# 180 Parenteral Lidocaine for Neuropathic Pain


Author(s): Jay Thomas MD, PhD

Background In recent years reports have described the use of parenteral lidocaine for neuropathic pain. This Fast Fact reviews the use of parenteral lidocaine for neuropathic pain.

Mechanism   Lidocaine is a local anesthetic that is a nonselective sodium channel blocker. Sodium channel blockade is thought to be responsible for analgesia. Studies in animals and humans demonstrate that injured nerves develop abnormal, spontaneously active sodium channels at sites of nerve injury, along damaged nerves, and at the dorsal root ganglia of damaged nerves. Lidocaine can suppress this ectopic, spontaneous firing of aberrant sodium channels at concentrations that do not affect normal nerve or cardiac conduction1.

Clinical Trial Data

  • Small controlled studies have established systemic lidocaine to be effective in the relief of diabetic neuropathy and post-herpetic neuralgia2, 3.
  • A meta-analysis concluded that systemic lidocaine is superior to placebo for neuropathic pain, is as effective as other adjuvant analgesics, and is well tolerated4.
  •  Two small controlled trials in cancer pain found no benefit of systemic lidocaine5, 6. However, other case reports and one retrospective study support its use7.
  • One trial indicated that an analgesic response to lidocaine is a predictor of a successful response to mexiletene, an oral congener of lidocaine8. In practice, the validity of this finding has been questioned, and a high rate of side effects (predominantly gastrointestinal) from mexiletene have limited its use.


  • Multiple regimens have been described.
  • Typically a bolus dose between 1-5 mg/kg is administered intravenously over 15 to 60 minutes depending on the dose.
  • Time to analgesia has been reported from being between 1-45 minutes9.
  • If patients respond to initial bolus, ongoing IV or subcutaneous infusions can be provided over days to months depending on response.
  • Serum lidocaine levels should be followed at steady state (t½ ~100 minutes, so 3-5 half-lives for steady state ~5-8 hrs) and intermittently afterwards as clinically indicated. A target level of 2-5 mg/liter is based on dose-response studies and avoidance of side effects as below9.

Adverse Reactions Lidocaine has dose-related side effects that become progressively more severe at levels higher than 5 mg/liter, including myoclonus (~8 mg/l), seizures (>10 mg/l), and cardiovascular collapse (>25 mg/l)10. Although lidocaine after a myocardial infarction has been associated with a trend towards increased risk of arrhythmias, cardiac monitoring during studies of normal volunteers and patients has noted no cardiac risks at clinically appropriate levels. Lidocaine is rapidly and extensively metabolized by the liver. Metabolites are excreted by the kidney, thus adjustments may be needed in the case of liver and renal insufficiency, guided by monitoring steady state blood levels.

Summary There is weak, largely non-controlled evidence that systemic lidocaine can relieve neuropathic pain in selected patients. Definitive evidence to support its use in cancer pain (both neuropathic and opioid-refractory) awaits further prospective trials. Most practitioners, however, would not use it as a first line treatment and a pain or palliative care consult should precede its use.


  1. Devor M, Wall PD, Catalan N. Systemic lidocaine silences ectopic neuroma and DRG discharge without blocking nerve conduction. Pain. 1992; 48(2):261-8.
  2. Kastrup J, Petersen P, Dejgard A, Angelo HR, Hilsted J. Intravenous lidocaine infusion--a new treatment of chronic painful diabetic neuropathy? Pain. 1987; 28(1):69-75.
  3. Rowbotham MC, Reisner-Keller LA, Fields HL. Both intravenous lidocaine and morphine reduce the pain of postherpetic neuralgia. Neurology. 1991; 41(7):1024-8.
  4. Challapalli V, Tremont-Lukats IW, McNicol ED, Lau J, Carr DB. Cochrane Database of Systematic Reviews 2005, Issue 4. Art. No.: CD003345. DOI: 10.1002/14651858.CD003345.pub2.
  5. Ellemann K, Sjogren P, Banning AM, Jensen TS, Smith T, Geertsen P. Trial of intravenous lidocaine on painful neuropathy in cancer patients. Clin J Pain. 1989; 5(4):291-4.
  6. Bruera E, Ripamonti C, Brenneis C, Macmillan K, Hanson J. A randomized double-blind crossover trial of intravenous lidocaine in the treatment of neuropathic cancer pain. J Pain Symptom Manage. 1992; 7(3):138-40.
  7. Thomas J, Kronenberg R, Cox MC, Naco GC, Wallace M, von Gunten CF. Intravenous lidocaine relieves severe pain: results of an inpatient hospice chart review. J Palliat Med. 2004; 7(5):660-7.
  8. Galer BS, Harle J, Rowbotham MC. Response to intravenous lidocaine infusion predicts subsequent response to oral mexiletine: a prospective study. J Pain Symptom Manage. 1996; 12(3):161-7.
  9. Ferrante FM, Paggioli J, Cherukuri S, Arthur GR. The analgesic response to intravenous lidocaine in the treatment of neuropathic pain. Anesth Analg. 1996; 82(1):91-7.
  10. Bridenbaugh PO, Cousins MJ. Neural blockade in clinical anesthesia and management of pain. Philadelphia, PA: Lippincott, Williams, & Wilkins; 1998.

Fast Facts and Concepts are edited by Drew A Rosielle MD, Palliative Care Center, Medical College of Wisconsin. For more information write to: drosiell@mcw.edu. More information, as well as the complete set of Fast Facts, are available at EPERC: www.eperc.mcw.edu.

Version History: Current version re-copy-edited in May 2009.

Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Thomas J. Parenteral Lidocaine for Neuropathic Pain. Fast Facts and Concepts. May 2007; 180. Available at: http://www.eperc.mcw.edu/EPERC/FastFactsIndex/ff_180.htm.

Disclaimer: Fast Facts and Concepts provide educational information. This information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Facts cite the use of a product in a dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.

ACGME Competencies: Patient Care

Keyword(s): Pain – Non-Opioids