Neuropathic Pain

Amanda Macone, MD; James A. D. Otis, MD, FAAN, DABPM


Semin Neurol. 2018;38(6):644-653. 

In This Article


Neuropathic pain can respond transiently to high doses of intravenous local anesthetics, such as lidocaine.[49–51] Systemic administration appears to suppress the activity of dorsal horn cells, which respond to noxious stimulation. Spontaneous firing of damaged cells and axons is also suppressed.[52] Other anesthetics studied for use in neuropathic pain include tocainide (now off the U.S. market) and mexiletine, which are used for cardiac arrhythmias. While evidence of its efficacy is mixed, mexiletine has less toxicity and has been studied more thoroughly than tocainide. Higher dose studies suggest benefit, in particular for continuous dysesthetic pain.[53] The starting dose is 150 mg/day, increasing in 150-mg increments every 3 to 5 days, up to a dose of 300 mg three times per day or until side effects occur. Common side effects are dose related, and include nausea, dizziness, and tremors. Hematologic reactions are idiosyncratic and rare, which may make oral preparations of anesthetics a possible alternative to traditional agents in patients with blood dyscrasias. The efficacy and adverse effects are similar to other drugs used in neuropathic pain (sedation, dizziness), but the acute onset is an advantage to the local anesthetics. Challapalli et al[54] performed a meta-analysis, which reviewed oral and intravenous local anesthetics and validated their efficacy and safety in acute settings. There are many recent small studies comparing intravenous and oral anesthetics to placebo and more traditional drugs for neuropathic pain (gabapentin, carbamazepine). Local anesthetics could be considered for acute pain syndromes and in inpatient settings, relating to cancer therapy and surgery.

Ketamine, an NMDA receptor agonist, has been studied in neuropathic pain. While it has been shown to be useful as an anesthetic, there is conflicting data about the effectiveness of topical ketamine. In one study of diabetic neuropathy, topical 5% ketamine cream was not significantly more effective than placebo.[55] However, in another study of chemotherapy-induced peripheral neuropathy, a gel form of ketamine was well tolerated and helpful with symptoms of tingling, shooting, and burning pain.[56] Additionally, a double-blind, placebo-controlled trial of 20 patients with complex regional pain syndrome demonstrated that topical 10% ketamine inhibited hyperalgesia and allodynia in the affected limb.[57] These studies are difficult to directly compare, as they used different formulations and potencies of ketamine, but suggest that topical ketamine could possibly be useful as an adjunctive agent in certain patient populations with refractory neuropathic pain. The most common side effects of systemic ketamine do not typically occur with topical use, but include vivid dreaming, dysphoria, cognitive impairment, nausea, vomiting, and dizziness.[57,58]