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International Journal of Molecular... Aug 2020Acidic environments, such as in inflamed tissues, favor the charged form of local anesthetics (LA). Hence, these drugs show less cell permeation and diminished potency....
Acidic environments, such as in inflamed tissues, favor the charged form of local anesthetics (LA). Hence, these drugs show less cell permeation and diminished potency. Since the analgesic capsaicin (CAP) triggers opening of the TRPV1 receptor pore, its combination with LAs could result in better uptake and improved anesthesia. We tested the above hypothesis and report here for the first time the analgesia effect of a two-drug combination (LA and CAP) on an inflamed tissue. First, CAP solubility increased up to 20 times with hydroxypropyl-beta-cyclodextrin (HP-β-CD), as shown by the phase solubility study. The resulting complex (HP-β-CD-CAP) showed 1:1 stoichiometry and high association constant, according to phase-solubility diagrams and isothermal titration calorimetry data. The inclusion complex formation was also confirmed and characterized by differential scanning calorimetry (DSC), X-ray diffraction, and H-NMR. The freeze-dried complex showed physicochemical stability for at least 12 months. To test in vivo performance, we used a pain model based on mouse paw edema. Results showed that 2% mepivacaine injection failed to anesthetize mice inflamed paw, but its combination with complexed CAP resulted in pain control up to 45 min. These promising results encourages deeper research of CAP as an adjuvant for anesthesia in inflamed tissues and cyclodextrin as a solubilizing agent for targeting molecules in drug delivery.
Topics: 2-Hydroxypropyl-beta-cyclodextrin; Anesthesia, Local; Anesthetics, Local; Animals; Calorimetry, Differential Scanning; Capsaicin; Carrageenan; Disease Models, Animal; Drug Compounding; Drug Stability; Drug Therapy, Combination; Excipients; Hyperalgesia; Inflammation; Magnetic Resonance Spectroscopy; Male; Mepivacaine; Mice; Microscopy, Electron, Scanning; Pain; Pain Management; Solubility; X-Ray Diffraction
PubMed: 32785200
DOI: 10.3390/ijms21165741 -
Brazilian Dental Journal 2016Inferior alveolar nerve block has a high failure rate in the treatment of mandibular posterior teeth with irreversible pulpitis. The aim of this study was to compare the... (Randomized Controlled Trial)
Randomized Controlled Trial
Inferior alveolar nerve block has a high failure rate in the treatment of mandibular posterior teeth with irreversible pulpitis. The aim of this study was to compare the anesthetic efficacy of 4% articaine, 2% lidocaine and 2% mepivacaine, all in combination with 1:100,000 epinephrine, in patients with irreversible pulpitis of permanent mandibular molars during a pulpectomy procedure. Sixty-six volunteers from the Emergency Center of the School of Dentistry, University of São Paulo, randomly received 3.6 mL of local anesthetic as a conventional inferior alveolar nerve block (IANB). The subjective signal of lip numbness, pulpal anesthesia and absence of pain during the pulpectomy procedure were evaluated respectively, by questioning the patient, stimulation using an electric pulp tester and a verbal analogue scale. All patients reported the subjective signal of lip numbness. Regarding pulpal anesthesia success as measured with the pulp tester, the success rate was respectively 68.2% for mepivacaine, 63.6% for articaine and 63.6% for lidocaine. Regarding patients who reported no pain or mild pain during the pulpectomy, the success rate was, respectively 72.7% for mepivacaine, 63.6% for articaine and 54.5% for lidocaine. These differences were not statistically significant. Neither of the solutions resulted in 100% anesthetic success in patients with irreversible pulpitis of mandibular molars.
Topics: Adolescent; Adult; Anesthetics; Female; Humans; Male; Middle Aged; Pulpitis; Young Adult
PubMed: 27652697
DOI: 10.1590/0103-6440201600663 -
BMC Anesthesiology Nov 2021Supraclavicular block (SCB) with long-acting local anaesthetic is commonly used for surgical repair of distal radial fractures (DRF). Studies have shown a risk for... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Supraclavicular block (SCB) with long-acting local anaesthetic is commonly used for surgical repair of distal radial fractures (DRF). Studies have shown a risk for rebound pain when the block fades. This randomised single-centre study aimed to compare pain and opioid consumption the first three days post-surgery between SCB-mepivacaine vs. SCB-ropivacaine, with general anaesthesia (GA) as control.
METHODS
Patients (n = 90) with ASA physical status 1-3 were prospectively randomised to receive; SCB with mepivacine 1%, 25-30 ml (n = 30), SCB with ropivacaine 0.5%, 25-30 ml (n = 30) or GA (n = 30) with propofol/fentanyl/sevoflurane. Study objectives compared postoperative pain with Numeric Rating Scale (NRS) and sum postoperative Opioid Equivalent Consumption (OEC) during the first 3 days post-surgery between study-groups.
RESULTS
The three groups showed significant differences in postoperative pain-profile. Mean NRS at 24 h was significantly lower for the SCB-mepivacaine group (p = 0.018). Further both median NRS and median OEC day 0 to 3 were significanly lower in the SCB-mepivacaine group as compared to the SCB-ropivacaine group during the first three days after surgery; pain NRS 1 (IQR 0.3-3.3) and 2.7 (IQR 1.3-4.2) (p = 0.017) and OEC 30 mg (IQR 10-80) and 85 mg (IQR 45-125) (p = 0.004), respectively. The GA-group was in between both in pain NRS and median sum OEC. Unplanned healthcare contacts were highest among SCB-ropivacaine patients (39.3%) vs. SCB-mepivacaine patients (0%) and GA-patients (3.4%).
CONCLUSIONS
The potential benefit of longer duration of analgesia, associated to a long-acting local anaesthetic agent, during the early postoperative course must be put in perspective of potential worse pain progression following block resolution.
TRIAL REGISTRATION
NCT03749174 (clinicaltrials.gov, Nov 21, 2018, retrospectively registered).
Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Anesthesia, General; Anesthetics, Local; Brachial Plexus Block; Female; Humans; Male; Mepivacaine; Middle Aged; Pain Measurement; Pain, Postoperative; Prospective Studies; Radius Fractures; Ropivacaine; Time Factors; Young Adult
PubMed: 34753423
DOI: 10.1186/s12871-021-01499-z -
Dental Research Journal 2023Although most of the metabolism of local anesthetics (LAs) takes place in the liver, no study has investigated the effect of these anesthetics on the kidney function of...
BACKGROUND
Although most of the metabolism of local anesthetics (LAs) takes place in the liver, no study has investigated the effect of these anesthetics on the kidney function of single-kidney humans or animals. The present study was conducted to examine the effect of LAs on renal function in single-kidney rats.
MATERIALS AND METHODS
The present experimental animal study with two control groups was done in an animal laboratory. Forty-two rats were randomly assigned to seven groups of six rats, including two control groups and five experimental groups. The experimental groups underwent intraperitoneal anesthesia with 2% lidocaine, 2% lidocaine with 1:80,000 epinephrine, 4% articaine, 3% prilocaine with 0.03 IU Felypressin, and 3% mepivacaine, respectively. Unilateral nephrectomy was done. After 24 h, the rats' blood urea nitrogen (BUN), serum creatinine (Cr), and blood specific gravity (BSG) were measured. A standard dose of anesthetics was injected into the peritoneum for 4 days afterward. Then, these indices were measured again 24 h after the last injection. Data were analyzed using IBM SPSS (version 21.0). One-way analysis of variance, Tukey's honestly significant difference , and paired -tests were used for statistical analysis. < 0.05 was considered statistically significant.
RESULTS
The results indicated significant differences among groups in the rats' BUN and serum Cr 24 h after nephrectomy ( < 0.05). However, there were no significant differences in BUN, BSG, and Cr among groups after the interventions.
CONCLUSION
LAs did not affect renal function in single-kidney rats. Therefore, dentists can use the anesthetics in single-kidney people.
PubMed: 38020254
DOI: No ID Found -
American Journal of Veterinary Research May 2023This study aims to assess intrathecal mepivacaine for euthanasia in anesthetized horses and compare it to a traditional euthanasia method using a single intravenous...
OBJECTIVES
This study aims to assess intrathecal mepivacaine for euthanasia in anesthetized horses and compare it to a traditional euthanasia method using a single intravenous injection of pentobarbital in sedated horses.
ANIMALS
Client-owned horses and horses requiring euthanasia due to involvement in concurrent research projects were used. Horses were randomly assigned to 1 of 2 groups: intrathecal mepivacaine after anesthesia or intravenous pentobarbital after sedation. All horses had normal vital parameters and no signs of infectious disease at the time of euthanasia.
PROCEDURES
The intrathecal mepivacaine group was anesthetized before the intrathecal injection of mepivacaine. The pentobarbital group was sedated, concurrently anesthetized and euthanized using intravenous pentobarbital, then received an intrathecal saline (0.9% NaCl) solution injection to a blind observer. Both groups were sedated with detomidine and the time from sedation to the cessation of vital parameters (respirations, pulse, corneal reflex, and ECG) was recorded. Euthanasias were recorded for review by a blinded anesthesiologist, using an independent scale to assess the quality of sedation, anesthesia induction, and lateral recumbency.
RESULTS
Time from detomidine administration to cessation of each vital parameter was significantly longer in the intrathecal mepivacaine group. There was no statistically significant difference in qualitative scores between groups for sedation or induction, but lateral recumbency was subjectively superior in the anesthetized intrathecal mepivacaine group.
CLINICAL RELEVANCE
Intrathecal mepivacaine provided a safe, effective, alternative method of euthanasia to intravenous pentobarbital and addresses concerns about barbiturate availability. This study also informs practitioners of what to expect (ie, longer cessation of vital parameters) when using the intrathecal mepivacaine method.
Topics: Horses; Animals; Pentobarbital; Mepivacaine; Euthanasia, Animal; Anesthesia, General; Administration, Intravenous
PubMed: 36921025
DOI: 10.2460/ajvr.22.11.0201 -
Equine Veterinary Journal Sep 2022A 10-year-old 466 kg mustang gelding presented to an equine referral hospital for surgical repair of nasal, frontal and lacrimal bone fractures from an unknown trauma.... (Review)
Review
A 10-year-old 466 kg mustang gelding presented to an equine referral hospital for surgical repair of nasal, frontal and lacrimal bone fractures from an unknown trauma. Surgical repair was performed under general anaesthesia, including a right-sided maxillary regional anaesthetic block with mepivacaine hydrochloride. Progressive hyperkalaemia was documented perianaesthetically (T-3 mins; 134 mins after induction; potassium 6.4 mmol/L (ref 3.5-5.1 mmol/L). Perianaesthetic bradycardia was attributed to alpha -2 agonist infusion administration, and other characteristic ECG changes (flattened P waves, narrow T waves of increased amplitude, prolonged QRS complex) were not documented. Asystole occurred 137 min after induction of anaesthesia; however, a review of the available literature suggests the degree of hyperkalaemia documented was unlikely to be the primary cause of asystole but may have been a contributing factor. It is hypothesised that a trigeminocardiac reflex was the primary contributory factor to asystole in the described case, and may represent a maxillomandibulocardiac reflex that has not been previously described in the horse.
Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; Heart Arrest; Horse Diseases; Horses; Hyperkalemia; Male; Reflex
PubMed: 34738246
DOI: 10.1111/evj.13535 -
International Journal of Molecular... Mar 2022Background. Local anesthetics (LAs) have potent anti-inflammatory properties. Inflammatory down-regulation is crucial in diseases with overactive immune reactions, such...
Background. Local anesthetics (LAs) have potent anti-inflammatory properties. Inflammatory down-regulation is crucial in diseases with overactive immune reactions, such as acute respiratory distress syndrome (ARDS) and chronic inflammation. We investigated the influence of four LAs, procaine, lidocaine, mepivacaine, and bupivacaine, on the reduction of tumor necrosis factor-alpha (TNF-α) secretion in lipopolysaccharide (LPS)-activated human leucocytes. Methods. Blood samples of 28 individuals were stimulated with LPS. The reduction of TNF-α production by each of the four LAs added (0.5 mg/mL) was measured and correlated with biometric variables. A response was defined as reduction to <85% of initial levels. Results. All four LAs down-regulated the TNF-α secretion in 44−61%: Bupivacaine (44.4%), lidocaine (61.5%), mepivacaine (44.4%), and procaine (50% of the individuals, “responders”). The TNF-α secretion was reduced to 67.4, 68.0, 63.6, and 67.1% of the initial values in responders. The effects in both patients and healthy persons were the same. Interindividual responses to LAs were not correlated with the duration or type of complaints, basal TNF-α serum level, sex, BMI, or age of responders. Conclusions. Four clinically relevant LAs (amid-LA and ester-LA) attenuate the inflammatory response provoked by LPS. They are potential candidates for drug repositioning in treating overactive immune reactions and chronic inflammation.
Topics: Anesthetics, Local; Anti-Inflammatory Agents; Bupivacaine; Humans; Inflammation; Lidocaine; Lipopolysaccharides; Mepivacaine; Procaine; Tumor Necrosis Factor-alpha
PubMed: 35328706
DOI: 10.3390/ijms23063283 -
Head & Face Medicine Feb 2015Long lasting anesthesia of the soft tissue beyond the dental treatment affects patients in daily routine. Therefore a sophisticated local anesthesia is needed. The...
INTRODUCTION
Long lasting anesthesia of the soft tissue beyond the dental treatment affects patients in daily routine. Therefore a sophisticated local anesthesia is needed. The purpose of this study was an evaluation of the clinical use of epinephrine-free local anesthetic solutions in routine short-time dental treatments.
MATERIALS AND METHODS
In a prospective, single-blind, non-randomized and controlled clinical trial, 31 patients (16 male, 15 female patients) undergoing short-time dental treatment under local anesthesia (plain solutions of articaine 4% and mepivacaine 3%) in area of maxillary canine were tested with quantitative sensory testing QST. Paired-Wilcoxon-testing (signed-rank-test) and Mc Nemar tests have been used for statistical results.
RESULTS
Significant differences in all tested parameters to the time of measurements were found. Mepivacaine showed a significantly stronger impact for the whole period of measurement (128 min) on thermal and mechanical test parameters and to the associated nerve fibers.
CONCLUSION
Plain articaine shows a faster onset of action associated with a shorter time of activity in comparison to plain mepivacaine. In addition to this articaine shows a significant low-graded effect on the tested nerve-fibers and therefore a least affected anesthesia to the patient. The clinical use of an epinephrine-free anesthetic solution can be stated as possible option in short dental routine treatments to the frequently used vasoconstrictor containing local anesthetics. Patients may benefit from shorter numbness.
Topics: Adult; Anesthesia, Dental; Anesthetics, Combined; Anesthetics, Local; Carticaine; Epinephrine; Evaluation Studies as Topic; Female; Humans; Male; Mepivacaine; Nerve Fibers; Pain Measurement; Prospective Studies; Sensory Receptor Cells; Sensory Thresholds; Single-Blind Method; Statistics, Nonparametric; Young Adult
PubMed: 25889698
DOI: 10.1186/s13005-015-0061-1 -
American Journal of Veterinary Research Jan 2020To assess onset of analgesia for 3% chloroprocaine hydrochloride and 2% mepivacaine hydrochloride when used for median and ulnar nerve blocks in lame horses.
OBJECTIVE
To assess onset of analgesia for 3% chloroprocaine hydrochloride and 2% mepivacaine hydrochloride when used for median and ulnar nerve blocks in lame horses.
ANIMALS
6 naturally lame horses.
PROCEDURES
A crossover experiment was conducted. Horses were assigned to 1 of 2 treatment groups (3% chloroprocaine or 2% mepivacaine first). Median and ulnar nerve blocks were performed in the lame limb with the assigned treatment. Lameness was objectively evaluated before treatment administration and at various points for 120 minutes after treatment with a wireless inertial sensor-based motion analysis system. Following a 7-day washout period, horses then received the other treatment and lameness evaluations were repeated.
RESULTS
Median and ulnar nerve blocks performed with 3% chloroprocaine resulted in more consistent, rapid, and profound amelioration of lameness than did blocks performed with 2% mepivacaine. Lameness decreased more between 20 and 40 minutes after injection when 3% chloroprocaine was used than when 2% mepivacaine was used. Complete resolution of lameness was detected a mean of 9 minutes after injection when median and ulnar nerve blocks were performed with 3% chloroprocaine and a mean of 28 minutes after injection when performed with 2% mepivacaine.
CONCLUSIONS AND CLINICAL RELEVANCE
3% chloroprocaine had a more rapid onset and provided better analgesia for median and ulnar nerve blocks in horses with naturally occurring lameness, compared with 2% mepivacaine. These favorable properties suggest that 3% chloroprocaine would be useful for performance of median and ulnar regional nerve blocks during complicated lameness evaluations.
Topics: Analgesia; Anesthetics, Local; Animals; Cross-Over Studies; Gait; Horse Diseases; Horses; Lameness, Animal; Male; Mepivacaine; Nerve Block; Pain; Procaine
PubMed: 31887088
DOI: 10.2460/ajvr.81.1.13 -
Bioengineered Dec 2021With the gradual recognition of the side effects of local anesthetics, the nerve injury caused by local anesthetics has received growing attention. This research...
With the gradual recognition of the side effects of local anesthetics, the nerve injury caused by local anesthetics has received growing attention. This research intended to delve into miR-183-5p changes in mepivacaine-mediated SH-SY5Y cell injury, as well as its modulatory mechanism on cell apoptosis. RT-qPCR was adopted for assaying miR-183-5p and PDCD4 mRNA expression. Our team respectively transfected miR-183-5p mimic and inhibitor to enhance or inhibit miR-183-5p function. We employed Western blot for detecting PDCD4 protein levels, as well as flow cytometry and Hoechst 33342/PI double staining for determining cell apoptosis rate. Additionally, our crew applied an ELISA kit for measuring TNF-α, IL-1β, IL-6, and IL-8 contents. The level of reactive oxygen species (ROS) production was examined by the Image-iT LIVE Green ROS detection Kit. As well as dual-luciferase reporter experiment for verifying the targeting link of miR-183-5p with PDCD4. In mepivacaine-induced cell apoptosis in SH-SY5Y cells, miR-183-5p expression was down-regulated. TNF-α, IL-1β, IL-6, and IL-8 contents were elevated. The rate of apoptosis increased visibly, cleaved caspase-3 and Bax levels waxed, whereas Bcl-2 level waned. MiR-183-5p could alleviate the damaging impact of mepivacaine. Dual-luciferase reporter experiments demonstrated that miR-183-5p directly targeted PDCD4. Collectively, we concluded that a high concentration of mepivacaine can cause SH-SY5Y cell damage, miR-183-5p functions crucially in mepivacaine-mediated cell damage. This study provides a theoretical basis for elucidating the mechanism of mepivacaine-induced nerve cell damage, and overexpressed miR-183-5p likely become a novel strategy to combat mepivacaine-induced nerve damage.Abbreviations:miRNA: Micro RNA; PDCD4: Programmed Cell Death 4; MDA: Malondialdehyde; SOD: Superoxide Dismutase; ROS: Reactive Oxygen Species; WT: Wild Type; Mut: Mutant; UTR: Untranslated Region; IL-6: Interleukin-6; IL-1β: Interleukin-1β; TNF-α: Tumor Necrosis Factor-α; IL-8: Interleukin-8; COX-2: Cyclooxygenase-2; iNOS: inducible NOS; MEP: Mepivacaine.
Topics: Apoptosis; Apoptosis Regulatory Proteins; Cell Line, Tumor; Cytokines; Humans; Mepivacaine; MicroRNAs; Protective Agents; RNA-Binding Proteins
PubMed: 34180760
DOI: 10.1080/21655979.2021.1946358