The leguminous lectin of Lonchocarpus araripensis promotes antinociception via mechanisms that include neuronal inhibition of Na(+) currents.

OBJECTIVE AND DESIGN: Sodium channels are highly expressed in nociceptive sensory neurons during hypernociceptive conditions. Based on the presence of a glycosidic portion in the sodium channel ß subunit associated to the antinociceptive effect of leguminous lectins via lectin domain, this study investigated the antinociceptive activity of the lectin isolated from Lonchocarpus araripensis seeds (LAL) in mice behavioral models and in NaV current in the nociceptor of rat dorsal root ganglion (DRG). MATERIAL/METHODS: LAL antinociceptive activity and the participation of opioid system, lectin domain and sodium channels were evaluated in Swiss mice models of nociception (formalin, capsaicin, hot plate, tail flick, von Frey) and in primary cultures of Wistar rats neurons of DRG (patch clamp). RESULTS: LAL presented inhibitory effects in the nociception induced by chemical and mechanical, but not by thermal stimuli and reduced total Na(+) current. LAL activity was inhibited by the lectin association with its binding sugar N-acethyl-glucosamine. CONCLUSION: LAL inhibits peripheral hypernociception by mechanisms that involve the lectin domain, inflammatory mediators and Na(+) channels. The innovative inhibitory action of leguminous lectins on NaV current brings new insights for the investigation of sodium channels role in nociception.

Inhibitory effect of terpinen-4-ol on voltage-dependent potassium currents in rat small sensory neurons.

The biological and pharmacological activities of the terpenoid terpinen-4-ol (1), which include depressant effects in the central nervous system, are of potential therapeutic interest. In the present study, the effects of 1 on neuronal excitability and voltage-dependent K(+) currents in the somatic sensory system were investigated. Intact and dissociated neurons of rat dorsal root ganglia (DRG) were used for intracellular and patch-clamp recordings, respectively. In neurons of intact DRG, 1 caused concentration-dependent depolarization of the resting membrane potential and increased input resistance. 1 also inhibited action potentials (AP) and decreased AP parameters, with the exception of AP duration, which was increased. In dissociated DRG neurons, 1 partially blocked the total K(+) current in a concentration-dependent manner. 1 inhibited I(A), I(D), and I(K) with IC50 values of 3.2 ± 03, 0.7 ± 0.1, and 1.6 ± 0.7 mM, respectively. 1 did not shift either the steady-state activation or inactivation curves of I(A), I(D), and I(K) but reduced the decay time course of I(A). The alterations in DRG reported here are consistent with the inhibition of K(+) currents and might partially explain the effect of 1 on excitable tissues.

Effects of 1,8-cineole on electrophysiological parameters of neurons of the rat superior cervical ganglion.

1. 1,8-Cineole is a non-toxic small terpenoid oxide believed to have medicinal properties in folk medicine. It has been shown to have various pharmacological effects, including blockade of the compound action potential (AP). In the present study, using intracellular recording techniques, we investigated the effects of 1,8-cineole on the electrophysiological parameters of neurons of the superior cervical ganglion (SCG) in rats. 2. 1,8-Cineole (0.1-6 mmol/L) showed reversible and concentration-dependent effects on various electrophysiological parameters. At 3 and 6 mmol/L, but not at 0.1 and 1 mmol/L, 1,8-cineole significantly diminished the input resistance (R(i)) and altered the resting potential (E(m)) to more positive values. At 6 mmol/L, 1,8-cineole completely blocked all APs within 2.7 +/- 0.6 min (n = 12). In neurons exposed to 3 and 1 mmol/L 1,8-cineole, the effects regarding excitability varied from complete AP blockade to minor inhibition of AP parameters. The depolarization of E(m) and the decrease in R(i) induced by 6 mmol/L 1,8-cineole were unaltered by 200 micromol/L niflumic acid, a well known blocker of Ca(2+)-activated Cl(-) currents. 3. Significant correlations (Pearson correlation test) were found between changes in E(m) and decreases in AP amplitude (r = -0.893; P < 0.00282) and maximum ascendant inclination (r = -0.799; P < 0.0173), but not for maximum descendant inclination (r = 0.598; P < 0.117). Application of current to restore the transmembrane potential equal to control E(m) values in the presence of 6 mmol/L 1,8-cineole resulted in the partial recovery of AP. 4. The present study shows that 1,8-cineole effectively blocks the excitability of SCG neurons, probably through various mechanisms, one of which acts indirectly via depolarization of the neuronal cytoplasmatic membrane.

Linalool blocks excitability in peripheral nerves and voltage-dependent Na+ current in dissociated dorsal root ganglia neurons.

Linalool is a terpene that occurs as a major constituent of essential oils of many plants of widespread distribution. It possesses several biological and pharmacological activities, including depressant effects on the central nervous system and olfactory receptors. The present study investigated whether linalool affects the excitability of peripheral components of the somatic sensory system. We used sciatic nerve and preparations of intact and dissociated neurons of dorsal root ganglion for extracellular, intracellular and patch-clamp recordings. Linalool concentration-dependently (0.3-2.0mM) and reversibly blocked the excitability of the sciatic nerve. It inhibited peak-to-peak amplitude of the compound action potential (IC(50) was 0.78+/-0.04 mM). At 0.8mM, it reversibly increased rheobase and chronaxy (from 3.2+/-0.1 V and 52.4+/-4.1 micros to 4.2+/-0.3 V and 71.2+/-5.5 micros (n=5), respectively) and inhibited with greater pharmacological potency the amplitude of the compound action potential components corresponding to axons with slower velocity of conduction. In a similar concentration range (0.1-6mM), linalool concentration-dependently and reversibly blocked the generation of action potentials of intact dorsal root ganglion neurons without alteration of resting membrane potential and input resistance, and inhibited the voltage-gated Na(+) current of dissociated dorsal root ganglion neurons. In conclusion, we demonstrated that linalool acts on the somatic sensory system with local anesthetic properties, since it blocked the action potential by acting on voltage-dependent Na(+) channels. This finding is important in showing the potential usefulness of linalool as a pharmacotherapeutic agent.