Abstract
Intravenous lidocaine administration produces an analgesic effect in various pain states, such as neuropathic and acute pain, although the underlying mechanisms remains unclear. Here, we hypothesized that intravenous lidocaine acts on spinal cord neurons and induces analgesia in acute pain. We therefore examined the action of intravenous lidocaine in the spinal cord using the in vivo patch-clamp technique. We first investigated the effects of intravenous lidocaine using behavioural measures in rats. We then performed in vivo patch-clamp recording from spinal substantia gelatinosa (SG) neurons. Intravenous lidocaine had a dose-dependent analgesic effect on the withdrawal response to noxious mechanical stimuli. In the electrophysiological experiments, intravenous lidocaine inhibited the excitatory postsynaptic currents (EPSCs) evoked by noxious pinch stimuli. Intravenous lidocaine also decreased the frequency, but did not change the amplitude, of both spontaneous and miniature EPSCs. However, it did not affect inhibitory postsynaptic currents. Furthermore, intravenous lidocaine induced outward currents in SG neurons. Intravenous lidocaine inhibits glutamate release from presynaptic terminals in spinal SG neurons. Concomitantly, it hyperpolarizes postsynaptic neurons by shifting the membrane potential. This decrease in the excitability of spinal dorsal horn neurons may be a possible mechanism for the analgesic action of intravenous lidocaine in acute pain.
Highlights
Intravenous lidocaine administration produces an analgesic effect in various pain states, such as neuropathic and acute pain, the underlying mechanisms remains unclear
To determine whether the site of the inhibitory action of intravenous lidocaine exists on the soma or presynaptic terminals, we further investigated the effects of intravenous lidocaine on miniature excitatory postsynaptic currents (EPSCs) in the presence of the Na+ channel blocker TTX (0.5 μM)
In the presence of TTX (0.5 μM), intravenous lidocaine (10 mg/kg) induced an outward current (12.1 ± 5.7 pA) in 7 of 10 (70%) neurons. These results suggest that intravenous lidocaine produces a postsynaptic outward current to hyperpolarize substantia gelatinosa (SG) neurons in the spinal dorsal horn
Summary
Intravenous lidocaine administration produces an analgesic effect in various pain states, such as neuropathic and acute pain, the underlying mechanisms remains unclear. Intravenous lidocaine inhibits glutamate release from presynaptic terminals in spinal SG neurons It hyperpolarizes postsynaptic neurons by shifting the membrane potential. This decrease in the excitability of spinal dorsal horn neurons may be a possible mechanism for the analgesic action of intravenous lidocaine in acute pain. In neuropathic or inflammatory pain animal models, intravenous lidocaine is thought to exert analgesic effects by blocking specific Na+ channels in injured nerves or dorsal root ganglia (DRG)[10,11,12,13] because these channels are more sensitive to lidocaine[14]. Interactions with other signalling systems have been reported for many years, but have not received much attention, because the clinical importance of such effects has never been firmly established
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