Dexmedetomidine Prolongs Lidocaine Intravenous Regional Anesthesia in Rats by Blocking the Hyperpolarization-Activated Cation Current.

Purpose: Intravenous regional anesthesia (IVRA) using lidocaine provides effective localized analgesia but its duration is limited. The mechanism by which dexmedetomidine enhances lidocaine IVRA is unclear but may involve modulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Materials and Methods: Lidocaine IVRA with varying dexmedetomidine concentrations was performed in the tails of Sprague-Dawley rats. Tail-flick and tail-clamping tests assessed IVRA analgesia and anesthesia efficacy and duration. Contributions of α2 adrenergic receptors and HCN channels were evaluated by incorporating an α adrenergic receptor antagonist, the HCN channel inhibitor ZD7288, and the HCN channel agonist forskolin. Furthermore, whole-cell patch clamp electrophysiology quantified the effects of dexmedetomidine on HCN channels mediating hyperpolarization-activated cation current (Ih) in isolated dorsal root ganglion neurons. Results: Dexmedetomidine dose-dependently extended lidocaine IVRA duration and analgesia, unaffected by α2 receptor blockade. The HCN channel inhibitor ZD7288 also prolonged lidocaine IVRA effects, while the HCN channel activator forskolin shortened effects. In dorsal root ganglion neurons, dexmedetomidine concentration-dependently inhibited Ih amplitude and shifted the voltage-dependence of HCN channel activation. Conclusion: Dexmedetomidine prolongs lidocaine IVRA duration by directly inhibiting HCN channel activity, independent of α2 adrenergic receptor activation. This HCN channel inhibition represents a novel mechanism underlying the anesthetic and analgesic adjuvant effects of dexmedetomidine in IVRA.

Lidocaine attenuates TMZ resistance and inhibits cell migration by modulating the MET pathway in glioblastoma cells.

Glioblastoma multiforme (GBM) is the most aggressive type of malignant brain tumor. Currently, the predominant clinical treatment is the combination of surgical resection with concurrent radiotherapy and chemotherapy, using temozolomide (TMZ) as the primary chemotherapy drug. Lidocaine, a widely used amide­based local anesthetic, has been found to have a significant anticancer effect. It has been reported that aberrant hepatocyte growth factor (HGF)/mesenchymal­epithelial transition factor (MET) signaling plays a role in the progression of brain tumors. However, it remains unclear whether lidocaine can regulate the MET pathway in GBM. In the present study, the clinical importance of the HGF/MET pathway was analyzed using bioinformatics. By establishing TMZ­resistant cell lines, the impact of combined treatment with lidocaine and TMZ was investigated. Additionally, the effects of lidocaine on cellular function were also examined and confirmed using knockdown techniques. The current findings revealed that the HGF/MET pathway played a key role in brain cancer, and its activation in GBM was associated with increased malignancy and poorer patient outcomes. Elevated HGF levels and activation of its receptor were found to be associated with TMZ resistance in GBM cells. Lidocaine effectively suppressed the HGF/MET pathway, thereby restoring TMZ sensitivity in TMZ­resistant cells. Furthermore, lidocaine also inhibited cell migration. Overall, these results indicated that inhibiting the HGF/MET pathway using lidocaine can enhance the sensitivity of GBM cells to TMZ and reduce cell migration, providing a potential basis for developing novel therapeutic strategies for GBM.

Targeted local anesthesia: a novel slow-release Fe3O4-lidocaine-PLGA microsphere endowed with a magnetic targeting function.

PURPOSE: Lidocaine microspheres can prolong the analgesic time to 24-48 h, which still cannot meet the need of postoperative analgesia lasting more than 3 days. Therefore, we added Fe3O4 to the lidocaine microspheres and used an applied magnetic field to attract Fe3O4 to fix the microspheres around the target nerves, reducing the diffusion of magnetic lidocaine microspheres to the surrounding tissues and prolonging the analgesic time. METHODS: Fe3O4-lidocaine-PLGA microspheres were prepared by the complex-emulsion volatilization method to characterize and study the release properties in vitro. The neural anchoring properties and in vivo morphology of the drug were obtained by magnetic resonance imaging. The nerve blocking effect and analgesic effect of magnetic lidocaine microspheres were evaluated by animal experiments. RESULTS: The mean diameter of magnetically responsive lidocaine microspheres: 9.04 ± 3.23 µm. The encapsulation and drug loading of the microspheres were 46.18 ± 3.26% and 6.02 ± 1.87%, respectively. Magnetic resonance imaging showed good imaging of Fe3O4-Lidocain-PLGA microspheres, a drug-carrying model that slowed down the diffusion of the microspheres in the presence of an applied magnetic field. Animal experiments demonstrated that this preparation had a significantly prolonged nerve block, analgesic effect, and a nerve anchoring function. CONCLUSION: Magnetically responsive lidocaine microspheres can prolong analgesia by slowly releasing lidocaine, which can be immobilized around the nerve by a magnetic field on the body surface, avoiding premature diffusion of the microspheres to surrounding tissues and improving drug targeting.

Lidocaine Inhibits Rat Prostate Cancer Cell Invasiveness and Voltage-Gated Sodium Channel Expression in Plasma Membrane.

There is increasing evidence, mostly from breast cancer, that use of local anaesthetics during surgery can inhibit disease recurrence by suppressing the motility of the cancer cells dependent on inherent voltage-gated sodium channels (VGSCs). Here, the possibility that lidocaine could affect cellular behaviours associated with metastasis was tested using the Dunning cell model of rat prostate cancer. Mostly, the strongly metastatic (VGSC-expressing) Mat-LyLu cells were used under both normoxic and hypoxic conditions. The weakly metastatic AT-2 cells served for comparison in some experiments. Lidocaine (1-500 µM) had no effect on cell viability or growth but suppressed Matrigel invasion dose dependently in both normoxia and hypoxia. Used as a control, tetrodotoxin produced similar effects. Exposure to hypoxia increased Nav1.7 mRNA expression but VGSCα protein level in plasma membrane was reduced. Lidocaine under both normoxia and hypoxia had no effect on Nav1.7 mRNA expression. VGSCα protein expression was suppressed by lidocaine under normoxia but no effect was seen in hypoxia. It is concluded that lidocaine can suppress prostate cancer invasiveness without effecting cellular growth or viability. Extended to the clinic, the results would suggest that use of lidocaine, and possibly other local anaesthetics, during surgery can suppress any tendency for post-operative progression of prostate cancer.

Effect of Intraligamentary Tramadol Hydrochloride on Anesthetic Success During Endodontic Management of Mandibular Molars: A Randomized Clinical Controlled Trial.

OBJECTIVE: Tramadol hydrochloride has shown local anesthetic properties similar to lidocaine, apart from a central analgesic effect. The present study evaluated the effect of the administration of tramadol alone or in addition to 2% lidocaine, as supplementary intraligamentary injections. METHODS: One hundred and five patients, with a failed primary inferior alveolar nerve block (IANB), were randomly allocated to one of the three supplementary intraligamentary groups: 2% lidocaine with 1: 80,000 epinephrine; tramadol hydrochloride (50 mg/mL); and 2% lidocaine with 1: 80,000 epinephrine plus tramadol hydrochloride. Patients received 1.2 mL doses (0.6 mL of each root). Patients reporting pain ≤54 on Heft Parker visual analogue scale (Heft-Parker VAS), were categorized as successful anesthesia. A finger pulse oximeter was used to measure the heart rates. The anesthetic success rates, gender, and type of tooth were compared using the Pearson chi-square test. The heart rates and age were statistically evaluated using the one-way analysis of variance test. The level of significance was set at 0.05 (p=0.05). RESULTS: The initial IANB was successful in 31% of cases. There were significant differences in the anesthetic success rates of different supplementary intraligamentary injections (χ2= 33.6, p<0.001, df=2). The 2% lidocaine-plus-tramadol resulted in significantly higher success rates than the two groups. There were no significant changes in the baseline heart rates of all groups (p>0.05). CONCLUSION: The addition of tramadol to 2% lidocaine with 1: 80,000 epinephrine, given as supplementary intraligamentary injection, can help in achieving successful anesthesia during the endodontic management of mandibular molars with irreversible pulpitis resistant to IANB injections.

Evaluation of pharmacological alternatives to reduce the pain and discomfort produced by electroejaculation in rams.

Electroejaculation (EE) represents the main technique for semen collection from domestic and wild animals independently of libido. However, the technique is associated with intense involuntary muscle contractions, vocalization, ataxia and lying down, caused by the electric stimulation of the nerves in the caudal epigastric region. These clinical manifestations represent important indicators of discomfort. In this context, the objective of this study was to evaluate two protocols of local anaesthetic blockade and two anatomical access for pharmacological desensitization of the caudal epigastric innervation as alternatives to promote comfort and reduce stress associated with EE in rams. For the study, four clinically healthy Dorper rams were selected. All animals were subjected to a design consisting of five semen collection treatments (n = 3 collections per treatment): T1-control, conventional EE without local anaesthetic blockade; T2, EE with ventral blockade (VB) of epigastric innervation using lidocaine hydrochloride 2%; T3, EE with VB of epigastric innervation using a combination of lidocaine hydrochloride 2% and fentanyl citrate; T4, EE with blockade of epigastric innervation through the perineal access using lidocaine hydrochloride 2%; T5, EE with blockade of epigastric innervation through the perineal access using a combination of lidocaine hydrochloride and fentanyl citrate. Seminal samples resulting from EE were subjectively evaluated for sperm motility and concentration, vigour and volume. Additionally, blood serum samples were collected for quantification of cortisol and creatine kinase (CK) enzyme. Assessments of stress and discomfort were conducted by measuring blood pressure, heart rate (HR) and respiratory rate (RR), as well as observing involuntary muscle contractions, ataxia and animal vocalization. No variations in blood pressure, sperm motility, vigour, CK, and cortisol were observed among the treatments. Individual variations were observed for the occurrence of vocalization (p = .0066), but there were no differences between the groups. Anaesthetic blockades conducted using the combination of lidocaine and fentanyl resulted in a lower incidence of ataxia during EE (p < .0001). It is concluded that the combination of fentanyl citrate and lidocaine hydrochloride results in less discomfort for animals undergoing EE, regardless of the anatomical access used for local anaesthetic blockades.

Adhesive polydopamine-based photothermal hybrid hydrogel for on-demand lidocaine delivery, effective anti-bacteria, and prolonged local long-lasting analgesia.

Considering the astonishing prevalence of localized pain affecting billions of patients worldwide, the development of advanced analgesic formulations or delivery systems to achieve clinical applicability is of great significance. In this study, an integrated PDA-based LiH@PDA@Ag@PAA@Gelatin system was designed for sustained delivery of lidocaine hydrochloride (LiH). By optimizing the preparation process and formulation of the hydrogel, the hydrogel exhibited superior mechanical properties, reversibility, adhesion strength, and self-healing attributes. Moreover, PDA@Ag nanoparticles were evenly dispersed within the hydrogel, and the optimized PDA@Ag@PAA@Gelatin showed a higher photothermal conversion efficiency than that of pure PDA. Importantly, LiH@PDA@Ag@PAA@Gelatin could effectively capture and eradicate bacteria through the synergistic interaction between near-infrared (NIR), PDA, Ag and LiH. In vitro and in vivo tests demonstrated that LiH@PDA@Ag@PAA@Gelatin exhibited higher drug delivery efficiency compared to commercial lidocaine patches. By evaluating the mechanical pain withdrawal threshold of the spared nerve injury (SNI) model in rats, it was proven that LiH@PDA@Ag@PAA@Gelatin enhanced and prolonged the analgesic effect of LiH. Furthermore, LiH@PDA@Ag@PAA@Gelatin induced by NIR possessed excellent on-demand photothermal analgesic ability. Therefore, this study develops a convenient method for preparing localized analgesic hydrogel patches, providing an important step towards advancing PDA-based on-demand pain relief applications.

Multifunctional electrospun polycaprolactone/chitosan/hEGF/lidocaine nanofibers for the treatment of 2 stage pressure ulcers.

In this study, a multifunctional nanofiber dressing that can promote antibacterial, analgesic and healing was prepared by electrospinning technology. Hydrophobic polycaprolactone (PCL)/chitosan (CS)/lidocaine hydrochloride (LID) and epidermal growth factor (EGF) were used as scaffold materials and dissolved in trifluoroacetic acid to prepare spinning solution. The morphology of PCEL dressing was observed by scanning electron microscopy. The fiber structure was dense and the average diameter was 297.0 nm. The water absorption capacity test and water contact angle measurement showed that the fiber had good water absorption and hydrophilicity (1302 %, 139.258°). Drug release was 84 % within 60 h. In the results of antibacterial experiment, the dressing showed certain antibacterial properties. The results of cell experiments show that the dressing can promote cell proliferation. In addition, coagulation experiments showed that the dressing could quickly coagulate the blood within 4 min. In addition, PCEL dressing promoted collagen deposition and vascularization through animal models of pressure sores. Therefore, multifunctional dressing can be used as an ideal auxiliary means for the treatment of pressure sores, and it is a promising alternative to chronic wound healing.

Age differences in pain sensitivity and effect of topical lidocaine on the tongue in healthy female subjects.

PURPOSE: To assess the sensitivity and the effect of topical lidocaine on the tongue by quantitative sensory testing, comparing healthy middle-aged female subjects with healthy young female subjects. METHODS: Sixteen healthy female subjects including eight in their fifties and eight in their twenties participated. They participated in two sessions at a 2-week interval in randomized order: lidocaine (experimental session) or placebo gel (placebo session) was applied on the tongue tip for 5min. The following parameters were taken on the tongue tip before and after application of the gel in each session: tactile detection threshold (TDT), filament-prick pain detection threshold (FPT), and numerical rating scale (NRS). RESULTS: An increase of both TDT and FPT and a decrease of NRS were found after lidocaine application in both middle-aged and young female subjects. In the elder females, an increase of TDT, FPT, and NRS was also found after placebo gel application. However, the changes were not statistically significant, except for FPT in middle-aged subjects. CONCLUSION: The reactions found after lidocaine application in middle-aged female subjects could be due to habituation as well as to the post-application effect of placebo gel. Placebo-induced changes appeared more pronounced in the elder females.

Comparison of lidocaine and lidocaine-xylazine for distal paravertebral anesthesia in dairy cattle.

OBJECTIVE: To determine the time of onset and duration of action of distal paravertebral blocks (DPB) in dairy cattle using lidocaine and lidocaine plus xylazine (LX). ANIMALS: 10 healthy adult Holstein cows. METHODS: Unilateral DPB were performed in 6 cows at L1, L2, and L4. They received 2 treatments (lidocaine and LX) in a blinded random crossover design. Due to treatment failure, 4 additional cows were enrolled. The lidocaine treatment received 1,800 mg (90 mL) of lidocaine, and treatment LX received 1,784 mg (89.2 mL) of lidocaine and 16 mg (0.8 mL) of xylazine. Anesthesia was assessed by response (rapid movements of the tail, directed movements of the feet, or turning of the head towards the site of the needle pricks) to 6 approximately 1-cm deep needle pricks to the paralumbar fossa with a 22-gauge hypodermic needle. The time of onset, duration of action, maximum sedation score, and average heart rate (HR) were compared between treatments. RESULTS: Duration of anesthesia was significantly prolonged after DPB in cows treated with LX (251.6 ± 96.94 minutes) compared to lidocaine (105.8 ± 35.9 minutes; P = .01). Treatment with LX was associated with significantly lower average heart rate (56 ± 3 beats/min) compared to cows treated with lidocaine (59 ± 3 beats/min; P = .045). The LX treatment was associated with mild sedation but was not significant (P = .063). CLINICAL RELEVANCE: The addition of xylazine to a lidocaine DPB provides a longer duration of anesthesia, is inexpensive and practical, and can be implemented with ease.

Lung Protection After Severe Thermal Burns With Adenosine, Lidocaine, and Magnesium (ALM) Resuscitation and Importance of Shams in a Rat Model.

The management of severe burns remains a complex challenge. Adenosine, lidocaine, and magnesium (ALM) resuscitation therapy has been shown to protect against hemorrhagic shock and traumatic injury. The aim of the present study was to investigate the early protective effects of small-volume ALM fluid resuscitation in a rat model of 30% total body surface area (TBSA) thermal injury. Male Sprague-Dawley rats (320-340 g; n = 25) were randomly assigned to: 1) Sham (surgical instrumentation and saline infusion, without burn, n = 5), 2) Saline resuscitation group (n = 10), or 3) ALM resuscitation group (n = 10). Treatments were initiated 15-min after burn trauma, including 0.7 mL/kg 3% NaCl ± ALM bolus and 0.25-0.5 mL/kg/h 0.9% NaCl ± ALM drip, with animals monitored to 8.25-hr post-burn. Hemodynamics, cardiac function, blood chemistry, hematology, endothelial injury markers and histopathology were assessed. Survival was 100% for Shams and 90% for both ALM and Saline groups. Shams underwent significant physiological, immune and hematological changes over time as a result of surgical traums. ALM significantly reduced malondialdehyde levels in the lungs compared to Saline (P = .023), and showed minimal alveolar destruction and inflammatory cell infiltration (P < .001). ALM also improved cardiac function and oxygen delivery (21%, P = .418 vs Saline), reduced gut injury (P < .001 vs Saline), and increased plasma adiponectin (P < .001 vs baseline). Circulating levels of the acute phase protein alpha 1-acid glycoprotein (AGP) increased 1.6-times (P < .001), which may have impacted ALM's therapeutic efficacy. We conclude that small-volume ALM therapy significantly reduced lung oxidative stress and preserved alveolar integrity following severe burn trauma. Further studies are required to assess higher ALM doses with longer monitoring periods.

Local Administration of the Phytochemical, Quercetin, Attenuates the Hyperexcitability of Rat Nociceptive Primary Sensory Neurons Following Inflammation Comparable to lidocaine.

Although in vivo local injection of quercetin into the peripheral receptive field suppresses the excitability of rat nociceptive trigeminal ganglion (TG) neurons, under inflammatory conditions, the acute effects of quercetin in vivo, particularly on nociceptive TG neurons, remain to be determined. The aim of this study was to examine whether acute local administration of quercetin into inflamed tissue attenuates the excitability of nociceptive TG neurons in response to mechanical stimulation. The mechanical escape threshold was significantly lower in complete Freund's adjuvant (CFA)-inflamed rats compared to before CFA injection. Extracellular single-unit recordings were made from TG neurons of CFA-induced inflammation in anesthetized rats in response to orofacial mechanical stimulation. The mean firing frequency of TG neurons in response to both non-noxious and noxious mechanical stimuli was reversibly inhibited by quercetin in a dose-dependent manner (1-10 mM). The mean firing frequency of inflamed TG neurons in response to mechanical stimuli was reversibly inhibited by the local anesthetic, 1% lidocaine (37 mM). The mean magnitude of inhibition on TG neuronal discharge frequency with 1 mM quercetin was significantly greater than that of 1% lidocaine. These results suggest that local injection of quercetin into inflamed tissue suppresses the excitability of nociceptive primary sensory TG neurons. PERSPECTIVE: Local administration of the phytochemical, quercetin, into inflamed tissues is a more potent local analgesic than voltage-gated sodium channel blockers as it inhibits the generation of both generator potentials and action potentials in nociceptive primary nerve terminals. As such, it contributes to the area of complementary and alternative medicines.

Dural and deep cervical musculature anesthetic blockade for atlantoaxial collection of cerebrospinal fluid in horses.

The analysis of cerebrospinal fluid has diagnostic, prognostic, and therapeutic value in neurological illnesses in horses. There are different methods for obtaining cerebrospinal fluid, with the collection between the C1 and C2 vertebrae being a more recent methodology, which allows the procedure to be performed in standing patients, without the limitations of general anesthesia and with a low contamination of the sample with blood, presenting itself as a practical alternative. This study evaluated the efficacy and safety of a local dural blockade in healthy horses submitted to cerebrospinal fluid collection by atlantoaxial puncture and the quality of the samples obtained by this procedure, which were submitted to physical, chemical, and cytological analyses. The animals were evaluated considering aspects such as pain, sensitivity, the presence of edema, temperature variations, and ultrasonographic alterations post-collection. Discrete local changes were observed after the puncture, and the procedure was considered safe and simple to perform. Lidocaine blockade could reduce the reaction elicited by the needle passing through the dura mater, and the samples obtained showed satisfactory quality and laboratory results consistent with the values compiled in the literature. Transient hyperthermia was observed in 70% (7/10) of the animals in the dural blockade group, and 80%(8/10) of the patients from the control group, totalizing 75% of all individuals evaluated. The rectal temperature alteration was observed 4 to 12 hours after the procedure and was entirely resolved without intervention by the 24-hour evaluation.

The anterior cingulate cortex and its interface with the dorsal periaqueductal grey regulating nitric oxide-mediated panic-like behaviour and defensive antinociception.

The anterior cingulate cortex (ACC) Cg1 (24b) area modulates glutamate-mediated unconditioned fear and antinociception organised by hypothalamus. However, it remains unknown whether 24b area also modulates these latter defensive responses through connections with the dorsal periaqueductal grey matter (dPAG), a midbrain structure implicated in the genesis of innate fear-induced defence. The aim of this work is to examine the correlation between the behavioural effects of intra-ACC microinjections of vehicle, NMDA (1 nmol) or lidocaine (2%) with Fos protein expression and nitrergic activity in the dPAG of male C57BL/6 mice that were threatened by snakes. In addition, the 24b area-dPAG pathways were also characterised by neural tract tracing procedures. Finally, the effect of dPAG pretreatment with the neuronal nitric oxide synthase inhibitor N(omega)-propyl-l-arginine (NPLA; 0.2, 0.4 or 0.8 nmol) 10 min before 24b area treatment with NMDA on behavioural and nociceptive responses of threatened mice was studied. The activation of 24b area N-methyl-d-aspartic acid receptors facilitated escape and freezing rather than risk assessment, and enhanced Fos expression and nitrite levels in dPAG, while lidocaine decreased escape and risk assessment as well as Fos and nitrergic activity in dPAG. In addition, dPAG pretreatment with NPLA suppressed intra-24b NMDA-facilitated panicogenic effects while increased nociception. Infusions of an antegrade neurotracer into 24b area showed axonal fibres surrounding both dorsomedial and dorsolateral PAG perikarya. Neurons were identified in 24b area after deposits of a retrograde neurotracer into dPAG. Our findings suggest that the ACC/24b area modulates innate defensive responses through the recruitment of dPAG nitrergic neurons.

Effect of Intraoperative Intravenous Lidocaine on Postoperative Delirium in Elderly Patients with Hip Fracture: A Prospective Randomized Controlled Trial.

Purpose: This study was performed to evaluate the effects of intraoperative intravenous lidocaine on postoperative delirium in elderly patients with hip fracture. Patients and methods: In total, 100 elderly patients undergoing hip fracture surgery were randomized to the lidocaine group (Group L) or saline (control) group (Group C). Before anesthetic induction, Group L received lidocaine at 1 mg/kg for more than 10 minutes followed by continuous infusion at 1.5 mg/kg/h until the end of surgery. Group C received normal saline, and the injection methods were consistent with those in Group L. General anesthesia was induced with propofol, sufentanil, and cis-atracurium. Anesthesia was maintained by propofol and remifentanil. The primary outcome was the incidence of postoperative delirium in the first 7 postoperative days. The secondary outcomes included the severity of delirium, onset and duration of delirium, emergence agitation, adverse events, total propofol dose, intraoperative opioid dosage, length of post-anesthesia care unit stay, extubation time, and patient satisfaction with postoperative pain management. Results: All 100 patients completed the study. The incidence of postoperative delirium was lower in Group L than in Group C (14% vs 36%, P = 0.011). The delirium severity scores were lower in Group L (3 [3-4]) than in Group C (4 [4-5]) (P = 0.017). In addition, the incidences of hypertension, tachycardia, and emergence agitation were significantly lower in Group L than in Group C. No cases of local anesthetic toxicity occurred in either group. Conclusion: Patients received lidocaine at 1 mg/kg for more than 10 minutes followed by continuous infusion at 1.5 mg/kg/h until the end of surgery, which can reduce the incidence of postoperative delirium in elderly patients undergoing hip fracture. In addition, the used regimen of lidocaine would not increase the risk of local anesthetic toxicity.

Buffered 2% articaine in buccal infiltration of mandibular molars: a randomized triple-blind clinical trial.

This crossover study aimed to compare the anesthetic effects of buffered 2% articaine with 1:200,000 epinephrine with that of non-buffered 4% articaine with 1:200,000 epinephrine. Forty-seven volunteers were administered two doses of anesthesia in the buccal region of the second mandibular molars in two sessions using 1.8 mL of different local anesthetic solutions. The onset time and duration of pulp anesthesia, soft tissue pressure pain threshold, and the score of pain on puncture and burning during injection were evaluated. The operator, volunteers, and statistician were blinded. There were no significant differences in the parameters: onset of soft tissue anesthesia (p = 0.80), duration of soft tissue anesthesia (p = 0.10), onset of pulpal anesthesia in the second (p = 0.28) and first molars (p = 0.45), duration of pulp anesthesia of the second (p = 0.60) and first molars (p = 0.30), pain during puncture (p = 0.82) and injection (p = 0.80). No significant adverse events were observed. Buffered 2% articaine with 1:200,000 epinephrine did not differ from non-buffered 4% articaine with 1:200,000 epinephrine considering anesthetic success, safety, onset, duration of anesthesia, and pain on injection.

Intraoperative intravenous infusion of lidocaine increases total and small vessel densities of sublingual microcirculation: a randomized prospective pilot study.

OBJECTIVE: Multiple organ failure can occur as a result of postoperative complications. Research has indicated that the underlying mechanism of organ dysfunction is a microcirculation disorder. Because of its antioxidant and anti-inflammatory properties, lidocaine has the potential to improve microvascular blood flow. This study was performed to assess the effect of intraoperative intravenous lidocaine infusion on the microcirculation and determine the incidence of postoperative complications. METHODS: In this prospective randomized double-blind pilot study, 12 patients scheduled for abdominal surgery were randomly allocated to receive an intraoperative infusion of either 1% lidocaine or the same volume of 0.9% sodium chloride solution. The microcirculation was monitored using sidestream dark-field imaging and the vascular occlusion test combined with near-infrared spectroscopy. RESULTS: Lidocaine significantly increased the total vascular density and small vessel density after 2 hours of infusion, with preservation of 99% to 100% of the capillary perfusion in both groups. No patients developed organ failure. CONCLUSIONS: An increase in vessel density may be beneficial in major abdominal surgeries because it is associated with better tissue perfusion and oxygen delivery. However, this finding requires further investigation in patients with increased surgical risk. Overall, this study indicates that lidocaine has potential to improve microvascular perfusion.Research Registry number: 9549 (https://www.researchregistry.com/browse-the-registry#home/registrationdetails/650ffd27b3f547002bd7635f/).

Lidocaine induces apoptosis in head and neck squamous cell carcinoma through activation of bitter taste receptor T2R14.

Head and neck squamous cell carcinomas (HNSCCs) have high mortality and significant treatment-related morbidity. It is vital to discover effective, minimally invasive therapies that improve survival and quality of life. Bitter taste receptors (T2Rs) are expressed in HNSCCs, and T2R activation can induce apoptosis. Lidocaine is a local anesthetic that also activates bitter taste receptor 14 (T2R14). Lidocaine has some anti-cancer effects, but the mechanisms are unclear. Here, we find that lidocaine causes intracellular Ca2+ mobilization through activation of T2R14 in HNSCC cells. T2R14 activation with lidocaine depolarizes mitochondria, inhibits proliferation, and induces apoptosis. Concomitant with mitochondrial Ca2+ influx, ROS production causes T2R14-dependent accumulation of poly-ubiquitinated proteins, suggesting that proteasome inhibition contributes to T2R14-induced apoptosis. Lidocaine may have therapeutic potential in HNSCCs as a topical gel or intratumor injection. In addition, we find that HPV-associated (HPV+) HNSCCs are associated with increased TAS2R14 expression. Lidocaine treatment may benefit these patients, warranting future clinical studies.

Effects of epinephrine, lidocaine, and prilocaine on viability and differentiation capacity of human adipose stem cells.

INTRODUCTION: Local anesthetics (LAs) are routinely administered in plastic and reconstructive surgery, e.g., as tumescent anesthesia adjunct in liposuction. Historically, these substances were assumed to act cytotoxically. Thus, the application of LA was avoided when handling adipose stem cells (ASCs). We recently determined that most LAs are not cytotoxic when ASCs are exposed to concentrations used for tumescent liposuction. However, there is limited information when combining LA with epinephrine and about the effects of prilocaine on ASCs. METHODS: We analyzed the effects of prilocaine or lidocaine in co-exposure with epinephrine on the viability of primary human ASCs, i.e., proliferation, metabolic activity, and cytotoxicity, using crystal violet-staining, PrestoBlue®-, and WST-1 assay. We quantified the impact of short-term incubation of lidocaine and epinephrine on the differentiation of ASCs into the adipogenic, chondrogenic, and osteogenic lineage. RESULTS: After 2 h, prilocaine (10 mM) significantly reduced metabolic activity and cell numbers, whereas lidocaine only inhibited metabolic activity. After 6 h, prilocaine (10 mM) and lidocaine significantly decreased metabolic activity as well as cell numbers. The application of high concentrations of epinephrine did not affect cell numbers but diminished metabolic activity. Combining lidocaine with epinephrine had no additional cytotoxic effect. Differentiation into the chondrogenic lineage was significantly inhibited by epinephrine. CONCLUSIONS: Deducing from our data, neither lidocaine combined with epinephrine nor prilocaine has a cytotoxic impact on ASCs in vitro at concentrations equivalent to those in tumescent anesthesia and has no long-lasting effect on the differentiation capacity of ASCs into the osteogenic and adipogenic lineage.

Effect of lidocaine on cognitively impaired rats: Anti-inflammatory and antioxidant mechanisms in combination with CRMP2 antiphosphorylation.

OBJECTIVE: Studies have shown that lidocaine has antioxidative stress, anti-inflammatory, and nerve-protective effects. The current study investigated the effects of lidocaine on cognitive function in rats with cognitive dysfunction. METHODS: A total of 48 rats were randomly assigned to four groups of 12 rats each: control group; L (lidocaine) + D (d-galactose) group, d-galactose group (D group); and D + L group. We assessed cognitive function using a Morris water maze (MWM) and pathologic changes of hippocampal sections. An enzyme-linked immunosorbent assay (ELIZA) was used to detect serum malondialdehyde (MDA) and superoxide dismutase (SOD) levels in rats, and protein immunoblotting (western blot) was used to detect brain tissue proteins (collapsing response mediator protein-2 [CRMP2], phosphorylated-collapsing response mediator protein-2 [P-CRMP2], and ß-amyloid protein [Aß]). RESULTS: The MWM showed that the d-gal group (284.09 ± 20.46, 5.20 ± 0.793) performed worse than the L + D (265.37 ± 22.34, 4.170 ± 0.577; p = .000) and D + L groups (254.72 ± 27.87, 3.750; p = .000) in escape latency and number of platform crossings, respectively. The L + D group (44.94 ± 2.92 pg/mL, 6.22 ± 0.50 pg/mL, and 460.02 ± 8.26 nmol/mL) and D + L group (46.88 ± 2.63 pg/mL, 5.90 ± 0.38 pg/mL, and 465.6 ± 16.07 nmol/mL) had significantly lower serum inflammatory levels of interleukin-6, tumor necrosis factor-α, and MDA than the d-gal group (57.79 ± 3.96 pg/mL, 11.25 ± 1.70 pg/mL, and 564.9 ± 15.90 nmol/mL), respectively. The L + D group (3.17 ± 0.41 µg/mL) and D + L group (3.08 ± 0.09 µg/mL) had significantly higher serum inflammatory levels of SOD than the d-gal group (2.20 ± 0.13 µg/mL) (all p = .000). The levels of CRMP2, P-CRMP2, and Aß in the brain tissue homogenates of the L + D group (0.87 ± 0.04, 0.57 ± 0.0, and 0.16 ± 0.02) and the D + L group (0.82 ± 0.05, 0.58 ± 0.09, and 0.15 ± 0.02) were significantly different than the d-gal group (0.67 ± 0.03, 0.96 ± 0.040, and 0.29 ± 0.05). CONCLUSIONS: Lidocaine was shown to reduce cognitive impairment in rats with cognitive dysfunction through anti-inflammatory and antioxidative stress mechanisms in combination with CRMP2 antiphosphorylation.