Molecular mechanisms of action of systemic lidocaine in acute and chronic pain: a narrative review

Abstract

Systemic administration of the local anaesthetic lidocaine is antinociceptive in both acute and chronic pain states, especially in acute postoperative and chronic neuropathic pain. These effects cannot be explained by its voltage-gated sodium channel blocking properties alone, but the responsible mechanisms are still elusive. This narrative review focuses on available experimental evidence of the molecular mechanisms by which systemic lidocaine exerts its clinically documented analgesic effects. These include effects on the peripheral nervous system and CNS, where lidocaine acts via silencing ectopic discharges, suppression of inflammatory processes, and modulation of inhibitory and excitatory neurotransmission. We highlight promising objectives for future research to further unravel these antinociceptive mechanisms, which subsequently may facilitate the development of new analgesic strategies and therapies for acute and chronic pain.

Inhibition of Fast Nerve Conduction Produced by Analgesics and Analgesic Adjuvants—Possible Involvement in Pain Alleviation

“…Local anesthetics have been used for the treatment of the neuropathic pain with an expectation of the inhibition of nerve AP conduction in animals [ 225 , 226 ] and humans [ 227 , 228 , 229 , 230 ], although other effects including neurotransmitter receptor and TRP channel activation are possibly involved in antinociception [ 231 ]. Many of local anesthetics reduce both voltage-gated Na + and K + channel current amplitudes ([ 71 ]; see [ 76 , 231 , 232 ] for reviews).…”

Perioperative intravenous lignocaine infusion for postoperative pain control in patients undergoing surgery of the spine: protocol for a systematic review and meta-analysis

“…These include: wound healing, coagulation, postoperative cognitive dysfunction, paralytic ileus and lung protection. 17 Why is it important to do this review? Analgesic strategies in patients undergoing spinal surgery are best implemented through multimodal regimens.…”

“…Voltage gated sodium channel (VGSC) Classic mechanism of action is through blockade of VGSC 17 ; Intravenous lignocaine may inhibit VGSC in peripheral nerves and/or dorsal root ganglia 23 ; Potassium channels Lignocaine effect on potassium channels is available through experimental evidence in animal models 60 ;…”

“…Calcium channels Lignocaine effect on calcium channels is available through experimental evidence in human animal models 17 ;…”

“… 16 17 The exact molecular mechanisms of lignocaine action in modifying both acute and chronic pain are still somewhat elusive. 17 As an anti-inflammatory agent, lignocaine inhibits leucocyte activation and adhesion to the site of injury in both in vitro and in vivo models. 18 Lignocaine protects cells from inflammation by blocking the priming of neutrophils and therefore inhibiting the release of superoxide anions and interleukin-1B (IL-1B).…”