Systemic lidocaine silences ectopic neuroma and DRG discharge without blocking nerve conduction

&NA; Systemic application of lidocaine in rats suppressed ectopic impulse discharge generated both at sites of experimental nerve injury and in axotomized dorsal root ganglion (DRG) cells. ED50 for DRGs was significantly lower than for the injury site. Lidocaine doses effective at blocking ectopic discharge failed to block the initiation or propagation of impulses by electrical stimulation, and only minimally affected normal sensory receptors. This selectivity may account for the effectiveness of systemic local anesthetics and other drugs that share the same mechanism of action (notably certain anticonvulsants and antiarrhythmics), in the management of neuropathic paresthesias and pain. In addition, it may account for the prolonged analgesia sometimes obtained using regional local anesthetic block.

[1]  E. Williams Classification of Antiarrhythmic Actions , 1989 .

[2]  B. Hille,et al.  Local anesthetics: hydrophilic and hydrophobic pathways for the drug- receptor reaction , 1977, The Journal of general physiology.

[3]  U. Lindblom,et al.  THE MECHANISM OF THE PAIN IN TRIGEMINAL NEURALGIA , 1959, Journal of neurology, neurosurgery, and psychiatry.

[4]  Y. Ito,et al.  Management of Intractable Pain in Adiposis Dolorosa with Intravenous Administration of Lidocaine , 1976, Anesthesia and analgesia.

[5]  M. Devor,et al.  Ongoing activity in severed nerves: source and variation with time , 1978, Brain Research.

[6]  M. Devor,et al.  Axoplasmic transport block reduces ectopic impulse generation in injured peripheral nerves , 1983, Pain.

[7]  S. Rapoport,et al.  Regulation of the microenvironment of peripheral nerve: Role of the blood-nerve barrier , 1987, Progress in Neurobiology.

[8]  L. Wiklund Human Hepatic Blood Flow and its Relation to Systemic Circulation during Intravenous Infusion of Bupivacaine or Etidocaine , 1977, Acta anaesthesiologica Scandinavica.

[9]  N. Benowitz,et al.  Clinical Pharmacokinetics of Lignocaine , 1978, Clinical pharmacokinetics.

[10]  L. C. Russell,et al.  Pain response to perineuromal injection of normal saline, epinephrine, and lidocaine in humans , 1992, Pain.

[11]  L. C. Russell,et al.  The effect of intravenous lidocaine, tocainide, and mexiletine on spontaneously active fibers originating in rat sciatic neuromas , 1989, Pain.

[12]  M. Devor,et al.  Afterdischarge and interactions among fibers in damaged peripheral nerve in the rat , 1987, Brain Research.

[13]  R. Meyer,et al.  Myelinated afferents signal the hyperalgesia associated with nerve injury , 1988, Pain.

[14]  C. Difazio,et al.  Lidocaine as an Analgesic for Experimental Pain , 1980, Anesthesiology.

[15]  W. Catterall Common modes of drug action on Na+ channels: local anesthetics, antiarrhythmics and anticonvulsants , 1987 .

[16]  G. Pickering The mechanism of pain. , 1946, Physiotherapy.

[17]  P. Thorne,et al.  The use of intravenous lignocaine in the diagnosis and treatment of tinnitus , 1978, The Journal of Laryngology & Otology.

[18]  K. Burchiel Carbamazepine inhibits spontaneous activity in experimental neuromas , 1988, Experimental Neurology.

[19]  N. Mor,et al.  The Sabra rat: definition of a laboratory animal. , 1984, Israel journal of medical sciences.

[20]  Patrick D. Wall,et al.  Ongoing activity in peripheral nerves: The physiology and pharmacology of impulses originating from a neuroma ☆ , 1974 .

[21]  J. Kastrup,et al.  MEXILETINE FOR TREATMENT OF CHRONIC PAINFUL DIABETIC NEUROPATHY , 1988, The Lancet.

[22]  U. Lindblom,et al.  Prolonged relief of neuralgia after regional anesthetic blocks. A call for further experimental and systematic clinical studies , 1990, Pain.

[23]  P. D. Wall,et al.  Sensory afferent impulses originate from dorsal root ganglia as well as from the periphery in normal and nerve injured rats , 1983, Pain.

[24]  M. Moskowitz,et al.  Relief of Vascular Headache with Intravenous Lidocaine: Clinical Observations and a Proposed Mechanism , 1988 .

[25]  E. Williams A Classification of Antiarrhythmic Actions Reassessed After a Decade of New Drugs , 1984 .

[26]  J. Jacobs,et al.  Vascular leakage in the dorsal root ganglia of the rat, studied with horseradish peroxidase , 1976, Journal of the Neurological Sciences.

[27]  C. Woolf,et al.  The systemic administration of local anaesthetics produces a selective depression of C-afferent fibre evoked activity in the spinal cord , 1985, Pain.

[28]  K. Burchiel Spontaneous impulse generation in normal and denervated dorsal root ganglia: Sensitivity to alpha-adrenergic stimulation and hypoxia , 1984, Experimental Neurology.

[29]  G. Haegerstam Effect of i.v. administration of lignocaine and tetrodotoxin on sensory units in the tooth of the cat. , 1979, British journal of anaesthesia.

[30]  U. Lindblom,et al.  The analgesic effect of tocainide in trigeminal neuralgia , 1987, Pain.

[31]  J. Kastrup,et al.  The effect of intravenous lidocaine on nociceptive processing in diabetic neuropathy , 1990, Pain.

[32]  A. Hodgkin,et al.  The frequency of nerve action potentials generated by applied currents , 1967, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[33]  Y. Yaari,et al.  Phenytoin suppresses spontaneous ectopic discharge in rat sciatic nerve neuromas , 1985, Neuroscience Letters.

[34]  M. Swerdlow Anticonvulsant drugs and chronic pain. , 1984, Clinical neuropharmacology.