Neuropathic pain


Most treatment for neuropathic pain is symptom management. Many neuropathic pain patients do not respond well to acetaminophen, NSAIDs, or weak opioids like codeine. 

Special Considerations: 

Although interventional management is normally reserved for patients who have tried and failed pharmacological treatment, it has been applied more frequently because of the limited efficacy and the considerable side effects of the neuropathic medications.

Pharmacological Management

First-line medications: Tricyclic antidepressant (TCA) like amitriptyline (Elavil) and nortriptyline (Pamelor), gabapentinoids like gabapentin (Neurontin) and pregabalin (Lyrica), and duloxetine (Cymbalta) are the first-line medications. TCA and duloxetine have similar mechanism in inhibiting the reuptake of serotonin and norepinephrine and thus facilitating the descending inhibitory pathway to reduce pain, but duloxetine has less side effects than TCA. Gabapentinoids bind to calcium channel a2d1 subunit. 

Second-line medications: Lidocaine 5% patch has modest therapeutic gain in treating postherpetic neuralgia (PHN). High-concentration capsaicin (8%) patch, which desensitizes TRPV1 nociceptive fibers, can be used to treat PHN, diabetic and non-diabetic painful neuropathies. Tramadol, a weak opioid agonist with additional effect in inhibiting serotonin and norepinephrine reuptake, is effective in treating peripheral neuropathic pain.

Third-line medications: Opioids are only mildly effective in managing neuropathic pain, with significant adverse effects. The effect of other neuropathic medications is either weak, negative, or inconclusive.

Interventional Management

Injections: Epidural steroid injection provides modest pain reduction with functional improvement for <3 months in treating cervical and lumbar radiculopathies, acute zoster-associated neuropathic pain, and compression-related peripheral neuropathic pain. Sympathetic ganglion blocks can be used to treat some complex regional pain syndrome patients.

Neuromodulation: Spinal cord stimulation (SCS) stimulated by classical square-wave monophasic pulse with frequency 30-100 Hz generates paresthesia in the painful region to replace neuropathic pain sensation. New generation SCS with burst stimulation of 40 Hz burst with five spikes at 500 Hz per burst, or high-frequency stimulation of 10 kHz with sinusoidal waveforms, provides similar or better pain reduction without generating paresthesia. Newly developed dorsal root ganglion (DRG) stimulation, peripheral nerve stimulation, and intrathecal pump can be effective to reduce neuropathic pain in a selected patient population. Psychological evaluation is a key component for the success for neuromodulation management. 

Physical therapy

It can be beneficial for many neuropathic pain patients. Specifically, mirror therapy is effective in managing patients with complex regional pain syndrome – phantom limb pain.

Psychological therapy

Many neuropathic pain patients have psychological comorbidity such as anxiety and depression. Cognitive-behavioral therapy (CBT) is the most common psychological tool to manage these patients.


Colloca L, Ludman T, Bouhassira D, et al. Neuropathic pain. Nat Rev Dis Primers. 2017;3:17002.

Su PP, Guan Z. Perioperative Use of Gabapentinoids: Comment. Anesthesiology. 2021;134(4):665-666.