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Updated: Dec 24, 2025

Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
Published on: October 6, 2022
Novel compound LL-a produces long and nociceptive-selective regional anesthesia via TRPV1 channels in rodents sciatic
Cheng Zhou1,2, Lei Tang1,2, Qinqin Yin1,2
1Laboratory of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, National Clinical Research Center for Geriatrics, National-Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Background And Objective:
Long-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.
Methods:
We 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.
Results:
LL-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.
Conclusions:
LL-a is a potential novel local anesthetic for long-lasting nociceptive-selective analgesia.
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