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Biomedicines Jun 2022Neuropathic pain is often closely associated with nerve injury or inflammation, and the role of traditional nonsteroidal anti-inflammatory drugs as adjuvants for...
Neuropathic pain is often closely associated with nerve injury or inflammation, and the role of traditional nonsteroidal anti-inflammatory drugs as adjuvants for treating chemotherapy-induced peripheral neuropathic pain remains unclear. In this study, the potential synergistic antinociceptive effects of indomethacin-pregabalin and meloxicam-pregabalin were evaluated in paclitaxel-induced neuropathic pain and carrageenan-induced inflammatory pain in rodents. Although indomethacin and meloxicam alone only slightly relieved mechanical allodynia in the above two models, isobolographic analysis showed that the combination of indomethacin or meloxicam with pregabalin produced significant synergistic antinociceptive effects for paclitaxel-induced neuropathic pain (IN-PGB, experimental ED = [4.41 (3.13-5.82)] mg/kg, theoretical ED = [8.50 (6.62-10.32)] mg/kg; MEL-PGB, experimental ED = [3.96 (2.62-5.46)] mg/kg, theoretical ED = [7.52 (5.73-9.39)] mg/kg). In addition, MEL-PGB dosed via intraplantar injection into the left paw, intragastric injection, or intraperitoneal injection reversed paclitaxel-induced allodynia, indicating that they may act at multiple sites in the neuroaxis and periphery. However, indomethacin-pregabalin and meloxicam-pregabalin exerted antagonistic antiallodynic interactions in carrageenan-induced inflammatory pain in rats. Taken together, coadministration of indomethacin or meloxicam with pregabalin may possess potential therapeutic advantages for treating chemotherapy-induced neuropathic pain.
PubMed: 35740434
DOI: 10.3390/biomedicines10061413 -
BMC Musculoskeletal Disorders Dec 2022Several studies have reported that glucosamine sulfate (GS) can improve knee osteoarthritis (OA) symptomatology. In parallel, the disease-modifying effects of... (Review)
Review
BACKGROUND
Several studies have reported that glucosamine sulfate (GS) can improve knee osteoarthritis (OA) symptomatology. In parallel, the disease-modifying effects of non-steroidal anti-inflammatory drugs (NSAIDs) in knee OA have also been investigated. However, limited literature has reported the combined effect of GS and NSAIDs. The aim of this scoping review is to describe the scope and volume of the literature investigating the potential benefits and synergistic effect of a combination of GS and NSAIDs in patients with knee OA.
METHODS
PubMed and Embase were searched for studies published from inception through April 2022, evaluating the effects of the combination of GS and NSAIDs in OA patients, versus either treatment alone. Data are reported narratively.
RESULTS
Five studies were included in this review; 4 were randomized control trials and one was a prospective observational study. The duration of combination treatment was 6 to 12 weeks. The combination was compared to celecoxib in 2 studies, meloxicam in 1, etoricoxib in 1, and a conventional NSAID in 1 (ibuprofen or piroxicam). All 5 studies reported that in patients with knee OA, the combination of GS plus NSAID yielded a significantly greater benefit than single-agent therapy, in terms of outcomes including pain reduction, function, joint stiffness, and markers of inflammatory activity and cartilage degradation.
CONCLUSION
The 5 studies included in this scoping review all report a significantly greater clinical benefit with a combination of GS plus NSAID compared to either treatment alone. The evidence supports efficacy in reducing pain, improving function, and possibly regulating joint damage. However, further randomized trials with larger sample sizes are warranted to confirm these findings.
Topics: Humans; Glucosamine; Anti-Inflammatory Agents, Non-Steroidal; Osteoarthritis, Knee; Celecoxib; Pain; Randomized Controlled Trials as Topic; Observational Studies as Topic
PubMed: 36510167
DOI: 10.1186/s12891-022-06046-6 -
Non-Steroidal Anti-Inflammatory Drugs: Pharmacokinetics and Mitigation of Procedural-Pain in Cattle.Animals : An Open Access Journal From... Jan 2021Common routine management practices in cattle, such as castration and disbudding, are recognized as being painful. In the United States (U.S.), these procedures are...
Common routine management practices in cattle, such as castration and disbudding, are recognized as being painful. In the United States (U.S.), these procedures are frequently performed without pain mitigation and there are currently no drugs federally approved for such use. Non-steroidal anti-inflammatory drugs, such as meloxicam, flunixin meglumine and aspirin, are the most commonly used analgesics in U.S. food-animal production systems. However, the body of research investigating the effectiveness of these pharmaceuticals to control pain in cattle at castration and disbudding has not been comprehensively evaluated. Therefore, this review examined existing literature to summarize meloxicam, flunixin and aspirin (1) pharmacokinetics (PK) and (2) administration outcome in regard to pain control during castration and disbudding procedures, in cattle. Following systematic searches and screening, 47 PK and 44 publications were extracted for data and are presented. The sample size contained notable variability and a general deficiency of validated and replicated methodologies for assessing pain in cattle remain substantial challenges within this research area. Future research should prioritize replication of pain assessment methodologies across different experimental conditions to close knowledge gaps identified by the present study and facilitate examination of analgesic efficacy.
PubMed: 33499412
DOI: 10.3390/ani11020282 -
Journal of Healthcare Engineering 2022To observe the effect of warm acupuncture combined with meloxicam and comprehensive nursing on pain improvement and joint function in patients with knee osteoarthritis. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To observe the effect of warm acupuncture combined with meloxicam and comprehensive nursing on pain improvement and joint function in patients with knee osteoarthritis.
METHOD
Eighty-one patients with KOA were randomly divided into control group (CG), traditional Chinese medicine group (TCMG), and combined group (JG). The CG was treated with meloxicam. The TCMG received warm acupuncture treatment. The JG was treated with meloxicam combined with warm acupuncture. Three groups were given comprehensive nursing intervention, and the course of treatment was 4 weeks. Knee function was assessed by knee pain, activity, stability, walking ability, and ability to walk up and down stairs. Improvement time of clinical symptoms of patients was assessed from knee pain, swelling, and movement limitation. Pain mediators (prostaglandin E2 (PGE2), substance P (SP), dopamine (DA), 5-hydroxytryptamine (5-HT)) were detected by enzyme-linked immunosorbent assay (ELISA). Oxidative stress indicators (superoxide dismutase (SOD) and malondialdehyde (MDA)) of the enrolled patients were detected by water-soluble tetrazolium-1 (WST-1) and the thiobarbituric acid (TBA) method. The clinical efficacy was assessed by the visual analog scale (VAS) score.
RESULTS
After treatment, the pain scores of the three groups decreased, and the scores of mobility, stability, walking ability, and the ability to walk up and down stairs increased. Compared with the CG and the TCMG, the JG had a greater range of changes in pain, mobility, stability, walking ability, and ability to walk up and down stairs after treatment. After 7 d, 14 d, and 28 d treatment, PGE2, SP, DA, 5-HT, and MDA in the three groups were decreased compared with before treatment, and the decrease in the JG was more obvious than that in the CG and the TCMG. SOD levels in the three groups were increased, and the increase in the JG was more obvious than that in the CG and the TCMG. The total effective rate of the JG (96.30%) was significantly different from that of the CG (77.78%) and the TCMG (81.48%). The improvement time of knee pain, swelling, and movement limitation in the JG was shorter than that in the CG and the TCMG, and the difference in the improvement time of movement limitation in the TCMG was statistically significant.
CONCLUSION
Warm acupuncture combined with meloxicam and comprehensive nursing can effectively improve knee swelling and pain in patients with KOA, and the mechanism may be related to reducing the content of inflammatory mediators.
Topics: Acupuncture Therapy; Dinoprostone; Humans; Knee Joint; Meloxicam; Osteoarthritis, Knee; Pain; Serotonin; Superoxide Dismutase; Treatment Outcome
PubMed: 35399845
DOI: 10.1155/2022/9167956 -
Animals : An Open Access Journal From... May 2020We evaluated the effect of pain mitigation strategies (isoflurane and meloxicam) on the behaviour and physiology of 3-week-old disbudded goat kids. Fifty Saanen does...
We evaluated the effect of pain mitigation strategies (isoflurane and meloxicam) on the behaviour and physiology of 3-week-old disbudded goat kids. Fifty Saanen does (mean ± SD, 21 ± 3 days old) were randomly allocated to one of five treatments: (1) cautery-disbudded (CAUT), (2) CAUT + isoflurane (ISO), (3) CAUT + isoflurane + meloxicam (ISO+MEL), (4) CAUT + meloxicam (MEL), and (5) handled without disbudding or pain relief (SHAM). Blood samples were taken immediately prior to treatment and at 15-, 60- and 120-min post-treatment to assess cortisol, glucose and lactate concentrations. Behaviour (head shaking and scratching, body shaking, feeding and self-grooming) was observed for 1 h pre- and post-treatment using video-cameras. ISO + MEL and ISO kids had lower cortisol concentrations than CAUT kids 15 min post-treatment ( ≤ 0.05). There was no effect of treatment or time for glucose and lactate concentrations ( ≥ 0.62). At 35 min post-treatment, CAUT, MEL and ISO kids performed more head shakes than SHAM kids ( ≤ 0.05). Isoflurane, with or without meloxicam, may reduce acute stress associated with disbudding of 3-week-old goat kids. More research is needed to assess whether isoflurane (with or without meloxicam) can provide sufficient pain relief for disbudding 3-week-old kids.
PubMed: 32443544
DOI: 10.3390/ani10050878 -
Frontiers in Veterinary Science 2022Meloxicam is commonly prescribed for treating chickens in backyard or small commercial operations despite a paucity of scientific data establishing tissue withdrawal...
Pharmacokinetic Parameters and Estimating Extra-Label Tissue Withdrawal Intervals Using Three Approaches and Various Matrices for Domestic Laying Chickens Following Meloxicam Administration.
Meloxicam is commonly prescribed for treating chickens in backyard or small commercial operations despite a paucity of scientific data establishing tissue withdrawal interval recommendations following extra-label drug use (ELDU). Historically, ELDU withdrawal intervals (WDIs) following meloxicam administration to chickens have been based on the time when meloxicam concentrations fall below detectable concentrations in plasma and egg samples. To date, no studies have addressed tissue residues. ELDU WDIs are commonly calculated using terminal elimination half-lives derived from pharmacokinetic studies. This study estimated pharmacokinetic parameters for laying hens following meloxicam administration and compared ELDU WDIs calculated using tissue terminal elimination half-lives vs. those calculated using FDA tolerance and EMA's maximum regulatory limit statistical methods, respectively. In addition, ELDU WDIs were calculated using plasma meloxicam concentrations from live birds to determine if plasma data could be used as a proxy for estimating tissue WDIs. Healthy domestic hens were administered meloxicam at 1 mg/kg intravenous (IV) once, 1 mg/kg orally (PO) once daily for eight doses or 1 mg/kg PO twice daily for 20 doses. Analytical method validation was performed and meloxicam concentrations were quantified using high-performance liquid chromatography. In general, the terminal elimination technique resulted in the longest ELDU WDIs, followed by the FDA tolerance and then EMA's maximum residue limit methods. The longest ELDU WDIs were 72, 96, and 384 (or 120 excluding fat) h for the IV, PO once daily for eight doses, and PO twice daily for 20 doses, respectively. Plasma data are a possible dataset for estimating a baseline for tissue ELDU WDI estimations when tissue data are not available for chickens treated with meloxicam. Finally, pharmacokinetic parameters were similar in laying hens to those published for other avian species.
PubMed: 35310412
DOI: 10.3389/fvets.2022.826367 -
Toxicology Letters Mar 2021Meloxicam is a thiazole-containing NSAID that was approved for marketing with favorable clinical outcomes despite being structurally similar to the hepatotoxic... (Comparative Study)
Comparative Study
Meloxicam is a thiazole-containing NSAID that was approved for marketing with favorable clinical outcomes despite being structurally similar to the hepatotoxic sudoxicam. Introduction of a single methyl group on the thiazole results in an overall lower toxic risk, yet the group's impact on P450 isozyme bioactivation is unclear. Through analytical methods, we used inhibitor phenotyping and recombinant P450s to identify contributing P450s, and then measured steady-state kinetics for bioactivation of sudoxicam and meloxicam by the recombinant P450s to determine relative efficiencies. Experiments showed that CYP2C8, 2C19, and 3A4 catalyze sudoxicam bioactivation, and CYP1A2 catalyzes meloxicam bioactivation, indicating that the methyl group not only impacts enzyme affinity for the drugs, but also alters which isozymes catalyze the metabolic pathways. Scaling of relative P450 efficiencies based on average liver concentration revealed that CYP2C8 dominates the sudoxicam bioactivation pathway and CYP2C9 dominates meloxicam detoxification. Dominant P450s were applied for an informatics assessment of electronic health records to identify potential correlations between meloxicam drug-drug interactions and drug-induced liver injury. Overall, our findings provide a cautionary tale on assumed impacts of even simple structural modifications on drug bioactivation while also revealing specific targets for clinical investigations of predictive factors that determine meloxicam-induced idiosyncratic liver injury.
Topics: Activation, Metabolic; Anti-Inflammatory Agents, Non-Steroidal; Chemical and Drug Induced Liver Injury; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2C8; Cytochrome P-450 CYP2C9; Data Mining; Deep Learning; Drug Interactions; Electronic Health Records; Female; Humans; Inactivation, Metabolic; Kinetics; Male; Meloxicam; Microsomes, Liver; Middle Aged; Substrate Specificity; Thiazines
PubMed: 33253783
DOI: 10.1016/j.toxlet.2020.11.015 -
Antibiotics (Basel, Switzerland) Jan 2023() is a worldwide leading versatile pathogen that causes a wide range of serious infections. The emergence of antimicrobial resistance against resulted in an urgent...
() is a worldwide leading versatile pathogen that causes a wide range of serious infections. The emergence of antimicrobial resistance against resulted in an urgent need to develop new antimicrobials in the new era. The methicillin-resistant (MRSA) prevalence in hospital and community settings necessitates the discovery of novel anti-pathogenic agents. Staphyloxanthin (STX) is a key virulence factor for the survival of MRSA against host innate immunity. The current work aimed to demonstrate the anti-virulence properties of meloxicam (MXM) as compared to diclofenac (DC), which was previously reported to mitigate the virulence of multidrug-resistant and test their activities in STX production. A total of 80 clinical isolates were included, wherein a qualitative and quantitative assessment of STX inhibition by diclofenac and meloxicam was performed. The quantitative gene expression of STX biosynthetic genes (M, N and B) and (coded for α-hemolysin) as a virulence gene with and without DC and MXM was conducted, followed by molecular docking analysis for further confirmation. DC and MXM potently inhibited the synthesis of STX at 47 and 59 µg/mL to reach 79.3-98% and 80.6-96.7% inhibition, respectively. Treated cells also revealed a significant downregulation of virulence genes responsible for STX synthesis, such as M, N and global transcriptional regulator B along with the gene. Furthermore, computational studies unveiled strong interactions between the CrtM binding site and DC/MXM. In conclusion, this study highlights the potential role and repurposing of DC and MXM as adjuvants to conventional antimicrobials and as an anti-virulent to combat MRSA infections.
PubMed: 36830188
DOI: 10.3390/antibiotics12020277 -
Neural Regeneration Research Apr 2021Alzheimer's disease (AD) is a progressive brain disorder and complex mechanisms are involved in the physiopathology of AD. However, there is data suggesting that...
Alzheimer's disease (AD) is a progressive brain disorder and complex mechanisms are involved in the physiopathology of AD. However, there is data suggesting that inflammation plays a role in its development and progression. Indeed, some non-steroidal anti-inflammatory drugs, such as meloxicam, which act by inhibiting cyclooxygenase-2 (COX-2) have been used as neuroprotective agents in different neurodegenerative disease models. The purpose of this study was to investigate the effects of co-nanoencapsulated curcumin and meloxicam in lipid core nanocapsules (LCN) on cognitive impairment induced by amyloid-beta peptide injection in mice. LCN were prepared by the nanoprecipitation method. Male Swiss mice received a single intracerebroventricular injection of amyloid-beta peptide aggregates (fragment 25-35, 3 nmol/3 μL) or vehicle and were subsequently treated with curcumin-loaded LCN (10 mg/kg) or meloxicam-loaded LCN (5 mg/kg) or meloxicam + curcumin-co-loaded LCN (5 and 10 mg/kg, respectively). Treatments were given on alternate days for 12 days (i.e., six doses, once every 48 hours, by intragastric gavage). Our data showed that amyloid-beta peptide infusion caused long-term memory deficits in the inhibitory avoidance and object recognition tests in mice. In the inhibitory avoidance test, both meloxicam and curcumin formulations (oil or co-loaded LCN) improved amyloid-beta-induced memory impairment in mice. However, only meloxicam and curcumin-co-loaded LCN attenuated non-aversive memory impairment in the object recognition test. Moreover, the beneficial effects of meloxicam and curcumin-co-loaded LCN could be explained by the anti-inflammatory properties of these drugs through cortical COX-2 downregulation. Our study suggests that the neuroprotective potential of meloxicam and curcumin co-nanoencapsulation is associated with cortical COX-2 modulation. This study was approved by the Committee on Care and Use of Experimental Animal Resources, the Federal University of Pampa, Brazil (approval No. 02-2015) on April 16, 2015.
PubMed: 33063743
DOI: 10.4103/1673-5374.295339 -
The Journal of Clinical Endocrinology... Jan 2022Recent evidence suggests that vasomotor symptoms (VMS) or hot flashes in the postmenopausal reproductive state and polycystic ovary syndrome (PCOS) in the premenopausal...
CONTEXT
Recent evidence suggests that vasomotor symptoms (VMS) or hot flashes in the postmenopausal reproductive state and polycystic ovary syndrome (PCOS) in the premenopausal reproductive state emanate from the hyperactivity of Kiss1 neurons in the hypothalamic infundibular/arcuate nucleus (KNDy neurons).
OBJECTIVE
We demonstrate in 2 murine models simulating menopause and PCOS that a peripherally restricted kappa receptor agonist (PRKA) inhibits hyperactive KNDy neurons (accessible from outside the blood-brain barrier) and impedes their downstream effects.
DESIGN
Case/control.
SETTING
Academic medical center.
PARTICIPANTS
Mice.
INTERVENTIONS
Administration of peripherally restricted kappa receptor agonists and frequent blood sampling to determine hormone release and body temperature.
MAIN OUTCOME MEASURES
LH pulse parameters and body temperature.
RESULTS
First, chronic administration of a PRKA to bilaterally ovariectomized mice with experimentally induced hyperactivity of KNDy neurons reduces the animals' elevated body temperature, mean plasma LH level, and mean peak LH per pulse. Second, chronic administration of a PRKA to a murine model of PCOS, having elevated plasma testosterone levels and irregular ovarian cycles, suppresses circulating levels of LH and testosterone and restores normal ovarian cyclicity.
CONCLUSION
The inhibition of kisspeptin neuronal activity by activation of kappa receptors shows promise as a novel therapeutic approach to treat both VMS and PCOS in humans.
Topics: Animals; Buprenorphine; Disease Models, Animal; Female; Hot Flashes; Humans; Kisspeptins; Meloxicam; Menopause; Mice; Neurons; Polycystic Ovary Syndrome; Receptors, Opioid, kappa; Vasomotor System
PubMed: 34387319
DOI: 10.1210/clinem/dgab602