Neuropathic Pain

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


Semin Neurol. 2018;38(6):644-653. 

In This Article


Managing neuropathic pain in patients can be challenging, and typically requires a multifaceted approach. Of the available pharmacologic agents, those with the strongest evidence supporting their use include tricyclic antidepressants, SNRIs, and certain antiseizure agents. While TCAs have few drug–drug interactions, their use may be limited due to sedation and side effects secondary to their anticholinergic properties. They should be used with caution in the elderly population and avoided in those with QTC prolongation. SNRIs tend to be better tolerated than the classic TCAs due to their decreased α-blockade and fewer anticholinergic effects and may be good alternative or adjunctive agents in managing neuropathic pain. Of the anticonvulsants, while phenytoin was the first AED utilized for pain management, its use in neuropathic pain has decreased following the approval of newer anticonvulsants with fewer side effects and drug interactions. Of the newer AEDs, gabapentin and pregabalin have proven effective in the management of most neuropathic pain conditions, and require less patient monitoring than their alternatives, such as valproic acid, carbamazepine, and oxcarbazepine. Topical agents, such as capsaicin and lidocaine patches, may be useful adjunctive agents in difficult-to-control neuropathic pain but are typically insufficient as sole therapy.

There are numerous nonpharmacologic therapies that have been utilized in the management of neuropathic pain, such as acupuncture, massage therapy, and reflexology. Despite their use as adjunctive therapies in clinical practice, the current evidence supporting their use is not strong, with a lack of well-conducted, randomized placebo-controlled trials. Despite the unclear efficacy of these alternative therapies at this time, with the exception of MIRE therapy, studies so far have at least shown that they appear safe with few adverse effects. While clear recommendations on their role cannot be made, these alternative therapies could be considered as adjunctive therapy in specific patient populations who have either been unable to tolerate traditional pharmacologic therapies or desire to pursue nonpharmacologic options.

In summary, there are multiple classes of nonopioid medications that produce varying degrees of pain reduction. For the management of neuropathic pain, combination therapies are likely useful, though studies supporting this practice are few. To date, there have been few high-quality studies reviewing the efficacy of nonpharmacologic therapies for the treatment of neuropathic pain. Going forward, randomized, placebo-controlled trials with appropriate sham therapy would be useful in further determining the true potential of adjunctive nonpharmacologic therapy in the management of neuropathic pain.