BACKGROUND: Chronic pain affects over 100 million Americans, with a disproportionately high number being Veterans. Chronic pain is often difficult to treat and responds variably to medications, with many providing minimal relief or having adverse side effects that preclude use. Cannabidiol (CBD) has emerged as a potential treatment for chronic pain, yet research in this area remains limited, with few studies examining CBD\'s analgesic potential. Because Veterans have a high need for improved pain care, we designed a clinical trial to investigate CBD\'s effectiveness in managing chronic pain symptoms among Veterans. We aim to determine whether CBD oral solution compared to placebo study medication is associated with greater improvement in the Patient Global Impression of Change (PGIC).
METHODS: We designed a randomized, double-blind, placebo-controlled, pragmatic clinical trial with 468 participants. Participants will be randomly assigned in a 1:1 ratio to receive either placebo or a CBD oral solution over a 4-week period. The trial is remote via a smartphone app and by shipping study materials, including study medication, to participants. We will compare the difference in PGIC between the CBD and placebo group after four weeks and impacts on secondary outcomes (e.g., pain severity, pain interference, anxiety, suicide ideation, and sleep disturbance).
CONCLUSIONS: Once complete, this trial will be among the largest to date investigating the efficacy of CBD for chronic pain. Findings from this clinical trial will contribute to a greater knowledge of CBD\'s analgesic potential and guide further research. Given the relative availability of CBD, our findings will help elucidate the potential of an accessible option for helping to manage chronic pain among Veterans.
BACKGROUND: This protocol is registered at clinicaltrials.gov under study number NCT06213233.

UNASSIGNED: Despite this growing interest, there remains a lack of comprehensive and systematic bibliometric analyses of ketamine research. This study aimed to summarize the progress in ketamine research through bibliometric analysis, providing insights into the development and direction of the field.
UNASSIGNED: Publications related to ketamine were retrieved from the Web of Science Core Collection (WoSCC) database on February 15, 2024. In conducting a comprehensive bibliometric analysis, a variety of bibliographic elements were meticulously collected to map the landscape of research within a specific field.
UNASSIGNED: Between January 1, 2014, and December 31, 2023, a total of 10,328 articles on ketamine research were published across 1,752 academic journals by 45,891 authors from 8,914 institutions in 128 countries. The publication volume has shown a steady increase over this period. The United States of America (USA) and the People\'s Republic of China lead in both publication and citation counts. The National Institute of Mental Health (NIMH) and Yale University emerge as the most active institutions in this research domain. Carlos Zarate of the NIH National Institute of Mental Health was noted for the highest number of significant publications and received the most co-citations. The analysis revealed key research themes including mechanism of action, adverse events, psychiatric applications, and perioperative implications.
UNASSIGNED: This study provided comprehensive bibliometric and knowledge mapping analysis of the global ketamine research landscape, offering valuable insights into the trends, key contributors, and thematic focus areas within the field. By delineating the evolution of ketamine research, this study aims to guide future scholarly endeavors and enhance our understanding of ketamine\'s therapeutic potential.

Mitragyna speciosa Korth (kratom) is a tropical indigenous tree of Southeast Asia. It is commonly consumed by the people due to its various pharmacological properties. The leaves of this plant are traditionally used for the treatment of several diseases including pain, fever, cough, anxiety, depression, obesity, diarrhoea, wound healing, diabetes, hypertension as well as for the prevention of cancer and improvement of sexual performance. Phytochemical investigations have confirmed the presence of more than forty alkaloids along with the presence of other bioactive secondary metabolites. Among the alkaloids isolated, mitragynine and 7-hydroxymitragynine along with their derivatives have been widely evaluated and reported to possess various pharmacological effects. Hence, the aim of this review is to shed light on the traditional uses of kratom and the scientific studies to justify the folkloric claims and active principles responsible for the various medicinal effects associated with the leaves of this plant. This review highlights the potential benefits and toxicities associated with M. speciosa leaves along with the phytochemistry. Moreover, the existing gaps in the field of M. speciosa study have been identified along with the future directions to further avail the benefits of this plant species.

The survival of an organism relies on its ability to repair the damage caused by trauma, toxic agents, and inflammation. This process involving cell proliferation and differentiation is driven by several growth factors and is critically dependent on the organization of the extracellular matrix. Since autologous platelet concentrates (APCs) are fibrin matrices in which cells, growth factors, and cytokines are trapped and delivered over time, they are able to influence that response at different levels. The present review thoroughly describes the molecular components present in one of these APCs, leukocyte- and platelet-rich fibrin (L-PRF), and summarizes the level of evidence regarding the influence of L-PRF on anti-inflammatory reactions, analgesia, hemostasis, antimicrobial capacity, and its biological mechanisms on bone/soft tissue regeneration.

UNASSIGNED: Diagnosing and treating lameness in horses is essential to improving their welfare. In equine orthopedic practice, infrared thermography (IRT) can indirectly detect soreness. Non-steroidal anti-inflammatory drugs can treat painful and inflammatory processes in horses. Using IRT, the efficacy of meloxicam (Maxicam Gel®) was evaluated in pre-treating transient synovitis in horses induced by a middle carpal joint injection of lipopolysaccharides (LPS) from E. coli 055:B5 at a dose of 10 endotoxin units.
UNASSIGNED: In a cross-over design, six healthy horses were randomly assigned to receive either 0.6 mg/kg of oral Maxicam Gel® (MAXVO) or a mock administration (control group, C) following a two-week washout period. IRT of the middle carpal joint, visual lameness assessment and joint circumference were recorded over time. Clinical and hematological evaluations were performed. Synovial fluid aspirates were analyzed for total nucleated cell count, total protein, and prostaglandin E2. A mixed effects analysis of variance was performed for repeated measures over time, followed by Tukey\'s test. A multinomial logistic regression was conducted to determine whether there is a relationship between a thermography temperature change and the lameness score.
UNASSIGNED: There were no changes in joint circumference. The MAXVO group showed a lower rectal temperature 4 h after synovitis induction. The C group presented an increase in neutrophils and a decrease in total hemoglobin and hematocrit 8 h after induction. No changes were observed in the synovial fluid between groups. The horses that received meloxicam did not show clinically significant lameness at any time, while the C group showed an increase in lameness 2, 4, and 8 h after synovitis induction.
UNASSIGNED: IRT indicated that the skin surface temperature of the middle carpal joint was lower in horses who received meloxicam, suggesting a reduction in the inflammatory process induced by LPS. It was observed that the maximum temperature peaks in the dorsopalmar and lateropalmar positions can be utilized to predict the severity of lameness, particularly when the temperature rises above 34°C. Horses pre-treated with meloxicam showed either reduced or no indication of mild to moderate pain and presented a lowehr thermographic temperature, which indicates the effectiveness of Maxicam Gel® as an anti-inflammatory.

BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID) use has been investigated as a modifiable risk factor for postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD). This study comprises a systematic review and meta-analysis examining the impact of perioperative NSAID use on rates of POPF after PD.
METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020-compliant systematic review was performed. Pooled mean differences (MD), odds ratios (OR), and risk ratios with 95% CIs were calculated.
RESULTS: Seven studies published from 2015 to 2021 were included, reporting 2851 PDs (1372 receiving NSAIDs and 1479 not receiving NSAIDs). There were no differences regarding blood loss (MD -99.40 mL; 95% CI, -201.71 to 2.91; P = .06), overall morbidity (OR 1.05; 95% CI, 0.68-1.61; P = .83), hemorrhage (OR 2.35; 95% CI, 0.48-11.59; P = .29), delayed gastric emptying (OR 0.98; 95% CI, 0.60-1.60; P = .93), bile leak (OR 0.68; 95% CI, 0.12-3.89; P = .66), surgical site infection (OR 1.02; 95% CI, 0.33-3.22; P = .97), abscess (OR 0.99; 95% CI, 0.51-1.91; P = .97), clinically relevant POPF (OR 1.18; 95% CI, 0.84-1.64; P = .33), readmission (OR 0.94; 95% CI, 0.61-1.46; P = .78), or reoperation (OR 0.82; 95% CI, 0.33-2.06; P = .68). NSAID use was associated with a shorter hospital stay (MD -1.05 days; 95% CI, -1.39 to 0.71; P < .00001).
CONCLUSIONS: The use of NSAIDs in the perioperative period for patients undergoing PD was not associated with increased rates of POPF.

UNASSIGNED: Pistacia chinensis is extensively employed in traditional medicine. This study aimed to isolate and evaluate the therapeutic effects of 3\'4\'78-tetrahydroxy-3-methoxyflavone from P. chinensis crude extract.
UNASSIGNED: The study utilized column chromatography for isolation. The plant extract and its isolated compound were assessed for in vivo analgesic (hot plate model), anti-inflammatory (carrageenan-induced paw edema), sedative (open field model), and muscle relaxing properties (inclined plane and traction test).
UNASSIGNED: In the thermal-induced analgesic model, a significant analgesic effect was observed for the extract (25, 50, and 100 mg/kg) and the isolated compound (2.5, 5, 10, and 15 mg/kg) at higher doses. The extract (100 mg/kg) significantly prolonged latency time (21.98 seconds) after 120 minutes of administration. The isolated compound elevated the latency time (20.03 seconds) after 30 minutes, remaining significant up to 120 minutes with a latency time of 24.11 seconds. The anti-inflammatory effect showed a reduction in inflammatory reactions by 50.23% (extract) and 67.09% (compound) after the fifth hour of treatment. Both samples demonstrated significant sedative effects, with the extract hindering movement by 54.11 lines crossed compared to the negative control (180.99 lines). The isolated compound reduced the number of lines crossed to 15.23±SEM compared to the negative control. Both samples were also significant muscle relaxants. Docking studies indicated that the compound\'s therapeutic effect is due to inhibiting COX and nociceptive pathways.
UNASSIGNED: The isolated compound from Pistacia chinensis exhibits significant analgesic, anti-inflammatory, sedative, and muscle relaxing properties, with potential therapeutic applications by inhibiting COX and nociceptive pathways.

UNASSIGNED: Cynara scolymus has bioactive constituents and has been used for therapeutic actions. The present study was undertaken to investigate the mechanisms underlying pain-relieving effects of the hydroethanolic extract of C. scolymus (HECS).
UNASSIGNED: The antinociceptive activity of HECS was assessed through formalin and acetic acid-induced writhing tests at doses of 50, 100 and 200 mg/kg intraperitoneally. Additionally, naloxone (non-selective opioid receptors antagonist, 2 mg/kg), atropine (non-selective muscarinic receptors antagonist, 1 mg/kg), chlorpheniramine (histamine HH1-receptor antagonist, 20 mg/kg), cimetidine (histamine H2-receptor antagonist, 12.5 mg/kg), flumazenil (GABAA/BDZ receptor antagonist, 5 mg/kg) and cyproheptadine (serotonin receptor antagonist, 4 mg/kg) were used to determine the systis implicated in HECS-induced analgesia. Impact of HECS on locomotor activity was executed by open-field test. Determination of total phenolic content (TPC) and total flavonoid content (TFC) was done. Evaluation of antioxidant activity was conducted iploying 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay.
UNASSIGNED: HECS (50, 100 and 200 mg/kg) significantly indicated dose dependent antinociceptive activity against pain-related behavior induced by formalin and acetic acid (P < 0.001). Pretreatment with naloxone, atropine and flumazenil significantly reversed HECS-induced analgesia. Antinociceptive effect of HECS riained unaffected by chlorpheniramine, cimetidine and cyproheptadine. Locomotor activity was not affected by HECS. TPC and TFC of HECS were 59.49 ± 5.57 mgGAE/g dry extract and 93.39 ± 17.16 mgRE/g dry extract, respectively. DPPH free radical scavenging activity (IC50) of HECS was 161.32 ± 0.03 μg/mL.
UNASSIGNED: HECS possesses antinociceptive activity which is mediated via opioidergic, cholinergic and GABAergic pathways.

UNASSIGNED: Drawing on the principles of wrist-ankle acupuncture (WAA), our research team has developed a portable device for WAA point compression, termed the acupressure wrist-ankle strap (AWA). The current study aims to evaluate the efficacy of the AWA in alleviating pain associated with primary dysmenorrhea.
UNASSIGNED: A single-blind, randomized clinical trial was conducted from April 1, 2019, to December 31, 2019. 78 participants with primary dysmenorrhea were recruited from Shanghai University of Traditional Chinese Medicine. All participants were treated on the first day of menstruation for 30 min. Participants in the AWA group used the AWA, the internal side of which is equipped with a tip compression component, while participants in the non-acupressure wrist-ankle acupuncture(NAWA)group used the NAWA, with the inside tip pressing parts removed. The main outcome was the difference in visual analogue scale (VAS) score between baseline and 30 minutes after randomization.
UNASSIGNED: A total of 78 participants aged 18 to 30 years were included in the intention-to-treat analyses. The VAS scores (mean [standard deviation]) in the AWA group were significantly lower than those in the NAWA group at each time point of intervention (5 minutes: 95% CI, [-1.27 to -0.68], p < 0.001; 10 minutes: 95% CI, [-2.34 to -1.51], p < 0.001; 30 minutes: 95% CI, [-3.74 to -2.72], p < 0.001). In the AWA group, 16 participants reported \"obvious relief\" of dysmenorrhea pain while 23 did not; the average onset time of analgesia they reported were (21.50 ± 3.65) min, while no subjects in NAWA group reported obvious pain relief. The pain threshold (mean [standard deviation]) at SP9 of both sides in AWA group decreased significantly after intervention that in NAWA group (Left: 95% CI, [-5.02 to -1.81], p < 0.001; Right: 95% CI, [-7.67 to -4.24], p < 0.001). There was no significant change in the temperature at CV4 in either group (95% CI, [-0.63 to -0.66], p = 0.970).
UNASSIGNED: This trial substantiates our hypothesis that the AWA provides immediate analgesic effects. The AWA represents an effective and safe non-invasive physical therapy option, which patients can self-administer to alleviate abdominal pain.

Evaluation of post-operative pain in children after receiving dental treatments under local anesthesia is of interest. Hence, a study consisting of 182 children aged from 4 to 12 years old, who received at least one of the following procedures: dental restoration, extraction, placement of stainless steel crown (SSC) with or without pulpotomy is completed. Parents were contacted by phone within 48 hours to assess post-operative pain by using Wong-Baker FACES Pain Rating Scale (WBF). Individuals who were reachable via phone (146 out of 182, response rate 80.2%). 30.8% of them reported experiencing pain or discomfort (WBF more than or equal 2). Pediatric patients who had SSC on their primary molars had a considerably higher incidence of reporting pain than any other dental procedures (44.8% at p < 0.001). However, there was no significant difference in reported pain between placements of SSC alone or SSC with pulpotomy (44.8% and 46.5%, respectively). Further, over-the-counter analgesics were administered in 19.9% of participants.