Abstract
Capsaicin, the active component of chili peppers, can produce sensory-selective peripheral nerve blockade. Coadministration of capsaicin and tetrodotoxin, a site-1 sodium channel blocker, can achieve a synergistic effect on duration of nerve blocks. However, capsaicin can be neurotoxic, and tetrodotoxin can cause systemic toxicity. We evaluated whether codelivery of capsaicin and tetrodotoxin liposomes can achieve prolonged local anesthesia without local or systemic toxicity. Capsaicin- and tetrodotoxin-loaded liposomes were developed. Male Sprague-Dawley rats were injected at the sciatic nerve with free capsaicin, capsaicin liposomes, free tetrodotoxin, tetrodotoxin liposomes, and blank liposomes, singly or in combination. Sensory and motor nerve blocks were assessed by a modified hotplate test and a weight-bearing test, respectively. Local toxicity was assessed by histologic scoring of tissues at the injection sites and transmission electron microscopic examination of the sciatic nerves. Systemic toxicity was assessed by rates of contralateral nerve deficits and/or mortality. The combination of capsaicin liposomes and tetrodotoxin liposomes achieved a mean duration of sensory block of 18.2 hours (3.8 hours) [mean (SD)], far longer than that from capsaicin liposomes [0.4 hours (0.5 hours)] (P < .001) or tetrodotoxin liposomes [0.4 hours (0.7 hours)] (P < .001) given separately with or without the second drug in free solution. This combination caused minimal myotoxicity and muscle inflammation, and there were no changes in the percentage or diameter of unmyelinated axons. There was no systemic toxicity. The combination of encapsulated tetrodotoxin and capsaicin achieved marked prolongation of nerve block. This combination did not cause detectable local or systemic toxicity. Capsaicin may be useful for its synergistic effects on other formulations even when used in very small, safe quantities.
Highlights
Local anesthetics are commonly used in peripheral nerve blockade for management of postoperative pain
This work paves the way for the development of safer and more effective local anesthetics
While capsaicin in solution has been commonly used for local anesthesia, including in combination with site-1 sodium channel blockers,[14,15,16] to our knowledge, this is the first time that capsaicin liposomes have been used for this purpose
Summary
Local anesthetics are commonly used in peripheral nerve blockade for management of postoperative pain. Capsaicin (8-methyl-N-vanillyl-6-nonenamide), the active component of chili peppers,[6,7,8] produces sensory-selective analgesia.[6,9,10] It selectively binds to the TRPV1 ion channel, which is expressed on primary afferent nociceptors and enables their depolarization and excitation, leading to nociceptive responses; after initial excitation, prolonged exposure to capsaicin appears to desensitize the TRPV1 channel, resulting in analgesia.[9,11,12,13] At low concentrations of capsaicin, nerve blockade is relatively brief. The duration of capsaicin-induced nerve blocks can be prolonged by its coadministration with several other compounds, including bupivacaine, lidocaine,[14] amitriptyline, and others.[15]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
