Lidocaine Treatment Research Articles

Lidocaine inhibits the lung cancer progression through decreasing the HIST1H2BL levels via SIRT5 mediated succinylation

Lung cancer is a malignant tumor originating from the bronchial mucosa or gland of the lung. Recently, lidocaine, a widely used amide local anesthetic, was demonstrated to inhibit many cancer progression. This research was performed to explore the specific mechanism of lidocaine in the lung cancer progression. The human normal lung epithelial cells (BEAS-2B), and NSCLC cell lines (A549 and H1299) were used and treated with lidocaine in this study. The cell biological behaviors were detected by CCK-8, wound healing and transwell assay. Besides, the mRNA and protein levels of related genes were detected by western blot. The results showed that lidocaine treatment significantly decreased the cell viability and migration of the A549 and H1299 cells. Furthermore, the lidocaine treatment significantly decreased the succinylation and protein levels of HIST1H2BL, which was reversed after SIRT5 knockdown. Additionally, HIST1H2BL knockdown decreased the cell viability and migration of the A549 and H1299 cells, while HIST1H2BL overexpression reversed the effects of lidocaine on the cell viability and migration of the A549 and H1299 cells. In conclusion, lidocaine treatment might inhibited the lung cancer progression through decreasing the SIRT5 mediated succinylation of HIST1H2BL.

Experience from a single-center study on multimodal medication therapy for patients with complex regional pain syndrome.

Despite the application of various therapeutic methods, pain caused by complex regional pain syndrome (CRPS) is not sufficiently managed and often progresses to a chronic stage. For the systematic and effective treatment of CRPS, we developed an algorithm for multimodal medication therapy based on the established pathophysiology of CRPS to control CRPS-related pain. In this study, we present the outcomes of our novel algorithm for multimodal medication therapy for patients with CRPS, consisting of three major components: multimodal oral medication, intravenous ketamine, and intravenous lidocaine therapy. We retrospectively investigated patients with CRPS who received multimodal therapy. Pain severity scores were evaluated using a numerical rating scale at four time points (P1, pain at initial consultation; P2, pain after oral medication; P3, pain after ketamine treatment; and P4, pain after lidocaine treatment). The effect of the multimodal medication therapy algorithm on pain management was evaluated at each time point. In patients with CRPS, multimodal oral medication, intravenous ketamine, and intravenous lidocaine therapies led to significantly improved pain control (p< 0.05). Additionally, the combination of these three therapies (through the multimodal medication therapy algorithm) resulted in significant pain relief in patients with CRPS (p< 0.05). Our multimodal medication therapy algorithm effectively controlled pain in patients with CRPS. However, further prospective studies with large sample sizes and randomized controlled trials are needed for more accurate generalization.

The utility of lidocaine in neonatal conviction syndrome

BACKGROUND: Lidocaine is a drug belonging to the local anesthetics; it is rapidly distributed in the body and metabolized in the liver. At commonly recommended doses, the therapeutic index of lidocaine remains very high and plasma concentrations remain largely below neurotoxic, cardiotoxic and other thresholds. It is used during various medical procedures, and in the nervous system it acts by binding to a specific site which is the sodium channel receptor of the neural membrane and blocking the passage of ions. The present study is of interest to know the potential usefulness of lidocaine in neonates with convulsive syndrome. In order to implement improvements in the treatment of those who need it. In this way, pediatric neurologists can achieve better results in the interventions to treat this pathology. Methods: In the present systematic review we try to answer and perform a literature search through pubmed and others to analyze the usefulness of lidocaine in neonatal convulsive syndrome and its potential benefit. Results: After the application of the inclusion and exclusion criteria, we will be able to identify the groups of newborns most at risk and the efficacy of lidocaine treatment. Conclusion: It is concluded that lidocaine is the third drug used in neonatal convulsive syndrome for maintenance where it is received as a continuous infusion and is effective in suppressing electroclinical seizures; excessive doses should be avoided as it can also produce convulsions and other adverse effects in children.

Toward a solid microneedle patch for rapid and enhanced local analgesic action.

Analgesic creams find widespread application as adjuncts for localized anesthesia prior to surgical procedures. Nevertheless, the onset of analgesic action is protracted due to the skin barrier's inherent characteristics, which necessitates prolonged intervals of patient and clinician waiting, consequently impinging upon patient compliance and clinician workflow efficiency. In this work, a biodegradable microneedles (MNs) patch was introduced to enhance the intradermal administration of lidocaine cream to achieve rapid analgesia through a minimally invasive and conveniently accessible modality. The polylactic acid (PLA) MNs were mass-produced using a simple hot-pressing method and served the purpose of creating microchannels across the skin's surface for rapid absorption of lidocaine cream. Optical and electron microscopes were applied to meticulously scrutinize the morphology of the fabricated MNs, and the comprehensive penetration tests involving dynamometer tests, evaluation on porcine cadaver skin, artificial film, optical coherence tomography (OCT), transepidermal water loss, and analysis on rats' skins, demonstrated the robust mechanical strength of PLA MNs for successful intradermal penetration. The behavioral pain sensitivity tests on living rats using Von Frey hair filaments revealed that the MN-assisted lidocaine treatment expeditiously accelerated the onset of action from 40 to 10min and substantially enhanced the efficacy of localized anesthesia. Furthermore, different treatment protocols encompassing the sequence of drug application relative to MN treatment, MN dimensions, and the frequency of MN insertions exhibited noteworthy influence on the resultant local anesthesia efficacy. Together, these results demonstrated that the lidocaine cream followed by diverse PLA MN treatments would be a promising strategy for rapid clinical local anesthesia with wide-ranging applications.

Lidocaine constant rate infusion improves the probability of survival in rabbits with gastrointestinal obstructions: 64 cases (2012-2021).

To determine the survival to discharge rate of rabbits with gastrointestinal obstructions treated with lidocaine constant rate infusion (CRI) and other factors associated with survival. Cases of gastrointestinal obstruction in rabbits (n = 56, including 64 events) that had presented to a veterinary teaching hospital from 2012 to 2021. This was a retrospective study in which data on rabbits with evidence of gastrointestinal obstruction were extracted from veterinary teaching hospital medical records over a 9-year period. Systemic lidocaine treatment, breed, sex, age, temperature at presentation, blood glucose at presentation, and time to discharge or death were evaluated with univariate and multivariate logistic regression to identify factors significantly associated with survival to hospital discharge in rabbits with gastrointestinal obstruction. Comparatively, 89.7% of rabbits treated with lidocaine CRI (n = 39) survived to hospital discharge, while only 56% of rabbits that were not treated with lidocaine CRI (25) survived. In the final multivariate analysis, 2 factors were associated with survival to discharge: rabbits treated with systemic lidocaine and male rabbits had increased odds of survival compared to those not treated with systemic lidocaine and female rabbits, respectively. Results demonstrated that rabbits with gastrointestinal obstruction and treated with a lidocaine CRI were more likely to survive compared to rabbits not treated with lidocaine CRI.

Lidocaine inhibits migrationof tenocytesby downregulating focal adhesion kinaseand paxillin phosphorylation.

Lidocaine is the most frequently applied local infiltration anesthetic agent for treating tendinopathies. However, studies have discovered lidocaine to negatively affect tendon healing. In the current study, the molecular mechanisms and effects of lidocaine on tenocyte migration were evaluated. We treated tenocytes intrinsic to the Achilles tendons of Sprague-Dawley rats with lidocaine. The migration ability of cells was analyzed using electric cell-substrate impedance sensing (ECIS) and scratch wound assay. We then used a microscope to evaluate the cell spread. We assessed filamentous actin (F-actin) cytoskeleton formation through immunofluorescence staining. In addition, we used Western blot analysis to analyze the expression of phospho-focal adhesion kinase (FAK), FAK, phospho-paxillin, paxillin, and F-actin. We discovered that lidocaine had an inhibitory effect on the migration of tenocytes in the scratch wound assay and on the ECIS chip. Lidocaine treatment suppressed cell spreading and changed the cell morphology and F-actin distribution. Lidocaine reduced F-actin formation in the tenocyte during cell spreading; furthermore, it inhibited phospho-FAK, F-actin, and phospho-paxillin expression in the tenocytes. Our study revealed that lidocaine inhibits the spread and migration of tenocytes. The molecular mechanism potentially underlying this effect is downregulation of F-actin, phospho-FAK, and phospho-paxillin expression when cells are treated with lidocaine.

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.

Lidocaine for headache prevention during chronic subdural hematoma embolization.

Middle meningeal artery embolization (MMAE) for the management of chronic subdural hematomas (CSDH) with ethylene vinyl alcohol (EVOH) causes an evident patient discomfort due to meningeal nociceptors stimulation. The aim of this study was to assess safety and efficacy of intra-arterial lidocaine (IAL) before MMAE of CSDH with EVOH. We analyzed all consecutive patients with bilateral CSDH undergoing MMAE with EVOH. We used a monolateral IAL injection, with casual allocation. We assessed the headache felt by patients during embolization with the visual analog scale (VAS) and compared scores obtained after embolization of both sides. We followed the STROBE guidelines for case-control studies. Paired t-test and χ2 test were used to compare the distribution of variables in IAL vs control group. Between September 2021 and March 2023, 32 patients underwent bilateral MMAE with EVOH for a CSDH. Lidocaine treatment resulted in a substantially lower VAS score compared to the control group (median 3 vs 7, p < 0.001), with no substantial side effect. Compliance also benefited from lidocaine administration. In patients with CSDH undergoing MMAE, IAL seems to reduce pain sensation associated with EVOH injection and to increase patients' compliance during treatment.

Efficacy of prolonged intravenous lidocaine infusion for postoperative movement-evoked pain following hepatectomy: a double-blinded, randomised, placebo-controlled trial

BackgroundThe analgesic effect of intravenous lidocaine varies with the duration of lidocaine infusion and surgery type. We tested the hypothesis that prolonged lidocaine infusion alleviates postoperative pain in patients recovering from hepatectomy over the first 3 postoperative days. MethodsPatients undergoing elective hepatectomy were randomly assigned to receive prolonged i.v. lidocaine treatment or placebo. The primary outcome was incidence of moderate-to-severe movement-evoked pain at 24 h postoperatively. The secondary outcomes included incidence of moderate-to-severe pain during movement and at rest throughout the first 3 postoperative days, postoperative opioid consumption, and pulmonary complications. Plasma lidocaine concentration was also monitored. ResultsWe enrolled 260 subjects. Intravenous lidocaine lowered the incidence of moderate-to-severe movement-evoked pain at 24 h and 48 h postoperatively (47.7% vs 67.7%, P=0.001; 38.5% vs 58.5%, P=0.001) and reduced movement-evoked pain scores (3.7 [1.7] vs 4.2 [1.6]; mean difference 0.5 [95% confidence interval {CI}: 0.1–0.9]; P=0.018) and morphine equivalent consumption (47.2 [16.7] mg vs 52.6 [19.2] mg; mean difference 5.4 mg [95% CI: 1.0–9.8]; P=0.016) at 24 h postoperatively. Lidocaine also lowered the incidence of postoperative pulmonary complications (23.1% vs 38.5%; P=0.007). Median plasma lidocaine concentrations were 1.5, 1.9, and 1.1 μg ml−1 (inter-quartile ranges: 1.1–2.1, 1.4–2.6, and 0.8–1.6, respectively) after bolus injection, at the end of the surgery, and 24 h postoperatively. ConclusionsProlonged intravenous lidocaine infusion reduced the incidence of moderate-to-severe movement-evoked pain for 48 h after hepatectomy. However, the reduction in pain scores and opioid consumption by lidocaine was below the minimal clinically important difference. Clinical trial registrationNCT04295330.

Preventive Effect of Local Lidocaine Administration on the Formation of Traumatic Neuroma

Traumatic neuroma is a common sequela of peripheral nerve injury or amputation, which often leads to severe neuropathic pain. The present study investigated the effect of local lidocaine administration on preventing the formation of traumatic neuroma. Forty-eight male Sprague-Dawley rats were randomly assigned to two groups. The lidocaine group underwent sciatic nerve transection, followed by an injection of lidocaine (0.5%) around the proximal of a severed sciatic nerve under ultrasound-guidance 2-7 days after neurectomy. In the control group, rats received an injection of saline following neurectomy. The autotomy score, mechanical allodynia, thermal hyperalgesia, histological assessment, expression of neuroma, and pain-related markers were detected. Lidocaine treatment reduced the autotomy score and attenuated mechanical allodynia and thermal hyperalgesia. The mRNA expression of α-SMA, NGF, TNF-α, and IL-1β all significantly decreased in the lidocaine group in comparison to those in the saline control group. The histological results showed nerve fibers, demyelination, and collagen hyperplasia in the proximal nerve stump in the saline control group, which were significantly inhibited in the lidocaine group. The present study demonstrated that local lidocaine administration could inhibit the formation of painful neuroma due to traumatic nerve injury.

Injection of the Abductor Hallucis Muscle in the Diagnosis and Treatment of Distal Tarsal Tunnel Syndrome.

Tarsal tunnel syndrome (TTS) can be divided into proximal TTS and distal TTS (DTTS). Research on methods to differentiate these two syndromes is sparse. A simple test and treatment is described as an adjunct to assist with diagnosing and providing treatment for DTTS. The suggested test and treatment is an injection of lidocaine mixed with dexamethasone administered into the abductor hallucis muscle at the site of entrapment of the distal branches of the tibial nerve. This treatment was studied with a retrospective medical record review in 44 patients with clinical suspicion of DTTS. The lidocaine injection test and treatment (LITT) was positive in 84% of patients. Of patients available for follow-up evaluation (35), 11% of those with a positive LITT test (four) had complete lasting symptom relief. One-quarter of patients with initial complete symptom relief at LITT administration (four of 16) maintained this level of symptom relief at follow-up. Thirty-seven percent of patients evaluated at follow-up (13 of 35) who had a positive response to the LITT experienced partial or complete symptom relief. No association was found between level of symptom relief maintenance and the immediate level of symptom relief (Fisher exact test = 0.751; P = .797). The results showed no difference in the distribution of immediate symptom relief by sex (Fisher exact test = 1.048; P = .653). The LITT is a simple, safe, invasive method to help diagnose and treat DTTS, and it provides an additional method to assist with differentiating DTTS from proximal TTS. The study also provides additional evidence that DTTS has a myofascial etiology. The proposed mechanism of action of the LITT suggests a new paradigm in diagnosing muscle-related nerve entrapments that may lead to nonsurgical treatments or less invasive surgical interventions for DTTS.

Systemic Lidocaine Infusions for Pediatric Patients with Cancer-Related Pain.

Pediatric patients with cancer experience significant distress from both treatment and cancer-related pain. Careful selection of an analgesic regimen should be based upon individual patient factors, including the level of pain, response to therapy, and physiologic profile. Refractory pain is a therapeutic dilemma frequently encountered in the pediatric cancer setting. Systemic lidocaine infusions have been described as both safe and efficacious, as prior studies show patients reporting decreased pain scores and improved quality of life after lidocaine treatment. Given the favorable side effect profile of lidocaine, it has the potential to be considered for analgesia in the setting of refractory pain. This review discusses the use of systemic lidocaine infusions for analgesia in pediatric oncology patients with cancer-related pain.

Lidocaine intensifies the anti-osteogenic effect on inflammation-induced human dental pulp stem cells via mitogen-activated protein kinase inhibition

Human dental pulp stem cells (hDPSCs) are an emerging source of mesenchymal stem cells (MSCs) for bone tissue regeneration and engineering. In bone regeneration using transplanted MSCs, the extracellular environment or co-injected drugs can affect their success or failure. In this study, we investigated the effects and signaling mechanisms of lidocaine on osteogenic differentiation of hDPSCs after inducing inflammatory conditions with lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-α). To investigate the effect of lidocaine on the osteogenic differentiation of LPS/TNF-α-treated hDPSCs, alkaline phosphatase (ALP) and Alizarin red S (ARS) staining were conducted. The expression of osteogenesis-related genes was assessed using quantitative real-time polymerase chain reaction and western blotting. The expression of mitogen-activated protein kinases was analyzed to evaluate the effect of lidocaine on osteogenic differentiation of LPS/TNF-α-treated hDPSCs. Various concentrations of lidocaine (0.05, 0.2, and 1mM) further decreased ALP and ARS staining of LPS/TNF-α-treated hDPSCs. Similarly, the mRNA and protein expression of osteogenesis-related genes was suppressed via lidocaine treatment in LPS/TNF-α-treated hDPSCs. Lidocaine treatment downregulated the protein expression of p-ERK and p-JNK in LPS/TNF-α-treated hDPSCs. Lidocaine intensified the inhibition of osteogenic differentiation on inflammation-induced hDPSCs by inhibiting the ERK and JNK signaling pathways. This invitro study suggested that lidocaine may have an inhibitory effect on bone regeneration.

Abstract 10669: Phenytoin, an Anti-Epileptic Sodium Channel Blocker, May Be a Novel Therapy for Type 3 Long Qt Syndrome Mediated by the Lidocaine-Insensitive SCN5A-F1760C Variant

Introduction: Gain-of-function mutations in SCN5A- encoded cardiac sodium channel (Na V 1.5) cause type 3 long QT syndrome (LQT3). Patients with SCN5A variants localizing to the local anesthetic binding domain might not be sensitive to lidocaine or mexiletine treatment. Hypothesis: Phenytoin, a sodium channel blocker used to treat epilepsy, may be a novel LQT3-directed therapy for a variant involving a critical residue of the Nav1.5’s local anesthetic binding domain. Methods: SCN5A-F1760C was identified in a now deceased infant with severe LQT3 (QTc of 680-1200 ms) who was refractory to left cardiac sympathetic denervation and pharmacological treatments with either lidocaine or mexiletine. SCN5A-F1760C was engineered by site directed mutagenesis and expressed in TSA201 cells. Patient-specific pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from the SCN5A-F1760C-positive infant and gene-edited/variant-corrected isogenic control (IC) iPSC-CMs were generated. Na V 1.5 currents were recorded in TSA201 cells transfected with SCN5A-WT/ F1760C and action potentials (APs) from iPSC-CMs were recorded before and after treatment with 5μM Phenytoin using the whole cell patch-clamp technique. Results: SCN5A-F1760C did not change the NaV1.5 current density. However, the V1/2 of inactivation was right-shifted significantly by +14.1 mV from -86.3±0.9 mV (WT) to -72.2±0.7 mV (F1760C, p&lt;0.0001) resulting in a marked increase in window current. F1760C increased sodium late current 2-fold from 0.18±0.04% in WT to 0.49±0.07% in F1760C (p=0.0005). Baseline APD to 90% repolarization (APD90) was prolonged significantly in F1760C-derived iPSC-CMs (641±40 ms) compared to IC iPSC-CMs (412±22 ms, p&lt;0.0001). Treatment with 5μM phenytoin normalized the APD90 in F1760C-derived iPSC-CMs to 423+34 ms (p&lt;0.0001), values approximating the ‘gene/variant-edited’ cure. Conclusions: Na V 1.5 gain-of-function caused by a novel SCN5A-F1760C variant results in marked APD90 prolongation which were rescued by phenytoin indicating the antiepileptic drug, phenytoin, may be a mutation-specific, LQT3-directed therapy for those LQT3-causative variants that disrupt the local anesthetic/lidocaine-binding domain.

Local anesthetic lidocaine induces growth suppression of HeLa cells by decreasing and changing the cellular localization of the proliferation marker Ki-67.

Although surgery is a basic therapy for cancer, it causes inflammation and immunosuppression, often resulting in recurrence and metastasis. Previous studies have suggested that anesthetic management influences the prognosis of cancer surgery patients. Administration of local anesthetics, such as lidocaine, for pain control reportedly improves their clinical outcomes; however, the precise underlying mechanism has not been fully elucidated. The growth of human embryonic kidney (HEK) 293T and cervical cancer HeLa cells was inhibited by lidocaine treatment and these cell lines showed different sensitivities for lidocaine. Ki-67 is a significant prognostic marker of cancer because it is expressed in the nucleus of actively proliferating cells. In lidocaine-treated HeLa cells, Ki-67 was detected not only in the nucleus but also in the cytoplasm. In addition, lidocaine-induced cytoplasmic Ki-67 partly colocalized with the increased ER chaperone, glucose-regulated protein 78, which is crucial for protein folding and maintenance of cellular homeostasis. Furthermore, lidocaine decreased Ki-67 levels and increased the population of HeLa cells in the G0/G1 phase. These results indicate that lidocaine plays a significant role in growth suppression by regulating the expression and distribution of Ki-67.

Deep Learning Classification of Treatment Response in Diabetic Painful Neuropathy: A Combined Machine Learning and Magnetic Resonance Neuroimaging Methodological Study

Functional magnetic resonance imaging (fMRI) has been shown successfully to assess and stratify patients with painful diabetic peripheral neuropathy (pDPN). This supports the idea of using neuroimaging as a mechanism-based technique to individualise therapy for patients with painful DPN. The aim of this study was to use deep learning to predict treatment response in patients with pDPN using resting state functional imaging (rs-fMRI). We divided 43 painful pDPN patients into responders and non-responders to lidocaine treatment (responders n = 29 and non-responders n = 14). We used rs-fMRI to extract functional connectivity features, using group independent component analysis (gICA), and performed automated treatment response deep learning classification with three-dimensional convolutional neural networks (3D-CNN). Using gICA we achieved an area under the receiver operating characteristic curve (AUC) of 96.60% and F1-Score of 95% in a ten-fold cross validation (CV) experiment using our described 3D-CNN algorithm. To our knowledge, this is the first study utilising deep learning methods to classify treatment response in pDPN.

Local anesthetic lidocaine-inducible gene, growth differentiation factor-15 suppresses the growth of cancer cell lines

Administration of local anesthetics, such as lidocaine, in the perioperative period improves outcomes of cancer patients. However, its precise mechanism is still unresolved. The growth of human cancer cell lines, including HeLa cells, are suppressed by lidocaine treatment. We identified that growth differentiation factor-15 (GDF-15) was commonly upregulated in lidocaine-treated cancer cell lines. GDF-15 is a divergent member of the transforming growth factor-β (TGF-β) superfamily and it is produced as an unprocessed pro-protein form and then cleaved to generate a mature form. In lidocaine-treated HeLa cells, increased production of GDF-15 in the endoplasmic reticulum (ER) was observed and unprocessed pro-protein form of GDF-15 was secreted extracellularly. Further, lidocaine induced apoptosis and apoptosis-inducible Tribbles homologue 3 (TRIB3) was also commonly upregulated in lidocaine-treated cancer cell lines. In addition, transcription factor C/EBP homologous protein (CHOP), which is a positive regulator of not only GDF-15 but TRIB3 was also induced by lidocaine. Lidocaine-induced growth suppression and apoptosis was suppressed by knockdown of GDF-15 or TRIB3 expression by small interference RNA (siRNA). These observations suggest that lidocaine suppresses the growth of cancer cells through increasing GDF-15 and TRIB3 expression, suggesting its potential application as cancer therapy.

Lidocaine reinforces the anti-inflammatory action of dexamethasone on myeloid and epithelial cells activated by inflammatory cytokines or SARS-CoV-2 infection

BackgroundSevere cases of Coronavirus Disease 2019 (COVID-19) that require admission to the Intensive Care Unit (ICU) and mechanical ventilation assistance show a high mortality rate with currently few therapeutic options available. Severe COVID-19 is characterized by a systemic inflammatory condition, also called “cytokine storm”, which can lead to various multi-organ complications and ultimately death. Lidocaine, a safe local anesthetic that given intravenously is used to treat arrhythmias, has long been reported to have an anti-inflammatory and pro-homeostatic activity. MethodsWe studied the capacity of lidocaine to modulate cytokine secretion of mouse and human myeloid cell lines activated by different cytokines or Toll Like Receptor (TLR) ligands (flagellin (FliC), Lipopolysaccharide (LPS), Polyinosinic:polycytidylic acid (Poly I:C) and N-Palmitoyl-S- [2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-(S)-seryl-(S)-lysyl-(S)-lysyl-(S)-lysyl-(S)-lysine x 3HCl (Pam3Cys-SKKKK)) or by Severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2) infection to epithelial cells. Reporter cell lines were used to study modulation of lidocaine of specific signaling pathways. ResultsLidocaine used in combination with dexamethasone, had an additive effect in the modulation of cellular inflammatory response triggered by Tumoral Necrosis Factor alpha (TNFα), Interleukin 1 beta (IL-1β) as well as different TLR ligands. We also found that lidocaine in combination with dexamethasone modulates the Nuclear factor kappa B (NF-κB) pathway, inflammasome activation as well as interferon gamma receptor (IFNγR) signaling without affecting the type I interferons (Type I IFNs) pathway. Furthermore, we showed that lidocaine and dexamethasone treatment of epithelial cells infected with SARS-CoV-2 modulated the expression of chemokines that contribute to pro-inflammatory effects in severe COVID. ConclusionsWe reported for the first time in vitro anti-inflammatory capacity of lidocaine on SARS-CoV-2 triggered immune pathways. These results indicated the potential of lidocaine to treat COVID-19 patients and add tools to the therapeutic options available for these concerning cases.

Acute and Chronic Effects of Fin Amputation on Behavior Performance of Adult Zebrafish in 3D Locomotion Test Assessed with Fractal Dimension and Entropy Analyses and Their Relationship to Fin Regeneration.

Simple SummaryFin amputation is a routinely conducted procedure for various experiments, especially in zebrafish. However, no study compares the acute and chronic effects of the amputation of each fin on their behaviors. In addition, although some analgesics have been applied after the fin amputation procedure, the long-term effects of these drugs in have not been evaluated yet. In this study, we found that amputation in the caudal fin resulted in the most pronounced behavior alterations and their behavior was fully recovered before the caudal fin was fully regenerated, indicating that these behavioral changes came from pain elicited from the fin amputation. Finally, while lidocaine treatment could ameliorate the behavioral effects after the amputation procedure, it did not accelerate the behavior recovery process; instead, it caused the fish to display some slight side effects.The fin is known to play an important role in swimming for many adult fish, including zebrafish. Zebrafish fins consist of paired pectoral and pelvic with unpaired dorsal, anal, and caudal tail fins with specific functions in fish locomotion. However, there was no study comparing the behavior effects caused by the absence of each fin. We amputated each fin of zebrafish and evaluated their behavior performance in the 3D locomotion test using fractal dimension and entropy analyses. Afterward, the behavior recovery after the tail fin amputation was also evaluated, together with the fin regeneration process to study their relationship. Finally, we conducted a further study to confirm whether the observed behavior alterations were from pain elicited by fin amputation procedure or not by using lidocaine, a pain-relieving drug. Amputation in the caudal fin resulted in the most pronounced behavior alterations, especially in their movement complexity. Furthermore, we also found that their behavior was fully recovered before the caudal fin was fully regenerated, indicating that these behavioral changes were not majorly due to a mechanical change in tail length; instead, they may come from pain elicited from the fin amputation, since treatment with lidocaine could ameliorate the behavioral effects after the amputation procedure. However, lidocaine did not accelerate the behavior recovery process; instead, it caused the fishes to display some slight side effects. This study highlights the potential moderate severity of fin amputation in zebrafish and the importance of analgesia usage. However, side effects may occur and need to be considered since fin amputation is routinely conducted for various research, especially genomic screening.

Lidocaine reduces pain behaviors by inhibiting the expression of Nav1.7 and Nav1.8 and diminishing sympathetic sprouting in SNI rats

Chronic neuropathic pain is a significant clinical challenge, and the mechanisms of neuropathic pain remain elusive. Previous studies have shown that spontaneous potential, which is triggered by Nav1.7 and Nav1.8 in the dorsal root ganglion (DRG), is crucial for the development of inflammatory and neuropathic pain. Functional coupling between the sympathetic nervous system and somatosensory nerves after a nerve injury has also been noted as an important factor in neuropathic pain. However, the relationship of sympathetic sprouting with Nav1.7 and Nav1.8 remains unclear. Therefore, we dynamically examined the mechanical withdrawal threshold (MWT), changes in Nav1.7 and Nav1.8, and sympathetic sprouting after lidocaine treatment in the spared nerve injury (SNI) model of rats. After lidocaine treatment, the MWT obviously increased, showing that hypersensitivity was significantly relieved and the abnormal expression of Nav1.7 and Nav1.8 caused by SNI was also significantly reduced. In addition, lidocaine distinctly inhibited sympathetic nerve sprouting and basket formation around the Nav1.7 and Nav1.8 neurons in the DRG. These results indicate that lidocaine may alleviate neuropathic pain by inhibiting the expression of Nav1.7 and Nav1.8, and diminishing sympathetic sprouting in DRG.