The relationship of depressive symptoms with pain and analgesic use in Turkish adolescents.

PROBLEM: This study aimed to determine the prevalence of depressive symptoms, pain (headache, abdominal pain, back pain) and analgesic use among Turkish adolescents. Additionally, it aimed to examine the association between depressive symptoms and pain and analgesic use in adolescents. METHODS: This cross-sectional, correlational study was conducted in Izmir, Turkey with 954 adolescents aged 11-19 years. Data were collected with the "socio-demographic questionnaires" and the "Center for Epidemiologic Studies Depression Scale for Children". Analyzes were performed using descriptive statistics and multiple logistic regression analysis. FINDINGS: Of the adolescents, 632 (66.2%) showed depressive symptoms. Of the adolescents, 424 (44.4%) experienced headache, 256 (26.8%) experienced abdominal pain, and 343 (36.0%) experienced back pain. A total of 309 (32.4%) adolescents used analgesics for headaches, 132 (13.8%) abdominal pain, and 47 (4.9%) for back pain. Female gender, high level maternal education, bad economic status, poor health perception, bad school success, pain and analgesic use were the correlated variables with adolescent depression. CONCLUSIONS: The depressive symptoms, headache and back pain, and use of analgesics especially for headaches were common among adolescents. The results showed depression in adolescent correlated with pain (headache, abdominal pain, and back pain) and analgesic use. Regular screening is needed to assure early intervention of depression among adolescents.

Pattern of Prescribing Analgesics and Their Response in Cancer Patients Attending Outpatient Department of Palliative Care Service in Two Teaching Hospitals of Bangladesh.

Palliative care is a valued aspect of clinical care which is an urgent humanitarian need for people worldwide with cancer and other chronic fatal diseases. Patients experience many different symptoms including severe pain in advanced cancer. Palliative care focuses on relief from symptoms, pain and stress by using different analgesics and adjuvant. The goal of palliative care is to improve the quality of life. So, this prospective observational study was carried out to assess pattern of drugs used and their response to pain in cancer patients attending out-patient department of palliative care service in two teaching hospitals of Bangladesh. One hundred forty (140) cancer patients were purposively selected who attended in out-patient department of palliative care unit in Bangabandhu Sheikh Mujib Medical University (BSMMU) and Dhaka Medical College Hospital (DMCH) from July 2018 to June 2019. Outcome variables were commonly presenting complaints, pain intensity, commonly prescribed drugs and analgesic prescription according to WHO three-step analgesic ladder, etc. The mean age ±SD of the respondents was 51.30±15.38 years, male-female ratio 1:1. Common sites of cancer were alimentary origin (20.0%), genitourinary system (17.86%), hepatobiliary system (11.43%), respiratory system (10.71%). The prescribed drugs were analgesics (96.4%), PPIs (74.3%), laxatives (62.1%), anti-emetics (38.6%), multivitamins (32.9%), H2 antagonists (17.1%), sedatives (17.1%), and corticosteroids (8.6%). Level 1 analgesics (Paracetamol or other NSAIDs) were prescribed to 42.65%, level 2 analgesics (Tramadol) were prescribed to 50.00% patients and level 3 analgesics (Morphine) were prescribed to 51.42% patients. The relation between and receiving three levels of analgesic prescriptions was statistically significant. The association between level of analgesic prescription was significant with site of cancer (p<0.001) and intensity of pain (p<0.001). This study showed that morphine was prescribed to more than half of the patients. Other level of analgesics were also used either single or in combination. Younger and male patients were treated more with level III analgesics. Prescribing analgesics were dependent on sites of cancer and intensity of pain.

Laparoscopic assisted versus ultrasound guided transversus abdominis plane block in laparoscopic bariatric surgery: a randomized controlled trial.

BACKGROUND: Transversus abdominis plane block (TAPB) guided by laparoscopy and ultrasound showed promise in enhancing the multimodal analgesic approach following several abdominal procedures. This study aimed to compare the efficacy and safety between Laparoscopic (LAP) TAP block (LTAP) and ultrasound-guided TAP block (UTAP) block in patients undergoing LAP bariatric surgery. PATIENTS AND METHODS: This non-inferiority randomized controlled single-blind study was conducted on 120 patients with obesity scheduled for LAP bariatric surgeries. Patients were allocated into two equal groups: LTAP and UTAP, administered with 20 mL of 0.25% bupivacaine on each side. RESULTS: There was no statistically significant difference in the total morphine consumption, Visual Analogue Scale (VAS) score at all times of measurements, and time to the first rescue analgesia (p > .05) between both groups. The duration of anesthesia and duration of block performance were significantly shorter in the LTAP group than in the UTAP group (p < .001). Both groups had comparable post-operative heart rate, mean arterial pressure, adverse effects, and patient satisfaction. CONCLUSIONS: In LAP bariatric surgery, the analgesic effect of LTAP is non-inferior to UTAP, as evidenced by comparable time to first rescue analgesia and total morphine consumption with similar safety blocking through the low incidence of post-operative complications and patient satisfaction. TRIAL REGISTRATION: The study was registered in Pan African Clinical Trials Registry (PACTR) (ID: PACTR202206871825386) on June 29, 2022.

A comparative study on prophylactic efficacy of cinnarizine and amitriptyline in childhood migraine: a randomized double-blind clinical trial.

BACKGROUND: Pediatric migraine prophylaxis is indicated when headaches are frequent and/or disabling. We aimed to conduct a study to compare the efficacy of cinnarizine and amitriptyline in pediatric migraine prophylaxis. METHODS: In a randomized, double-blind trial, patients aged 4-17 years with migraine who were eligible for prophylaxis enrolled. The primary outcome was a reduction response rate of ≥50% with p < 0.005 with respect to headache characteristics. The secondary outcome was migraine disability assessment. We evaluated patients every four weeks for three months: T1: week 4, T2: week 8 and T3: week 12. The safety profile was also assessed. RESULTS: Thirty patients were randomly assigned to each group. However, 43 patients completed the trial. Headache frequency decreased in amitriptyline group more effectively in T1 (p = 0.004). Amitriptyline was more successful in reducing the headache duration in all three periods (p < 0.005). There was no significant difference in severity improvement and reducing disability score between the two groups (p > 0.005). No serious adverse events were observed. CONCLUSIONS: Both medications are effective in ameliorating migraine headaches and related disabilities. However, amitriptyline appears be a preferable option over cinnarizine, given its faster onset of action, efficacy in reducing headache duration and longer-lasting effects.Trial Registration: The study was registered with the Iranian Registry of Clinical Trials (IRCT) under the code IRCT-20191112045413N1.

Low-dose ketamine safely reduces acute pain in the ED with a more rapid and shorter effect than morphine.

SOURCE CITATION: Guo J, Zhao F, Bian J, et al. Low-dose ketamine versus morphine in the treatment of acute pain in the emergency department: a meta-analysis of 15 randomized controlled trials. Am J Emerg Med. 2024;76:140-149. 38071883.

The Effect of Depth of Anesthesia on Postoperative Pain in Laparoscopic Sleeve Gastrectomy: A Randomized Controlled Trial.

BACKGROUND: Patients with obesity are more sensitive to pain and more likely to have acute postoperative pain (APP). Studies have shown that the depth of anesthesia may affect the incidence of APP. The purpose of the study was to look into the connection between APP and depth of anesthesia in patients with obesity undergoing laparoscopic sleeve gastrectomy. METHODS: This is a prospective, double-blinded randomized clinical trial, 90 patients undergoing laparoscopic sleeve gastrectomy were randomly divided into two groups: the light anesthesia group (Bispectral Index of 50, BIS 50) and the deep anesthesia group (BIS 35). The degree of pain was evaluated by the visual analogue scale (VAS) at 0, 12, 24, 48, and 72 h after surgery. The use of analgesics, grade of postoperative nausea and vomiting (PONV), and the Quality of Recovery-15 (QoR-15) score were recorded. RESULTS: The VAS scores at rest or coughing at 0, 12, and 24 h after surgery in the BIS 35 group were lower than those in the BIS 50 group (P < 0.05). Fewer patients in the deep anesthesia group needed analgesia during the recovery period, and patient satisfaction was higher on the 3rd day after surgery (P < 0.015, P < 0.032, respectively). CONCLUSIONS: For patients with obesity, maintaining a deeper depth of anesthesia during surgery is beneficial to reduce APP causes less need for additional analgesic drugs, and improves patient satisfaction.

Analgesic Peptides: From Natural Diversity to Rational Design.

Pain affects one-third of the global population and is a significant public health issue. The use of opioid drugs, which are the strongest painkillers, is associated with several side effects, such as tolerance, addiction, overdose, and even death. An increasing demand for novel, safer analgesic agents is a driving force for exploring natural sources of bioactive peptides with antinociceptive activity. Since the G protein-coupled receptors (GPCRs) play a crucial role in pain modulation, the discovery of new peptide ligands for GPCRs is a significant challenge for novel drug development. The aim of this review is to present peptides of human and animal origin with antinociceptive potential and to show the possibilities of their modification, as well as the design of novel structures. The study presents the current knowledge on structure-activity relationship in the design of peptide-based biomimetic compounds, the modification strategies directed at increasing the antinociceptive activity, and improvement of metabolic stability and pharmacodynamic profile. The procedures employed in prolonged drug delivery of emerging compounds are also discussed. The work summarizes the conditions leading to the development of potential morphine replacements.

Effect of epidural dexmedetomidine in single-dose combined with ropivacaine for cesarean section.

BACKGROUND: Dexmedetomidine has arousal sedation and analgesic effects. We hypothesize that epidural dexmedetomidine in single-dose combined with ropivacaine improves the experience of parturient undergoing cesarean section under epidural anesthesia. This study is to investigate the effect of 0.5 µg/kg epidural dexmedetomidine combined with epidural anesthesia (EA) in parturients undergoing cesarean section. METHODS: A total of 92 parturients were randomly divided into Group R (receiveing epidural ropivacaine alone) Group RD (receiveing epidural ropivacaine with 0.5 µg/kg dexmedetomidine). The primary outcome and second outcome will be intraoperative NRS pain scores and Ramsay Sedation Scale. RESULTS: All 92 parturients were included in the analysis. The NRS were significantly lower in Group RD compared to Group R at all observation timepoint (P > 0.05). Higher Ramsay Sedation Scale was found in Group RD compared to Group R (P < 0.001). No parturient has experienced sedation score of 4 and above. No significant difference regarding the incidence of hypotension, bradycardia and nausea or vomiting, Apgar scores and the overall satisfaction with anesthesia was found between Group R and Group RD (P > 0.05). CONCLUSION: Epidural dexmedetomidine of 0.5 µg/kg added slightly extra analgesic effect to ropivacaine in EA for cesarean section. The sedation of 0.5 µg/kg epidural dexmedetomidine did not cause mother-baby bonding deficit. Satisfaction with anesthesia wasn't significantly improved by epidural dexmedetomidine of 0.5 µg/kg. No additional side effect allows larger dose of epidural dexmedetomidine attempt. TRIAL REGISTRATION: This study was registered at www.chictr.org.cn (ChiCTR2000038853).

Fentanyl Analogs Exert Antinociceptive Effects via Sodium Channel Blockade in Mice.

The formalin test is one approach to studying acute pain in rodents. Similar to formalin, injection with glutamate and veratrine can also produce a nociceptive response. This study investigated whether opioid-related compounds could suppress glutamate- and veratrine-induced nociceptive responses in mice at the same dose. The administration of morphine (3 mg/kg), hydromorphone (0.4 mg/kg), or fentanyl (0.03 mg/kg) suppressed glutamate-induced nociceptive response, but not veratrine-induced nociceptive response at the same doses. However, high doses of morphine (10 mg/kg), hydromorphone (2 mg/kg), or fentanyl (0.1 mg/kg) produced a significant reduction in the veratrine-induced nociceptive response. These results indicate that high doses are required when using morphine, hydromorphone, or fentanyl for sodium channel-related neuropathic pain, such as ectopic activity. As a result, concerns have arisen about overdose and abuse if the dose of opioids is steadily increased to relieve pain. In contrast, trimebutine (100 mg/kg) and fentanyl analog isobutyrylfentanyl (iBF; 0.1 mg/kg) suppressed both glutamate- and veratrine-induced nociceptive response. Furthermore, nor-isobutyrylfentanyl (nor-iBF; 1 mg/kg), which is a metabolite of iBF, suppressed veratrine-induced nociceptive response. Besides, the optimal antinociceptive dose of iBF, unlike fentanyl, only slightly increased locomotor activity and did not slow gastrointestinal transit. Cancer pain is a complex condition driven by inflammatory, neuropathic, and cancer-specific mechanisms. Thus, iBF may have the potential to be a superior analgesic than fentanyl.

Trends and prescribing patterns of antimigraine medicines in nine major cities in China from 2018 to 2022: a retrospective prescription analysis.

BACKGROUND: The objective of this study was to investigate the trends and prescribing patterns of antimigraine medicines in China. METHODS: The prescription data of outpatients diagnosed with migraine between 2018 and 2022 were extracted from the Hospital Prescription Analysis Cooperative Project of China. The demographic characteristics of migraine patients, prescription trends, and corresponding expenditures on antimigraine medicines were analyzed. We also investigated prescribing patterns of combination therapy and medicine overuse. RESULTS: A total of 32,246 outpatients who were diagnosed with migraine at 103 hospitals were included in this study. There were no significant trend changes in total outpatient visits, migraine prescriptions, or corresponding expenditures during the study period. Of the patients who were prescribed therapeutic medicines, 70.23% received analgesics, and 26.41% received migraine-specific agents. Nonsteroidal anti-inflammatory drugs (NSAIDs; 28.03%), caffeine-containing agents (22.15%), and opioids (16.00%) were the most commonly prescribed analgesics, with corresponding cost proportions of 11.35%, 4.08%, and 19.61%, respectively. Oral triptans (26.12%) were the most commonly prescribed migraine-specific agents and accounted for 62.21% of the total therapeutic expenditures. The proportion of patients receiving analgesic prescriptions increased from 65.25% in 2018 to 75.68% in 2022, and the proportion of patients receiving concomitant triptans decreased from 29.54% in 2018 to 21.55% in 2022 (both P <  0.001). The most frequently prescribed preventive medication classes were calcium channel blockers (CCBs; 51.59%), followed by antidepressants (20.59%) and anticonvulsants (15.82%), which accounted for 21.90%, 34.18%, and 24.15%, respectively, of the total preventive expenditures. Flunarizine (51.41%) was the most commonly prescribed preventive drug. Flupentixol/melitracen (7.53%) was the most commonly prescribed antidepressant. The most commonly prescribed anticonvulsant was topiramate (9.33%), which increased from 6.26% to 12.75% (both P <  0.001). A total of 3.88% of the patients received combined therapy for acute migraine treatment, and 18.63% received combined therapy for prevention. The prescriptions for 69.21% of opioids, 38.53% of caffeine-containing agents, 26.61% of NSAIDs, 13.97% of acetaminophen, and 6.03% of triptans were considered written medicine overuse. CONCLUSIONS: Migraine treatment gradually converges toward evidence-based and guideline-recommended treatment. Attention should be given to opioid prescribing, weak evidence-based antidepressant use, and medication overuse in migraine treatment.

Unsatisfactory response to acute medications does not affect the medication overuse headache development in pediatric chronic migraine.

BACKGROUND: Chronic migraine (CM) negatively impacts the quality of life of 2 to 4% of pediatric patients. In adults, CM is frequently linked to medication overuse headache (MOH), but there is a much lower prevalence of MOH in children. A suboptimal response to acute therapies may lead to their reduced use, thus preventing MOH development in children and adolescents. The frequency of patients with CM who do not respond to acute therapies was examined in the present study. We investigated whether the prevalence of MOH was different between responders and non-responders. We also examined whether patients receiving prophylactic therapy had an improved response to acute therapy. Finally, we investigated if there was a difference in the frequency of psychiatric comorbidities between responders and non-responders. METHODS: We retrospectively analysed clinical data of all chronic pediatric migraineurs under the age of 18 referred to the Headache Centre at Bambino Gesù Children Hospital in June 2021 and February 2023. ICHD3 criteria were used to diagnose CM and MOH. We collected demographic data, including the age at onset of migraine and the age of the CM course. At baseline and after 3 months of preventive treatment, we evaluated the response to acute medications. Neuropsychiatric comorbidities were referred by the children's parents during the first attendance evaluation. RESULTS: Seventy patients with CM were assessed during the chosen period. Paracetamol was tried by 41 patients (58.5%), NSAIDs by 56 patients (80.0%), and triptans by 1 patient (1.4%). Fifty-one participants (73%) were non-responder to the abortive treatment. The presence of MOH was detected in 27.1% of the whole populations. Regarding our primary aim, MOH was diagnosed in 29% of non-responder patients and 22% of responders (p > 0.05). All patients received preventative treatment. After 3 months of preventive pharmacological therapy, 65.4% of patients who did not respond to acute medications achieved a response, while 34.6% of patients who were non-responder remain non-responder (p < 0.05). Prophylactic therapy was also effective in 69% of patients who responded to acute medication (p < 0.05). Psychiatric comorbidities were detected in 68.6% of patients, with no difference between responders and non-responders (72.2% vs. 67.3%; p = 0.05). CONCLUSIONS: Despite the high prevalence of unresponsiveness to acute therapies in pediatric CM, it does not act as a protective factor for MOH. Moreover, responsiveness to acute drugs is improved by pharmacological preventive treatment and it is not affected by concomitant psychiatric comorbidities.

Cellular and molecular mechanisms involved in the analgesic effects of botulinum neurotoxin: A literature review.

Botulinum neurotoxins (BoNTs), derived from Clostridium botulinum, have been employed to treat a range of central and peripheral neurological disease. Some studies indicate that BoNT may be beneficial for pain conditions as well. It has been hypothesized that BoNTs may exert their analgesic effects by preventing the release of pain-related neurotransmitters and neuroinflammatory agents from sensory nerve endings, suppressing glial activation, and inhibiting the transmission of pain-related receptors to the neuronal cell membrane. In addition, there is evidence to suggest that the central analgesic effects of BoNTs are mediated through their retrograde axonal transport. The purpose of this review is to summarize the experimental evidence of the analgesic functions of BoNTs and discuss the cellular and molecular mechanisms by which they can act on pain conditions. Most of the studies reviewed in this article were conducted using BoNT/A. The PubMed database was searched from 1995 to December 2022 to identify relevant literature.

Comparison of the effects of ultrasound-guided quadratus lumborum block and erector spinae plane block on postoperative pain in abdominal surgeries: a protocol for systematic review and meta-analysis.

INTRODUCTION: Ultrasound-guided quadratus lumborum block and erector spinae plane block are widely used for postoperative analgesia in adult patients undergoing abdominal surgeries. This protocol aims to compare the analgesic effects between ultrasound-guided quadratus lumborum block and erector spinae plane block on postoperative pain in abdominal surgeries. METHODS AND ANALYSIS: Four databases, including PubMed, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL), will be searched. Randomised controlled trials that compared the analgesic effects between ultrasound-guided quadratus lumborum block and erector spinae plane block on postoperative pain in adult patients will be identified. The primary outcomes are time to the first analgesic request and postoperative analgesic consumption over 24 hours. Secondary outcomes will include postoperative pain scores and the incidence of side effects. RevMan V.5.3 software will be used for data processing and statistical analysis. The Grading of Recommendation, Assessment, Development and Evaluation approach will be used to assess the evidence quality of outcomes. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. Results of this present study will be submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023445802.

Relation between neutrophil-to-lymphocyte ratio with epidural analgesia timing and thoracotomy pain.

OBJECTIVE: This study investigated the relationship of the pre-operative neutrophil/lymphocyte ratio (NLR) to the timing of epidural analgesia administration and post-operative acute and chronic pain in thoracotomy. MATERIALS AND METHODS: The study was conducted on 60 patients, with NLR ≥ 2 (Group A) and NLR < 2 (Group B). Each group was divided into subgroups pre-emptive analgesia (Group P) and control group (Group C). Epidural analgesic solution was administered as a bolus before the surgical incision in Group P and at the end of the operation in Group C. NRS was questioned postoperatively at the 2nd, 4th, 8th, 12th, 24th h, 1st, and 3rd months and also additional analgesic needs were recorded. RESULTS: In Group A, the pain scores of the patients who received pre-emptive epidural analgesia were lower at the post-operative 2nd, 4th, and 8th h and analgesic consumption was less in the post-operative first 24 h. CONCLUSION: It was observed that pre-emptive epidural analgesia reduced pain levels and additional analgesic consumption in the acute post-operative period in patients with pre-operative NLR ≥ 2.

OBJETIVO: Este estudio investigó la relación de la relación neutrófilos/linfocitos (NLR) preoperatoria con el momento de la administración de la analgesia epidural y el dolor agudo y crónico posoperatorio en la toracotomía. MATERIALES Y MÉTODOS: El estudio se realizó en 60 pacientes, como NLR ≥ 2 (Grupo A) y NLR < 2 (Grupo B). Cada grupo se dividió en subgrupos de analgesia preventiva (Grupo P) y grupo control (Grupo C). La solución analgésica epidural se administró en bolo antes de la incisión quirúrgica en el Grupo P y al final de la operación en el Grupo C. La NRS se cuestionó posoperatoriamente a las 2, 4, 8, 12, 24 horas, 1 y 3 meses también adicionales Se registraron las necesidades analgésicas. RESULTADOS: En el Grupo A, los puntajes de dolor de los pacientes que recibieron analgesia epidural preventiva fueron menores a las 2, 4 y 8 horas postoperatorias y el consumo de analgésicos fue menor en las primeras 24 horas postoperatorias. CONCLUSIÓN: Se observó que la analgesia epidural preventiva redujo los niveles de dolor y el consumo adicional de analgésicos en el postoperatorio agudo en pacientes con NLR preoperatorio ≥ 2.

Duloxetine reduces opioid consumption and pain after total hip or knee arthroplasty: a meta-analysis of randomized controlled trials.

PURPOSE: There is no consensus in the current literature on the analgesic role of duloxetine after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Thus, we designed this meta-analysis to reveal the analgesic effectiveness and safety of duloxetine in TKA or THA. METHODS: As of October 2022, two authors (L.C. and W.Q.J.) independently searched five main databases (EMBASE, Web of Science, PubMed, Cochrane Library, and Google Scholar) to find relevant studies. Duloxetine vs. placebo in randomized controlled trials (RCTs) for THA or TKA were included. We set perioperative total opioid consumption as the primary outcome. Secondary outcomes included resting or dynamic pain scores over time, gastrointestinal adverse events, neurological adverse events, and other adverse reactions. RESULTS: Eight RCTs with 695 patients were incorporated in our study. This meta-analysis showed high evidence that duloxetine was effective in reducing perioperative opioid consumption (Standard mean difference [SMD] = - 0.50, 95% confidence intervals [CI]: -0.70 to - 0.31, P < 0.00001) and low to moderate evidence that duloxetine could reduce pain within three weeks after surgery. Low to high evidence showed no differences between the two groups for most adverse events. Substantial evidence suggests that duloxetine can reduce nausea and vomiting after surgery (Risk ratio [RR] = 0.69, 95% CI: 0.50 to 0.95, P = 0.02, I2 = 4%). However, moderate evidence suggested that duloxetine might be associated with increased postoperative drowsiness (RR = 1.83, 95% CI: 1.08 to 3.09, P = 0.02, I2 = 0%). CONCLUSION: Duloxetine reduced overall opioid consumption in the perioperative period and relieved pain within three weeks after surgery without increasing the risk of adverse drug events. Duloxetine can be part of a multimodal management regimen in patients with THA and TKA.

Curcumin analogue NL04 inhibits spinal cord central sensitization in rats with bone cancer pain by inhibiting NLRP3 inflammasome activation and reducing IL-1ß production.

The management and therapy of bone cancer pain (BCP) remain formidable clinical challenges. Curcumin and its analogues have been shown to have anti-inflammatory and analgesic properties. In the present study, we investigated the efficacy of curcumin analogue NL04 (NL04) in modulating inflammation in spinal dorsal horn (SDH), thereby exploring its potential to reduce central sensitization of BCP in a rat model. Differing doses of NL04 and curcumin were administered intrathecally either once (on day 12 of BCP) or over seven consecutive days (from day 6-12 of BCP). Results indicated that the ED50 for NL04 and curcumin ameliorating BCP-induced mechanical hyperalgesia is 49.08 µg/kg and 489.6 µg/kg, respectively. The analgesic effects at various doses of NL04 lasted between 4 and 8 h, with sustained administration over a week maintaining pain relief for 1-4 days, while also ameliorating locomotor gait via gait analysis and reducing depressive and anxiety-like behaviors via open-field and light-dark transition tests. The analgesic effects at various doses of curcumin lasted 4 h, with sustained administration over a week maintaining pain relief for 0-2 days. ELISA, Western blotting, qPCR, and immunofluorescence assays substantiated that intrathecal administration of NL04 on days 6-12 of BCP dose-dependently lowered spinal IL-1ß and IL-18 levels and significantly reduced the expression of IKKß genes and proteins, as well as the downstream cleavage of the trans-Golgi network (TGN). Whole-cell patch-clamp results demonstrated that NL04 inhibits potassium ion efflux in rat primary spinal neurons. Thus, NL04 exhibits significant analgesic effects in a BCP rat model by downregulating IKKß expression and inhibiting neuronal potassium ion efflux, which, in turn, suppresses the activation of NLRP3 inflammasomes and reduces IL-1ß production, potentially ameliorating pain management in BCP.

Evaluating Knowledge, Self-Reported Confidence Levels, and Prescription Patterns among Dental Practitioners Regarding Analgesics in Dentistry: A Cross-Sectional Study.

Background and Objectives: Dental pain is a common problem that often leads to unscheduled dental visits and requires a comprehensive understanding of analgesics, including their indications and contraindications. The aim of this study was to investigate dentists' knowledge, self-reported confidence levels, and prescribing patterns of analgesics in dentistry. Materials and Methods: A nationwide cross-sectional online survey was conducted, resulting in 379 responses. Of these, 68.6% were general dentists, and 31.4% were specialists. The collected data included sociodemographic information, levels of knowledge, and prescription patterns. The survey questionnaire explored self-perceived practices, patient information during prescription, and guiding factors. Descriptive statistics and a generalized linear model for regression were used for data analysis. Results: Higher levels of knowledge were observed in specific contexts such as secondary/tertiary healthcare (p = 0.022), specialization in endodontics (p = 0.003), and a higher number of working hours with patients (p = 0.038). Conversely, increased self-confidence was observed among endodontists (p = 0.008), oral surgeons (p = 0.011), and dentists with more than 6 h of patient interaction (p ≤ 0.001). Orthodontists and prosthodontists demonstrated lower knowledge levels, while specialists in family dentistry exhibited lower self-confidence. Self-confidence and knowledge displayed a significant positive correlation (r = 0.039, p < 0.001). The most frequently prescribed medication was ibuprofen (97.9%), primarily for surgical (83.9%) and endodontic procedures (60.9%), with the main indications being pulpal (85.8%), periradicular (57.3%), and postoperative pain (40.1%). Conclusions: This study reveals significant knowledge and confidence gaps among dentists, including limited awareness of the efficacy of nonsteroidal anti-inflammatory drugs for odontogenic pain, a lack of time for effective counseling, and perceived deficits in pharmacology education. To address these issues, targeted educational interventions are recommended to improve analgesic prescribing practice, close knowledge gaps, and increase dentists' confidence in more effective pain management.

Utilizing combination intrathecal baclofen and analgesic medication to manage spasticity and pain in patients with pediatric-onset disability: Case series.

PURPOSE: The use of intrathecal medications for the management of spasticity and various pain syndromes in the adult population has been previously reported. However, no evidence-based guidelines currently exist in the pediatric population. This case series presents patients (n = 8) with pediatric-onset disability who underwent placement of intrathecal baclofen pumps initially for management of severe spasticity. Despite titration of dose and use of oral analgesia, their uncontrolled pain persisted. Each patient was transitioned to a combination of baclofen and analgesic intrathecal therapy. The outcome in pain improvement and quality of life, as reported by patients and/or caregivers, were retrospectively reviewed. METHODS: Retrospective review of the background and decision-making process regarding transition to combination intrathecal therapy identified patient selection characteristics. Each patient and/or their caregivers completed a survey regarding improvements in pain, spasticity, function, and quality of life following initiation of combination intrathecal medications. RESULTS: Survey results revealed improvements in functional and pain assessments after initiation of combination baclofen and analgesic intrathecal medication. Patients and caregivers reported decreases in pain and oral spasticity medications. CONCLUSION: Use of pumps with antispasmodic and analgesic medication for combination intrathecal medication delivery should be considered in the management of patients with childhood-onset disabilities who have both severe spasticity and pain.

Electroacupuncture promotes macrophage/microglial M2 polarization and suppresses inflammatory pain through AMPK.

Inflammatory pain, the most prevalent disease globally, remains challenging to manage. Electroacupuncture emerges as an effective therapy, yet its underlying mechanisms are not fully understood. This study investigates whether adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-regulated silent information regulator 1 (SIRT1) contributes to electroacupuncture's antinociceptive effects by modulating macrophage/microglial polarization in the spinal dorsal horn of a mouse model of inflammatory pain. In this study, mice, introduced to inflammatory pain through subcutaneous injections of complete freund's adjuvant (CFA) in the plantar area, underwent electroacupuncture therapy every alternate day for 30-min sessions. The assessment of mechanical allodynia and thermal hyperalgesia in these subjects was carried out using paw withdrawal frequency and paw withdrawal latency measurements, respectively. Western blot analysis measured levels of AMPK, phosphorylation-adenosine 5'-monophosphate (AMP)-activated protein kinase, SIRT1, inducible nitric oxide synthase, cluster of differentiation 86, arginase 1, and interleukin 10. In contrast to the group treated solely with CFA, the cohort receiving both CFA and electroacupuncture demonstrated notable decreases in both thermal hyperalgesia and mechanical allodynia. This was accompanied by a marked enhancement in AMPK phosphorylation levels. AMPK knockdown reversed electroacupuncture's analgesic effects and reduced M2 macrophage/microglial polarization enhancement. Additionally, AMPK knockdown significantly weakened electroacupuncture-induced SIRT1 upregulation, and EX-527 injection attenuated electroacupuncture's facilitation of M2 macrophage/microglial polarization without affecting AMPK phosphorylation levels. Furthermore, combining electroacupuncture with SRT1720 enhanced the analgesic effect of SRT1720. Our findings suggest that AMPK regulation of SIRT1 plays a critical role in electroacupuncture's antinociceptive effect through the promotion of M2 macrophage/microglial polarization.

Analgesia for rib fractures: a narrative review.

PURPOSE: Rib fracture(s) is a common and painful injury often associated with significant morbidity (e.g., respiratory complications) and high mortality rates, especially in the elderly. Risk stratification and prompt implementation of analgesic pathways using a multimodal analgesia approach comprise a primary endpoint of care to reduce morbidity and mortality associated with rib fractures. This narrative review aims to describe the most recent evidence and care pathways currently available, including risk stratification tools and pharmacologic and regional analgesic blocks frequently used as part of the broadly recommended multimodal analgesic approach. SOURCE: Available literature was searched using PubMed and Embase databases for each topic addressed herein and reviewed by content experts. PRINCIPAL FINDINGS: Four risk stratification tools were identified, with the Study of the Management of Blunt Chest Wall Trauma score as most predictive. Current evidence on pharmacologic (i.e., acetaminophen, nonsteroidal anti-inflammatory drugs, gabapentinoids, ketamine, lidocaine, and dexmedetomidine) and regional analgesia (i.e., thoracic epidural analgesia, thoracic paravertebral block, erector spinae plane block, and serratus anterior plane block) techniques was reviewed, as was the pathophysiology of rib fracture(s) and its associated complications, including the development of chronic pain and disabilities. CONCLUSION: Rib fracture(s) continues to be a serious diagnosis, with high rates of mortality, development of chronic pain, and disability. A multidisciplinary approach to management, combined with appropriate analgesia and adherence to care bundles/protocols, has been shown to decrease morbidity and mortality. Most of the risk-stratifying care pathways identified perform poorly in predicting mortality and complications after rib fracture(s).

RéSUMé: OBJECTIF: Les fractures des côtes sont des blessures courantes et douloureuses souvent associées à une morbidité importante (p. ex., complications respiratoires) et à des taux de mortalité élevés, surtout chez les personnes âgées. La stratification des risques et la mise en œuvre rapide de voies analgésiques à l'aide d'une approche d'analgésie multimodale constituent un critère d'évaluation principal des soins visant à réduire la morbidité et la mortalité associées aux fractures des côtes. Ce compte rendu narratif a pour objectif de décrire les données probantes les plus récentes et les parcours de soins actuellement disponibles, y compris les outils de stratification des risques et les blocs analgésiques pharmacologiques et régionaux fréquemment utilisés dans le cadre de l'approche analgésique multimodale largement recommandée. SOURCES: La littérature disponible a été recherchée à l'aide des bases de données PubMed et Embase pour chaque sujet abordé dans le présent compte rendu et examinée par des expert·es en contenu. CONSTATATIONS PRINCIPALES: Quatre outils de stratification des risques ont été identifiés, le score de l'Étude de la prise en charge des traumatismes contondants de la paroi thoracique (Study of the Management of Blunt Chest Wall Trauma) étant le plus prédictif. Les données probantes actuelles sur les techniques d'analgésie pharmacologiques (c.-à-d. acétaminophène, anti-inflammatoires non stéroïdiens, gabapentinoïdes, kétamine, lidocaïne et dexmédétomidine) et d'analgésie régionale (c.-à-d. analgésie péridurale thoracique, bloc paravertébral thoracique, bloc du plan des muscles érecteurs du rachis et bloc du plan du muscle grand dentelé) ont été examinées, de même que la physiopathologie de la ou des fractures des côtes et de leurs complications associées, y compris l'apparition de douleurs chroniques et d'incapacités. CONCLUSION: Les fractures des côtes continuent d'être un diagnostic grave, avec des taux élevés de mortalité, de développement de douleurs chroniques et d'invalidité. Il a été démontré qu'une approche multidisciplinaire de la prise en charge, combinée à une analgésie appropriée et à l'adhésion aux ensembles et protocoles de soins, réduit la morbidité et la mortalité. La plupart des parcours de soins de stratification des risques identifiés sont peu performants pour prédire la mortalité et les complications après une ou plusieurs fractures de côtes.