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

The effects of lignocaine [lidocaine] HCl (0.6 μ M –1 m M ) 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 . 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 μ M ) whereas higher concentrations (300 μ M –1 m M ) had no effect on R i . Lignocaine (10–100 μ M ) depolarized VPL neurones up to 14 mV in a reversible manner. 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 (d V /d t max ) of spikes. 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. Higher concentrations of lignocaine (300 μ M –1 m M ), not associated with a decrease in R i , elevated the voltage threshold for firing and reduced the d V /d t max of spikes in a concentration‐dependent fashion. 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 .British Journal of Pharmacology (1998) 124 , 1633–1642; doi: 10.1038/sj.bjp.0702015