Myofascial pain - A major player in musculoskeletal pain.

Myofascial pain is a soft tissue pain syndrome with local and referred musculoskeletal pain arising from trigger points. Myofascial pain and myofascial pain syndromes are among some of the most common acute and chronic pain conditions. Myofascial pain can exist independently of other pain generators or can coexist with or is secondary to other acute and chronic painful musculoskeletal conditions. Myofascial pain is most effectively treated with a multimodal treatment plan including injection therapy (known as trigger point injections, physical therapy, postural or ergonomic correction, and treatment of underlying musculoskeletal pain generators. The objectives of this review are to outline the prevalence of myofascial pain, describe the known pathophysiology of myofascial pain and trigger points, discuss the clinical presentation of myofascial pain, and present evidence-based best practices for pharmacologic, non-pharmacologic, and interventional treatments for myofascial pain.

Assessing CRNA Knowledge of Local Anesthetic Systemic Toxicity Treatment.

Local anesthetic systemic toxicity (LAST) is a rare life-threatening adverse event. Due to the potential for devastating patient outcomes, it is crucial for anesthesia providers to understand appropriate LAST management. The primary aim of this study was to assess certified registered nurse anesthetist (CRNA) knowledge of the 2020 American Society of Regional Anesthesia and Pain Medicine (ASRA) LAST treatment guidelines. The secondary aim was to determine whether there was a relationship between the frequency of CRNAs' exposure to perioperative local anesthetic use and their knowledge level. A quantitative descriptive study and national American Association of Nurse Anesthetists electronic survey solicited practicing CRNAs. Survey findings revealed knowledge scores averaging 47.3% among 184 respondents. Almost all (97.8%) recognized the importance of early lipid emulsion administration. Over half (54.3%) were unaware of the recommended epinephrine dosing during LAST. No relationship was found between knowledge level and CRNAs' exposure to local anesthetics. Those who reported having immediate access to written or electronic guidelines in the event of LAST had significantly higher knowledge scores than those without access (P = .049). Implementing cognitive aids may help bridge knowledge gaps identified in this study and ensure critical steps are not missed. Further studies examining the use of cognitive aids to improve CRNA knowledge of LAST management may be beneficial in the future.

Local Anesthetic Systemic Toxicity During Transversus Abdominis Plane Block With Liposomal Bupivacaine.

Local anesthetic systemic toxicity (LAST) is a rare but potentially fatal outcome associated with local anesthetic administration. Liposomal bupivacaine (LB; EXPAREL®) is a widely used local anesthetic with extended-release and liposomal formulation that carries an improved cardiac and central nervous system safety profile. However, there is limited data regarding LAST associated with liposomal bupivacaine. Here is described a case of local anesthetic systemic toxicity in a 68-year-old male who presented with obstructing sigmoid adenocarcinoma and underwent open sigmoidectomy with end descending colostomy. The operation was complicated by LAST following transversus abdominis plane block injection with liposomal bupivacaine resulting in cardiac arrest. Return of spontaneous circulation was achieved following advanced cardiac life support and infusion of 20% I.V. fat emulsion. Given the widespread use of local anesthetics, providers must be aware of the pathophysiology, diagnosis, and immediate treatment of LAST.

Standing sedation management of a domesticated reindeer for third eyelid removal.

Background: Reindeer are becoming popular animals within petting farms. Few case reports describe the sedation of domesticated reindeer, but none describe the use of ocular local anesthetic blocks in this species. Case Description: A 9-year-old, female, Svalbard reindeer (Rangifer tarandus platyrhynchus) presenting for removal of a squamous cell carcinoma involving the third eyelid. Standing sedation was performed using initial boluses of medetomidine and butorphanol via intramuscular injection before catheter placement and maintenance with a variable rate infusion of medetomidine. Supraorbital, auriculopalpebral, infratrochlear blocks and local infiltration of the base of the third eyelid were performed using mepivacaine. Following the surgical removal of the third eyelid, atipamazole was administered intramuscularly to antagonize the effects of medetomidine. The patient recovered without complications. Conclusion: Medetomidine-butorphanol in combination with local anesthetic blocks provided a sufficient plane of sedation and analgesia for extra ocular surgery in a domesticated reindeer.

A Patient with Known Allergy to Local Anesthesia Presenting for a Dental Restoration.

Dentists should be equipped to treat an allergic reaction in a dental office, and in this scenario, the potential allergic reaction is noted after administration of a common local anesthetic lidocaine with epinephrine. The allergic reaction quickly escalates to a full-blown anaphylaxis, and the management of such an episode is detailed in this article.

Sustained release of levobupivacaine from temperature-sensitive injectable hydrogel for long-term local anesthesia in postoperative pain management.

Postoperative pain is a major concern for most of the surgical patients, and an inadequate postoperative pain control may cause a series of complications. With an effective pain control and lesser side effects, local anesthetics are preferred for use in postoperative pain management. However, the action duration of current local anesthetics is too short to meet the requirements of postoperative analgesia. In this study, an injectable levobupivacaine (LB)-loaded thermo-sensitive hydrogel system based on biodegradable poly(D,L-lactide)-poly(ethylene glycol)-poly(D,L-lactide) (PLEL) was developed for long-acting local anesthetic, in which the soluble charged cation form of LB (LB HCl) was partly alkalified to the poorly soluble base form (LB base). This hybrid LB loaded PLEL system (hLB/PLEL) is a free flowable liquid at room temperature and changes into a semi-solid hydrogel once injection in response to the physiological temperature. Then, the dissolved LB HCl could release firstly from the hydrogel contributing to a quick work, and the insoluble LB base dissolved and released gradually as the decrease of the pH during the biodegradation of PLEL hydrogel, resulting in a long-term LB release in local. The drug release behavior, pharmacokinetic, and biocompatibility of the thermo-sensitive hLB/PLEL were studied in vitro and in vivo. The anesthetic effects of hLB/PLEL system were evaluated in the rat models of sciatic nerve block, subcutaneous infiltration anesthesia and postoperative pain as well. This hLB/PLEL system generated a significantly prolonged analgesic effect in rat models, which produced approximately 7 times longer duration than 0.75% LB HCl and effectively relieved the spontaneous pain for 3 days. In general, the presented hLB/PLEL system can not only achieve a fast-acting but also sustainably release LB to block the nerve and significantly extend the effect of local analgesia, which means a promising candidate for long-acting postoperative pain management.

Comparative study of two different computer-controlled local anesthesia injection systems in children: a randomized clinical trial.

PURPOSE: To compare pain perception associated with two computer-controlled local anesthesia devices, the WAND™ STA (Milestone Scientific Inc., Livingston, NJ, USA) and the Calaject (Rønvig dental MFG, Daugaard, Denmark) in young children. METHODS: A split-mouth randomized clinical trial comprising 30 patients, aged 6-12 years, received randomly, in two separate sessions, a local anesthesia injection in the maxillary using either the wand STA or the Calaject. Pain perception was evaluated using the patient's heart rate, an 11-point numerical scale (NRS), and the Sound, Eye, and Motor (SEM) body movements. Statistical difference was set at p = 0.05. Repeated measures analysis of variance were conducted to compare the mean pulse for Calaject and STA at different times. It was followed by univariate analysis and Bonferroni multiple comparisons tests. Wilcoxon tests were performed to compare NRS, SEM, and injection duration between Calaject and STA. RESULTS: There was no significant statistical difference between Calaject and STA in pulse rate before injection (p = 0.720), during injection (p = 0.767), and after injection (p = 0.757). The mean NRS score was significantly greater with STA in comparison with Calaject (p = 0.017). The mean SEM score was also significantly greater with STA in comparison with Calaject (p = 0.002). However, the mean duration was significantly longer with Calaject (p = 0.001). CONCLUSIONS: Calaject was more effective than STA in reducing pain perception associated with periapical injection in young children.

Evaluation of the Local Anesthetic Activity, Acute Toxicity, and Structure-Toxicity Relationship in Series of Synthesized 1-Aryltetrahydroisoquinoline Alkaloid Derivatives In Vivo and In Silico.

Isoquinoline alkaloids constitute one of the most common classes of alkaloids that have shown a pronounced role in curing various diseases. Finding ways to reduce the toxicity of these molecules and to increase their therapeutic margin is an urgent matter. Here, a one-step method for the synthesis of a series of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines was performed in 85-98% yield by the Pictet-Spengler reaction. This was accomplished using the reaction between 3,4-dimethoxyphenylethylamine and substituted benzaldehydes boiling in trifluoroacetic acid. Furthermore, 1-(3'-amino-, 4'-aminophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines were obtained in 94% and 97% yield by reduction in 1-(3'-nitro-, 4'-nitrophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines with SnCl2 × 2H2O. The structures of the substances obtained were confirmed by infrared (IR) and nuclear magnetic resonance (1H and 13C NMR) spectra. ADMET/TOPKAT in silico study concluded that the synthesized compounds exhibited acceptable pharmacodynamic and pharmacokinetic properties without carcinogenic or mutagenic potential but with variable hepatotoxicity. The acute toxicity and structure-toxicity relationship (STR) in the series of 20 derivatives of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines (3a-r, 4a, b) was studied via determination of acute toxicity and resorptive action in white mice employing intragastric step-by-step administration. The first compound, 1-phenyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3a), showed the highest toxicity with LD50 of 280 mg/kg in contrast to 1-(3'-bromo -4'-hydroxyphenyl)-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3e) which proved to be the safest of the compounds studied. Its toxicity was 13.75 times lower than that of the parent compound 3a. All compounds investigated showed high local anesthetic activity on rabbit eyes in the concentrations studied. Only 3r, 3n, and 4a caused eye irritation and redness. All investigated derivatives (except 4b) in 1% concentration were more active than lidocaine, providing longer duration of complete anesthesia. Therefore, based on the obtained results of in silico tests, local anesthesia, and acute toxicity, a conclusion can be drawn that the experimental compounds need further extensive future investigations and possible modifications so that they can act as promising drug candidates.

The Benefits of Local Anesthesia Used in Mastectomy Without Reconstruction.

BACKGROUND: The opioid epidemic has driven renewed interest in local anesthesia to reduce postoperative opioid use. Our objective was to determine if local anesthesia decreased hospital pain scores, oral morphine equivalents (OME), length of stay (LOS), and nausea/vomiting. METHODS: Single institution retrospective study of females who underwent mastectomy without reconstruction. RESULTS: Overall, 712 patients were included; 63 (8.8%) received bupivacaine (B), 512 (72%) liposomal bupivacaine (LB), and 137 (19%) no local. 95% were discharged on POD1. Liposomal bupivacaine use increased from 2014 to 2019. Additional factors associated with use of local regimen were surgeon and extent of axillary surgery. Fewer patients used postop opioids during their hospital stay if any local was used compared to none (76 vs 88%; 0.003). Compared to none, local had shorter mean PACU LOS (95 vs 87 min; P = .02), lower mean intraoperative-OME (96 vs 106; P < .001), and lower mean postoperative OME/hr (1.4 vs 1.8 P = .001). Multivariable analysis (MVA) showed lower OME/hr with LB compared to B and none (P = .002); this translates to 22 mg and 30 mg of oxycodone in a 24-hr period, respectively. MVA showed lower POD1 pain scores with LB relative to none (P = .049). Local did not impact nausea/emesis. CONCLUSION: Local anesthesia was superior to no local in several measures. However, a consistent benefit of a specific local anesthetic agent was not demonstrated (LB vs B). A prospective study is warranted to determine the optimal local regimen for this cohort and further inform clinical relevance.

Effects of Ottonia anisum plant extract on local anesthetic, analgesic, anti-inflammatory and HCl­induced acute lung injury activities: a study in animal models.

Ottonia anisum (O. anisum), belonging to the family Piperaceae, is renowned for its medicinal properties. The plant is rich in alkaloids, terpenoids and flavonoids with recorded bioactivities. The stems, roots, and leaves, of the O. anisum have been extensively used in the folk medicine. Therefore, the present study was conducted to examine the pharmacological activities of O. anisum root extract. Methanolic root extract of O. anisum was assessed for local anesthetic, analgesic, anti-inflammatory and HCl-induced acute lung injury activities in animal models. Local anesthetic activity assessed in frog and guinea pigs through foot withdrawal reflex and intradermal wheal method, respectively, revealed the dose-dependent onset time of anesthesia response. In the case of HCl-induced ALI, the mice group orally administered with O. anisum extract were assessed for bronchoalveolar lavage fluid (BLF) contents, oxidative stress, and proinflammatory molecules. The analysis revealed the reduction in inflammatory molecules, neutrophils, and oxidative stress in the extract treated mice group. In addition, the redox homeostasis, reduced GSH and the catalase activity was found to be restored in the treated groups. Intriguingly, the genes associated with the NFkB expression was found to be downregulated in O. anisum extract treated groups. Moreover, the extract unveiled the significant analgesic and anti-inflammatory activities. Overall, the findings emphasize the clinical applicability of O. anisum extract in the treatment of ALI as well as the potential usage in local anesthetic, analgesic, and anti-inflammatory agents during the treatments.

Comparison of pain perception between computer-controlled local anesthetic delivery and the conventional syringe for inferior alveolar nerve block in children.

BACKGROUND: Local anesthesia (LA) is commonly used for pain control in clinical dental practice. However, it is often perceived as the most painful part of the treatment and the factor leading to the avoidance of dental care. Hence, research on better means of pain management is being conducted. OBJECTIVES: The aim of the study was to evaluate and compare pain perception using the No Pain III™ computer-controlled local anesthesia delivery (CCLAD) system and the conventional syringe, for inferior alveolar nerve block (IANB) in children. MATERIAL AND METHODS: Thirty children aged 6-12 years were included in the study. Children were randomly allocated into 2 groups by the flip of a coin. Group A received LA by conventional syringe and group B received LA by No Pain III™, on the contralateral side. Physiological parameters including blood pressure (BP), heart rate (HR) and respiratory rate (RR) were assessed at baseline, during the deposition and after the deposition of LA. A subjective evaluation of pain perception was assessed using the Wong-Baker FACES Pain Rating Scale (WBS). The measured values were subjected to statistical analysis. RESULTS: A statistically significant difference was observed between group A and group B for pain perception using the WBS, systolic BP and RR. CONCLUSIONS: The use of the No Pain III™ CCLAD system resulted in reduced pain perception and better acceptance when compared to the use of the conventional syringe, for IANB in children.

[Aspiration test as dental anesthesia safety criterion]. / Aspiratsionnyi test kak kriterii bezopasnosti obezbolivaniya v stomatologii.

Intravascular anesthetic injection can lead to acute toxic reaction even the minimal dose of the drug was administered. The aspiration test is a generally accepted standard for local anesthesia in medicine, specially designed to reduce the risk of emergency conditions. Medical instruments should be adapted for aspiration test, the local anesthetic carpule should have a retention notch, and the dental syringe plunger need to have retention elements. The aspiration test protocol may vary. For legal protection of the doctor the aspiration test result should be described in the patient's medical record.

Complications After Dental Sedation: A Myotonic Mystery Case Report.

Myotonic dystrophy (dystrophia myotonica; DM) is an uncommon progressive hereditary muscle disorder that can present with variable severity at birth, in early childhood, or most commonly as an adult. Patients with DM, especially type 1 (DM1), are extremely sensitive to the respiratory depressant effects of sedative-hypnotics, anxiolytics, and opioid agonists. This case report describes a 37-year-old male patient with previously undiagnosed DM1 who received dental care under minimal sedation using intravenous midazolam. During the case, the patient experienced 2 brief episodes of hypoxemia, the second of which required emergency intubation after propofol and succinylcholine and resulted in extended hospital admission. A lipid emulsion (Liposyn II 20%) infusion was given approximately 2 hours after the last local anesthetic injection due to slight ST elevation and suspicion of local anesthetic toxicity (LAST). Months after treatment, the patient suffered a fall resulting in a fatal traumatic brain injury. Complications noted in this case report were primarily attributed to the unknown diagnosis of DM1, although additional precipitating factors were likely present. This report also provides a basic review of the literature and clinical guidelines for managing myotonic dystrophy patients for dental care with local anesthesia, sedation, or general anesthesia.

Effectiveness Of Local Anaesthetic In Reducing Postoperative Pain At Port Site After Laparoscopic Cholecystectomy.

Background: Laparoscopy has become the highest quality level way to deal with cholecystectomy since its inception 30 years preceding, and is perhaps the most normally performed general surgeries. Pain being a significant issue after laparoscopic cholecystectomy bringing about extended admissions or readmissions. With significant varieties in pain relieving conventions an integrated approach is important to diminish pain. The aim of this study is to assess the effectiveness of Bupivacaine as local anesthetic agent at port sites after laparoscopic cholecystectomy. Method: Study population of 84 patients was divided into control group (receiving no local anesthetic) and study group (receiving Bupivacaine as local anesthetic). Visual analogue scale was used to quantify and compare pain perceived by each group; at fixed intervals of 6, 12 and 24 hours after shifting of the patients back to the ward. Results: Each group comprised 42 patients. At 6 hours post operative pain score in study group, 4.5±0.32 was significantly lower than in control group, 7.6±0.41 (p<0.05). Though pain assessments at 12 and 24 hours didn't reveal any significant differences among the two groups; postoperative requirement of Tramadol was significantly (p<0.05) lower in study group (92±0.064mg) in comparison to control group (158±0.21mg). Conclusion: Use of long-acting local anesthetic injections at port sites after laparoscopic cholecystectomy significantly lowers pain during first 6 hours post operatively and also lowers narcotic analgesics requirements during post operative period.

The clinical efficacy of minocycline mouth rinse on recurrent aphthous stomatitis-A randomized controlled trial.

Introduction: Recurrent aphthous stomatitis (RAS) is one of the most common ulcerative diseases affecting the general population. The present study aimed to evaluate the clinical efficiency of 0.5% minocycline mouth rinse prescribed along with the topical anesthetic gel and vitamin supplement over the topical anesthetic gel and vitamin supplement prescribed alone for treating RAS. Materials and Methods: A total of 60 participants were randomly divided into two groups-experimental group: 0.5% minocycline mouth rinse prescribed along with vitamin supplement and topical anesthetic gel; and control group: vitamin supplement and topical anesthetic gel alone. The pain symptoms were evaluated using the VAS scores at baseline and first follow-up visits. The data were analyzed using Student's t test. Results: A significant reduction in the pain scores was observed in participants using the 0.5% minocycline mouth rinse prescribed along with vitamin supplement and topical anesthetic gel on the first follow-up visit (P = < 0.001). Conclusion: The 0.5% minocycline mouth rinse prescribed along with vitamin supplement and topical anesthetic gel had shown more reduction in the pain symptoms when compared to topical anesthetic gel and vitamin supplement prescribed alone for the treatment of RAS.

Local anesthetic systemic toxicity: A narrative review for emergency clinicians.

INTRODUCTION: Emergency clinicians utilize local anesthetics for a variety of procedures in the emergency department (ED) setting. Local anesthetic systemic toxicity (LAST) is a potentially deadly complication. OBJECTIVE: This narrative review provides emergency clinicians with the most current evidence regarding the pathophysiology, evaluation, and management of patients with LAST. DISCUSSION: LAST is an uncommon but potentially life-threatening complication of local anesthetic use that may be encountered in the ED. Patients at extremes of age or with organ dysfunction are at higher risk. Inadvertent intra-arterial or intravenous injection, as well as repeated doses and higher doses of local anesthetics are associated with greater risk of developing LAST. Neurologic and cardiovascular manifestations can occur. Early recognition and intervention, including supportive care and intravenous lipid emulsion 20%, are the mainstays of treatment. Using ultrasound guidance, aspirating prior to injection, and utilizing the minimal local anesthetic dose needed are techniques that can reduce the risk of LAST. CONCLUSIONS: This focused review provides an update for the emergency clinician to manage patients with LAST.

Neuronal Nitric Oxide Synthase Suppression Confers the Prolonged Analgesic Effect of Sciatic Nerve Block With Perineural Dexamethasone in Postoperative Pain Model Mice.

Dexamethasone supplementation to local anesthetics prolongs its action, yet the underlying mechanism is unclear. Previous studies have reported that increased p-p38 mitogen-activated protein kinase (MAPK) in the dorsal root ganglia (DRG) is associated with pain-associated behavior and that nitric oxide (NO), which is known to be a pronociceptive substance, directly inhibits sciatic nerve conduction. Here, we investigated the temporal changes in the hyperalgesic effect and p-p38 MAPK and NO synthase (NOS) expression levels in the DRG when dexamethasone was added to ropivacaine used for a sciatic nerve block (SNB) in postoperative pain model mice. Dexamethasone supplementation to ropivacaine significantly prolonged the analgesic effect of SNB via glucocorticoid receptor activation. Histological examination revealed that ropivacaine suppressed p-p38 MAPK expression in the DRG regardless of dexamethasone supplementation, suggesting that p-p38 MAPK was not involved in the prolonging effect of dexamethasone on nerve block. Contrastingly, plantar incision markedly increased the expression of neuronal NOS (nNOS) in DRG, and dexamethasone supplementation to ropivacaine significantly suppressed nNOS expression. Supplementation of L-NAME, an inhibitor of NOS, to ropivacaine markedly prolonged the effect of SNB, similar to dexamethasone. These results suggest that dexamethasone supplementation to local anesthetics prolongs the analgesic effect by inhibiting nNOS activity. PERSPECTIVE: The current study revealed that dexamethasone supplementation to local anesthetics prolongs the analgesic effect by inhibiting the activity of neuronal NOS and that p-p38 MAPK may not be involved in this phenomenon. Our findings offer a new target for the discovery of long-acting local anesthetics.

Trigger Point Injections.

Myofascial pain and myofascial pain syndromes are among some of the most common acute and chronic pain conditions. Many interventional procedures can be performed in both an acute and chronic pain setting to address myofascial pain syndromes. Trigger point injections can be performed with or without imaging guidance such as fluoroscopy and ultrasound; however, the use of imaging in years past has been recommended to improve patient outcome and safety. Injections can be performed using no injectate (dry needling), or can involve the administration of local anesthetics, botulinum toxin, or corticosteroids.

A Novel Photoswitchable Azobenzene-Containing Local Anesthetic Ethercaine with Light-Controlled Biological Activity In Vivo.

Pain is a common symptom that impairs the quality of life for people around the world. Local anesthetics widely used for pain relief have a number of side effects, which makes the development of both new drugs and new ways to control their activity particularly important. Photopharmacology makes it possible to reduce the side effects of an anesthetic and control its biological activity in the body. The purpose of this work was to create a new light-controlled local anesthetic and study its biological activity in animals. A compound with a simple scheme of synthesis was chosen to shift the UV-Vis absorption band towards the visible range of the spectrum and was synthesized for the first time. Some computer calculations were performed to make sure that the aforementioned changes would not lead to loss of biological activity. The micellar form of the new compound was prepared, and in vivo biological studies were carried out in rabbits. The existence of a local anesthetic effect, which disappeared almost completely on irradiation with light (λ = 395 nm), was shown using the surface anesthesia model. Moreover, the possibility of multiple reversible changes in the biological activity of ethercaine under the action of light was demonstrated. The latter compound manifests no local irritating effect, either. The data obtained indicate the prospects for the development of new compounds based on azobenzene for light-controlled local anesthesia.

Design of hydroxy-α-sanshool loaded nanostructured lipid carriers as a potential local anesthetic.

Hydroxy-α-sanshool (HAS), extracted from Zanthoxylum piperitum, is commonly used in oral surgery to relief pain. However, the application of HAS is limited in clinical practice due to its poor stability. This study focuses on the design of a novel nano-formulation delivery system for HAS to improve its stability and local anesthetic effect. Hydroxy-α-sanshool loaded nanostructured lipid carriers (HAS-NLCs) were prepared by melting emulsification and ultra-sonication using monostearate (GMS) and oleic acid (OA) as lipid carriers, and poloxamer-188 (F68) as a stabilizer. Besides, the formulation was optimized by response surface methodology (RSM). Then, the best formulation was characterized for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE%), drug loading (DL%), differential scanning calorimetry (DSC), and morphology (transmission electron microscopy, TEM). The obtained HAS-NLCs were homogeneous, near spherical particles with high DL% capacity. The stability of HAS-NLCs against oxygen, light, and heat was greatly improved over 10.79 times, 3.25 times, and 2.09 times, respectively, compared to free HAS. In addition, HAS-NLCs could exhibit sustained release in 24 h following a double-phase kinetics model in vitro release study. Finally, HAS-NLCs had excellent anesthetic effect at low dose in formalin test compared with free HAS and lidocaine, which indicated HAS-NLCs were a potential local anesthesia formulation in practice.