• Cheng Zhou, Lei Tang, Qinqin Yin, Linghui Yang, Deying Gong, Yi Kang, Hangxue Cao, Jing Fan, Yujun Zhang, Duo Qian, Qianqian Zhang, Bowen Ke, Jin Liu, Wensheng Zhang, and Jun Yang.
• Laboratory 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.
• Reg Anesth Pain Med. 2020 Jun 1; 45 (6): 412-418.

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.© American Society of Regional Anesthesia & Pain Medicine 2020. No commercial re-use. See rights and permissions. Published by BMJ.

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