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PMID: 10863041 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S. Review

Systemic lidocaine for neuropathic pain relief.

Pain ·Vol. 87 ·No. 1 ·2000-07-00 ·Pages 7-17

Mao J, Chen LL

Abstract

The effectiveness of systemic lidocaine in relieving acute and chronic pain has been recognized for over 35 years. In particular, systemic lidocaine has been utilized both as a diagnostic and therapeutic tool for intractable neuropathic pain during the last decade. The introduction of oral lidocaine congeners such as mexiletine has significantly extended the usage of lidocaine therapy in chronic pain settings. However, a number of clinical issues remain to be addressed including (1) an effective, meaningful dose range for the clinical lidocaine test, (2) the predictive value of the lidocaine test for an oral trial of lidocaine congeners, (3) identification of pain symptoms and signs relieved by systemic lidocaine, (4) comparisons of therapeutic effects between systemic lidocaine and its oral congeners, and (5) long-term outcomes of systemic lidocaine and its oral congeners. Mechanisms of neuropathic pain relief from lidocaine therapy are yet to be understood. Both central and peripheral mechanisms have been postulated. Systemic lidocaine is thought to have its suppressive effects on spontaneous ectopic discharges of the injured nerve without blocking normal nerve conduction. However, there remain inconsistencies in the scientific basis underlying the clinical application of lidocaine therapy. Recent demonstration of changes in tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels following nerve injury and their link to certain neuropathic pain symptoms may lead to the development of subtype-specific sodium channel blockers. The thoughtful use of lidocaine therapy and the potential application of subtype-specific sodium channel blockers could provide better management of distinctive neuropathic pain symptoms.

MeSH Terms
Administration, Oral Analgesics/administration & dosage,therapeutic use Animals Humans Lidocaine/administration & dosage,therapeutic use Mexiletine/therapeutic use Neuralgia/drug therapy,metabolism Sodium Channel Blockers
Chemicals
Analgesics Sodium Channel Blockers Mexiletine Lidocaine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Mao Jianren
MGH Pain Center, Massachusetts General Hospital, Harvard Medical School, 15 Parkman Street, Suite WACC-324, Boston, MA 02114, USA Arnold Pain Center, Beth Isareal and Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Chen Lucy L
References (63)
63 references, click to expand
  1. Abdi S, Lee DH, Chung JM. The anti-allodynic effects of amytriptyline, gabapentin, and lidocaine in a rat model of neuropathic pain. Anesth Analg. 1998;87:1360-1366.
  2. Akopian AN, Sivilotti L, Wood JN. A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons. Nature. 1996;379:257-262.
  3. Akopian AN, Souslova V, England S, Okuse K, Ogata N, Ure J, Smith A, Kerr BJ, McMahon SB, Boyce S, Hill R, Stanfa L, Dickenson AH, Wood JN. The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways. Nat Neurosci. 1999;2:541-548.
  4. Awerbuch GI, Sandyk R. Mexiletine for thalamic pain syndrome. Int J Neurosci. 1990;55:129-133.
  5. Bartlett EE, Hutaserani O. Xylocaine for the relief of postoperative pain. Anesth Analg. 1961;40:296-304.
  6. Bath FW, Jensen TS, Kastrup J, Stigsby B, Dejgard A. The effect of intravenous lidocaine on nociceptive processing in diabetic neuropathy. Pain. 1990;40:29-34.
  7. Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain. 1988;33:87-107.
  8. Boas RA, Covino BG, Shahnarian A. Analgesic responses to I.V. lidocaine. Br J Anesth. 1982;54:501-505.
  9. Brose W, Cousins MJ. Subcutaneous lidocaine for treatment of neuropathic cancer pain. Pain. 1991;45:145-148.
  10. Calissi PT, Jaber LA. Peripheral diabetic neuropathy: current concepts in treatment. Ann Pharmacol. 1995;29:769-776.
  11. Cassuto J, Wallin G, Hogstrom S, Faxen A, Ricmback G. Inhibition of postoperative pain by continuous low-dose intravenous infusion of lidocaine. Anesth Analg. 1985;64:971-974.
  12. Chabal C, Russell LC, Burchial KJ. The effect of intravenous lidocaine, tocainide, and mexiletine on spontaneously active fibers originating in rat sciatic neuromas. Pain. 1989;38:333-338.
  13. Chabal C, Jacobson L, Mariano A, Chaney E, Britell CW. The use of oral mexiletine for the treatment of pain after peripheral nerve injury. Anesthesiology. 1992;76:513-517.
  14. Chaplan SR, Bach FW, Shafer SL, Yaksh TL. Prolonged alleviation of tactile allodynia by intravenous lidocaine in neuropathic rats. Anesthesiology. 1995;83:775-785.
  15. Chapman V, Ng J, Dickenson AH. A novel spinal action of mexiletine in spinal somatosensory transmission of nerve injured rats. Pain. 1998;77:289-296.
  16. Chong SF, Bretscher ME, Mailliard JA, Tschetter LK, Kimmel DW, Hatfield AK, Loprinz CL. Pilot study evaluating local anesthetics administered systemically for treatment of pain in patients with advanced cancer. J Pain Sympt Manage. 1997;13:112-117.
  17. Chouu-Tan FY, Tuel SM, Johnson JC. Effect of mexiletine on spinal cord injury dysesthetic pain. Am J Phys Med Rehab. 1996;75:84-87.
  18. Cummins TR, Waxman SG. Downregulation of tetrodotoxin-resistant sodium currents and upregulation of a rapidly repriming tetrodotoxin-sensitive sodium current in small spinal sensory neurons after nerve injury. J Neurosci. 1997;17:3503-3514.
  19. Davis RW. Successful treatment for phantom limb pain. Orthopedics. 1993;16:691-695.
  20. Dejgard A, Petersen P, Kastrup J. Mexiletine for treatment of chronic painful diabetic neuropathy. Lancet. 1988;2:9-11.
  21. Devor M. Neuropathic pain and injured nerve: peripheral mechanisms. Br Med Bull. 1991;47:619-630.
  22. Devor M, Wall PD. Cross-excitation in dorsal root ganglia of nerve-injured and intact rats. J Neurophysiol. 1990;64:1733-1746.
  23. Devor M, Wall PD, Catalan N. Systemic lidocaine silences ectopic neuroma and DRG discharges without blocking nerve conduction. Pain. 1992;48:261-268.
  24. Devulder JE, Ghys L, Dhondt W, Rolly G. Neuropathic pain in a cancer patient responding to subcutaneously administered lignocaine. Clin J Pain. 1993;9:220-223.
  25. Edmondson EA, Simpson RK Jr, Stubler DK, Beric A. Systemic lidocaine therapy for poststroke pain. South Med J. 1993;86:1093-1096.
  26. Edwards WT, Habib F, Burney RG, Begin G. Intravenous lidocaine in the management of various chronic pain states. A review of 211 cases. Reg Anesth. 1985;10:1-6.
  27. Ferrante FM, Paggiol J, Cherukuri S, Arthur GR. The analgesic response to intravenous lidocaine in the treatment of neuropathic pain. Anesth Analg. 1996;82:91-97.
  28. Galer BS, Miller KV, Rowbotham MC. Responses to intravenous lidocaine infusion differs based on clinical diagnosis and site of nervous system injury. Neurology. 1993;43:1233-1235.
  29. Galer BS, Harle J, Rowbotham MC. Response to intravenous lidocaine infusion predicts subsequent response to oral mexiletine: a prospective study. J Pain Sympt Manage. 1996;12:161-167.
  30. Gracely RH, Lynch SA, Bennett GJ. Painful neuropathy: altered central processing maintained dynamically by peripheral input. Pain. 1992;51:175-194.
  31. Hunter JC, Gogas KR, Hedley LR, Jacobson LO, Kassotakis L, Thompson J, Fontana D. The effect of novel anti-epileptic drugs in rat experimental models of acute and chronic pain. Eur J Pharmacol. 1997;324:153-160.
  32. Jarvis B, Coukell AJ. Mexiletine: a review of its therapeutic use in painful diabetic neuropathy. Drugs. 1998;56:691-707.
  33. Jasmin L, Kohan L, Franssen M, Janni G, Goff JR. The cold plate as a test of nociceptive behaviors: description and application to the study of chronic neuropathic and inflammatory pain models. Pain. 1998;75:367-382.
  34. Jett MF, McGuirk J, Waligora D, Hunter JC. The effect of mexiletine, desipramine and fluoxetine in rat models involving central sensitization. Pain. 1997;69:161-169.
  35. Kajander KC, Wakisaka S, Bennett GJ. Spontaneous discharge originates in the dorsal root ganglion at the onset of a painful peripheral neuropathy in the rat. Neurosci Lett. 1992;138:225-228.
  36. Kastrup J, Petersen P, Dejgard A, Angelo HR, Hilsted J. Intravenous lidocaine infusion – a new treatment of chronic painful diabetic neuropathy. Pain. 1987;28:69-75.
  37. Kim SH, Chung JM. An experimental model of peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain. 1992;50:355-363.
  38. Lee DH, Liu X, Kim HT, Chung K, Chung JM. Receptor subtype mediating the adrenergic sensitivity of pain behavior and ectopic discharges in neuropathic Lewis rats. J Neurophysiol. 1999;81:2226-2233.
  39. Mao J, Price DD, Mayer DJ, Lu J, Hayes RL. Intrathecal MK-801 and local nerve anesthesia synergistically reduce nociceptive behaviors in rats with experimental peripheral mononeuropathy. Brain Res. 1992;576:254-262.
  40. Mao J, Price DD, Mayer DJ. Mechanisms of hyperalgesia and opiate tolerance: a current view of their possible interactions. Pain. 1995;62:259-274.
  41. Marchettini P, Lacerenza M, Marangoni C, Pellegata G, Sotgiu ML, Smirne S. Lidocaine test in neuralgia. Pain. 1992;48:377-382.
  42. Nordin M, Nystrom B, Wallin U, Hagbarth KE. Ectopic sensory discharges and paresthesia in patients with disorders of peripheral nerves, dorsal roots and dorsal column. Pain. 1984;20:231-245.
  43. Nystrom B, Hagbarth KE. Microelectrode recordings from transected nerves in amputees with phantom limb pain. Neurosci Lett. 1981;27:211-216.
  44. Omana-Zapata I, Khabbaz MA, Hunter JC, Bley KR. QX-314 inhibits ectopic nerve activity associated with neuropathic pain. Brain Res. 1997;771:228-237.
  45. Porreca F, Lai J, Bian D, Wegert S, Ossipov MH, Eglen RM, Kassotakis L, Novakovic S, Rabert D, Sangggameswaran L, Hunter JC. A comparison of the potential role of the tetrodotoxin-insensitive sodium channels, PN3/SNS and NaN/SNS2, in rat model of chronic pain. Proc Natl Acad Sci USA. 1999;96:7640-7644.
  46. Quashoff S, Grosskreutz J, Schroder JM, Schneider U, Grafe P. Calcium potentials and tetrodotoxin-resistant sodium potentials in unmyelinated c-fibers of biopsied human sural nerve. Neuroscience. 1995;69:955-965.
  47. Rowbotham M, Reisner-Keller LA, Fields HL. Both intravenous lidocaine and morphine reduced the pain of postherpetic neuralgia. Neurology. 1991;41:1024-1028.
  48. Rowbotham MC, Davies PS, Fields HL. Topical lidocaine gel relieves postherpetic neuralgia. Ann Neurol. 1995;37:246-253.
  49. Roy ML, Narahashi T. Differential properties of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in rat dorsal root ganglion neurons. J Neurosci. 1992;12:2104-2111.
  50. Schnider TW, Gaeta R, Minto CFB, Gregg KM, Shafer SL. Derivation and cross-validation of pharmacokinetic parameters for computer-controlled infusion of lidocaine in pain therapy. Anesthesiology. 1996;84:1045-1050.
  51. Seltzer Z, Cohn S, Ginzgurg R, Berlin B. Modulation of neuropathic pain behavior in rats by spinal disinhibition and NMDA receptor blockade of injury discharges. Pain. 1991;45:69-75.
  52. Sinnott CJ, Garfield JM, Strichartz GR. Differential efficacy of intravenous lidocaine in alleviating ipsilateral versus contralateral neuropathic pain in the rat. Pain. 1999;80:521-531.
  53. Sotgiu ML, Biella G, Castagna A, Lacerenza M, Marchettini P. Different time-courses of IV lidocaine effect on ganglionic and spinal units in neuropathic rats. NeuroReport. 1994;5:873-876.
  54. Stebbing MJ, Eschenfelder S, Habler HJ, Acosta MC, Janig W, McLachlan EM. Changes in the action potential in sensory neurons after axotomy in vivo. NeuroReport. 1999;10:201-206.
  55. Strichartz GR. Protracted relief of experimental neuropathic pain by systemic local anesthetics. Anesthesiology. 1995;83:654-655.
  56. Tanelian D, Brose W. Neuropathic pain can be relieved by drugs that are use-dependent sodium channel blockers: lidocaine, carbamazepine, and mexiletine. Anesthesiology. 1991;74:949-951.
  57. Tanelian D, MacIver MB. Analgesic concentrations of lidocaine suppress tonic A-delta and C fiber discharges produced by acute injury. Anesthesiology. 1991;74:934-936.
  58. Wall PD, Gutnick M. Properties of afferent nerve impulses originating from a neuroma. Nature. 1974;248:740-743.
  59. Wallace MS, Dyck JB, Rossi SS, Yaksh TL. Computer-controlled lidocaine infusion for the evaluation of neuropathic pain after peripheral nerve injury. Pain. 1996;66:69-77.
  60. Wallace MS, Laitin S, Licht D, Yaksh TL. Concentration-effect relations for intravenous lidocaine infusions in human volunteers: effects on acute sensory thresholds and capsaicin-evoked hyperpathia. Anesthesiology. 1997;86:1261-1272.
  61. Waxman SG, Dib-Hajj S, Cummins TR, Black JA. Sodium channels and pain. Proc Natl Acad Sci USA. 1999;96:7635-7639.
  62. Woolf CJ, Wiesenfeld-Hallin Z. The systemic administration of local anesthetics produces a selective depression of C-afferent fiber evoked activity in the spinal cord. Pain. 1985;23:361-374.
  63. Zhang JM, Song XJ, LaMotte RH. An in vitro study of ectopic discharge generation and adrenergic sensitivity in the intact, nerve-injured rat dorsal root ganglion. Pain. 1997;72:51-57.
Article Info
Journal
Pain
Abbr.
Pain
ISSN
0304-3959
DOI
10.1016/S0304-3959(00)00229-3
Published
2000-07-00
Pages
7-17
Language
English
Region
United States
NLM ID
7508686
Subset
IM
Grants
NIDA NIH HHS · DA08835 · United States
External Links
PubMed source DOI: 10.1016/S0304-3959(00)00229-3 View journal details
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