Analgesic Medicines Research Articles

Isorhapontigenin alleviates acetaminophen-induced liver injury by promoting fatty acid oxidation

Acetaminophen (APAP) is a widely used analgesic and antipyretic medicine. It is frequently employed to alleviate pain and mitigate fever-related symptoms, but it can cause liver injury or even liver failure when overdosed. Isorhapontigenin, a compound derived from Chinese herbs and grapes, has been demonstrated to exhibit antioxidant and anti-inflammatory effects. This study focused on evaluating the effect of isorhapontigenin in alleviating APAP-induced liver injury. In the study, a single intraperitoneal administration of APAP was employed to induce liver injury, and isorhapontigenin was given orally 3 days before or 1 h after APAP administration. The results revealed that isorhapontigenin significantly mitigated liver injury by effectively inhibiting APAP-induced apoptosis, oxidative stress, and inflammation. Furthermore, transcriptomic RNA sequencing of liver tissues indicated that isorhapontigenin probably protected against APAP-induced liver injury by promoting fatty acid oxidation. Pharmacological experiments also demonstrated that isorhapontigenin treatment led to a significant reduction in triglyceride accumulation, increased ATP levels and direct fatty acid oxidation activity, as well as enhanced expression of proteins associated with fatty acid oxidation, including PPAR-α, PGC-1α, and CPT-1A. Moreover, the protective effects of isorhapontigenin against APAP-induced liver injury were abolished by a CPT-1A inhibitor, etomoxir. Notably, we found that combining isorhapontigenin with NAC (N-acetyl-L-cysteine) resulted in a more significant alleviation of APAP-induced liver injury compared to NAC alone. In conclusion, our study indicates that isorhapontigenin is a potential therapeutic strategy that works by regulating fatty acid oxidation to alleviate APAP-induced liver injury.

Use of over-the-counter supplements, sleep aids and analgesic medicines in rheumatology: results of a cross-sectional survey.

Pain, fatigue and sleep disturbances are common symptoms in patients with rheumatic and musculoskeletal diseases (RMDs) that may prompt the use of over-the-counter (OTC) supplements, sleep aids and analgesics as self-management strategies. This study evaluated the prevalence of OTC supplements, sleep aids and pain relievers and the financial burden associated with their use in rheumatology. A web-based survey developed with patients was administered in rheumatology clinics in an English hospital. Participants shared demographic information and detailed their use of OTC supplements, sleep aids and pain relief in the past week. The data were analysed using descriptive statistics and logistic regression models to identify influencing factors. A total of 876 people consented to participate in the survey. More than half of patients (54.5%) reported daily supplement intake, typically spending £10/month (interquartile range 5-20), ranging up to £200/month. The most commonly administered supplements were vitamin D, multivitamins, vitamin C, vitamin B/B complex and omega-3/-6 supplements, with multiple overlaps. Prescription, OTC or non-prescription pain relief use was reported by 82% of respondents, with sleep aids being used by 13%. Of the 327 patients who took NSAIDs, 165 (50.4%) also reported taking OTC supplements, while among the 131 patients using opioids (20.5%), 66 (50.3%) reported supplement use, some of which have documented interactions. The use of OTC supplements, pain relief and sleep aids is common in patients with RMDs. Healthcare professionals should be encouraged to proactively ask about these during consultations, especially from a drug safety perspective, but also to provide timely, reliable advice about such strategies that may be sought by patients.

The Essential and Optimal Analgesic and Anti-Inflammatory Medicines for Athletes at the Olympic Games

BackgroundIn 2019, the International Olympic Committee published the first Olympic and Paralympic Model Formulary (OPF), which defined the standardised set of medications required at every Olympic and Paralympic Games for the treatment of athletes. This study aimed to test the OPF to determine whether it meets the clinical needs of the athlete population with respect to medications used for pain and/or inflammation (PI), and to present a revised set of essential PI medications for the OPF based on prevalence of athlete use. Medication-use data of athletes at the Tokyo 2020 and Beijing 2022 Olympic Games (n = 6155) from three sources were used to establish prevalence of PI medicine use and to revise the OPF: (i) doping control forms, (ii) pharmacy dispensing reports, and (iii) injection declaration forms. This revised list was further validated through (iv) medication importation declarations by teams (n = 156), and (v) survey of team physicians (n = 382).ResultsOverall prevalence of PI medication use was 36.7%, with higher use by female athletes (female: 44.1%; male: 30.0%; p < 0.001), with non-steroidal anti-inflammatory drugs being the most used class (27%). Use of medications with safety risks were identified, including nimesulide, piroxicam and metamizole. A revised list of 48 PI medications was recommended for the OPF.ConclusionThe research led to a revised set of essential medications for the treatment of pain and inflammation to be available for athletes at the Olympic Games, which would lead to a 7% improvement in the numbers of athletes who could have their exact PI medication requirements met by the OPF.

Potential Drugs in COVID-19 Management.

The SARS-CoV-2 virus first emerged in China in December 2019 and quickly spread worldwide. Despite the absence of a vaccination or authorized drug specifically developed to combat this infection, certain medications recommended for other diseases have shown potential effectiveness in treating COVID-19, although without definitive confirmation. This review aims to evaluate the existing literature on the efficacy of these medications against COVID-19. The review encompasses various potential treatments, including antiviral medications, anti-malaria and anti-rheumatic drugs, vaccines, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), antipyretic and analgesic medicines, antiparasitic drugs, and statins. The analysis also addresses the potential benefits and drawbacks of these medications, as well as their effects on hypertension and diabetes. Although these therapies hold promise against COVID-19, further research, including suitable product production or clinical testing, is needed to establish their therapeutic efficacy.

Analgesic and anti-inflammatory activities of NPK 500 capsules, a Cassia sieberiana DC. - Based herbal analgesic medicine used to treat dysmenorrhea and peptic ulcer, is mediated through the inhibition of PGE2 and iNOS

Ethnopharmacological relevancePain and inflammation are the most frequent reasons for which people seek medical care. Currently available analgesics against these conditions produce fatal adverse effects. NPK 500 capsules is an alternative herbal analgesic employed to treat dysmenorrhea, peptic ulcer and pain. NPK 500 is produced from Cassia sieberiana. A plant used in traditional medicine to treat pain and inflammation. Aim of the studyThis study reports the analysis, phytochemical characterization and mechanism of analgesic and anti-inflammatory activities of two NPK 500 capsules, called old and new NPK500 capsules (ONPK500 and NNPK500) respectively. Materials and methodsPhysicochemical, organoleptic, GC-MS and LC-MS methods were employed to analyze the NPK 500 capsules. Analgesic activity was evaluated using tail immersion, Randall-Selitto and acetic acid induced writing tests. Anti-inflammatory activity was evaluated using carrageenan-induced rat paw inflammation. Additionally, pro-inflammatory mediators such as prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase 1 and 2 (COX-2 and COX-1) were quantified in the sera of the rats using Enzyme Linked Immunosorbent Assay (ELISA) kits. ResultsThirteen major compounds were characterized in the NNPK 500 capsules via the GC-MS and LC-MS spectroscopies. Kaempferol was the major compound characterized in addition to physcion, β-sitosterol 3-O-β-D-glucopyranoside, betulinic acid and nine others. Physicochemical and organoleptic indices of the capsules were also derived for its authentication and quality control. Furthermore, NNPK 500 0.5–1.5 mg/kg p.o. produce significant (P < 0.5) analgesic activity (160–197%) higher than that of ONPK500 (109.8%) and Morphine (101%) in the tail immersion test. The analgesic activity of NNPK 500 0.5–1.5 mg/kg p.o. (171.0–258.3%) and ONPK 500 (179.5%) were also significant (P < 0.01) and higher than that of Aspirin (103.00%) in the Randall-Selitto test. Both capsules also demonstrated significant (P < 0.5) analgesic and anti-inflammatory activities in the acetic acid-induced writhing and carrageenan-indued paw edema tests respectively. The two NPK500 capsules also, significantly (P < 0.5) inhibited PGE2 and iNOS but not COX-2 and COX-1 in the carrageenan-indued paw edema test. ConclusionThese results show that NNPK 500 and ONPK 500 capsules possessed potent analgesic and anti-inflammatory activities via inhibition of PGE2 and iNOS as a result of their chemical constituents. NPK500 capsules thus, relief acute pain and inflammation without causing gastrointestinal, renal or hepatic injuries, since they did not inhibit COX-1.

Rectal versus intravenous administration of acetaminophen; Clinical investigation of plasma level, analgesic, and antipyretic effects on 6-month to 6-year-old children in Zabol city, Iran

Acetaminophen is the most widely antipyretic analgesic medicine used in adults and children worldwide. Rectal acetaminophen is widely used in children who resist or cannot take oral medications. This study was designed to compare the efficacy of rectal and IV acetaminophen in children with fever and mild to moderate pain. Total 60 children aged six months to 6years, with fever and pain, that were treated with rectal or intravenous acetaminophen were selected and assigned in two groups. The IV group received 10mg/kg paracetamol as an IV infusion, and the rectal group received a 15mg/kg dose immediately after admission. Pain score was calculated using the FLACC method, and the axillary temperature was recorded at baseline and then 0.5, 1, 2, 4, and 6hours after drug administration. Blood samples were collected at baseline and then at 30min-intervals for the first 90minutes. The trend of changes in mean pain score at different time intervals was significantly different between the two groups. Body temperature decrease was more prominent in the IV group. The plasma concentration increased in both groups significantly with time. This increase was sharper in the IV group, just in the first 60minutes after drug administration. IV acetaminophen has more rapid onset of action, while rectal dosage form control fever and pain for longer duration. Considering its favorable effects with ease of administration and lower cost, rectal acetaminophen can be a reasonable option in selected patients with pain or fever.

Analgesic and Anti-Inflammatory Activity: A Comprehensive Review on Invitro and In Vivo Screening Methods

Modern pharmacotherapy includes analgesic and anti-inflammatory medicines as essential components to relieve pain and inflammation brought on by a variety of medical diseases. Robust screening techniques are essential for the identification of possible candidates with appropriate safety and effectiveness profiles in the search and development of new analgesic and anti-inflammatory medications. This study looks at the many screening methods used in preclinical studies to assess new drugs' analgesic and anti-inflammatory quality. Conventional techniques like the tail flick, hot plate, and writhing’s tests measure analgesic activity by having animals respond to unpleasant stimuli. Comparably, anti-inflammatory activity is frequently assessed using assays like the cotton pellet granuloma test, which gauges tissue granuloma formation, and the carrageenan-induced paw edema model, which measures inflammation. These traditional techniques offer insightful information about the pharmacological effects of test substances. Despite the wide range of screening techniques available, each strategy has advantages and disadvantages. Preclinical studies are more reliable and have higher predictive value when various assays and techniques are integrated into a tiered screening strategy. Furthermore, the successful translation of preclinical findings to human applications depends on taking into account translational variables including species differences and clinical relevancies. As a result, choosing the right screening techniques is critical to the effective identification and characterization of new analgesic and anti-inflammatory drugs.

Neuroprotective effects of methanolic extract from Chuanxiong Rhizoma in mice with middle cerebral artery occlusion-induced ischemic stroke: suppression of astrocyte- and microglia-related inflammatory response

BackgroundIn traditional Asian medicine, dried rhizomes of Ligusticum chuanxiong Hort. (Chuanxiong Rhizoma [CR]) have long been used to treat pain disorders that affect the head and face such as headaches. Furthermore, they have been used primarily for blood circulation improvement or as an analgesic and anti-inflammatory medicine. This study aimed to investigate the neuroprotective effects of a methanol extract of CR (CRex) on ischemic stroke in mice caused by middle cerebral artery occlusion (MCAO).MethodsC57BL/6 mice were given a 1.5-h transient MCAO (MCAO control and CRex groups); CRex was administered in the mice of the CRex group at 1,000–3,000 mg/kg either once (single dose) or twice (twice dose) before MCAO. The mechanism behind the neuroprotective effects of CRex was examined using the following techniques: brain infarction volume, edema, neurological deficit, novel object recognition test (NORT), forepaw grip strength, and immuno-fluorescence staining.ResultsPretreating the mice with CRex once at 1,000 or 3,000 mg/kg and twice at 1,000 mg/kg 1 h before MCAO, brought about a significantly decrease in the infarction volumes. Furthermore, pretreating mice with CRex once at 3,000 mg/kg 1 h before MCAO significantly suppressed the reduction of forepaw grip strength of MCAO-induced mice. In the MCAO-induced group, preadministration of CRex inhibited the reduction in the discrimination ratio brought on by MCAO in a similar manner. CRex exhibited these effects by suppressing the activation of astrocytes and microglia, which regulated the inflammatory response.ConclusionsThis study proposes a novel development for the treatment of ischemic stroke and provides evidence favoring the use of L. chuanxiong rhizomes against ischemic stroke.

Evaluation of analgesic, antioxidant, and anti-inflammatory potential of Dianthus crinitus using mice as a research animal

In the past, natural resources were used as best therapeutic sources for different diseases. Among several herbal resources, certain plant families are known for their analgesic activities, such as Dianthus crinitus, which showed a good curative potential. The mentioned plant has been used traditionally for the healing of several illnesses such as pain, inflammation, injuries, etc. The current study, therefore, evaluated the analgesic and anti-antioxidant activities of ethanolic extracts of leaves, flowers, and seeds of Dianthus crinitus in mice. For analgesic activity, acetic acid and a hot plate thermal stimulation method were used to induce writhes in mice, followed by a tail emersion process. Results showed that the extract demonstrated analgesic potential in mice, signifying both peripheral and central modes of action. Furthermore, extract also significantly inhibited the rat paw edema triggered by carrageenan seaweed and dextran as revealed by neutrophil migration toward the peritoneal cavities of animals and enhanced vascular permeability. The data suggested that the extract exhibited a dose-dependent antioxidant action. These preliminary observations provided support for further exploration and justification for the potential development of a new class of analgesic and anti-inflammatory medicines from the constituents of Dianthus crinitus extract.

Use of Analgesic and Anti-Inflammatory Medicines before and after Initiation of Biological Disease-Modifying Antirheumatic Drugs for Rheumatoid Arthritis

Background. Rheumatoid arthritis (RA) is an inflammatory condition that causes joint damage and is associated with pain. The biological disease-modifying antirheumatic drugs (bDMARDs) for RA are linked to additional therapeutic benefits as they suppress the inflammatory process, which in turn prevents joint erosion and reduces pain. Thus, the use of bDMARDs has the potential to reduce the need for other analgesic and anti-inflammatory therapies for RA. The aim of this study was to examine the analgesic and anti-inflammatory use around the initiation of bDMARDs. Methods. A cohort study was conducted using a 10% random sample of the population dispensing medicines under the Australian Pharmaceutical Benefits Scheme. People who initiated the first bDMARD for RA between 2014 and 2018 were included. The proportion who received any analgesic or anti-inflammatory, including nonsteroidal anti-inflammatory drugs, opioids, or glucocorticoids, in the twelve months prior to and post-bDMARD initiation was determined and compared using regression models. Results. There were 18,360 persons in the cohort, with a mean age of 55 years, and 69% were women. The use of any analgesic or anti-inflammatory in both tumor necrosis factor inhibitor (TNFi) and non-TNF initiators increased prior to initiation of bDMARD–from 43% to 52% in TNFi and from 52% to 63% in non-TNF initiators. In both groups, overall use decreased significantly post initiation to 37% and 42% in TNFi and non-TNF initiators, respectively (p&lt;0.0001). bDMARD initiation was associated with lower use of glucocorticoid therapy, but there was no decreasing effect on opioid use. Conclusion. While the use of any analgesic or anti-inflammatories decreased post-initiation of bDMARDs for RA, more than one-third of people were dispensed analgesic or anti-inflammatory agents twelve months post initiation. Ongoing review of the need for analgesic and glucocorticoids appears warranted, with assessment of nonpharmacological approaches to support pain management.

A CLINICAL STUDY ON VEDANASTHAPAN MAHAKASHAYA OINTMENT AND VEDANASTHAPAN GHANVATI IN THE MANAGEMENT OF PARIKARTIKA W.S.R. TO ACUTE FISSURE-IN-ANO

Parikartika (anorectal fissure) has become the most common and painful condition in anorectal disorders. Nowadays, people have faulty lifestyles and improper food habits, leading to the vitiation of doshas, particularly Apana vayu, which is a significant factor for deterioration in anal conditions leading to fissures in the ano with severe pain in the anal region. In Modern science, various treatment modalities, including antibiotics, laxatics, sphincterectomy, fissurectomy, etc., are expensive and require long hospitalisation with other unwanted complications. Hence, pain management is the first step by Vedanasthapan drugs, which results in pain-relieving and rapid healing of the fissure. The lack of analgesics in ayurvedic medicines is a disadvantage, and there is a constant quest for an ideal ayurvedic analgesic medicine like vedana-sthapana drugs. The properties of Vedanasthapanamahakashaya ointment and Vedanasthapana ghanvati are the group of drugs which subside pain and restore all vitiated doshas in the body to an equilibrium state. So, the Vedanasthapan Mahakashaya, on the basis of the chemical constituents of each drug, can be estimated that the part of drugs which is used to subside the pain in the body and these classes of drugs have the qualities of analgesic, anti-inflammatory and wound healing properties.

Acceptability, values, and preferences of older people for chronic low back pain management; a qualitative evidence synthesis

BackgroundChronic primary low back pain (CPLBP) and other musculoskeletal conditions represent a sizable attribution to the global burden of disability, with rates greatest in older age. There are multiple and varied interventions for CPLBP, delivered by a wide range of health and care workers. However, it is not known if these are acceptable to or align with the values and preferences of care recipients. The objective of this synthesis was to understand the key factors influencing the acceptability of, and values and preferences for, interventions/care for CPLBP from the perspective of people over 60 and their caregivers.MethodsWe searched MEDLINE, CINAHL and OpenAlex, for eligible studies from inception until April 2022. We included studies that used qualitative methods for data collection and analysis; explored the perceptions and experiences of older people and their caregivers about interventions to treat CPLBP; from any setting globally. We conducted a best fit framework synthesis using a framework developed specifically for this review. We assessed our certainty in the findings using GRADE-CERQual.ResultsAll 22 included studies represented older people’s experiences and had representation across a range of geographies and economic contexts. No studies were identified on caregivers. Older people living with CPLBP express values and preferences for their care that relate to therapeutic encounters and the importance of therapeutic alliance, irrespective of the type of treatment, choice of intervention, and intervention delivery modalities. Older people with CPLBP value therapeutic encounters that validate, legitimise, and respect their pain experience, consider their context holistically, prioritise their needs and preferences, adopt a person-centred and tailored approach to care, and are supported by interprofessional communication. Older people valued care that provided benefit to them, included interventions beyond analgesic medicines alone and was financially and geographically accessible.ConclusionsThese findings provide critical context to the implementation of clinical guidelines into practice, particularly related to how care providers interact with older people and how components of care are delivered, their location and their cost. Further research is needed focusing on low- and middle-income settings, vulnerable populations, and caregivers.

Prevalence of chronic pain or analgesic use in children and young people and its long-term impact on substance misuse, mental illness, and prescription opioid use: a retrospective longitudinal cohort study

Epidemiological studies suggest chronic and recurrent pain affects around a quarter of children, while 8% report intense and frequent pain. The long-term implications of chronic pain in childhood are uncertain. Using electronic health records (EHRs) we used both disease codes and medicines prescription records to investigate the scale of chronic pain and long-term analgesic use in children and young people (CYP), and if chronic pain and/or use of analgesic medicines at an early age is associated with substance misuse, use of prescription opioids, and poor mental health in adulthood. We conducted a cohort study using data from IQVIA Medical Research Data UK. We identified individuals aged 2-24 with exposure to either a diagnostic code indicating chronic pain (diagnosis-exposed), repeat prescription for medicines commonly used to treat pain (prescription-exposed), or both. Follow-up began at 25, and the unexposed population acted as comparators. We calculated hazard ratios (HR) for mental health and substance misuse outcomes, and rate ratios (RR) for opioid prescriptions in adulthood. Additionally, we investigated which diagnoses, if any, were over-represented in the prescription-exposed subgroup. The cohort constituted 853,625 individuals; 146,431 had one or more of the exposures of interest (diagnosis-exposed=115,101, prescription-exposed=20,298, both-exposed=11,032), leaving 707,194 as comparators. Median age at index exposure was 18.7 years (IQR 14.7-22.3). On average during follow-up, the pooled exposed group had, respectively, a 31% and 17% higher risk of adverse mental health and substance misuse outcomes (adjusted HR [95% CI] of 1.31 [1.29-1.32] and 1.17 [1.11-1.24]). Exposed individuals also received prescription opioids at double the rate of unexposed individuals on average during follow-up (adjusted RR 2.01 [95% CI 1.95-2.10]). Outcomes varied between exposure subgroups, with prescription- and both-exposure tending to have worse outcomes. Unlike these two subgroups, in the diagnosis-exposed subgroup we did not detect a greater risk of substance misuse. Chronic pain in CYP is associated with increased prescription opioid use and adverse mental health outcomes in adulthood, as is repeat prescription for analgesic medicines, but only the latter is also associated with substance misuse in adulthood. It is essential to avoid the harms of under-treating pain in CYP while giving due consideration to the risks posed by analgesic medicines. Early recognition of chronic pain in CYP and utilising non-pharmacological management options may help minimise overprescribing, and long-term reliance on dependence-forming-drugs. AL is an NIHR funded academic clinical fellow, and was supported by funding from UCLH Charities while carrying out this work. RS and DS are part of the Advanced Pain Discovery Platform and were supported by a UKRI and Versus Arthritis grant (MR/W002566/1) as part of the Consortium Against Pain Inequality. AW was supported by the Wellcome Trust (220558/Z/20/Z).

Based on spinal central sensitization creating analgesic screening approach to excavate anti-neuropathic pain ingredients of Corydalis yanhusuo W.T.Wang

Ethnopharmacological relevanceCorydalis Rhizome (RC) as a traditional analgesic Chinese medicine is the dried tuber of Corydalis yanhusuo W.T.Wang. Many efforts have revealed that RC could effectively alleviate neuropathic pain, while its active ingredients in neuropathic pain are still not clear. Aim of the studySpinal central sensitization contributes greatly to neuropathic pain, and neuron, astrocyte and microglia play important roles in spinal central sensitization. The aim of the present study is to excavate active compounds in RC regulating spinal central sensitization to inhibit neuropathic pain. Materials and methodsImmunofluorescence and western blotting were used to determine protein expression levels. Gene expression levels were detected by RT-PCR. PC12 neuronal cells, C6 astrocyte cells, and BV2 microglia cells were cultured for in vitro studies. Targeting multi types of cells extraction combined with HPLC-Q-TOF-MS/MS was established to identify components binding to above cells. Animal studies were used to verify the analgesic activities of components. ResultsTotal alkaloids of RC (RC-TA) significantly relieved neuropathic pain in chronic constriction injury (CCI) rats and repressed spinal central sensitization. Eight components of RC-TA were found to bind to PC12, C6, or BV2 cells. They could respectively suppress the activation of cells in vitro and alleviate CCI-induced neuropathic pain, among which glaucine and dehydrocorydaline induced antinociception was stronger than l-THP. Meanwhile, glaucine had no effect on acute or chronic inflammatory pain, and its antinociception in neuropathic pain could be abolished by dopamine D1 receptor agonist. ConclusionsEmploying multi types of cells based on spinal central sensitization rather than single cell may allow for more thorough excavation of active substances. Glaucine was firstly found could attenuate neuropathic pain but not other types of pain which indicated that different alkaloids in RC exert distinct analgesic effects on different pain models, and gluacine has the potential to be developed as an analgesic drug specifically for neuropathic pain relieving.

Course-, dose-, and stage-dependent toxic effects of prenatal acetaminophen exposure on fetal long bone development

Acetaminophen is a common analgesic and fever reduction medicine for pregnant women. Epidemiological studies suggest that prenatal acetaminophen exposure (PAcE) affects offspring health and development. However, the effects of PAcE on fetal long bone development and its potential mechanisms have not been elucidated. Based on clinical dosing characteristics, fetal mouse femurs were obtained for detection after oral gavage of acetaminophen at different doses (0, 100 or 400 mg/kg d), courses (single or multiple times) or stages (mid- or late pregnancy) during pregnancy in Kunming mice. The results showed that compared with the control group, PAcE reduced the length of total femur and the primary ossification center (POC), delayed the mineralization of POC and the ossification of epiphyseal region, and down-regulated the mRNA expression of osteogenic function markers (such as Runx2, Bsp, Ocn , Col1a1) in fetal femur, particularly in the high dose, multiple courses, and mid-pregnancy group. Meanwhile, the osteoclast and angiogenic function were also inhibited by PAcE at high dose, multiple courses, and mid-pregnancy, but the inhibition level was less than osteogenic function. Moreover, the alteration of canonical Wnt signalling pathway in PAcE fetal bone were consistent with its osteogenesis function changes. In conclusion, PAcE caused development toxicity and multi-cellular function inhibition in fetal long bone, particularly in the high dose, multiple treatments and mid-pregnancy group, and the alteration of canonical Wnt signalling pathway may be its potential mechanism.

Phytochemical Screening of Ultrasonic Extracts of Salix Species and Molecular Docking Study of Salix-Derived Bioactive Compounds Targeting Pro-Inflammatory Cytokines.

Willow bark (Salix spp., Salicaceae) is a traditional analgesic and antirheumatic herbal medicine. The aim of this study was to evaluate and compare the phytochemical and antioxidant profiles of leaf and bark extracts of six species of the genus Salix obtained by ultrasound-assisted extraction (UAE) and to examine the inhibitory potential of target bioactive compounds against two inflammatory mediators, tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), through in silico molecular docking. The total phenolic and flavonoid content of the extracts was estimated using spectrophotometric methods and the antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and hydroxyl radical (•OH) scavenging assays. Chemical profiling of extracts was carried out using high-performance liquid chromatography coupled with a diode array detector (HPLC-DAD). Principal component analysis (PCA) was performed to differentiate the sample extracts based on their phytochemical profiles and amounts of target bioactive compounds. Chemical composition varied among the analyzed willow species and also among the plant organs of the same species. The major bioactive compounds of the extracts were salicin, chlorogenic acid, rutin and epicatechin. The extracts exhibited significant DPPH● and ●OH scavenging activities. Results of molecular docking revealed that chlorogenic acid had the highest binding affinity toward TNF-α and IL-6. UAE extracts represent valuable sources of antioxidant and anti-inflammatory compounds.

Licochalcone Mediates the Pain Relief by Targeting the Voltage-Gated Sodium Channel.

Licorice is a traditional Chinese medicine and recorded to have pain relief effects in national pharmacopoeia, but the mechanisms behind these effects have not been fully explored. Among the hundreds of compounds in licorice, licochalcone A (LCA) and licochalcone B (LCB) are two important components belonging to the chalcone family. In this study, we compared the analgesic effects of these two licochalcones and the molecular mechanisms. LCA and LCB were applied in cultured dorsal root ganglion (DRG) neurons, and the voltage-gated sodium (NaV) currents and action potentials were recorded. The electrophysiological experiments showed that LCA can inhibit NaV currents and dampen excitabilities of DRG neurons, whereas LCB did not show inhibition effect on NaV currents. Because the NaV1.7 channel can modulate Subthreshold membrane potential oscillations in DRG neuron, which can palliate neuropathic pain, HEK293T cells were transfected with NaV1.7 channel and recorded with whole-cell patch clamp. LCA can also inhibit NaV1.7 channels exogenously expressed in HEK293T cells. We further explored the analgesic effects of LCA and LCB on formalin-induced pain animal models. The animal behavior tests revealed that LCA can inhibit the pain responses during phase 1 and phase 2 of formalin test, and LCB can inhibit the pain responses during phase 2. The differences of the effects on NaV currents between LCA and LCB provide us with the basis for developing NaV channel inhibitors, and the novel findings of analgesic effects indicate that licochalcones can be developed into effective analgesic medicines. SIGNIFICANCE STATEMENT: This study found that licochalcone A (LCA) can inhibit voltage-gated sodium (NaV) currents, dampen excitabilities of dorsal root ganglion neurons, and inhibit the NaV1.7 channels exogenously expressed in HEK293T cells. Animal behavior tests showed that LCA can inhibit the pain responses during phase 1 and phase 2 of formalin test, whereas licochalcone B can inhibit the pain responses during phase 2. These findings indicate that licochalcones could be the leading compounds for developing NaV channel inhibitors and effective analgesic medicines.

Theoretical investigation on the transformation of ketamine initiated by ⋅OH/SO4−⋅ in aqueous solution: Mechanisms, kinetics and ecotoxicity assessment

Ketamine (KET), as an analgesic medicine, has raised considerable attention due to its widespread existence and potential environmental hazards. This study researched the transformation mechanisms, kinetics, and potential ecology risks of KET degradation initiated by ⋅OH/SO4−⋅ through density functional theory (DFT). The calculation results show that the H15 atom belongs to the -CH3 group is more likely to be extracted by ⋅OH or SO4−⋅, generating the most active dehydrogenated radical intermediate IM21, which could further transform into the principal products (P1, P2, P3, P5, P6, and P8) in the aquatic environment. Furthermore, the subsequent degradation pathways of other active intermediates IM2, IM16, and IM19 were also considered. At 298 K, the calculated ktotal of KET reacting with ⋅OH and SO4−⋅ are 1.34 × 1010 and 1.11 × 1010 M−1 s−1, respectively, demonstrating that the ⋅OH shows slightly higher initiation performance than SO4−⋅. In terms of the half-lives, the values in ⋅OH-initiated AOPs are at the range of 0.05–5.75 s, while the half-lives of KET reaction oxidized by SO4−⋅ range from 0.01 to 437.03 d in 273–313 K. Based on the toxicity evaluation, the majority of degradation products present toxicity decreasing, but some of them remain at toxic or very toxic levels, such as P1, P3, P13, and P20. In addition, the accumulative effects, developmental toxicity, mutagenicity, and carcinogenicity of multiple transformation products increase compared with parent KET. This work could contribute to enhancing the comprehension of KET mineralization in liquid ecosystems and establish a theoretical basis for prospective industrial applications.

Effects of Heat Treatment On Dysmenorrhea and Its Mental Health Outcomes: A Randomized Clinical Trial

This randomized controlled prospective experimental trial was conducted with 46 students with dysmenorrhea who were randomized in a 1:1 ratio to the heat treatment group (HTG) ( n = 23) and control group (CG) ( n = 23). To HTG, dry heat was applied for 20 minutes to the lower abdominal region of the subjects when their dysmenorrhea was most severe. Visual Analogue Scale (VAS), the Short Form McGill Pain Questionnaire (SF-MPQ), the Menstrual Attitude Questionnaire (MAQ), and the Depression Anxiety and Stress Scale (DASS) were used in this study. At the first menstrual cycle, both groups received the questionnaires, and no treatment was applied. At the second, third, and fourth menstrual cycles, VAS and SF-MPQ were applied before the treatment (T1), right after the treatment (T2), and 2 hours after the treatment (T3). MAQ and DASS were applied right after the treatment. Seven subjects from HTG and four subjects from CG were excluded from the study on account of their analgesic medicine usage, inability to menstruate, or by their own requests. When HTG and CG were compared, the decrease in the dysmenorrhea pain after the heat treatment in each of the three menstrual cycles was found to be statistically significant ( P &lt; 0.05). In each of the four menstrual cycles, depression, anxiety, and stress were detected in each subject in both groups. However, the effectiveness of the treatment was not determined ( P &gt; 0.05). In HTG, awareness of the changes during menstruation was diminished with time. [ Psychiatr Ann . 2023;53(6):270–281.]

Opioid prescribing patterns among medical practitioners in New South Wales, Australia.

Prescriber behaviour is important for understanding opioid use patterns. We described variations in practitioner-level opioid prescribing in New South Wales, Australia (2013-2018). We quantified opioid prescribing patterns among medical practitioners using population-level dispensing claims data, and used partitioning around medoids to identify clusters of practitioners who prescribe opioids based on prescribing patterns and patient characteristics identified from linked dispensing claims, hospitalisations and mortality data. The number of opioid prescribers ranged from 20,179 in 2013 to 23,408 in 2018. The top 1% of practitioners prescribed 15% of all oral morphine equivalent (OME) milligrams dispensed annually, with a median of 1382 OME grams (interquartile range [IQR], 1234-1654) per practitioner; the bottom 50% prescribed 1% of OMEs dispensed, with a median of 0.9 OME grams (IQR 0.2-2.6). Based on 63.6% of practitioners with ≥10 patients filling opioid prescriptions in 2018, we identified four distinct practitioner clusters. The largest cluster prescribed multiple analgesic medicines for older patients (23.7% of practitioners) accounted for 76.7% of all OMEs dispensed and comprised 93.0% of the top 1% of practitioners by opioid volume dispensed. The cluster prescribing analgesics for younger patients with high rates of surgery (18.7% of practitioners) prescribed only 1.6% of OMEs. The remaining two clusters comprised 21.2% of prescribers and 20.9% of OMEs dispensed. We observed substantial variation in opioid prescribing among practitioners, clustered around four general patterns. We did not assess appropriateness but some prescribing patterns are concerning. Our findings provide insights for targeted interventions to curb potentially harmful practices.