Novel compound LL-a produces long and nociceptive-selective regional anesthesia via TRPV1 channels in rodents sciatic nerve block model

2020 ◽  
Vol 45 (6) ◽  
pp. 412-418
Author(s):  
Cheng Zhou ◽  
Lei Tang ◽  
Qinqin Yin ◽  
Linghui Yang ◽  
Deying Gong ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Regional Anesthesia ◽  
Nerve Block ◽  
Motor Block ◽  
Sensory Block ◽  
Sciatic Nerve Block ◽  
Block Model ◽  
Voltage Gated ◽  
Trpv1 Channels ◽  
Channel Currents

Background and objectiveLong-acting nociceptive-selective regional anesthesia has remained an elusive clinical goal. We aspired to identify a novel compound that would produce nociceptive-selective regional anesthesia through the transient receptor potential vanilloid 1 (TRPV1) channels.MethodsWe designed and synthesized a novel compound (LL-a) that penetrates the cell membrane through TRPV1 channels and binds to voltage-gated sodium channels. The regional anesthetic effect of LL-a was evaluated in a rodent sciatic nerve block model. Electrophysiological recording was applied to test the inhibition of LL-a on voltage-gated sodium channel currents.ResultsLL-a inhibited sodium channel currents on the dorsal root ganglion neurons of mice and this action was diminished by TRPV1 channel knockout. In a sciatic nerve block model of a rat, 0.2% and 0.4% (w/v) LL-a produced selective sensory block with median (IQR) durations of 42.0 (24.0, 48.0) and 72.0 (69.0, 78.0) hours, respectively. No motor block was found for 0.2% LL-a. 0.4% LL-a produced a motor block with a median (IQR) duration of 3.0 (0.0, 6.0) hours. This selective sensory block was not observed on TRPV1 knockout mice. As a positive control, 0.5% and 0.75% levobupivacaine produced a non-selective sciatic nerve block with median (IQR) durations of 2.8 (2.6, 2.8) and 3.8 (3.8, 4.8) hours, respectively. No systemic or local irritation was observed during injection of LL-a and sensory and motor function completely recovered for all the animals.ConclusionsLL-a is a potential novel local anesthetic for long-lasting nociceptive-selective analgesia.

Sex-dependent prolongation of sciatic nerve blockade in diabetes patients: a prospective cohort study

2019 ◽  
Vol 44 (9) ◽  
pp. 860-865 ◽  
Author(s):  
Shuai Tang ◽  
Jin Wang ◽  
Yi Tian ◽  
Xu Li ◽  
Qiuju Cui ◽  
...  
Keyword(s):  
Cohort Study ◽  
Sciatic Nerve ◽  
Nerve Block ◽  
Motor Block ◽  
Plantar Flexion ◽  
Sensory Block ◽  
Sciatic Nerve Block ◽  
Sensory Threshold ◽  
Nerve Blockade ◽  
Diabetes Patients

IntroductionDiabetes may affect the duration of nerve block after regional anesthesia. This study aimed to compare the durations of sensory and motor block in diabetes versus non-diabetes patients after lower limb nerve block and delineate any sex-based differences in the duration of sensory and motor blocks of both diabetes and non-diabetes patients.MethodsThis prospective single-blinded cohort study recruited 86 patients who underwent unilateral lower extremity surgery; 52 patients were non-diabetic and 34 were diabetic. Each patient received an ultrasound-guided nerve stimulator-assisted subgluteal sciatic nerve block with 0.75% ropivacaine. Duration of sensory block was assessed with the Semmes-Weinstein monofilament test, and duration of motor block was assessed with dorsal and plantar flexion of the foot.ResultsThe sensory and motor block durations of diabetes patients were significantly prolonged versus non-diabetes patients (19.8±6.0 hours vs 15.6±5.1 hours; p<0.05) and (19.5±8.1 hours vs 14.8±5.7 hours, p=0.005), respectively. The durations of sensory and motor block were comparable between male diabetes and non-diabetes patients, but they were significantly longer in female diabetes patients. Multiple regression analysis further revealed that, after adjustment for age and preoperative sensory threshold, diabetes, fasting plasma glucose and HbA1c levels were significantly associated with sensory and motor blocks. Sex analysis showed the association was only present in female diabetes patients, not male diabetes patients.ConclusionThe durations of sensory and motor block are significantly prolonged after subgluteal sciatic nerve block in diabetes patients. Furthermore, the prolonged nerve blockade is present only in diabetes women, not diabetes men.Trial registration numberNCT02482831.

scholarly journals Efficacy of perineural versus systemic dexamethasone in prolonging analgesia after ultrasound guided femoral and sciatic nerve block for patients undergoing below knee surgeries

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
A A Abdelaziz ◽  
H M Elzahaby ◽  
A A Elshebeiny ◽  
D M Heiba
Keyword(s):  
Sciatic Nerve ◽  
Nerve Block ◽  
Onset Time ◽  
Analgesic Efficacy ◽  
Sensory Block ◽  
Postoperative Pain Management ◽  
Sciatic Nerve Block ◽  
Dexamethasone Group ◽  
Significant Difference ◽  
Group B

Abstract Background Poorly controlled acute pain after surgery is associated with a variety of unwanted postoperative consequences, including patient suffering, distress, myocardial ischemia, prolonged hospital stay and increase of chronic pain. Neuroaxial block is used for postoperative pain management and decrease analgesic use. Objective to compare the analgesic efficacy of both, intravenous and perineural administration of dexamethasone during femoral and sciatic nerve block using bupivacaine in patients undergoing below knee surgeries. Patients and Methods In our study, 50 patients were randomly divided into two equal groups: Group A (Perineural Dexamethasone group) [n = 25]: Those cases received 2ml volume of dexamethasone (8mg) combined with the 20 ml of bupivacaine of 0.5% concentration in each block, followed by injecting 5 ml saline intravenous. Group B (Systemic Dexamethasone group) [n = 25]: Those cases received 2 ml of dexamethasone (8mg) diluted over 3 cm saline in a 5 ml syringe following injection of the perineural 20 ml bupivacaine (0.5%) combined with 2 ml saline to have the same syringe volume for each block. Results Our study showed that onset time for sensory block was (25.39 ± 3.79) mins for systemic group and (18.85 ± 4.11) mins in perineural group with a significant statistical difference (P &lt; 0.001) between both groups as the onset of sensory block in perineural group was significantly shorter than the systemic group and the duration of sensory block was (650.00 ± 62.8) mins in systemic group and (718.52 ± 62.06) mins in perineural group. The duration of sensory block was significantly shorter in systemic group than in perineural group with statistically high significant difference between groups (P &lt; 0.001). Onset time for motor block was (30.61 ± 4.89) mins in systemic group and (27.59 ± 3.31) mins in perineural group. Perineural group had shorter time of onset than systemic dexamethasone group with a significant difference between groups (P = 0.013). The duration of analgesia was significantly longer in perineural group than systemic group (P &lt; 0.001) Conclusion Dexamethasone was seen to be a potent adjunct to local anesthetic to prolong post operative analgesia with negligible side effects & better outcome to the perineural route.

scholarly journals Two clinical cases of unintentionally prolonged sciatic nerve block

2021 ◽  
Vol 15 (2) ◽  
pp. 163-168
Author(s):  
Vasiliy G. Tsvetkov ◽  
Roman E. Lakhin ◽  
Anatoliy V. Stukalov
Keyword(s):  
Sciatic Nerve ◽  
Nerve Block ◽  
Motor Block ◽  
Tissue Perfusion ◽  
Sciatic Nerve Block ◽  
Related Factors ◽  
Expected Time ◽  
Age Related ◽  
Long Duration ◽  
Clinical Cases

This study describes two clinical cases of unexpectedly long duration of motor block after anterior sciatic nerve block. In two patients who underwent total knee replacement, the motor block reversion in the area of sciatic nerve innervation did not occur at the expected time. Ultrasound examination revealed the deposition of a local anesthetic near the sciatic nerve. In these two clinical cases, unintentionally prolonged sciatic nerve blockade was caused by combined age-related factors of reduced tissue perfusion and the vasoconstrictor properties of levobupivacaine. Subsequently, the block was successfully resolved in 3638 h without any neurological consequences.

Entrapping bupivacaine-loaded emulsions in a crosslinked-hydrogel increases anesthetic effect and duration in a rat sciatic nerve block model

2020 ◽  
Vol 588 ◽  
pp. 119703
Author(s):  
Brett Davis ◽  
Sierra Erickson ◽  
Susan Wojtalewicz ◽  
Andrew Simpson ◽  
Cameron Metcalf ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Block ◽  
Sciatic Nerve Block ◽  
Block Model ◽  
Rat Sciatic Nerve ◽  
Anesthetic Effect

A New Anterior Approach to the Sciatic Nerve Block 

1999 ◽  
Vol 91 (6) ◽  
pp. 1655-1655 ◽  
Author(s):  
Jacques E. Chelly ◽  
Laurent Delaunay
Keyword(s):  
Sciatic Nerve ◽  
Nerve Block ◽  
Anterior Approach ◽  
Peroneal Nerve ◽  
Tibial Nerve ◽  
Common Peroneal Nerve ◽  
Sensory Block ◽  
Pubic Symphysis ◽  
Sciatic Nerve Block ◽  
Nerve Blocks

Background Although several anterior approaches to sciatic nerve block have been described, they are used infrequently. The authors describe a new anterior approach that allows access to the sciatic nerve with the patient in the supine position. Method Sciatic nerve blocks were performed in 22 patients. A line was drawn between the inferior border of the anterosuperior iliac spine and the superior angle of the pubic symphysis tubercle. Next, a perpendicular line bisecting the initial line was drawn and extended 8 cm caudad. The needle was inserted perpendicularly to the skin, and the sciatic nerve was identified at a depth of 10.5 cm (9.5-13.5 cm; median and range) using a nerve stimulator and a 15-cm b-beveled insulated needle. After appropriate localization, either 30 ml mepivacaine, 1.5% (group 1 = knee arthroscopy; n = 16), or 15 ml mepivacaine, 1.5%, plus 15 ml ropivacaine, 0.75%, (group 2 = other procedures; n = 6) was injected. Results Appropriate landmarks were determined within 1.3 min (0.5-2.0 min). The sciatic nerve was identified in all patients within 2.5 min (1.2-5 min), starting from the beginning of the appropriate landmark determination to the stimulation of its common peroneal nerve component in 13 cases and its tibial nerve component in 9 cases. A complete sensory block in the distribution of both the common peroneal nerve component and the tibial nerve component was obtained within 15 min (5-30 min). A shorter onset was observed in patients who received mepivacaine alone compared with those who received a mixture of mepivacaine plus ropivacaine (10 min [5-25 min] vs. 20 min [10-30 min]; P &lt; 0.05). Recovery time was 4.6 h (2.5-5.5 h) after mepivacaine administration. The addition of ropivacaine produced a block of a much longer duration 13.8 h (5.2-23.6 h); P &lt; 0.05. No complications were observed. Conclusions This approach represents an easy and reliable anterior technique for performing sciatic nerve blocks.

Hyperpolarization-activated Cyclic Nucleotide-gated Channels May Contribute to Regional Anesthetic Effects of Lidocaine

2015 ◽  
Vol 122 (3) ◽  
pp. 606-618 ◽  
Author(s):  
Cheng Zhou ◽  
Bowen Ke ◽  
Yi Zhao ◽  
Peng Liang ◽  
Daqing Liao ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Block ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Sciatic Nerve Block ◽  
Membrane Properties ◽  
Hcn Channels ◽  
Dorsal Root Ganglia Neurons ◽  
Channel Currents ◽  
Regional Anesthetic

Abstract Background: Local anesthetics (e.g., lidocaine) have been found to inhibit hyperpolarization-activated cyclic nucleotide-gated (HCN) channels besides sodium channels. However, the exact role of HCN channels in regional anesthesia in vivo is still elusive. Methods: Sciatic nerve block and intrathecal anesthesia were performed using lidocaine in wild-type and HCN1 channel knockout (HCN1−/−) mice. EC50 of lidocaine and durations of 1% lidocaine were determined. In electrophysiologic recordings, effects of lidocaine on HCN channel currents, voltage-gated sodium channel currents, and neural membrane properties were recorded on dorsal root ganglia neurons. Results: In both sciatic nerve block and intrathecal anesthesia, EC50 of lidocaine for tactile sensory blockade (2 g von Frey fiber) was significantly increased in HCN1−/− mice, whereas EC50 of lidocaine for pinprick blockade was unaffected. Durations of 1% lidocaine were significantly shorter in HCN1−/− mice for both sciatic nerve block and intrathecal anesthesia (n = 10). ZD7288 (HCN blocker) could significantly prolong durations of 1% lidocaine including pinprick blockade in sciatic nerve block (n = 10). Forskolin (raising cyclic adenosine monophosphate to enhance HCN2) could significantly shorten duration of pinprick blockade of 1% lidocaine in sciatic nerve block (n = 10). In electrophysiologic recordings, lidocaine could nonselectively inhibit HCN channel and sodium channel currents both in large and in small dorsal root ganglia neurons (n = 5 to 6). Meanwhile, lidocaine caused neural membrane hyperpolarization and increased input resistance of dorsal root ganglia neurons but not in large dorsal root ganglia neurons from HCN1−/− mice (n = 5–7). Conclusions: These data indicate that HCN channels may contribute to regional anesthetic effects of lidocaine. By inhibiting HCN channels, lidocaine could alter membrane properties of neurons.

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