Effects of peripheral nerve block adjuvants with and without local anesthetic on ex vivo rodent nerve A-alpha/beta, A-delta, and C fiber activity

INTRODUCTION: Preclinical and clinical studies have shown enhanced analgesia when some adjuvant medications are combined with local anesthetics during peripheral nerve (PN) blockade. However, the effects of many adjuvants on individual PN fibers, that is, A-alpha/beta, A-delta, and C, remain poorly characterized. METHODS: Using ex vivo rat sciatic nerve electrophysiology, changes in action potential amplitude (AMP) and area under the curve (AUC) for A-alpha/beta, A-delta, and C fibers were used to determine the half-maximal effective concentrations (EC50) for four adjuvants (dexmedetomidine, magnesium, epinephrine, ketorolac) with and without bupivacaine. At a clinically relevant "high" concentration, each adjuvant's effects on AMP, AUC, and latency to 100% peak AMP were evaluated with and without bupivacaine, then statistically compared with control (no drug) and bupivacaine-alone conditions. RESULTS: EC50s for the four adjuvants were determined for some fibers: dexmedetomidine (A-alpha/beta, A-delta, C fibers), magnesium (A-delta fibers), epinephrine (C fibers), and ketorolac (A-alpha/beta and A-delta fibers). At the high concentrations, adjuvants alone produced few significant differences when compared with control, and adjuvants with bupivacaine produced few significant differences when compared with bupivacaine alone. DISCUSSION: Using ex vivo electrophysiology, we identified EC50s of dexmedetomidine, magnesium, epinephrine, and ketorolac for A-alpha/beta, A-delta, and/or C fiber AMP, demonstrating that these adjuvants have direct effects on PN fibers. Future investigations may benefit by testing different concentrations of adjuvants and bupivacaine in an in vivo model incorporating a broader range of time points.