Paradoxical Enhancement of Bupivacaine Anesthesia in Mice by Drugs That Open Sodium Channels

Abstract

Sodium channel drugs were used to modulate the anesthetic effects of bupivacaine in mice. Anesthesia was measured following perisciatic injection of bupivacaine with vehicle or neurotoxin in the popliteal region. The site 1 Na⁺ channel blocker tetrodotoxin alone was inactive, but increased the anesthetic effects of bupivacaine. We hypothesized that the site 2 and site 3 Na⁺ channel openers veratridine and anemone toxin II (ATXII), respectively, would antagonize bupivacaine. Paradoxically, both drugs enhanced bupivacaine. In bupivacaine-treated mice, a significant correlation was observed between limb weakness scores and paw withdrawal latencies. The correlation coefficients were higher when tetrodotoxin, veratridine, or ATXII was coadministered with bupivacaine. In conclusion, veratridine and ATXII may have increased the stimulus-dependent binding of bupivacaine to Na⁺ channels, thereby increasing the anesthetic effects of bupivacaine.

Enhancement of bupivacaine local anesthesia with the potassium channel blocker ibutilide

“…We have previously demonstrated that drugs that alter calcium channels or calcium release from intracellular pools can also change the potency of bupivacaine in a several tests of radiant heat nociception Smith and Lindsay, 2003;Smith et al, 2004). We have previously demonstrated that drugs that alter calcium channels or calcium release from intracellular pools can also change the potency of bupivacaine in a several tests of radiant heat nociception Smith and Lindsay, 2003;Smith et al, 2004).…”

“…To our knowledge, this is the first study to determine the influence of ibutilide alone and co-administered with bupivacaine in a test of nociception. We have previously demonstrated that drugs that alter calcium channels or calcium release from intracellular pools can also change the potency of bupivacaine in a several tests of radiant heat nociception Smith and Lindsay, 2003;Smith et al, 2004). Within the popliteal region, the sensory and motor axons of the sciatic nerve bifurcate into the common fibular nerve and the tibial branch which innervate the lower leg and paw.…”