Use of bulleyaconitine A as an adjuvant for prolonged cutaneous analgesia in the rat.

Published

Journal Article

BACKGROUND: Bulleyaconitine A (BLA) is an analgesic and antiinflammatory drug isolated from Aconitum plants. BLA has several potential targets, including voltage-gated Na+ channels. We tested whether BLA elicited long-lasting cutaneous analgesia, when co-injected with lidocaine and epinephrine, as a model for prolonged infiltration anesthesia. METHODS: The local anesthetic properties of BLA were assessed by the patch-clamp technique in HEK293t cells expressing Nav1.7 and Nav1.8 neuronal Na+ channels, both crucial for nociception. Drug solutions (0.6 mL) were injected subcutaneously via rat shaved dorsal skin. Inhibition of the cutaneous trunci muscle reflex was evaluated by pinpricks. Skin cross-sections were stained with hematoxylin and eosin or with antibodies against PGP9.5. RESULTS: BLA at 10 microM interacted minimally with resting or inactivated Nav1.7 and Nav1.8 Na+ channels when infrequently stimulated to +50 mV for 3 ms. However, when stimulated at 2 Hz for 1000 pulses, their peak Na+ currents were >90% reduced by BLA. This use-dependent inhibition was not significantly reversed after 15-min washing. Complete nociceptive blockade after injection of lidocaine (0.5%)/epinephrine (1:200,000) lasted for approximately 1 h in rats; full recovery occurred after approximately 6 h. Co-injection of 0.125 mM BLA with lidocaine/epinephrine increased the duration of complete nociceptive blockade to 24 h. Full recovery occurred after approximately 6 days. Skin histology including peripheral nerve fibers appeared unaffected by BLA. CONCLUSIONS: BLA inhibits Nav1.7 and Nav1.8 Na+ currents in a use-dependent manner. Co-injection of BLA at

Full Text

Duke Authors

Cited Authors

  • Wang, C-F; Gerner, P; Schmidt, B; Xu, ZZ; Nau, C; Wang, S-Y; Ji, R-R; Wang, GK

Published Date

  • October 2008

Published In

Volume / Issue

  • 107 / 4

Start / End Page

  • 1397 - 1405

PubMed ID

  • 18806059

Pubmed Central ID

  • 18806059

Electronic International Standard Serial Number (EISSN)

  • 1526-7598

Digital Object Identifier (DOI)

  • 10.1213/ane.0b013e318182401b

Language

  • eng

Conference Location

  • United States