoperative opioid use was lower in the methadone group (49.9 ± 31.0 vs. 76.1 ± 39.6 MME, p < 0.001). Postoperatively, MME use was significantly lower in the methadone group at all time points: 12 h (38.4 ± 48.1 vs. 56.4 ± 53.5; p = 0.017), 24 h (76.7 ± 81.2 vs. 122.4 ± 109.7; p < 0.001), 36 h (103.8 ± 106.2 vs. 176.9 ± 156.9; p < 0.001), 48 h (139.4 ± 135.6 vs. 229.6 ± 210.7; p < 0.001), and 72 h (173.5 ± 173.5 vs. 304.0 ± 286.1; p < 0.001). Time to first opioid was longer (225.6 ± 296.5 vs. 41.6 ± 69.8 min, p < 0.001). Pain scores were similar in the first 72 h; at two weeks, they were lower with methadone (0.69 ± 1.42 vs. 1.43 ± 2.55, p = 0.009). Side effect rates were similar. Conclusions: Intraoperative methadone is associated with reduced postoperative opioid use without increasing side effects. Full article

Chronic pain affects millions of individuals globally and continues to pose a major burden on patients and healthcare systems. Traditional analgesics, such as opioids and nonsteroidal anti-inflammatory drugs, often provide only partial relief and are frequently associated with significant side effects and risks of misuse. In recent years, vaccines that target molecules involved in pain signaling have emerged as an innovative therapeutic strategy. These vaccines aim to induce long-lasting immune responses against key mediators of nociception, including nerve growth factor (NGF), calcitonin gene-related peptide (CGRP), substance P, and voltage-gated sodium channels such as Nav1.7. By promoting the production of specific antibodies, anti-pain vaccines have the potential to achieve analgesic effects with longer duration, reduced need for frequent administration, and improved accessibility. Multiple vaccine platforms are under investigation, including virus-like particles, peptide-protein conjugates, and nucleic acid technologies. Although preclinical studies have shown promising efficacy and safety profiles, clinical evidence is still limited to early-stage trials, particularly for migraine. This narrative review summarizes current knowledge on therapeutic vaccines for pain, discusses the immunological and technological advances in the field, and outlines future directions. Full article

Background: The rise of opioid drug usage in the U.S. correlates with increasing recognition of gastrointestinal side effects, especially in the esophagus. The literature has recently noted that abnormalities in the upper esophageal sphincter (UES) are a poor prognostic factor in Achalasia treatment response. A better understanding of the relationship between opioid therapy and esophageal motility and sphincter function may shape our management guidelines for esophageal dysmotilities. This study aimed to evaluate dysmotility patterns, specifically UES function, among the veteran population, where opioid use is reportedly high. Methods: We performed a retrospective search of all the veterans at a large urban veteran affairs hospital who had undergone esophageal manometry from 2013 to 2022, collecting data on patient demographics, indication for procedure, diagnosis, sphincter pressure values, and presence of chronic opioid use. Results: Of 395 patients, 29% had a history of chronic opioid therapy. Notably, patients that were diagnosed with Achalasia had a greater proportion of chronic opioid use as compared to those who were not. Additionally, there was a statistically significant lower average upper esophageal resting pressure in opioid patients compared to non-opioid patients. Conclusions: Veteran patients with Achalasia have a greater proportion of chronic opioid use as compared to those without. There are significant manometric pressure differences at the upper esophageal sphincter among chronic opioid users when compared to non-opioid users. Full article

Context and objective: Post-amputation pain (PAP) is an umbrella term that includes residual limb pain (RLP) and phantom limb pain (PLP), posing a significant challenge to recovery and quality of life after limb loss. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has gained interest for its potential to manage PAP, particularly in refractory cases. This narrative review explores the efficacy of ketamine for PAP and the emerging role of pharmacogenomics in guiding its use. Methods: A literature review of PubMed, Embase, and Cochrane databases was conducted, focusing on clinical trials, systematic reviews, and genetic influences on ketamine metabolism and response. Studies suggest that perioperative ketamine can reduce PAP severity and opioid use. However, outcomes vary, with some patients experiencing transient relief and others achieving prolonged benefit. Results: This variability may be linked to genetic differences in CYP2B6, CYP3A4/5, COMT Val158Met, SLC6A2, and KCNS1, which affect ketamine’s metabolism, efficacy and side effect profile. Understanding these pharmacogenomic factors could enable more personalized and effective ketamine therapy. Conclusion: Despite its promise, inconsistent dosing regimens and limited integration of genetic data hinder standardization. Further research into genotype-guided ketamine protocols may improve treatment outcomes and support precision analgesia in amputee care. Full article

Background/Objectives: Intravenous patient-controlled analgesia (IV-PCA) is commonly used for pain control following arthroscopic rotator cuff repair (ARCR), but its use is limited by adverse effects such as nausea and vomiting. The suprascapular nerve block (SSNB) has emerged as an effective regional analgesic alternative. This retrospective cohort study aimed to compare the analgesic efficacy and safety of continuous intra-operative suprascapular nerve block (CI-SSNB) alone versus CI-SSNB combined with fentanyl-based IV-PCA (CI-SSNB + IV-PCA). Methods: A total of 40 patients undergoing ARCR under general anesthesia with a single-shot interscalene block (ISB) were allocated to either CI-SSNB alone (n = 20) or CI-SSNB + IV-PCA (n = 20). Pain scores were assessed using a 0–10 visual analog scale from 0 to 72 h postoperatively at predetermined intervals, along with opioid consumption and adverse events. Results: At post-operative day 0 (POD 0, 10 p.m.), mean pain scores were 5.75 ± 2.59 in the CI-SSNB + IV-PCA group vs. 3.95 ± 3.00 in the CI-SSNB group (p = 0.050). The total number of rescue pethidine doses up to post-operative day 3 was 1.80 ± 2.02 vs. 0.95 ± 1.10, respectively (p = 0.108). However, adverse effects such as nausea and vomiting occurred only in the CI-SSNB + IV-PCA group. Conclusions: CI-SSNB provides comparable analgesia to CI-SSNB + IV-PCA, while avoiding IV-PCA-related side effects, suggesting that IV-PCA may not be necessary when CI-SSNB is employed for post-operative analgesia following ARCR. Full article

Although opioids are effective in treating pain, they cause serious side effects. The use of regional anesthesia, although effective in the perioperative period, may not be suitable if mobility and lack of numbness is desired. Hence, there is a clear need for novel pain therapies. Low-voltage activated (T-type) calcium channels (Ca_V3.2 isoform) could be a promising therapeutic target for the development of novel pain therapies. Indeed, our published findings suggest that novel neuroactive steroid (NAS) analogs that modulate the activity of Ca_V3.2 channels have unique anti-nociceptive properties. However, the concern with current NASs appears to be their hypnotic/sedative properties, thus potentially hindering the future development of NASs for novel pain therapies. Hence, we developed a new line of NASs that are effective blockers of neuronal Ca_V3.2 channels in pain pathways while having more favorable pharmacodynamic properties, i.e., lack of sedative/hypnotic side effects. We present two promising novel analogs of NASs—B372 ((3β,5α,17β)-3-Hydroxyandrostan-17-carbonitrile) and YX23 ((3β,5α,17β)-3-Methoxyestran-17-ol). Using an in vitro approach, we show that B372 and YX23 are effective in blocking Ca_V3.2 channels. Using an in vivo approach, we show that they are effective anti-nociceptives in wild-type but not Ca_V3.2 knock-out mice. Importantly, we show that they lack sedative/hypnotic effects. Full article

Post-craniotomy pain is common yet often sub-optimally managed because systemic opioids can obscure postoperative neurologic examinations. The superficial cervical plexus block (SCPB) has, therefore, emerged as a targeted regional anesthesia option for occipital craniotomies. The SCPB targets the C2–C4 nerves to anesthetize the occipital scalp region, covering the lesser occipital nerve territory that lies within typical posterior scalp incisions. Clinical evidence shows the block is effective in reducing acute postoperative pain after occipital craniotomy and diminishes opioid requirements. Studies have demonstrated successful and long-lasting analgesia, reductions in 24-h opioid consumption, and a lower incidence of severe pain. Moreover, the technique exhibits a low complication rate and is safer than a deep cervical plexus block because the injection remains superficial and avoids critical vascular and neural structures. When delivered under ultrasound guidance, major adverse events are exceedingly rare. By reducing opioid use, the SCPB can help reduce postoperative complications, allowing earlier neurological assessments and fewer opioid-related side effects. Incorporation of the SCPB into multimodal analgesia regimens can, therefore, accelerate postoperative recovery by providing regionally focused, opioid-sparing pain control without clinically significant sedation. Overall, current data support the SCPB as a dependable, well-tolerated, and clinically practical approach for managing post-craniotomy pain in patients undergoing occipital approaches. In this narrative review, we will discuss the mechanism of action and anatomy, the clinical application, safety and tolerability, patient outcomes, and emerging future directions of the superficial cervical plexus block and how it mitigates post-occipital craniotomy pain. Full article

Opioids are among the most effective drugs for treating moderate to severe pain. Unfortunately, opioid use, even short-term, can lead to addiction, tolerance, overdose, and respiratory depression. Therefore, efforts to design and develop novel compounds that would retain analgesic activity while reducing side effects continue unabated. The present study was designed to investigate the respiratory and cardiovascular effects of the hybrid peptide LENART01, which has evidenced potent antinociceptive and antimicrobial activity. This hybrid peptide, composed of N-terminally located dermorphin and C-terminal modified ranatensin pharmacophore, was tested in vivo in anesthetized rats. The main effect of LENART01 was apnea in 70% of examined animals, sighing, and a significant increase in blood pressure. Interestingly, the hybrid induced sighs less frequently than ranatensin, and apnea dependent on vagus nerve mu opioid receptor activation much less frequently and less intensely than dermorphin itself. This shows that LENART01 is a safer opioid system-related agent as compared to dermorphin for its prospective use in the treatment of pain. Full article

Background/Objective: Fentanyl plays a pivotal role in the opioid epidemic, defined by four waves of overdose deaths. To analyse fentanyl research trends, examining its links to mental health, pharmaceutical development, healthcare, diseases, and pathophysiology within the broader social and health context of the time. Methods: To understand the evolution of scientific publications on fentanyl and its relationship to the opioid crisis, a search using Web of Science Core Collection and PubMed was conducted. A total of 53,670 documents were retrieved related to opioid scientific production, among which 1423 articles (3%) focused specifically on fentanyl. The 21,546 MeSH terms identified in these documents were analysed by publication year and specific fields: Psychiatry and Psychology, Chemicals and Drugs, Healthcare, Diseases, and Phenomena and Processes. R-statistical/FactoMineR libraries were used for the correspondence analysis. Results: In the first overdose death wave, research focused on improving therapies and reducing side effects. The second wave emphasised detoxification methods with naltrexone, methadone, and behavioural therapies. The third wave addressed psychological treatments and HIV-syringe-sharing prevention. The fourth wave prioritised less addictive analogues and understanding consumer profiles to combat the epidemic. Conclusions: Fentanyl research has evolved alongside real-world challenges, reinforcing the connection between patients’ needs, healthcare professionals’ roles, illicit users, policymakers, and the research community’s contributions to addressing both therapeutic use and its broader societal impact. These findings highlight the necessity for an interdisciplinary approach to scientific research integrating prevention, treatment, education, legal reform, and social support, emphasising the need for public health policies and collaborative research to mitigate its impact. Full article