Local Lidocaine Research Articles

Office-based olfactory mucosa biopsies.

Requests from researchers for olfactory mucosal biopsies are increasing as a result of advances in the fields of neuroscience and stem cell biology. Published studies report variable rates of success in obtaining true olfactory tissue, often below 50%. In cases where biopsies are not obtained carefully and confirmed through histological techniques, erroneous conclusions are made. Attention to the epithelium alone without submucosal analysis may add to the confusion. A consistent biopsy technique can help rhinologists obtain higher yields of olfactory mucosa. Confirmatory tissue staining analysis assures olfactory mucosa has been obtained, thereby strengthening clinical correlations and scientific conclusions. Biopsies of the septum within the anterior olfactory cleft were obtained under endoscopic guidance in an office procedure room using topical local anesthetic (lidocaine). After mucosal incision, a small, cupped, biopsy forceps was used to obtain specimens approximately 2 to 3 mm in size. Specimens were sectioned and analyzed with immunohistochemistry for presence of olfactory epithelium and/or olfactory fascicles. A total of 14 subjects were biopsied in this analysis. Four subjects had biopsies in the operating room (OR). The remaining 10 underwent biopsies in the clinic. All biopsies obtained in the OR revealed evidence of olfactory mucosa. Of the 10 clinic biopsies, 8 (80%) revealed evidence of olfactory mucosa. No complications were encountered. High yields of olfactory mucosa can be obtained safely in an office-based setting. Technique, including attention to the area of biopsy, and confirmatory analysis are important in assuring presence of olfactory tissue.

Molecular Scale Prediction of Lidocaine Interaction with the Pore Domain of Human Nav1.5

A primary hindrance to ion channel based drug discovery and design is that no experimental technique exists for identifying drug-target interactions at the molecular scale. In the case of the dominant cardiac Na+ channel isoform Nav1.5, the persistent lack of approaches to investigate drug-channel interactions means that there is no way to differentiate between potentially useful and harmful drugs. For example, no method exists to distinguish between drugs that slow conduction or widen the QRS complex on the ECG like flecainide, and those that have a strong safety profile in the clinic, such as lidocaine. To address this problem, we have begun to probe the interaction of the local anesthetic molecule lidocaine with closed and open states of Nav1.5 using a computational approach that combines homology modeling with all-atom molecular dynamics (MD) simulation. Models of the pore domain of Nav1.5 in putative open and closed conformational states based on the crystallographic bacterial orthologs NavRh and NavMs were developed using Rosetta software suit. The lidocaine molecule was parameterized according to CHARMM standards, and MD simulations were run in order to identify the molecular determinants of interaction of the drug within each pore model. Free energy surface projections from the MD simulations suggested binding sites for lidocaine within our channel models. Preliminary structural analysis suggests that the aromatic group of lidocaine interacts with phenylalanine (F1759) on the S6 helix of domain IV via π-interactions in both open and closed states. In addition, the carbonyl oxygen of lidocaine was predicted to interact with lysine (K1418) of domain III in the open state, indicating a stabilized configuration in which its amide tail physically occludes the pore.

Effect of local anesthesia on facial nerve blood flow and muscle action potential

Background & objectiveThe effect of direct application of local lidocaine with epinephrine on the facial nerve (FN) has not been reported. The aim of this study is to assess the effects of 2% lidocaine with 1:100,000 epinephrine at clinically relevant concentrations in a rat FN model with respect to facial nerve blood flow (FNBF) and subsequent electrophysiological changes. Materials and methodsTo assess the influence of drugs on FNBF and electrically evoked muscle action potential (EMAP), small pieces of gelfoam were soaked in PBS 100μl (n=5, control group), 50μl (n=5, treatment group A) and 100μl (n=5, group B) of 2% lidocaine with 1:100,000 epinephrine, and 50μl (n=5, group C) and 100μl (n=5, group D) of 2% lidocaine. After 5min of stable recordings, we applied a 2% lidocaine with or without 1:100,000 epinephrine impregnated gelfoam over the main trunk of the facial nerve of rats for 30min. After removing the applied gelfoam, FNBF and threshold of EMAP were measured separately in each group. ResultsCompared to the control group, the treatment groups showed a significant reduction in FNBF in a dose-dependent manner. The maximal reductions in FNBF were observed in all treatment groups for a period after 10min of the application. Synergistic reduction in FNBF was greater in groups A and B than in the lidocaine applied groups (C and D). The maximal increase in the EMAP threshold was observed immediately after the respective drug application in all groups. The greatest increase in the EMAP threshold was observed in group B. The increased EMAP threshold returned to the baseline value within 120min in groups A and C. ConclusionFrom these results, it can be considered that the topical application of lidocaine with epinephrine caused reduction in FNBF and elevation of EMAP threshold. These acute reductions in FNBF and elevations in the EMAP threshold were restored in a time-dependent manner.

Efficacy and Safety of a Lidocaine and Ropivacaine Mixture for Scalp Nerve Block and Local Infiltration Anesthesia in Patients Undergoing Awake Craniotomy.

Mixtures of various local anesthetics, such as lidocaine and ropivacaine, have been widely used. However, their efficacy and safety for scalp nerve blocks and local infiltration during awake craniotomy have not been fully elucidated. We prospectively investigated 53 patients who underwent awake craniotomy. Scalp block was performed for the blockade of the supraorbital, supratrochlear, zygomaticotemporal, auriculotemporal, greater occipital, and lesser occipital nerves with a mixture containing equal volumes of 2% lidocaine and 0.75% ropivacaine, including 5 μg/mL of epinephrine. Infiltration anesthesia was applied at the site of skin incision using the same mixture. The study outcomes included changes in heart rate and blood pressure after head pinning and skin incision, and incidence of severe pain on emergence from anesthesia. Total doses and plasma concentrations of lidocaine and ropivacaine were measured at different time points after performing the block. The heart rate and blood pressure after head pinning were marginally, but significantly, increased when compared with baseline values. There were no significant differences in heart rate and blood pressure before and after the skin incision. Nineteen percent of the patients (10/53) complained of incisional pain at emergence from anesthesia. The highest observed blood concentrations of lidocaine and ropivacaine were 1.9±0.9 and 1.1±0.4 μg/mL, respectively. No acute anesthetic toxicity symptom was observed. Scalp block with a mixture of lidocaine and ropivacaine seems to provide effective and safe anesthetic management in patients undergoing awake craniotomy.

Acute physiological responses to castration-related pain in piglets: the effect of two local anesthetics with or without meloxicam

Methods to reduce castration-related pain in piglets are still issues of concern and interest for authorities and producers. Our objectives were to estimate the effectiveness of two protocols of local anesthesia (lidocaine and the combination of lidocaine+bupivacaine) as well as the use of meloxicam as a postoperative analgesic in alleviating castration-related pain, measured by acute physiological responses. Eight groups (15 piglets/group) were included in the study: (1) castration without anesthesia or analgesia, without meloxicam (TRAD WITHOUT), (2) castration without anesthesia or analgesia, but with meloxicam (TRAD WITH), (3) handling without meloxicam (SHAM WITHOUT), (4) handling with meloxicam (SHAM WITH), (5) castration after local anesthesia with lidocaine but without meloxicam (LIDO WITHOUT), (6) castration after local anesthesia with lidocaine and meloxicam (LIDO WITH), (7) castration after local anesthesia with lidocaine+bupivacaine without meloxicam (LIDO+BUPI WITHOUT), (8) castration after local anesthesia with lidocaine+bupivacaine and meloxicam (LIDO+BUPI WITH). Acute physiological responses measured included skin surface temperature and serum glucose and cortisol concentrations. On days 4 and 11 post-castration BW was recorded and average daily gain was calculated over this period. Furthermore, piglet mortality was recorded over the 11-day post-castration period. Administration of local anesthetic or meloxicam did not prevent the decrease in skin surface temperature associated with castration. Lidocaine reduced the increase in glucose concentration associated with castration. For castrated pigs, the joint use of lidocaine and meloxicam caused a significant decrease in cortisol concentration; the combination of intratesticular lidocaine and bupivacaine did not seem to be more effective than lidocaine alone. No effect of treatments on mortality and growth were detected.

The efficacy of eutectic mixture of local anesthetics as a topical anesthetic agent used for dental procedures: A brief review

Dental pain management is one of the most critical aspects of modern dentistry which might affect patient's quality of life. Several methods are suggested to provide a painless situation for patients. Desensitization of the oral site using topical anesthetics is one of those methods. The improvements of topical anesthetic agents are probably one of the most important advances in dental science in the past 100 years. Most of them are safe and can be applied on oral mucosa with minimal irritation and allergic reactions. At present, these agents are various with different potent and indications. Eutectic mixture of local anesthetics (EMLA) (lidocaine + prilocaine) is a commercial anesthetic agent which has got acceptance among dental clinicians. This article provides a brief review about the efficacy of EMLA as a topical anesthetic agent when used during dental procedures.

Local anesthesia with monitored anesthesia care for patients undergoing thyroidectomy: a case series

Because the current trend favors minimally invasive surgery for thyroid disease, increasing interest has developed for thyroidectomy under local anesthesia with monitored anesthesia care (MAC). Here, we retrospectively reviewed 18 cases of thyroidectomy performed under local anesthesia with MAC in a single center. All of the procedures were performed by a single surgeon, using local lidocaine infiltration around the incisional site and propofol plus remifentanil target-controlled infusion. Sore throat (4/18), hypocalcemia (1/18), and transient voice color change (1/18) were observed, but the patients recovered during the follow-up period. No cases of postoperative nausea and vomiting, hematoma, wound problems, or vocal cord paralysis were observed. Local anesthesia with MAC provided satisfactory sedation in most patients without conversion to general anesthesia.

Vaginal hysterectomy using local anesthesia and analgesics

Context: Vaginal hysterectomy for pelvic organ prolapse is often performed under general or regional anesthesia. However, the performance of this operative procedure under local anesthetic has potential benefits, especially in resource-poor settings. Aims: The aim of this study was to review the outcome of vaginal hysterectomy and pelvic floor repair using local anesthesia and supplementary analgesia. Settings and Design: The study was retrospective and the setting was a cottage hospital in the northern Nigeria. Subjects and Methods: A review of the case records of women who underwent a vaginal hysterectomy and pelvic floor repair for uncomplicated 4th degree (Stage III) uterovaginal prolapse, using local lidocaine infiltration and supplemental pentazocine injection. Statistical Analysis Used: Descriptive statistics and frequencies were used to describe the population and outcomes of surgery. Results: Eighteen women successfully had vaginal hysterectomy and pelvic floor repair using local anesthesia with supplemental pentazocine intramuscular injection. Four (22.2%) of the women required supplemental pentazocine injection. The mean duration of surgery was 101.67 (± 14.14) min and the average hospital stay was 36.22 (± 17.16) h. Thirteen (72.2%) women were satisfied with the surgery, anesthesia, and early ambulation while the others desired a totally painless surgery in addition to the early ambulation and short hospitalization. Conclusions: The use of local anesthesia for vaginal hysterectomy and pelvic floor repair was successful in patients with severe uterovaginal prolapse. A larger, randomized controlled study is recommended.

Peculiarities of changes of echocardiographic parameters in patients with coronary artery disease during epidural anesthesia under administration of different local anesthetics

The aim – to investigate the effect of epidural anesthesia on myocardial function in patients with coronary artery disease (CAD).Materials and methods. One hundred thirty four males who were operated for the inguinal hernia under an epidural anesthesia were examined. Group 1 included 77 patients with a coronary arterydisease, stable angina (CCSA classes I- III); the group 2 included 57 healthy individuals. Patients of two groups were divided randomly in to 3 subgroups depending on administered local anesthetic (lidocaine 2%, ropivacaine 0.75% or bupivacaine 0.5 %). All patients under went echocardiography before anesthesia and in the early postoperative period.Results. Epidural anesthesia didn’t significantly affect ejection fraction of left ventricle in both groups of patients. Instead, the average level of myocardial performance index (MPI) significantly increased by 18.92% in the post operative period. Increasing of MPI in the examined cohort was caused by prolongation of isovolumetric relaxation time (IVRT) (at 9.58%, pВ0.05) and a shortening the time of systole (IVCT) (at 1.65%, pВ0.05). Duration of isovolumetric contraction time prolonged at 10.12% in persons without CAD, and shortened at 6.44% in patients with CAD. Prolongation of isovolumetric relaxation time in patients without CAD was less pronounced as compare with patients with CAD – at 5.73 % and 8.16%, respectively. Due to the dynamics described above pathological changes of MPI prevailed in patients with CAD. There was a statistically significant increasing of lateral part of mitral anular plane excurtion by 6.97% in all patients. This dynamic was observed almost equivalent in both groups – by 7.02 % in patients with CAD and by 6.92 % – without CAD. Instead, tricuspid annular plane systolic excursion (TAPSE) decreased by 7.96% in patients with CAD and by 5.85 % in patients with out CAD. Analysis of the examined parameters in subgroups of patients, depending on the administered LA and the presence of CAD, revealed statistically significant changes of IVCT, IVRT and TAPSE in patients with CAD who were administered bupivacaine.

Local Injection of Methylcobalamin Combined with Lidocaine for Acute Herpetic Neuralgia.

To determine the efficacy of methylcobalamin combined with lidocaine for acute herpetic neuralgia. Randomized controlled trial with longitudinal analysis. The authors recruited 204 patients (>50 years) with T5-10 dermatomal acute herpetic neuralgia with rash onset within 7 days. Patients were divided into two groups based on the time of onset: immediate-early (IE, 1-3 days) and early stage (ES, 4-7 days) groups and then subdivided randomly into control (IE-Ctl, ES-Ctl) and treatment (IE-Tr, ES-Tr) groups. Control groups received intramuscular methylcobalamin in addition to local lidocaine injection, while treatment groups received local methylcobalamin combined with lidocaine injection for 14 days. Treatment efficacy was assessed based on rash healing time, alteration in pain intensity, and interference with quality of life. Multilevel mixed modeling and survival analysis were employed to examine treatment responses. There was no significant difference in the rash healing time between IE and ES. The mean pain scores in IE-Tr (2.4 ± 0.7) and ES-Tr (1.3 ± 0.7) decreased significantly compared with those in the control groups. The median satisfactory response time was 6 days in ES-Tr and 11 days in IE-Tr. The benefit ratio for ES-Tr versus IE-Tr was 14.94. The subjects in IE-Tr and ES-Tr had higher quality of life scores (81.2 ± 6.9 vs 88.3 ± 8.6, respectively) than those in the control groups. The incidence of postherpetic neuralgia was 1.1% at 3 months. Local methylcobalamin combined with lidocaine, optimally administered within 4-7 days of onset, may be an effective therapeutic option for acute herpetic neuralgia.

Efeitos comparativos de vitamina C sobre os efeitos dos anestésicos locais ropivacaína, bupivacaína e lidocaína em condrócitos humanos

BackgroundIntra‐articular injections of local anesthetics are commonly used to enhance post‐operative analgesia following orthopedic surgery as arthroscopic surgeries. Nevertheless, recent reports of severe complications due to the use of intra‐articular local anesthetic have raised concerns. ObjectivesThe study aims to assess use of vitamin C in reducing adverse effects of the most commonly employed anesthetics – ropivacaine, bupivacaine and lidocaine – on human chondrocytes. MethodsThe chondrocyte viability following exposure to 0.5% bupivacaine or 0.75% ropivacaine or 1.0% lidocaine and/or vitamin C at doses 125, 250 and 500μM was determined by Live/Dead assay and annexin V staining. Expression levels of caspases 3 and 9 were assessed using antibodies by Western blotting. Flow cytometry was performed to analyze the generation of reactive oxygen species. ResultsOn exposure to the local anesthetics, chondrotoxicity was found in the order ropivacaine<bupivacaine<lidocaine. Vitamin C effectively improved the reduced chondrocyte viability and decreased the raised apoptosis levels following exposure to anesthesia. At higher doses, vitamin C was found efficient in reducing the generation of reactive oxygen species and as well down‐regulate the expressions of caspases 3 and 9. ConclusionsVitamin C was observed to effectively protect chondrocytes against the toxic insult of local anesthetics ropivacaine, bupivacaine and lidocaine.

Medicinal plant constituents interact with membrane-acting local anesthetics

Specific constituents in medicinal plants have been suggested to act on lipid bilayers and modify the physicochemical properties of biomembranes as well as amphiphilic membrane-active drugs. The interactions between selected phytochemicals and local anesthetics were studied at a membrane lipid level to verify the possibility that their concomitant use may influence local anesthesia. Biomimetic lipid bilayer membranes were prepared as unilamellar vesicle suspensions by the injection method using different phospholipids and cholesterol to mimic the lipid composition of neuronal membranes. They were treated at 37 °C for 30 min with apple flavonoid phloretin, chili pepper capsaicinoid capsaicin, harmala alkaloid tetrahydroharman and local anesthetic lidocaine separately or in combination, followed by measuring fluorescence polarization to determine their induced membrane fluidity changes. Lidocaine increased the fluidity of biomimetic membranes at clinically-relevant concentrations. In contrast, phloretin (10 – 50 µM) and tetrahydroharman (10 – 500 nM) decreased the membrane fluidity, but capsaicin (50 – 100 µM) increased. Phloretin (25 µM) and tetrahydroharman (˜15 nM) inhibited or counteracted the membrane-fluidizing effects of lidocaine (0.05 – 1 mg/mL), whereas capsaicin (50 µM) potentiated. Such membrane interactions were also found in bupivacaine. Local anesthetics mechanistically act on neuronal membranes besides voltage-gated sodium channels. The antagonistic or synergistic membrane interactions with medicinal plant constituents suggest the potentially beneficial or adverse effects that the counteraction by phloretin would successfully discontinue anesthesia after the treatment and the cooperation with capsaicin should prolong the duration of nerve block, while the inhibition by tetrahydroharman might reduce the anesthetic efficacy in certain patients. The membrane interactivity will be also an experimental clue to discover the drug leads for anesthetic adjuncts.

Applications of disposable circumcision stapler with lidocaine cream combined with lidocaine injection anesthesia in circumcision

Objective To investigate the application efficacy of disposable circumcision stapler with compound lidocaine cream combined with lidocaine injection in the circumcision. Methods From September 2013 to November 2014, 120 cases (11 cases of redundant prepuce phimosis patients), were divided into disposable circumcision suture group (S group, 60 cases) and conventional circumcision (T group, 60 cases), two groups had no statistically significant difference at patient age and wrapping case (6 cases phimosis of S group, 5 cases phimosis of T group)(P>0.05. Patient's age ranged from 11 to 49 years. 30 patients in each group were treated with lidocaine cream combined with lidocaine injection, and another 30 patients were treated with a local anesthetic lidocaine injection. Comparisons were conducted among the four groups on the operation time, anesthesia, intraoperative and postoperative pain score, blood loss and postoperative complications, postoperative appearance satisfaction, wound healing time. Results For the disposable circumcision stapler with lidocaine cream combined with lidocaine injection group, disposable circumcision stapler with lidocaine injection group, sleeve circumcision with lidocaine cream combined with lidocaine injection group and sleeve circumcision with lidocaine injection group, the operation time was (5.3±1.5)min, (4.9±1.4)min, (31.6±3.4)min, (32.0±3.3)min respectively, blood loss was (0.6±0.4)ml, (0.8±0.5)ml, (6.9±2.4)ml, (7.5±2.1)ml respectively, narcotic pain score was 0.6±0.6, 3.2±3.9, 2.5±1.0, 0.5±0.6, intraoperative pain score was 0.8±0.9, 1.4±0.8, 2.2±1.1, 3.1±1.1, postoperative 24 h pain score was 1.6±0.9, 2.2±0.8, 2.6±1.3, 4.4±1.1, postoperative 48h pain score was 0.7±0.6, 0.8±0.9, 2.4±0.8, 2.8±0.7, wound healing time was (13.7±1.5)d, (13.5±1.7)d, (14.2±1.3)d, (14.1±1.6)d, the rate of postoperative complications was 6.6% (2/30), 10.0%(3/30), 26.6%(8/30), 33.4%(10/30), satisfaction rate of appearance was 93.4%(28/30), 96.7%(29/30), 70.4%(22/30), 80.0%(24/30). Compared with sleeve circumcision with lidocain injection group, disposable circumcision stapler with lidocaine cream combined with lidocaine injection had a shorter operation time, less pain, less bleeding, higher appearance satisfaction rate and lower incidence of complications (P 0.05). Conclusion Application of the disposable circumcision stapler with lidocaine cream combined with lidocaine injection on circumcision is safe and has got better clinical outcomes. Key words: Redundant prepuce; Disposable circumcision suture device; Compound lidocaine cream; Lidocaine injection

Radial artery blood gas sampling: a randomized controlled trial of lidocaine local anesthesia.

Radial artery puncture is a common procedure and yet the role of local anesthesia for reducing the pain of this procedure continues to be debated. Clinical practice is variable and there is potential for substantial financial savings. This is the first randomized trial to investigate the effectiveness of subcutaneously injected lidocaine anesthesia on the perceived pain of radial artery puncture and the financial impact. Between December 2012 and April 2013, 43 patients in the Emergency Department were randomized into the intervention group to receive lidocaine 1% 1 mL subcutaneously or the control group (to receive no local anesthesia) prior to radial artery puncture for blood gas sampling. Pain was rated on a 10 cm visual analogue scale and procedural variables collected for between group analyses. Overall, 41 participants were included. Subcutaneously injected lidocaine anesthesia did not reduce the median pain of radial artery puncture (control 1.8 vs. intervention 1.6 cm, P = 0.938). Those patients who had other systemically acting analgesia appeared to report reduced pain for radial artery puncture (0.60 vs. 2.30 cm, P = 0.105) as did those where a smaller 25-gauge needle was used compared to the standard 22-gauge (1.40 vs. 4.35 cm, P = 0.150), although these were not statistically significant. Anxious patients and those requesting local anesthesia experienced relatively higher levels of pain. Local anesthesia did not reduce the perceived pain of radial artery puncture.

Efficacy of Local Anesthetics in Detachment of Normal 3T3 Mouse Fibroblasts and Prostate Cancer AT-2 Cells from Substrata, in Maintenance of Viable Cells in a Non-Adherent State, and in Preservation of Cell Surface Markers Detected with FlowSight Image Cytometry.

The local anesthetics procaine, lidocaine and tetracaine permit the reversible detachment of viable cells and their passaging or preservation in a non-adherent state in the absence of proteolytic enzymes. The effects of these anesthetics, dissolved in various media, on cell viability, cell detachment from substrata and preservation of cells in a non-adherent state, were compared using the AT-2 line of rat prostate carcinoma cells of moderate malignancy and the 3T3 mouse fibroblast cell line. It was found that all three local anesthetics can induce cell rounding followed by detachment of over 95% of viable cells in both lines in Ca2+/Mg(2+)-free PBS. Tetracaine in 1 mM concentration was the most effective in induction of fast cell detachment. However, procaine and lidocaine in 16 mM concentrations were found to be optimal for preservation of cells in a non-adherent state and for the maintenance of cell viability for at least 2 h. The tested anesthetics also cause cell rounding and detachment when present in various cell culture media but these processes occurred much more slowly and less efficiently than in Ca2+/Mg(2+)-free PBS. Normal 3T3 mouse fibroblasts after detachment and passaging undertake growth reaching the same saturation density in cultures after detachment with procaine or lidocaine as after passaging using trypsin solution. The results suggest that the application of local anesthetics can be a very simple and effective technique for cell passaging in tissue cultures. This technique might decrease side-effects and cell injury caused by trypsinization or cell scraping. The preservation of cells in suspension in a non-adherent state may facilitate analysis of cell surface properties and fractionation of cell mixtures. Avoiding the use of trypsin allows for the preservation of cell surface proteins ICAM, CXCR4, and HCAM analyzed with FlowSight image flow cytometry.

Electrospun nanofibrous CMC/PEO as a part of an effective pain-relieving wound dressing

A novel two-layered pain-relieving wound dressing was prepared from a combination of biocompatible polymers: carboxymethylcellulose and polyethyleneoxide, and two types of pain-relieving drugs: the non-steroid anti-inflammatory diclofenac and the local anesthetic lidocaine. To achieve the two-layered structure, electrospinning and impregnation of a commercially available wound dressing Aquacel® were used for preparation of respective layers. The electrospun nanofibers have been shown to possess similar features as found in the extracellular matrix, an important component of the skin. This characteristic could significantly contribute to the efficiency of wound healing. The second layer is based on Aquacel®, an important wound dressing in modern wound care. Since pain can drastically lower the wound healing process, as well as it is known to decrease the overall quality of patient life, pain-relieving drugs are very interesting for wound care applications. For efficient pain reduction, two types of drugs were used. When combined, these can cover different types of wound-related pain (due to the cause and treatment) and hence additionally aid the wound healing process. The combined features of the incorporated pain-relieving drugs and the mentioned materials are therefore very interesting for future studies toward clinical testing of possible prototype products.

Comparative effects of vitamin C on the effects of local anesthetics ropivacaine, bupivacaine, and lidocaine on human chondrocytes

BackgroundIntra-articular injections of local anesthetics are commonly used to enhance post-operative analgesia following orthopedic surgery as arthroscopic surgeries. Nevertheless, recent reports of severe complications due to the use of intra-articular local anesthetic have raised concerns. ObjectivesThe study aims to assess use of vitamin C in reducing adverse effects of the most commonly employed anesthetics – ropivacaine, bupivacaine and lidocaine – on human chondrocytes. MethodsThe chondrocyte viability following exposure to 0.5% bupivacaine or 0.75% ropivacaine or 1.0% lidocaine and/or vitamin C at doses 125, 250 and 500μM was determined by LIVE/DEAD assay and annexin V staining. Expression levels of caspases 3 and 9 were assessed using antibodies by Western blotting. Flow cytometry was performed to analyze the generation of reactive oxygen species. ResultsOn exposure to the local anesthetics, chondrotoxicity was found in the order ropivacaine<bupivacaine<lidocaine. Vitamin C effectively improved the reduced chondrocyte viability and decreased the raised apoptosis levels following exposure to anesthesia. At higher doses, vitamin C was found efficient in reducing the generation of reactive oxygen species and as well down-regulate the expressions of caspases 3 and 9. ConclusionsVitamin C was observed to effectively protect chondrocytes against the toxic insult of local anesthetics ropivacaine, bupivacaine and lidocaine.

Subcutaneous l-tyrosine elicits cutaneous analgesia in response to local skin pinprick in rats

The purpose of the study was to estimate the ability of l-tyrosine to induce cutaneous analgesia and to investigate the interaction between l-tyrosine and the local anesthetic lidocaine. After subcutaneously injecting the rats with l-tyrosine and lidocaine in a dose-dependent manner, cutaneous analgesia (by blocking the cutaneous trunci muscle reflex-CTMR) was evaluated in response to the local pinprick. The drug–drug interaction was analyzed by using an isobolographic method. We showed that both l-tyrosine and lidocaine produced dose-dependent cutaneous analgesia. On the 50% effective dose (ED50) basis, the rank of drug potency was lidocaine (5.09 [4.88–5.38]μmol)>l-tyrosine (39.1 [36.5–41.8]μmol) (P<0.05). At the equipotent doses (ED25, ED50, and ED75), the duration of cutaneous analgesia caused by l-tyrosine lasted longer than that caused by lidocaine (P<0.01). Lidocaine co-administered with l-tyrosine exhibited an additive effect on infiltrative cutaneous analgesia. Our pre-clinical study demonstrated that l-tyrosine elicits the local/cutaneous analgesia, and the interaction between l-tyrosine and lidocaine is additive. l-tyrosine has a lower potency but much greater duration of cutaneous analgesia than lidocaine. Adding l-tyrosine to lidocaine preparations showed greater duration of cutaneous analgesia compared with lidocaine alone.

Memantine elicits spinal blockades of motor function, proprioception, and nociception in rats.

Although memantine blocks sodium currents and produces local skin anesthesia, spinal anesthesia with memantine is unknown. The purpose of the study was to evaluate the local anesthetic effect of memantine in spinal anesthesia and its comparison with a widely used local anesthetic lidocaine. After intrathecally injecting the rats with five doses of each drug, the dose-response curves of memantine and lidocaine were constructed. The potencies of the drugs and durations of spinal anesthetic effects onmotor function, proprioception, and nociception were compared with those of lidocaine. We showed that memantine produced dose-dependent spinal blockades in motor function, proprioception, and nociception. On a 50% effective dose (ED50 ) basis, the rank of potency was lidocaine greater than memantine (P<0.05 for the differences). At the equipotent doses (ED25 , ED50 , ED75 ), the block duration produced by memantine was longer than that produced by lidocaine (P<0.05 for the differences). Memantine, but not lidocaine, displayed more sensory/nociceptive block than motor block. The preclinical data demonstrated that memantine is less potent than lidocaine, whereas memantine produces longer duration of spinal anesthesia than lidocaine. Memantine shows a more sensory-selective action over motor blockade.

Mechanism of Modification, by Lidocaine, of Fast and Slow Recovery from Inactivation of Voltage-Gated Na⁺ Channels.

The clinically important suppression of high-frequency discharges of excitable cells by local anesthetics (LA) is largely determined by drug-induced prolongation of the time course of repriming (recovery from inactivation) of voltage-gated Na(+) channels. This prolongation may result from periodic drug-binding to a high-affinity binding site during the action potentials and subsequent slow dissociation from the site between action potentials ("dissociation hypothesis"). For many drugs it has been suggested that the fast inactivated state represents the high-affinity binding state. Alternatively, LAs may bind with high affinity to a native slow-inactivated state, thereby accelerating the development of this state during action potentials ("stabilization hypothesis"). In this case, slow recovery between action potentials occurs from enhanced native slow inactivation. To test these two hypotheses we produced serial cysteine mutations of domain IV segment 6 in rNav1.4 that resulted in constructs with varying propensities to enter fast- and slow-inactivated states. We tested the effect of the LA lidocaine on the time course of recovery from short and long depolarizing prepulses, which, under drug-free conditions, recruited mainly fast- and slow-inactivated states, respectively. Among the tested constructs the mutation-induced changes in native slow recovery induced by long depolarizations were not correlated with the respective lidocaine-induced slow recovery after short depolarizations. On the other hand, for long depolarizations the mutation-induced alterations in native slow recovery were significantly correlated with the kinetics of lidocaine-induced slow recovery. These results favor the "dissociation hypothesis" for short depolarizations but the "stabilization hypothesis" for long depolarizations.