Search Results (87)

Background/Objectives: Heliotropium indicum (H. indicum) is a medicinal plant traditionally used for conditions associated with inflammation, but its active antinociceptive constituents remain poorly defined. This study evaluated the antinociceptive activity of the aerial parts of H. indicum through a bioassay-guided approach and explored the mechanism of action of the active compound isolated in the formalin test. Methods: Three extracts of H. indicum (hexane, dichloromethane, and methanol) were evaluated in male Swiss albino CD-1 mice using the formalin test. The most active extract was fractionated, and its major fractions were screened for antinociceptive activity. Based on the active fraction and previous phytochemical data, (E)-ethyl-12-cyclohexyl-4,5-dihydroxydodec-2-enoate (ECDE) was selected for further pharmacological evaluation in the same model. Antagonist pretreatments were used to investigate the involvement of opioid, serotonergic, gamma-aminobutyric acid (GABA_A), and Nitric Oxide (NO)–soluble Guanylyl Cyclase (sGC) pathways. Results: The three extracts reduced nociceptive behavior, mainly during phase II of the formalin test, whereas the dichloromethane extract showed the broadest activity profile and was selected for fractionation. The six fractions significantly reduced phase II nociception, and fraction F5 was selected for purification. ECDE produced a clear dose-dependent antinociceptive effect in phase II, with minimal effect on phase I, and its efficacy was compared with that of ketorolac, a standard antinociceptive drug. Dose–response analysis estimated a DE₅₀ of 0.76 mg/kg for ECDE. Pretreatment with N-nitro-L-arginine methyl ester (L-NAME) and [1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ) significantly attenuated the effect of ECDE, whereas naloxone, methiothepin, and bicuculline did not. Conclusions: ECDE was identified in H. indicum as one of the compounds contributing to this effect. Its activity appears to be directed mainly toward inflammatory nociception and to depend, at least in part, on the NO–sGC pathway. Full article

Background/Objectives: Wound infections represent a major clinical challenge due to their polymicrobial nature, biofilm formation, and increasing antimicrobial resistance, which compromise conventional treatments. This study aimed to develop and evaluate ligand-stabilized silver nanoparticles (AgNPs) with improved antimicrobial activity and cytocompatibility, and to investigate their incorporation into electrospun nanofibers for wound management. Methods: Four AgNP formulations stabilized with citrate, cysteine, ketorolac, and diclofenac were synthesized via chemical reduction. Physicochemical characterization included surface plasmon resonance and zeta potential measurements. Antimicrobial activity was assessed through minimum inhibitory concentration (MIC) and bactericidal assays against Gram-positive, Gram-negative, and fungal strains. Toxicity was evaluated using the HET-CAM assay, while cytocompatibility was determined in fibroblasts, MG-63 cells, and mesenchymal stem cells. Diclofenac-stabilized AgNPs were incorporated into electrospun PCL/PEO nanofibers to generate a functional nanocomposite system. Results: All AgNPs exhibited a characteristic SPR at ~400 nm and high colloidal stability. Diclofenac-stabilized AgNPs (dc-AgNPs) showed the highest antimicrobial activity, with MIC values of 18.8 mg/L against Staphylococcus aureus and Pseudomonas aeruginosa, and 4.7 mg/L against Candida albicans, along with strong bactericidal effects. HET-CAM assays indicated negligible irritation at concentrations up to 75 mg/L. Cytocompatibility results revealed a dose-dependent response, with fibroblasts being more sensitive. Electrospun nanofibers loaded with dc-AgNPs achieved a 2.6 log reduction against Streptococcus mutans and moderate reductions (0.4–0.7 log) against other pathogens. Conclusions: Ligand engineering critically influences the antimicrobial efficacy and biocompatibility of AgNPs. The incorporation of dc-AgNPs into electrospun nanofibers represents a promising approach for treating biofilm-associated wound infections. Full article

Acute pain is the most common presentation in the emergency department (ED), accounting for approximately 78% of visits and highlighting the need for rapid and effective pain management. Ketamine is a well-established analgesic that can serve as an alternative when opioids are contraindicated. Recently, low-dose ketamine (LDK), also known as sub-dissociative or subanesthetic ketamine, has emerged as a potential option for acute pain control in ED settings; however, evidence regarding its efficacy and safety remains inconsistent. This systematic review aimed to evaluate the effectiveness and safety of LDK for acute pain management in the emergency department. A comprehensive search of SCOPUS, PubMed, and Web of Science was conducted using predefined keywords related to ketamine, acute pain, and emergency care. Peer-reviewed randomized controlled trials (RCTs) published in English between 2015 and 2025 involving adults aged ≥ 18 years were included, and the risk of bias was assessed using the Cochrane Risk of Bias 2 (ROB-2) tool. Sixteen RCTs including 1908 adult patients met the inclusion criteria. The findings were heterogeneous: several studies demonstrated that LDK provided effective pain reduction within 30 min compared with commonly used analgesics such as morphine, ketorolac, and fentanyl, whereas others found no significant superiority, including one placebo-controlled trial. The analgesic effect appeared dose- and administration-dependent, with short intravenous infusions showing better tolerability than bolus dosing. Transient neuropsychiatric adverse effects were reported, but no serious adverse events were identified. Larger multicenter studies are needed to further clarify optimal dosing strategies and confirm the safety profile of LDK in ED pain management. Full article

Background/Objectives: Postoperative pain in lower extremity orthopedic surgery remains inadequately controlled. Magnesium sulfate may serve as an effective adjunct to reduce pain and opioid use. To evaluate the efficacy and safety of intravenous magnesium sulfate (30 mg/kg) as an adjuvant to ketorolac. Methods: Randomized, double-blind, placebo-controlled, parallel-group superiority trial. Sixty adult patients undergoing elective lower limb orthopedic surgery were randomized (1:1) to receive either intravenous magnesium sulfate (30 mg/kg) or placebo over 60 min before surgery. All patients received standard anesthesia and postoperative ketorolac with morphine PCA. The primary outcomes were postoperative pain (VAS) and morphine consumption over 24 h. Secondary outcomes included time to first analgesic request, serum magnesium levels, and adverse events. Allocation was concealed via opaque envelopes, and blinding was maintained for participants, clinicians, assessors, and analysts. Results: All 60 patients completed the trial. The magnesium group showed significantly lower VAS scores and reduced 24 h morphine use (median 6 mg vs. 8 mg, p < 0.001), with longer time to first analgesic request (540 vs. 300 min, p < 0.001). Four patients (13%) in the magnesium group had transient hypotension; no serious adverse events occurred. Conclusions: Low-dose intravenous magnesium sulfate safely reduced pain and opioid needs in orthopedic surgery and may be considered in multimodal analgesia strategies. Full article

Background/Objectives: Streptococcus intermedius, a member of the Streptococcus anginosus group, is characterized by a marked propensity for abscess formation but only rarely causes native-joint septic arthritis. Involvement of the acromioclavicular (AC) joint is particularly uncommon. We describe a case of native AC joint septic arthritis due to S. intermedius in a patient with multiple predisposing factors and highlight diagnostic and management considerations. Methods: We report the clinical course of a 72-year-old man with poorly controlled type 2 diabetes mellitus who presented with progressive right shoulder pain, erythema, and swelling following recurrent minor skin abrasions from a newly adopted dog. Initial management for presumed inflammatory shoulder pathology included brief systemic corticosteroids and an ultrasound-guided intra-articular ketorolac injection. Magnetic resonance imaging (MRI) was performed after symptom progression. The patient underwent operative irrigation and debridement with collection of synovial fluid and deep tissue cultures. Blood cultures and transthoracic echocardiography were obtained to evaluate for systemic involvement. Results: MRI demonstrated multiloculated periarticular abscesses and osteolysis centered on the AC joint. Operative cultures yielded high colony counts of S. intermedius from synovial fluid and deep tissues. Blood cultures and echocardiography were negative. The patient required multiple operative debridements with irrigation, adjunctive local antibiotic therapy, and prolonged targeted β-lactam treatment. Clinical and radiographic improvement was achieved following surgical source control and antimicrobial therapy. Conclusions: Native AC joint septic arthritis due to S. intermedius is rare. Older age, uncontrolled diabetes, recent intra-articular intervention, and possible zoonotic inoculation from canine wound licking may represent contributory risk factors. Early imaging, prompt surgical source control, and guideline-concordant antimicrobial therapy are essential when bone and soft tissue involvement is present. Full article

Background/Objective: Ketorolac is an effective alternative and addition to opioids for postoperative pain control; however, there is concern of perioperative bleeding risk with its use. Within gynecology, this risk has not yet been explored in the context of hysterectomy. This study aimed to evaluate the risk of postoperative bleeding complications with ketorolac administration in the context of hysterectomy. Methods: This was a retrospective cohort study that included all patients who underwent hysterectomy for benign indications between 2015 and 2024 at a quaternary care academic hospital. Inclusion criteria were any type of hysterectomy during the study period, while exclusion criteria were malignancy and peripartum status. Complication data for up to thirty days post operation were collected. Multivariable regression analysis, including age, American Society of Anesthesiology category, use of celecoxib before surgery, anticoagulant treatment, uterus size, surgical approach, increased surgical complexity, and lysis of adhesions, was performed to identify the adjusted odds of postoperative bleeding complications. The primary outcome was a composite of any postoperative bleeding complications by use of postoperative ketorolac, including postoperative transfusion, readmission, or reoperation for bleeding. Results: In total, 4236 patients underwent hysterectomy for benign indications during our study period, of which 76% (n = 3236) received ketorolac postoperatively. The composite postoperative bleeding rate was lower in the ketorolac group (2.1% vs. 4.1%, p = 0.001). There was no association between ketorolac use and risk of postoperative bleeding in multivariable regression analysis (aOR 1.02, 95% CI 0.36–2.88). There was no difference in overall intraoperative or perioperative complications (p = 0.070 for both). Major perioperative complications were less likely in the ketorolac group (p = 0.046). Additionally, there were no differences in postoperative complications except for ileus, which was less likely in the ketorolac group (p = 0.034). Conclusions: Ketorolac administration was not associated with a higher risk of bleeding complications after hysterectomy, including when celecoxib was used preoperatively as part of an enhanced recovery protocol. It may safely be administered as an opioid-sparing pain medication in this setting. Full article

Background/Objectives: Balloon eustachian tuboplasty (BET) is an effective surgical option for obstructive eustachian tube dysfunction (OETD). However, the feasibility of performing BET under local anesthesia (LA) using simplified analgesic protocols remains underexplored. We examined the feasibility of a streamlined LA-BET protocol. Methods: Fifty patients (sixty-four ears) diagnosed with primary OETD between March 2024 and December 2025 were enrolled. All patients underwent BET under LA using intramuscular ketorolac and topical lidocaine gel without sedation or nerve blocks. Pain scores, blood pressure changes, and patient acceptance were analyzed for each patient; Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7) scores, tympanogram types, and Valsalva results were analyzed for each ear. All outcome measures were assessed 3 months postoperatively. Results: The mean ETDQ-7 score significantly improved from 24.9 ± 7.4 to 11.9 ± 5.4 (p < 0.001). The minimal clinically important difference (MCID ≥ 3.7) was achieved in 90.6% of ears, and normalization (ETDQ-7 ≤ 14.5) in 75.0%. The proportion of ears with positive Valsalva maneuvers increased from 39.1 to 76.6% (p < 0.01), and type A tympanograms improved from 64.1 to 84.4% (p = 0.018). Mean pain scores were 3.5 during insertion, 2.1 during balloon inflation, and 0.6 after deflation. All patients completed the procedure, and 96% would undergo LA again. Conclusions: LA-BET performed using intramuscular ketorolac and topical lidocaine gel is safe, tolerable, and effective. This protocol provides symptom relief and functional improvement without sedation or nerve block and offers a practical outpatient alternative for chronic OETD management. Full article

This umbrella review summarized evidence from systematic reviews of randomized clinical trials regarding the efficacy of systemic and local premedication on anesthetic success in nonsurgical root canal treatment of teeth with symptomatic irreversible pulpitis. Searches were conducted in PubMed, Scopus, Web of Science, Cochrane Library, EMBASE, LILACS/BBO, and gray literature sources up to February 2025. Methodological quality was assessed using AMSTAR-2. The risk of bias was evaluated using the ROBIS tool. The Corrected Covered Area (CCA) was calculated to quantify the primary study overlap. Data regarding risk ratios and anesthetic success rates were synthesized qualitatively. Sixteen systematic reviews were included. The narrative synthesis suggests that oral NSAIDs (particularly ibuprofen > 400 mg and ketorolac 10–20 mg) and corticosteroids (dexamethasone) are associated with increased anesthetic success compared to placebo, with no significant difference between systemic and local administration. However, the reliability of these findings is impacted by the quality of the primary evidence: according to the appraisal, 13 reviews presented a high overall risk of bias/low methodological quality, while only three were classified as having low risk of bias. Furthermore, the CCA was 19.5%, indicating a high degree of redundancy among reviews. Consequently, while premedication appears effective, these conclusions must be interpreted with caution due to the substantial overlap and predominantly high risk of bias in the available literature. Full article

Background and Objectives: This systematic review and network meta-analysis evaluated the effects of postoperative opioid use on nausea and vomiting in women undergoing laparoscopic hysterectomy. Materials and Methods: A systematic search of PubMed, EMBASE, the Cochrane Library, and RISS was conducted to identify randomized controlled trials that met the eligibility criteria. The Cochrane Risk of Bias 2 tool was used to assess the quality of the included studies. A frequentist network meta-analysis was performed to compare the risks of opioid-associated postoperative nausea and vomiting (O-PONV). Quantitative statistics were presented in forest plots, and the ranking of treatments was determined using the P-score. Results: Seventeen studies involving 1315 participants and 18 postoperative analgesic interventions were included. No significant differences were found among the opioid monotherapies—buprenorphine, butorphanol, fentanyl, oxycodone, sufentanil, and tapentadol. However, among the combination therapies, oxycodone/ketorolac therapy was associated with a significantly higher risk of O-PONV than other ketorolac-containing regimens, including dexmedetomidine, remifentanil, and fentanyl. Conclusions: No significant differences in O-PONV risk were observed among the six opioid monotherapy groups. An opioid-sparing regimen, such as dexmedetomidine/ketorolac, showed a lower risk of O-PONV than an oxycodone-based regimen, underscoring the importance of incorporating patient-centered considerations, such as patient preference and route of administration, into postoperative pain management. Full article

Background/Objectives: Inflammatory processes, both acute and chronic, encompass a wide range of autoimmune, metabolic, and neurodegenerative conditions. Conventional treatments, primarily anti-inflammatories and immunosuppressants, provide partial relief but are often hampered by adverse effects and limited durability. Mesenchymal stem cells (MSCs) have emerged as a powerful new treatment due to their immunomodulatory and anti-inflammatory properties, primarily mediated through their secretome, which is a complex mixture of bioactive factors. Secretome-based therapeutic strategies show strong potential for controlling inflammation, mitigating oxidative stress, and supporting tissue regeneration and repair. However, the therapeutic efficacy of MSCs’ secretome is subject to modification by concurrent anti-inflammatory drug regimens used in clinical settings. Methods: To evaluate the effect of combinatorial treatment strategies on the secretome of the MSCs, we employed an in vitro retinal inflammation model to investigate whether the exposure of the MSCs to five representative anti-inflammatory drugs (ketorolac, diclofenac, α-lipoic acid, N-acetyl-L-cysteine, and nicotinamide) impacts the functionality of the resulting secretome. Specifically, we evaluated the effect of the above-mentioned drugs on the anti-inflammatory properties of the secretome in relation to the secreted levels of two main MSC secretome factors—the Brain-Derived Neurotrophic Factor (BDNF) and the Vascular Endothelial Growth Factor (VEGF)—and on the secretome’s pro-metabolic activity. Results: Our findings provide evidence that the presence of any of the tested drugs during MSC secretome production does not compromise its anti-inflammatory activity; BDNF and VEGF levels remain stable, and the secretome retains a high degree of its pro-metabolic effect. Conclusions: These results underscore the robustness and clinical resilience of MSC-based therapies, even when administered alongside pharmacological agents. This work advances the translational viability of MSC therapies for inflammatory diseases and supports the development of safe, combinatorial treatment strategies. Full article

The objective of this study was to determine the pharmacological interaction of some common NSAIDs in the presence of quercetin (QUER). Indomethacin (IND), ketorolac (KET), or celecoxib (CEL) were assessed alone and in combination with QUER using experimental gout-arthritic pain and the carrageenan-induced edema test in rats to evaluate their antinociceptive and anti-inflammatory effects, respectively. The antinociceptive effect of each NSAID was also analyzed after the repeated administration of QUER for 10 days. Molecular docking analysis on COX-1/COX-2 with each drug was explored to analyze the pharmacological interaction. QUER produced minimal antinociceptive or anti-inflammatory effects on experimental gout-arthritic pain or on the carrageenan-induced edema in rats. Additionally, QUER reduced the antinociceptive effect of NSAIDs, mainly those COX-1 inhibitors (IND and KET), when they were combined. However, QUER did not modify the anti-inflammatory effect of these COX-1 inhibitors and slightly improved the anti-inflammatory effect of the COX-2 inhibitor (CEL). According to the docking analysis, COX-1 and COX-2 are likely implicated in these pharmacological interactions. In conclusion, QUER, a known bioactive natural product, may alter the antinociceptive efficacy of NSAIDs commonly used to relieve gout-like pain and suggests not using them together to prevent a negative therapeutic interaction in this effect. Full article

Background/Objectives: Ketorolac is commonly used for pain management after orthopedic surgery, but concerns regarding its effects on postoperative complications remain. This study evaluates the impact of ketorolac use on short- and long-term outcomes in adult patients undergoing uncemented primary total hip arthroplasty (THA), where implant stability relies on biological fixation through bone ingrowth into a porous-coated prosthesis rather than bone cement. Methods: A retrospective cohort study was conducted using the TriNetX Research Network. Patients aged 18 years or older who underwent uncemented primary THA between 1 January 2004 and 1 January 2024 were included. Two cohorts were compared: those who received ketorolac on the day of or within one week of surgery and those who did not. Cohorts were propensity score-matched. Outcomes were assessed at 30 days, 1 year, and 5 years postoperatively. Results: At 30 days, ketorolac use was associated with significantly lower risks of transfusion (RR: 0.6, p < 0.01). However, it was linked to higher rates of acute posthemorrhagic anemia (RR: 1.2, p < 0.01) and periprosthetic fracture (RR: 1.4, p < 0.01). At 1 year, ketorolac use was associated with reduced risks of death (RR: 0.8, p < 0.01) and transfusion (RR: 0.7, p < 0.01), but increased risks of acute posthemorrhagic anemia (RR: 1.2, p < 0.01), deep surgical site infection (SSI) (RR: 1.8, p = 0.01), superficial SSI (RR: 1.9, p < 0.01), periprosthetic joint infection (RR: 1.1, p < 0.01), wound dehiscence (RR: 1.2, p < 0.01), periprosthetic mechanical complication (RR: 1.2, p < 0.01), and periprosthetic fracture (RR: 1.5, p < 0.01). Conclusions: Our findings highlight the complex risk profile of ketorolac in uncemented THA patients and suggest that clinicians should carefully consider individual patient factors and engage in shared decision-making when counseling patients on the use of ketorolac in the perioperative setting. Full article

Orthodontic treatment is commonly associated with pain, leading to reduced patient compliance and treatment adherence. Non-steroidal anti-inflammatory drugs (NSAIDs) are effective in reducing this pain by inhibiting prostaglandin synthesis. However, this mechanism may also interfere with orthodontic tooth movement (OTM) by affecting bone remodeling. This narrative review investigates the existing literature published between 2004 and 2024 to assess the impact of various NSAIDs on OTM and identify those that balance pain relief with minimal impact on tooth movement. Evidence shows that NSAIDs such as aspirin, ketorolac, diclofenac, and nimesulide significantly reduce OTM. The results for ibuprofen, meloxicam, and celecoxib were inconsistent with both no influence or a reduction in OTM, depending on dosage, mode, and duration of administration. Conversely, tenoxicam, nabumetone, etoricoxib, and parecoxib appear to have no effect on OTM. Among these, etoricoxib appears particularly promising due to its favorable gastrointestinal profile, high COX-2 selectivity, and negligible influence on OTM in clinical doses. However, the limited number of human trials highlights the need for further research to develop evidence-based guidelines for pain management that preserve treatment efficiency in orthodontics. Full article

Objectives: This study aimed to determine the number needed to treat (NNT) of ketorolac in comparison to placebo after third molar surgery. Methods: Studies located in PubMed, Scopus, and Web of Science were evaluated with the Cochrane Risk of Bias assessment tool. Data on the onset of analgesia, the number of patients requiring rescue medication, the global or general evaluation of the study medication, and adverse effects were extracted. Data analysis was performed using Review Manager 5.3 software for Windows. Results: The qualitative assessment of the included studies showed that ketorolac was more effective than a placebo and the quantitative evaluation on the onset of analgesia (NNT = 1.6 (95%CIs = 1.4, 1.9), n = 301), the number of patients who took rescue analgesics (NNT = 3.6 (95%CIs = 2.8 to 4.9), n = 563), and the global evaluation of the treatments (NNT = 1.7 (95%CIs = 1.5 to 1.9), n = 475) showed estimates of analgesic efficacy with a statistical difference in favor of ketorolac when compared with a placebo. No statistical difference was observed in adverse effects between ketorolac and placebo (n = 739). Conclusions: There is scientific evidence of moderate quality that allows estimators of the analgesic efficacy of ketorolac to be calculated, which will significantly help the clinician who performs pharmacological treatment after third molar surgery. Full article

Pain is a widespread global issue and one of the most common disabling conditions in daily life. A wide range of medications are available to reduce or eliminate pain, with nonsteroidal anti-inflammatory drugs (NSAIDs) being among those most commonly used. Additionally, new analgesic approaches, such as antioxidants (Ascorbic Acid), have been explored for their potential to relieve acute pain after surgery, cancer-related pain, and chronic pain not related to cancer with fewer adverse effects. Furthermore, the use of pharmacological combinations is an alternative treatment strategy to obtain a higher efficacy using lower drug concentrations, at which side effects are minimal. Background/Objectives: The aim of this study was to evaluate the pharmacological synergism of ketorolac and ascorbic acid in an inflammatory pain model. Methods: The individual and combined effects of ketorolac and ascorbic acid were evaluated in a formalin-induced pain model in mice. Four experimental groups were established: control (vehicle), ketorolac (KET), ascorbic acid (AA), and combination (KET/AA). Results: The combination of ketorolac and ascorbic acid produced a greater antinociceptive effect compared to the vehicle and individual treatments in the formalin model. Notably, even the lowest dose of the combination (KET 6.26/AA 3.21 µg/paw) exhibited a stronger effect than the maximum doses of each individual treatment KET (100 µg/paw) and AA (100 µg/paw). The effective concentration that produced 30% of antinociception (EC₃₀) for the tested treatments were determined, and an isobologram analysis confirmed the presence of a synergistic interaction in these combinations. Conclusions: These findings suggest that the combination of ketorolac and ascorbic acid produces a synergistic antinociceptive effect in the formalin-induced pain model. The enhanced efficacy of the combination indicates a potential therapeutic advantage in pain management by reducing the required dosage of each compound while maintaining or improving analgesic effects. Full article