Analgesic Potency Research Articles

Safety of nurse-directed triage intranasal fentanyl protocol for acute pain management in a European pediatric emergency department: A retrospective observational analysis.

Nurse-directed pain protocols for intranasal fentanyl administration are not widely implemented in European (EU) pediatric emergency departments (PED). Barriers include perceived safety concerns for intranasal (IN) fentanyl. The aim of this study is to describe our experience with a nurse-directed triage IN fentanyl protocol with a focus on safety in a tertiary EU PED. We conducted a retrospective analysis of patient records of children aged 0-16 years who received nurse-directed IN fentanyl between January 2019 and December 2021 at the PED of the University Children's Hospital of Bern, Switzerland. Extracted data points included demographics, presenting complaint, pain score, IN fentanyl dosage, concomitant pain medication use, and adverse events. A total of 314 patients were identified with ages ranging from 9 months to 15 years. The main indication for nurse-directed fentanyl administration was musculoskeletal pain due to trauma (n = 284, 90%). Mild adverse events (vertigo) were reported in two patients (0.6%), without a correlation to concomitant pain medication or protocol violation. The only reported severe adverse event of syncope and hypoxia in a 14-year-old adolescent occurred in a setting where the institutional nurse-directed protocol was violated. In accordance with previous studies outside of Europe, our data support the case that when appropriately used, nurse-directed IN fentanyl is a safe potent opioid analgesic for pediatric acute pain management. We strongly encourage the introduction of nurse-directed triage fentanyl protocols Europe-wide in order to provide effective and adequate acute pain management in children.

LC-MS/MS and GC/MS Profiling of Petroselinum sativum Hoffm. and Its Topical Application on Burn Wound Healing and Related Analgesic Potential in Rats.

Parsley (Petroselinum sativum Hoffm.) is renowned for its ethnomedicinal uses including managing pain, wound, and dermal diseases. We previously highlighted the estrogenic and anti-inflammatory properties of parsley and profiled the phytochemistry of its polyphenolic fraction using HPLC-DAD. To extend our investigation, we here characterized the phytochemical composition of the hydro-ethanolic extract using LC-MS/MS and GC-MS upon silylation, and evaluated the antioxidant, analgesic, antimicrobial, and wound healing activities of its hydro-ethanolic and polyphenolic fraction. The antioxidant property was assessed using FRAP, DPPH, and TAC assays. The antimicrobial activity was tested against four wound infectious microbes (Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans). The analgesic effect was studied using acetic acid (counting the number of writhes) and formalin (recording the licking and biting times) injections while the wound healing activity was evaluated using burn model in vivo. The LC-MS/MS showed that the hydro-ethanolic contains four polyphenols (oleuropein, arbutin, myricetin, and naringin) while GC-MS revealed that it contains 20 compounds including malic acid, D-glucose, and galactofuranoside. The hydro-ethanolic (1000 mg/kg) decreased abdominal writhes (38.96%) and licking time (37.34%). It also elicited a strong antioxidant activity using DPPH method (IC50 = 19.38 ± 0.15 µg/mL). Polyphenols exhibited a good antimicrobial effect (MIC = 3.125-12.5 mg/mL). Moreover, both extracts showed high wound contraction by 97.17% and 94.98%, respectively. This study provides evidence that P. sativum could serve as a source of bio-compounds exhibiting analgesic effect and their promising application in mitigating ROS-related disorders, impeding wound infections, and enhancing burn healing.

Utilization Sesbania grandiflora (L.) Pers. as traditional medicine and its bioactivity

Sesbania grandiflora (Fabaceae) has been long used as food and traditional medicine. This study aims to explain the botany, benefits and bioactivity of S. glandiflora. The method is library research of various articles published online on Google Scholar using the keywords S. glandiflora, uses of S. glandiflora and bioactivities of S. glandiflora. In traditional medicine, S. glandiflora is used to treat diarrhea, snake bites, malaria, smallpox, fever, scabies, ulcers, and gastric disorders. S. glandiflora bioactivity includes anti-diabetes mellitus, anti-bacterial, antioxidant, anti-helminthic, anti-hyperlipidemic, anti-diarrheal and anti-cancer. The bioactivity of S. glandiflora is related to the content of its secondary metabolites. The tocopherols contained in S. glandiflora seeds showed potential as antioxidants while the phytosterols showed anti-inflammatory, analgesic and antipyretic potential. S. glandiflora has the potential to be developed as a natural food preservative because it has antimicrobial activity.

In Vivo and In Silico Analgesic Activity of Ficus populifolia Extract Containing 2-O-β-D-(3',4',6'-Tri-acetyl)-glucopyranosyl-3-methyl Pentanoic Acid.

Natural product-based structural templates have immensely shaped small molecule drug discovery, and new biogenic natural products have randomly provided the leads and molecular targets in anti-analgesic activity spheres. Pain relief achieved through opiates and non-steroidal anti-inflammatory drugs (NSAIDs) has been under constant scrutiny owing to their tolerance, dependency, and other organs toxicities and tissue damage, including harm to the gastrointestinal tract (GIT) and renal tissues. A new, 3',4',6'-triacetylated-glucoside, 2-O-β-D-(3',4',6'-tri-acetyl)-glucopyranosyl-3-methyl pentanoic acid was obtained from Ficus populifolia, and characterized through a detailed NMR spectroscopic analysis, i.e., 1H-NMR, 13C-DEPT-135, and the 2D nuclear magnetic resonance (NMR) correlations. The product was in silico investigated for its analgesic prowess, COX-2 binding feasibility and scores, drug likeliness, ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties, possible biosystem's toxicity using the Discovery Studio®, and other molecular studies computational software programs. The glycosidic product showed strong potential as an analgesic agent. However, an in vivo evaluation, though at strong levels of pain-relieving action, was estimated on the compound's extract owing to the quantity and yield issues of the glycosidic product. Nonetheless, the F. populifolia extract showed the analgesic potency in eight-week-old male mice on day seven of the administration of the extract's dose in acetic acid-induced writhing and hot-plate methods. Acetic acid-induced abdominal writhing for all the treated groups decreased significantly (p < 0.0001), as compared to the control group (n = 6) by 62.9%, 67.9%, and 70.9% of a dose of 100 mg/kg (n = 6), 200 mg/kg (n = 6), and 400 mg/kg (n = 6), respectively. Similarly, using the analgesia meter, the reaction time to pain sensation increased significantly (p < 0.0001), as compared to the control (n = 6). The findings indicated peripheral and central-nervous-system-mediated analgesic action of the product obtained from the corresponding extract.

Basic physiological effects of ketamine-xylazine mixture as a general anesthetic preparation for rodent surgeries

Among the numerous general anesthetics utilized in rodent surgical procedures, the co-administration of ketamine and xylazine is the current standard for induction and maintenance of surgical planes of anesthesia and pain control. In contrast to classical GABAergic anesthetics, which act to inhibit CNS activity, inducing muscle relaxation, sedation, hypothermia, and brain hypoxia, ketamine and xylazine act through different mechanisms to induce similar effects while also providing potent analgesia. By using three-point thermorecording in freely moving rats, we show that the ketamine-xylazine mixture induces modest brain hyperthermia, resulting from increased intra-cerebral heat production due to metabolic brain activation and increased heat loss due to skin vasodilation. The first effect derives from ketamine, which alone increases brain and body temperatures due to brain metabolic activation and skin vasoconstriction. The second effect derives from xylazine, which increases heat loss due to potent skin vasodilation. By using oxygen sensors coupled with amperometry, we show that the ketamine-xylazine mixture modestly decreases brain oxygen levels that results from relatively weak respiratory depression. This tonic pharmacological effect was preceded by a strong but transient oxygen increase that may result from a stressful injection or unknown, possibly peripheral action of this drug combination. This pattern of physiological effects elicited by the ketamine-xylazine mixture differs from the effects of other general anesthetic drugs, particularly barbiturates.

Highly oxygenated grayanane diterpenoids with structural diversity from the flowers of Rhododendron dauricum and their analgesic activities

Twenty-eight grayanane diterpenoids (1–28) including 13 new ones, named daublossomins A–M (1–13), and two new natural products, 3-O-acetylgrayanotoxin II (14) and 10-epi-grayanotoxin III (15), were isolated from the flowers of Rhododendron dauricum L. (Ericaceae). Their structures were elucidated by means of comprehensive spectroscopic methods and quantum chemical calculations (13C NMR-DP4+ analysis and calculated ECD), and the absolute configurations of ten grayanane diterpenoids 1, 4, 5, 7, 8, 22, 23, 25, 27, and 28 were determined by X-ray crystallographic analysis. Daublossomin A (1) represents the first example of an 11,16-epoxygrayan-6-one diterpenoid. Daublossomins B (2) and C (3) are the first examples of 9β,10β-epoxygrayanane diterpenoids, and daublossomin I (9) is the second conjugated grayan-1(5),6(7),9(10)-triene diterpenoid. Compounds 1–11 and 13–27 were evaluated for their analgesic activities in the HOAc-induced writhing test in mice, and 1–8, 10, 11, 13, 15, 17, 18, 22–24, and 26 exhibited significant analgesic effects at a dose of 5.0 mg/kg (inhibition rates > 50%). Among them, daublossomins A (1) and F (6) still showed potent analgesic activity even at a lower dose of 0.2 mg/kg with the inhibition rates of 54.4% and 55.2%, respectively. Grayanotoxin III (20) showed more potent analgesic activities than the positive control, morphine, at a dose of 0.04 mg/kg. A preliminary structure–activity relationship for the analgesic grayanane diterpenoids was discussed, providing some useful clues to design and develop structurally novel potent analgesics.

Deciphering optimal management options for headache

Headache is one of the most common, painful, and disabling conditions that affects people of all ages worldwide and can have a substantial impact on quality of life of those affected. Stress is one of their main aggravating factor for headache across geographies, more so in millennials and females. Headache disorders are most troublesome in the productive years of life with lost working days and reduced productivity. Majority of those with headache have primary headache disorder especially migraine, tension-type headache and medication-overuse headache. Without proper treatment, headaches can be severe and interfere with day-to-day activities and can also become chronic or recurring affecting the well-being of an individual and predispose them to other illnesses. Self-care with simple analgesics in managing primary headache disorders can help reduce frequency of attack and severity with positive effect on physical symptoms and functional capacity. Paracetamol (acetaminophen) is a safe analgesic with good gastrointestinal tolerance and is recommended as 1 line treatment option to reduce pain in various conditions including primary headache disorders. Caffeine, a common additive to analgesic drugs is known to increase the analgesic potency. The anti-nociception enhancing effect of caffeine when given with acetaminophen significantly improves efficacy over use of only paracetamol.

Carfentanil structural analogs found in street drugs by paper spray mass spectrometry and their characterization by high-resolution mass spectrometry.

Carfentanil is one of the most potent synthetic opioids ever developed, with an estimated analgesic potency approximately 20-100 times that of fentanyl and 10,000 times that of morphine. Carfentanil has been appearing in the illicit drug supply in many regions and has been linked to fatal overdose events. A subset of 59 street drug samples obtained in Victoria, B.C., that were confirmed to contain carfentanil were analyzed by mass spectrometry for this study. Carfentanil quantitation by paper spray mass spectrometry ranged from 0.05 to 2.95 w/w% (median =0.32%) in the original drug sample. Paper spray mass spectrometry analysis also detected two unknown peaks at m/z 380.2 and 381.2 in 31 of these 59 samples (53%). Initial tandem mass spectrometry experiments revealed structural similarities between these unknown compounds and carfentanil, suggesting they were potential structural analogs, possibly arising from incomplete purification during synthesis. High-resolution mass spectrometry determined the chemical formulas of these compounds as C23 H29 N3 O2 (m/z 380.2333) and C23 H29 N2 O3 (m/z 381.2137). Literature and tandem mass spectrometry results were used to determine the identity of these potential new psychoactive substances, C23 H29 N3 O2 as desmethylcarfentanil amide and C23 H29 N2 O3 as desmethylcarfentanil acid. μ-Opioid receptor binding modeling determined that the binding poses of these analogs were nearly identical to that of carfentanil with relative binding energy calculations of 0.544 kJ/mol (desmethylcarfentanil amide) and -0.171 kJ/mol (desmethylcarfentanil acid); these data suggest they may share the toxic effects of carfentanil and have similar potencies.

Opening the amino acid toolbox for peptide-based NTS2-selective ligands as promising lead compounds for pain management.

Chronic pain is one of the most critical health issues worldwide. Despite considerable efforts to find therapeutic alternatives, opioid drugs remain the gold standard for pain management. The administration of μ-opioid receptor (MOR) agonists is associated with detrimental and limiting adverse effects. Overall, these adverse effects strongly overshadow the effectiveness of opioid therapy. In this context, the development of neurotensin (NT) ligands has shown to be a promising approach for the management of chronic and acute pain. NT exerts its opioid-independent analgesic effects through the binding of two G protein-coupled receptors (GPCRs), NTS1 and NTS2. In the last decades, modified NT analogues have been proven to provide potent analgesia in vivo. However, selective NTS1 and nonselective NTS1/NTS2 ligands cause antinociception associated with hypothermia and hypotension, whereas selective NTS2 ligands induce analgesia without altering the body temperature and blood pressure. In light of this, various structure-activity relationship (SAR) studies provided findings addressing the binding affinity of ligands towards NTS2. Herein, we comprehensively review peptide-based NTS2-selective ligands as a robust alternative for future pain management. Particular emphasis is placed on SAR studies governing the desired selectivity and associated in vivo results.

Are psychedelics the answer to chronic pain: A review of current literature.

We aim to provide an evidence-based overview of the use of psychedelics in chronic pain, specifically LSD and psilocybin. Chronic pain is a common and complex problem, with an unknown etiology. Psychedelics like lysergic acid diethylamide (LSD) and psilocybin, may play a role in the management of chronic pain. Through activation of the serotonin-2A (5-HT2A) receptor, several neurophysiological responses result in the disruption of functional connections in brain regions associated with chronic pain. Healthy reconnections can be made through neuroplastic effects, resulting in sustained pain relief. However, this process is not fully understood, and evidence of efficacy is limited and of low quality. In cancer and palliative related pain, the analgesic potential of psychedelics was established decades ago, and the current literature shows promising results on efficacy and safety in patients with cancer-related psychological distress. In other areas, patients suffering from severe headache disorders like migraine and cluster headache who have self-medicated with psychedelics report both acute and prophylactic efficacy of LSD and psilocybin. Randomized control trials are now being conducted to study the effects in cluster headache Furthermore, psychedelics have a generally favorable safety profile especially when compared to other analgesics like opioids. In addition, psychedelics do not have the addictive potential of opioids. Given the current epidemic use of opioids, and that patients are in desperate need of an alternative treatment, it is important that further research is conducted on the efficacy of psychedelics in chronic pain conditions.

Investigation of antioxidant, anti-ulcer, and analgesic potential of a metal-curcumin complex.

The goal of the current study was to investigate the antioxidant, anti-ulcer, and analgesic properties of a metal-curcumin complex (MCC) utilizing different mouse and rat models. The antioxidant component of the analysis was completed in vitro, whereas the other activities were completed in vivo. The 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical cation scavenging test, the ferric-reducing antioxidant power (FRAP) assay, and the 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical scavenging assay were used to measure the antioxidant activity. MCC demonstrated potent radical scavenging abilities. In all three experiments, Trolox served as the reference substance. When curcumin's radical scavenging abilities were compared, it became clear that MCC was a superior radical scavenger. Using the ethanol-induced technique on Sprague-Dawley rats, the anti-ulcerogenic effect was assessed. It shows that at an oral dosage of 100mg/kg body weight, MCC might provide gastroprotection (b.w.). Additionally, we have examined MCC's potential as an analgesic. Swiss albino mice were used to measure the analgesic activity of MCC using the hot plate technique. At an oral dosage of 50mg/kg b.w., MCC displayed analgesic efficacy. As a result, MCC could be useful in the management of inflammatory diseases.

Discovery of BAY-390, a Selective CNS Penetrant Chemical Probe as Transient Receptor Potential Ankyrin 1 (TRPA1) Antagonist.

Transient receptor potential ankyrin 1 (TRPA1) is a voltage-dependent, ligand-gated ion channel, and activation thereof is linked to a variety of painful conditions. Preclinical studies have demonstrated the role of TRPA1 receptors in a broad range of animal models of acute, inflammatory, and neuropathic pain. In addition, a clinical study using the TRPA1 antagonist GRC-17536 (Glenmark Pharmaceuticals) demonstrated efficacy in a subgroup of patients with painful diabetic neuropathy. Consequently, there is an increasing interest in TRPA1 inhibitors as potential analgesics. Herein, we report the identification of a fragment-like hit from a high-throughput screening (HTS) campaign and subsequent optimization to provide a novel and brain-penetrant TRPA1 inhibitor (compound 18, BAY-390), which is now being made available to the research community as an open-source in vivo probe.

Evaluation of Analgesic & Anti-Inflammatory Potential of Formulation of Essential Oils

Evaluation of Analgesic & Anti-Inflammatory Potential of Formulation of Essential Oils

Offering an Alternative to Persons with Chronic Pain: How Access to Cannabis May Provide an Off-Ramp from Undesired Prescription Opioid Use.

Chronic pain (CP) is experienced by as many as 50 million Americans and can negatively impact physical and mental health. Prescribing opioids is the most common approach to address moderate to severe CP though these potent analgesics are associated with a significant number of side effects. One alternative some Americans are turning to for CP management is cannabis. In addition to serving as an alternative, many individuals with CP use cannabis in addition to using prescription opioids. This study examined individuals with CP who enrolled in the state of Illinois' opioid diversion program, the Opioid Alternative Pilot Program (OAPP), which offers individuals aged 21 and older a separate pathway to access medical cannabis if they have or could receive a prescription for opioids as certified by a licensed physician. Cross-sectional survey data were collected from 450 participants. We described participants and compared those who use only cannabis with those who use cannabis and opioids. While 16% of the respondents were cannabis-only users, 84% of the respondents were co-users of opioids and cannabis. Both groups considered opioid use risky (100% cannabis-only, 89% co-users,). The majority (73%) of respondents sought to completely stop or never start using opioids for CP. Cannabis-only users reported lower levels of pain compared to co-users. Co-users (85%) were more likely to have their routine provider as a cannabis certifying physician than cannabis-only users (69%). With increasing clinical evidence, legalization and acceptance, researchers should continue to examine how cannabis may be a viable alternative to reduce the risk of prescription opioid side effects, misuse, or dependence. Our findings also inform health care providers and state policymakers who increasingly are being asked to consider how cannabis may reduce the potential for harmful outcomes among persons with CP who use prescription opioids.

Pethidine-related neurotoxicity in pediatric sickle cell disease: a systematic review

Sickle cell disease describes a set of related blood disorders that result from defective production of hemoglobin that causes rigid fibers to form in the red blood cells, bending them into a characteristic sickle shape. These misshapen blood cells are then prone to becoming lodged in smaller blood vessels, resulting in a vaso-occlusive crisis, which can be very painful. Rapid and potent analgesia is crucial in the care of patients presenting with sickle cell crisis, and opioid analgesics, such as pethidine and morphine, have been the mainstay of treatment for decades. However, there are reports in the literature of seizures associated with pethidine use, particularly if used for more than a few days or in patients with kidney disease. A systematic review of the literature was conducted to identify any case reports or studies of the use of pethidine in children presenting with painful sickle cell crisis with a specific focus on the prevalence of seizures in this patient group. The pharmacology and pharmacokinetics of pethidine and its active metabolite norpethidine are briefly explored, along with alternative analgesic approaches, both pharmacological and nonpharmacological.

Review of Ayurvedic phytomedicines in Sri Lanka with analgesic potential

Review of Ayurvedic phytomedicines in Sri Lanka with analgesic potential

Preliminary Phytochemical Screening and Determination of Anxiolytic, Analgesic, and Antibacterial Potentials of a Medicinal Plant – Alpinia conchigera Griff

Preliminary Phytochemical Screening and Determination of Anxiolytic, Analgesic, and Antibacterial Potentials of a Medicinal Plant – Alpinia conchigera Griff

Analgesic, Anti-inflammatory, and Antioxidant potential of S-adenosyl L-Methionine on Nitroglycerine induced Migraine in mice Models

Analgesic, Anti-inflammatory, and Antioxidant potential of S-adenosyl L-Methionine on Nitroglycerine induced Migraine in mice Models

Efficacy and analgesic potency of cannabinoids considering current available data

Efficacy and analgesic potency of cannabinoids considering current available data

Identification and Pharmacological Evaluation of Syzygium cumini Derived Fixed Oils

Syzygium cumini L is an evergreen medicinal plant belonging to the family Myrtaceae, and is one of the important species of the genus Syzygium. S. cumini is traditionally used to treat various infections such as sore throat, bronchitis, dysentery, and other painful conditions. The aim of the current study was to evaluate fixed oil extracted from S. cumini for various in vitro and in vivo biological activities and identification of its fatty acids constituents. GC-MS analysis of the fixed oil revealed that the major constituents are palmitic acid methyl ester (56.45%) and stearic acid methyl ester (29.54%). Fixed oil isolated from S. cumini exhibited significant effect against Staphylococcus aureus, Shigella flexenari, and Bacillus subtilis with zone of inhibition of 28.09, 27.34, and 22.76 mm, respectively. In addition, the oil exhibited antifungal effect against Aspergillus flavus, Candida glabrata, Microsporum canis, and Fusarium solani with zone of inhibition of 80.77, 75.08, 70.98, and 65.56 mm, respectively. The oil also exerted analgesic potential at the dose of 10, 20, 40, and 60 mg/Kg with 35.44, 50.45, 65.98, and 80.34 % activity in acetic acid-induced writhing model. A mild muscle relaxant effect was noted in animal models. Taken all together, the fixed oil from S. cumini exhibits significant antimicrobial, antifungal and analgesic effects, which justifies the use of this plant in folk medicine.