Analgesic and sedative concentrations of lignocaine shunt tonic and burst firing in thalamocortical neurones.
The effects of lignocaine [lidocaine] HCl (0.6 microM(-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. Bath application of lignocaine reversibly decreased the input resistance (Ri) of VPL neurones. This effect was observed at low, clinically sedative and analgesic concentrations (i.e., maximal amplitude at 10 microM) whereas higher concentrations (300 microM(-1) mM) had no effect on Ri. Lignocaine (10-100 microM) depolarized VPL neurones up to 14 mV in a reversible manner. Consistent with a decreased Ri, 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. 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 microM - 1 mM), not associated with a decrease in Ri, elevated the voltage threshold for firing and reduced the dV/dt(max) of spikes in a concentration-dependent fashion. In conclusion, low concentrations of lignocaine shunted tonic and burst firing in VPL neurones by decreasing Ri, 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.
Department of Pharmacology & Therapeutics, The University of British Columbia, Vancouver, Canada.
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Schwarz
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D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects*; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013787:Thalamic Nuclei / Q000166:cytology* / Q000187:drug effects*
D018712:Analgesics, Non-Narcotic; D000779:Anesthetics, Local; D006993:Hypnotics and Sedatives; D008012:Lidocaine