Inhibition by non-steroidal anti-inflammatory drugs of compound action potentials in frog sciatic nerve fibers

Abstract

Aims: Although antinociception produced by non-steroidal anti-inflammatory drugs (NSAIDs) is partly attributed to nerve conduction inhibition, this has not been thoroughly examined yet. The aim of the present study was to reveal quantitatively how various types of NSAIDs affect compound action potentials (CAPs), a measure of nerve conduction.

Main methods: CAPs were recorded from the frog sciatic nerve by using the air-gap method.

Key findings: Soaking the sciatic nerve with acetic acid-based NSAIDs (diclofenac and aceclofenac) reduced the peak amplitude of CAP in a concentration-dependent manner; their IC₅₀ values were 0.94 and 0.47 mM, respectively. Other acetic acid-based NSAIDs (indomethacin, acemetacin and etodolac) also inhibited CAPs [the extent of inhibition: some 40% (1 mM), 40% (0.5 mM) and 15% (1 mM), respectively], except for sulindac and felbinac at 1 mM that had no effects on CAP peak amplitudes. A similar inhibition was produced by fenamic acid-based NSAIDs [tolfenamic acid (IC₅₀ = 0.29 mM), meclofenamic acid (0.19 mM), flufenamic acid (0.22 mM) and mefenamic acid] which are similar in chemical structure to diclofenac and aceclofenac; their derivatives (2,6-dichlorodiphenylamine and N-phenylanthranilic acid) also inhibited. On the other hand, salicylic acid-based (aspirin), propionic acid-based (ketoprofen, naproxen, ibuprofen, loxoprofen and flurbiprofen) and enolic acid-based (meloxicam and piroxicam) NSAIDs had no effects on CAP peak amplitudes.

Significance: At least a part of antinociception produced by NSAIDs used as a dermatological drug to alleviate pain may be attributed to their inhibitory effects on nerve conduction, which depend on the chemical structures of NSAIDs.

Keywords: Antinociception; Compound action potential; Conduction inhibition; Frog; NSAID; Sciatic nerve.