Neuropathic Pain

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


Semin Neurol. 2018;38(6):644-653. 

In This Article

Nonpharmacologic Therapy

In the management of neuropathic pain, there are several alternative, nonpharmacologic therapies that have been proposed as potentially beneficial. Some of these therapies include massage, reflexology, acupuncture, magnetic insoles, monochromic infrared energy therapy, transcutaneous electrical stimulation, and transcranial magnetic stimulation. While most of these alternative therapies have sparse high-quality evidence supporting their effectiveness, they are frequently sought out by patients as either an alternative or adjunctive treatment to their current medical therapies.

Acupuncture is based on the belief that an individual's state of health depends on maintaining balance and level energy in the body, and that stimulation of certain acupoints may correct imbalances in the flow of Qi through channels, known as meridian. Multiple types of acupuncture exist, with manual acupuncture being the most widely used, which refers to the insertion of thin, solid needles into acupuncture points on the skin.[85] Numerous trials have looked into the use of acupuncture in neuropathy, with the vast majority of the randomized control trials occurring in China. Overall, meta-analysis of the available RCTs finds overwhelmingly positive results, but there is concern regarding the quality and high risk of bias in these studies.[85,86] All trials utilized different acupuncture points without clear guidelines for selection; acupuncture points were not standardized between trials; and subjects in the treatment arm were frequently treated differently, with more investigator visits, raising concern that subject expectations and the role of placebo in general were not adequately addressed.[85–87] Therefore, more studies are needed to assess the true utility of acupuncture in the management of neuropathic pain.

The number of RCTs assessing massage therapy is limited and mixed. One study from Korea compared 30 minutes of massage every other day to foot bathing in patients with chemotherapy-induced peripheral neuropathy. They found no statistical difference in subjective neuropathy scales between the groups.[88] A separate randomized, open-label trial from Turkey compared aromatherapy massage three times a week to routine care over a 4-week period in 46 patients with diabetic peripheral neuropathy. At the end of their study, statistically significant improvement was seen in both pain and quality-of-life scores in the massage group compared with the control group.[89] Results for reflexology are similarly mixed. One randomized, open-label, control trial compared reflexology to standard treatment in 60 patients with chemotherapy-induced peripheral neuropathy. They found no statistically significant improvement in the peripheral neuropathy symptoms and in quality of life after 3 weeks.[90] A separate randomized, open-label, controlled trial from India compared reflexology twice daily to conventional therapy in 58 patients with diabetic neuropathy. After 5 months of treatment, they reported statistically improved pain scores at the end of a 6-month period.[91]

Repetitive transcranial magnetic stimulation (rTMS) has been investigated as a possible therapy for individuals with unilateral chronic neuropathic pain (e.g., trigeminal neuralgia, poststroke pain, postherpetic pain). Its proposed mechanism is through high-frequency stimulation of the primary motor cortex with a figure-of-eight coil parallel to the hemispheric midline. Numerous studies have found positive results with rTMS at both short term (1 week after stimulation) with a single rTMS session and midterm (1–6 weeks) with daily treatment for at least 5 days.[92–94] These studies did have limitations, though, including lack of standardization on the number of pulses per session, number of stimulations, and frequency used.[92] Two other small studies comparing rTMS to sham TMS failed to meet their primary endpoints and found no statistically significant difference between pain relief scores after rTMS use compared with sham TMS.[95,96] More trials are needed to further assess the utility of rTMS in the management of unilateral chronic neuropathic pain.

Magnetic sole inserts, monochromic infrared energy therapy, and transcutaneous electrical stimulation do not currently have sufficient evidence to support their use in the management of neuropathic pain. One randomized, double-blind, placebo-controlled trial compared magnetic sole inserts to placebo inserts in 259 patients with diabetic peripheral neuropathy. Patients wore the inserts for 4 months, and while not explicitly stated in the study, there was no statistically significant difference in the primary endpoint, which was improvement in pain scores from baseline to 4 months.[97] Najafi et al[98] performed a randomized, double-blind, sham-controlled trial to assess whether aqueous transcutaneous electrical stimulation could improve pain in patients with diabetic neuropathy. Fifty-four patients received five 30-minute treatments a week for 6 weeks in total. At the end of the study, while they suggest a positive trend in the active treatment group, there was no statistically significant difference between pain levels in the two groups. Monochromatic infrared energy (MIRE) devices were first approved by the Food and Drug Administration in 1994 to reduce pain and increase circulation and have been used in patients with soft-tissue trauma or wounds.[99] Three randomized control trials compared MIRE treatment to sham treatment in diabetic peripheral neuropathy.[99–101] All three of the trials did not find significant improvement in pain levels with MIRE treatment compared with placebo. Furthermore, in one of the studies, two patients in the active MIRE group developed superficial burns secondary to treatment.[99]