Inhibition of the compound action potentials of frog sciatic nerves by aroma oil compounds having various chemical structures

Abstract

Plant-derived chemicals including aroma oil compounds have an ability to inhibit nerve conduction and modulate transient receptor potential (TRP) channels. Although applying aroma oils to the skin produces a local anesthetic effect, this has not been yet examined throughly. The aim of the present study was to know how nerve conduction inhibitions by aroma oil compounds are related to their chemical structures and whether these activities are mediated by TRP activation. Compound action potentials (CAPs) were recorded from the frog sciatic nerve by using the air-gap method. Citral (aldehyde), which activates various types of TRP channels, attenuated the peak amplitude of CAP with the half-maximal inhibitory concentration (IC50) value of 0.46 mmol/L. Another aldehyde (citronellal), alcohol (citronellol, geraniol, (±)-linalool, (−)-linalool, (+)-borneol, (−)-borneol, α-terpineol), ester (geranyl acetate, linalyl acetate, bornyl acetate), and oxide (rose oxide) compounds also reduced CAP peak amplitudes (IC50: 0.50, 0.35, 0.53, 1.7, 2.0, 1.5, 2.3, 2.7, 0.51, 0.71, 0.44, and 2.6 mmol/L, respectively). On the other hand, the amplitudes were reduced by a small extent by hydrocarbons (myrcene and p-cymene) and ketone (camphor) at high concentrations (2–5 mmol/L). The activities of citral and other TRP agonists ((+)-borneol and camphor) were resistant to TRP antagonist ruthenium red. An efficacy sequence for the CAP inhibitions was generally aldehydes ≥ esters ≥ alcohols > oxides >> hydrocarbons. The CAP inhibition by the aroma oil compound was not related to its octanol–water partition coefficient. It is suggested that aroma oil compounds inhibit nerve conduction in a manner specific to their chemical structures without TRP activation.

The essential oil of Lippia alba and its components affect Drosophila behavior and synaptic physiology

“…For local anesthetics, there was a correlation between potency and lipid solubility as measured by the octanol/water partition coefficient (Strichartz et al, 1990); however, this relationship was not seen for monoterpenes. Instead, their relative potency in reducing the CAP amplitude was monoterpene aldehydes≥alcohols≥ketones >> hydrocarbons (Ohtsubo et al, 2015). The relative potency of our EO components in inhibiting synaptic transmission was consistent with these studies of the CAP amplitude.…”

“…through VG Ca 2+ channels. Citral, carvone and limonene reduced the compound action potential (CAP) amplitude in frog sciatic nerve; citral was the most potent (IC 50 0.5 mmol l −1 ) followed by carvone (IC 50 1.4-2.0 mmol l −1 ), and limonene produced a slight reduction in CAP at 10 mmol l −1 (Kawasaki et al, 2013;Ohtsubo et al, 2015). This reduction in CAP amplitude presumably resulted from inhibition of VG Na + channels since a correlation between a reduction in CAP amplitude and VG Na + currents was demonstrated for the monoterpenes linalool and carvacrol (Joca et al, 2012;Leal-Cardoso et al, 2010).…”

α-Terpineol Induces Gastric Retention of Liquids by Inhibiting Vagal Parasympathetic Pathways in Rats

“…It was suggested that compounds with different chemical structures could inhibit nerve conduction possibly without TRP activation. In this direction, functional tests performed in the presence of TRPV1 or TRPA1 antagonists failed to demonstrate a role for TRPs in the pharmacological effects of linalool [20] or β-citronellol [21,22], two volatile compounds possessing the ability to activate TRPs [19,23]. Thus, the chances to obtain a positive result in experiments that combine α-terpineol and antagonists of TRPs under our experimental conditions appear small.…”

“…Such findings raise the possibility that α-terpineol is a candidate to induce inhibition of nerve conduction by acting on TRP proteins. However, a recent study compared the inhibitory effects of α-terpineol and other volatile compounds on frog sciatic nerves [19]. It was suggested that compounds with different chemical structures could inhibit nerve conduction possibly without TRP activation.…”

Inhibition of Fast Nerve Conduction Produced by Analgesics and Analgesic Adjuvants—Possible Involvement in Pain Alleviation

“…CAP inhibitory actions similar to those of analgesic adjuvants and NSAIDs were seen by plant-derived compounds that are known to produce antinociception by their oral, intraperitoneal or intrathecal administration (see [257,258] for reviews). Thus, frog sciatic nerve CAPs were inhibited by plant-derived compounds whose IC 50 values were close to those of analgesic adjuvants and NSAIDs ( [27,[259][260][261]; see [262] for review). Carvacrol, thymol, citronellol, bornyl acetate, citral, citronellal and geranyl acetate had IC 50 values of 0.34, 0.34, 0.35, 0.44, 0.46, 0.50 and 0.51 mM, respectively, in reducing CAP peak amplitudes.…”