Systemic Administration of Local Anesthetics to Relieve Neuropathic Pain: A Systematic Review and Meta-Analysis

Abstract

We reviewed randomized controlled trials to determine the efficacy and safety of systemically administered local anesthetics compared with placebo or active drugs. Of 41 retrieved studies, 27 trials of diverse quality were included in the systematic review. Ten lidocaine and nine mexiletine trials had data suitable for meta-analysis (n = 706 patients total). Lidocaine (most commonly 5 mg/kg IV over 30-60 min) and mexiletine (median dose, 600 mg daily) were superior to placebo (weighted mean difference on a 0-100 mm pain intensity visual analog scale = -10.60; 95% confidence interval: -14.52 to -6.68; P < 0.00001) and equal to morphine, gabapentin, amitriptyline, and amantadine (weighted mean difference = -0.60; 95% confidence interval: -6.96 to 5.75) for neuropathic pain. The therapeutic benefit was more consistent for peripheral pain (trauma, diabetes) and central pain. The most common adverse effects of lidocaine and mexiletine were drowsiness, fatigue, nausea, and dizziness. The adverse event rate for systemically administered local anesthetics was more than for placebo but equivalent to morphine, amitriptyline, or gabapentin (odds ratio: 1.23; 95% confidence interval: 0.22 to 6.90). Lidocaine and mexiletine produced no major adverse events in controlled clinical trials, were superior to placebo to relieve neuropathic pain, and were as effective as other analgesics used for this condition.

Mexiletine Therapy for Chronic Pain: Survival Analysis Identifies Factors Predicting Clinical Success

“…Tremont-Lukats et al recently confirmed mexiletine's analgesic efficacy for neuropathic pain in a meta-analysis. 2 However, the mean decrease on a 100-point VAS score was only 11, leading experts to question mexiletine's clinical use and specifically call for an integrated assessment of mexiletine's efficacy and side effects. 3 However, historically there has been no consensus on how to evaluate the overall clinical performance of an analgesic drug such as mexiletine, one that has inconsistent analgesia and common overwhelming side effects.…”

“…1 Tremont-Lukats et al recently confirmed mexiletine's analgesic efficacy for neuropathic pain in a meta-analysis. 2 However, mexiletine induces nausea in up to 40% of patients and dizziness in up to 26% of patients.…”

Management of Fibromyalgia Syndrome

“…In controlled studies, intravenous lidocaine was effective in different Pain Manag. (2016) 6(4) 390 REviEW Okifuji, Gao, Bokat & Hare future science group dosages and regimens for the treatment of a variety of neuropathic pain states such as poststroke pain, peripheral neuropathy, diabetic neuropathy and complex regional pain syndrome I and II [130].…”

“…Intravenous lidocaine promotes a decrease in spinal sensitization, reducing spontaneous pain, dysesthesia, hyperalgesia and allodynia [129]. In controlled studies, intravenous lidocaine was effective in different REviEW Okifuji, Gao, Bokat & Hare future science group dosages and regimens for the treatment of a variety of neuropathic pain states such as poststroke pain, peripheral neuropathy, diabetic neuropathy and complex regional pain syndrome I and II [130].…”

“…In controlled studies, intravenous lidocaine was effective in different Pain Manag. (2016) 6(4) 390 REviEW Okifuji, Gao, Bokat & Hare future science group dosages and regimens for the treatment of a variety of neuropathic pain states such as poststroke pain, peripheral neuropathy, diabetic neuropathy and complex regional pain syndrome I and II [130].For FM, the small uncontrolled studies in the 1990s [131,132] have shown promising results in pain reduction in those who received lidocaine infusion therapy. Another recent open trial [133] showed statistically significant, although small, reduction in pain and other FM symptoms at post-infusion as well as 30 days after five consecutive intravenous lidocaine infusion of escalating dose to 5 mg/kg.…”