Analgesic and sedative concentrations of lignocaine shunt tonic and burst firing in thalamocortical neurones

Abstract

1. The effects of lignocaine [lidocaine] HCl (0.6 μM–1 mM) on the membrane electrical properties and action potential firing of neurones of the ventral posterolateral (VPL) nucleus of the thalamus were investigated using whole cell recording techniques in rat brain slices in vitro.

2. Bath application of lignocaine reversibly decreased the input resistance (R_i) of VPL neurones. This effect was observed at low, clinically sedative and analgesic concentrations (i.e., maximal amplitude at 10 μM) whereas higher concentrations (300 μM–1 mM) had no effect on R_i.

3. Lignocaine (10–100 μM) depolarized VPL neurones up to 14 mV in a reversible manner.

4. Consistent with a decreased R_i, low concentrations of lignocaine shunted the current required for spike generation in the tonic pattern. Lignocaine increased the threshold amplitude of current required for firing and decreased the tonic firing frequency, without concomitant elevation of the voltage threshold for firing or reduction in the maximal rate of rise (dV/dt_max) of spikes.

5. Low concentrations of lignocaine shunted low threshold spike (LTS) burst firing evoked either from hyperpolarized potentials or as rebound bursts on depolarization from prepulse-conditioned potentials.

6. Higher concentrations of lignocaine (300 μM–1 mM), not associated with a decrease in R_i, elevated the voltage threshold for firing and reduced the dV/dt_max of spikes in a concentration-dependent fashion.

7. In conclusion, low concentrations of lignocaine shunted tonic and burst firing in VPL neurones by decreasing R_i, a mechanism not previously described for local anaesthetics in the CNS. We suggest that a decreased resistance in thalamocortical neurones contributes to the sedative, analgesic, and anaesthetic properties of systemic lignocaine in vivo.

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