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.

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.

Neuromedin U inhibits T-type Ca2+ channel currents and decreases membrane excitability in small dorsal root ganglia neurons in mice

Cell Calcium ◽  
2011 ◽  
Vol 49 (1) ◽  
pp. 12-22 ◽  
Author(s):  
Fen Wang ◽  
Yuan Zhang ◽  
Xinghong Jiang ◽  
Yiming Zhang ◽  
Ling Zhang ◽  
...  
Keyword(s):  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Membrane Excitability ◽  
Dorsal Root Ganglia Neurons ◽  
Channel Currents

scholarly journals Liposomal Bupivacaine versus Continuous Popliteal Nerve Block in Total Ankle Arthroplasty

2017 ◽  
Vol 2 (3) ◽  
pp. 2473011417S0003
Author(s):  
Ryan Mulligan ◽  
Joel Morash ◽  
James DeOrio ◽  
Selene Parekh
Keyword(s):  
Postoperative Pain ◽  
Sciatic Nerve ◽  
Pain Score ◽  
Nerve Block ◽  
Total Ankle Arthroplasty ◽  
Sciatic Nerve Block ◽  
Foot And Ankle ◽  
Ankle Arthroplasty ◽  
Ankle Surgery ◽  
Regional Anesthetic

Category: Ankle, Ankle Arthritis Introduction/Purpose: The use of liposomal bupivacaine (LB) has recently gained popularity in joint arthroplasty. Despite it’s proven safety and efficacy, there is little reported on the use of LB in foot and ankle surgery. Catheter placement for a continuous popliteal sciatic nerve block (CPSNB) has an excellent track record for pain relief, and is commonly used by our group for major foot and ankle reconstructions. The purpose of this study was to compare the use of intraoperative LB injection to CPSNB as a regional anesthetic for total ankle arthroplasty (TAA), with attention to postoperative pain scores, narcotic use, and complications. Methods: Retrospective review of TAA patients treated by two fellowship-trained orthopedic foot and ankle surgeons was performed. Patient demographic data, operative, and postoperative details were collected, including type of regional anesthetic used. Patient’s received either preoperative single-shot popliteal sciatic nerve block with 0.25% bupivacaine followed by intraoperative injection of LB, or preoperative CPSNB alone. Outcomes examined were VAS pain score at 8 hours, 24 hours, 1 week, and 3 weeks following surgery, need for opioid pain medication refill, physician office notification for pain issues or other adverse events, and complications within the first 90 days following surgery. Standard statistical analysis was performed and p < 0.05 was considered significant. Results: 75 patients were identified who underwent TAA and met inclusion criteria. 41 received LB and 34 received CPSNB. No statistical difference was seen between groups with regard to complications, emergency department visits, readmissions, reoperations, VAS pain score at any time point, physician office contacts, and narcotic refills. Mean VAS with LB use was 1.8, 3.5, 2.6, and 2.2 at 8 hours, 24 hours, 1 week, and 3 weeks respectively, compared with mean VAS 2.1, 3.2, 2.2, and 1.9 at similar time points for CPSNB (p=0.59, 0.65, 0.27, and 0.40, respectively). 16 of 41 LB patients needed narcotic refills, versus 12 of 34 CPSNB patients (p=0.81). 3 of 41 LB patients had a complication postoperatively, versus 4 of 34 CPSNB patients. Conclusion: This is the first study evaluating the use of LB for total ankle arthroplasty. LB was both safe and effective for postoperative pain control, with comparable results to CPSNB. As LB gains more widespread use in foot and ankle surgery, further investigation is warranted to determine potential unseen complications and cost-effectiveness.

Effect of FGF-2 and sciatic nerve grafting on ChAT expression in dorsal root ganglia neurons of spinal cord transected rats

2016 ◽  
Vol 616 ◽  
pp. 43-48 ◽  
Author(s):  
Fausto Pierdoná Guzen ◽  
Dayane Pessoa de Araújo ◽  
Eudes Euler de Souza Lucena ◽  
Hécio Henrique Araújo de Morais ◽  
José Rodolfo Lopes de Paiva Cavalcanti ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Sciatic Nerve ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Nerve Grafting ◽  
Dorsal Root Ganglia Neurons

scholarly journals Capsazepine prolongation of the duration of lidocaine block of sensory transmission in mice may be mediated by modulation of HCN channel currents

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7111 ◽  
Author(s):  
Wenling Zhao ◽  
Peng Liang ◽  
Jin Liu ◽  
Huan Li ◽  
Daqing Liao ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Block ◽  
Sensory Block ◽  
Hcn Channel ◽  
Lidocaine Group ◽  
Hek 293 ◽  
293 Cells ◽  
Channel Currents ◽  
Regional Anesthetic

Background and objectives Hyperpolarization-activation cyclic nucleotide-gated (HCN) channels contribute to the effects of lidocaine. Capsazepine (CPZ), a competitive inhibitor of capsaicin of transient receptor potential vanilloid-1 channel, has also been found to inhibit HCN channel currents (Ih). This study was designed to investigate whether CPZ could prolong durations of lidocaine in regional anesthesia. Methods Mouse HCN1 and HCN2 channels were expressed in human embryonic kidney 293 (HEK 293) cells. The effect of CPZ on Ih was measured by whole-cell patch-clamping recording. Sciatic nerve block model in mice was used for the study in vivo. The mice were randomly divided into seven groups, respectively, receiving lidocaine, CPZ, ZD7288 (HCN channel blocker), CPZ + lidocaine, ZD7288 + lidocaine, ZD7288 + CPZ + lidocaine, forskolin (an activator of adenylyl cyclase) + CPZ + lidocaine. Regional anesthetic durations of lidocaine were determined. Voltage-gated sodium channel currents (INa) and Ih were recorded in dorsal root ganglion neurons of mice. The effects of CPZ on INa and Ih with or without Cyclic adenosine monophosphate (cAMP) were assessed. Isolated mice sciatic nerve was prepared to evaluate the effect of CPZ on the compound action potentials (CAP). Results Capsazepine non-selectively inhibited transfected mHCN1 and mHCN2 channel currents in HEK 293 cells. In sciatic nerve block in vivo, compared to lidocaine alone, adding CPZ extended the durations of lidocaine for noxious sensory block (35.1 ± 3.3 vs. 20.3 ± 1.7 min), tactile sensory block (25.5 ± 4.4 vs. 20.0 ± 3.7 min), thermal sensory block (39.6 ± 6.6 vs. 26.8 ± 5.5 min), and motor function block (28.6 ± 4.1 vs. 20.9 ± 4.2 min). Duration of thermal sensory block was longer in CPZ + lidocaine group than that of ZD7288 + lidocaine group (39.6 ± 6.6 vs. 33.4 ± 4.5 min). Forskolin reversed the prolongation by CPZ on lidocaine durations. CPZ or ZD7288 alone did not produce typical regional anesthetic effects. Increased intracellular concentration of cAMP reversed the inhibition of CPZ on Ih. Although CPZ alone inhibited INa at the concentration more than 30 μM, it did not inhibit the CAP amplitudes in isolated sciatic nerves. CPZ dose-dependently enhanced the inhibitory effect of 1% lidocaine on the CAP amplitudes. Conclusions Capsazepine may prolong durations of lidocaine in peripheral nerve block by modulation of HCN channel currents.

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