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Julka IS, Alvaro M, Kumar D. Beneficial effects of electrical stimulation on neuropathic symptoms in diabetes patients. Journal of Foot and Ankle Surgery 1998; 37(3): 191-198.

Forty-one (76%) patients reported a 44.0 ± 4.0% subjective improvement in their neuropathic pain. The overall improvement in pain was also significant on an analog scale of 10 (p < .01), and correlated well with the percent amelioration data (12=.65). These data suggest an effectiveness of electrotherapy in managing neuropathic pain as an adjunct to the analgesics.

A significantly higher incidence of ulcers of feet was seen in the treatment failure group (p < .03). Four of the 10 patients in the treatment failure group and 2 of 24 electrotherapy responders had ulcers.

Kumar D, Marshall HJ. Diabetic peripheral neuropathy: amelioration of pain with transcutaneous electrostimulation. Diabetes Care 1997; 20(11): 1702-1705.

In the electrotherapy group (n = 18), symptomatic improvement was seen in 15 (83%) cases, 3 of which were completely asymptomatic.T

The pain score declined from 3.17 ± 0.12 to 1.44 ± 0.25 (P < 0.01) and the posttreatment pain scores were considerably lower (P < 0.03), indicating a substantial treatment effect over and above any placebo influence.

Patients in the electrotherapy group reported greater reduction in symptoms (52 ± 7% vs. 27 ± 10% in control subjects, P < 0.05) on an analog scale.

Dubinsky RM, Miyasaki JM. Assessment: efficacy of transcutaneous electric nerve stimulation in the treatment of pain in neurologic disorders (an evidence-based review). Neurology 2010; 74: 173-176.

TENS should be considered in the treatment of painful diabetic neuropathy

Two Class II studies compared TENS to TENS-sham, and 1 Class III study compared high-frequency muscle stimulation to TENS in the relief of pain associated with mild diabetic peripheral neuropathy (distal symmetric neuropathy, excluding patients with mononeuropathies and plexopathies).

A modest reduction in VAS was found for TENS compared to TENS-sham, and a larger proportion felt benefit with the high frequency muscle stimulation compared to TENS.

Hamza et al. Percutaneous electrical nerve stimulation: a novel analgesic therapy for diabetic neuropathic pain. Diabetes Care 2000; 23: 365-370.

Compared with the pain VAS scores before active (6.2 ± 1.0) and sham (6.4 ± 0.9) treatments, pain scores after treatment were reduced to 2.5 ± 0.8 and 6.3 ± 1.1, respectively.

60% reduction in pain noted with TENS.

Active PENS treatments produced significant pain relief, increased levels of mood and physical activity, and improved quality of sleep compared with the sham treatments during the course of the 3-week treatment period.

Although the precise mechanism of PENS-induced analgesia is not known at this time, it appears to be related to both neural modulation and an increase in endogenous opioid-like substances (e.g., dynorphins, endorphins, enkephalins) within the central nervous system.

Interestingly, both Cameron et al. and Mo et al. have reported that peripheral electrical stimulation can normalize the changes in nerve conduction velocity when using an experimental diabetic rat model.

Walsh et al. also observed a decrease in nerve conduction latency and mechanical pain threshold when TENS was applied directly over the nerve.

In addition, clinical studies have suggested that the use of electrotherapy in diabetic patients produces decreases in mechanical pain threshold, a local vasodilatory effect, and enhanced wound healing.

Somers DL and Clemente FR. Contralateral high or a combination of high and low-frequency transcutaneous electrical nerve stimulation reduces mechanical allodynia and alters dorsal horn neurotransmitter content in neuropathic rats. The Journal of Pain 2009; 10(2): 221-229.

Daily, high frequency or a combination of high- and low-frequency TENS reduced mechanical (P < .001), but not thermal allodynia in the right hind paw when compared with untreated CCI rats.

Daily high frequency TENS elevated the dorsal horn synaptosomal content of GABA bilaterally (P < .014) and a combination of high- and low-frequency TENS elevated the dorsal horn content of aspartate (P < .001), glutamate (P < .001) and glycine (P < .001) bilaterally over that seen in untreated CCI rats.

The present findings support a contralateral approach to the application of TENS and suggest that distinct strategies for TENS application may differentially alter neurotransmission in the central nervous system.

Reichstein L, Labrenz S, Ziegler D, Martin S. Effective treatment of symptomatic diabetic polyneuropathy by high-frequency external muscle stimulation. Diabetologia 2005; 48: 824-828.

This pilot study shows, for the first time, that HF can ameliorate the discomfort and pain associated with DSP, and suggests that HF is more effective than TENS.

Subgroup analysis revealed that HF was more effective than TENS in relieving the symptoms of non-painful neuropathy (HF100%, seven out of seven; TENS: 44%, four out of nine; p<0.05) and painful neuropathy (HF: 69%, nine out of 13; TENS: 25%, three out of 12; p<0.05).

Kloth LC. Electrical stimulation for wound healing: a review of evidence from in vitro studies, animal experiments, and clinical trials. Lower Extremity Wounds 2005; 4(1): 23-44.

Electrically induced acceleration of the closure of wounds caused by nonischemic diabetic neuropathy has been demonstrated in 4 studies, including 2 randomized controlled clinical trials.

In a randomized controlled trial, Lundeberg et al evaluated the effect of biphasic asymmetric PC on wound healing. Sixty four patients with chronic diabetic neuropathic foot ulcers were randomized to receive either active ES (parameters not given) or sham control ES for 20 minutes twice a day for 12weeks in addition to standard wound care. Polarity of the treatment electrode was changed each session. After 12 weeks, there was a statistically significant treatment effect based on the closure of 42% of wounds in the active ES group compared to 15% of the controls.

Baker et al 144 conducted a randomized trial involving 80 individuals with diabetes and 114 open wounds. Wounds were randomized to be treated either with symmetrical or biphasic asymmetrical PC plus standard care or with standard care alone. The authors demonstrated that both waveforms combined with standard care enhanced the wound-healing rate by nearly 60% over control wounds treated with only standard care.

Jin DM, Xu Y, Geng DF, Yan TB. Effect of transcutaneous electrical nerve stimulation on symptomatic diabetic peripheral neuropathy: a meta-analysis of randomized controlled trials. Diabetes Research and Clinical Practice 2010; 89: 10-15.

The reductions in mean pain score were significantly greater in TENS group than in placebo TENS group in 4 weeks and 6 weeks follow-up.

TENS therapy was associated with significantly subjective improvement in overall neuropathic symptoms in 12 weeks follow-up.

It is reported that the annual cost of DPN together with its complications in the US varies between 4.6 billion and 13.7 billion dollars.

Kumar et al. reported that 16.6–36% of patients in TENS group even had complete pain relief.

A clinical study, which evaluated the effect of the different frequency of the electrical stimulus of TENS on the postoperative pain, illustrated that TENS at mixed (2 Hz and 100 Hz) frequencies of stimulation produced a slightly greater analgesic effect than either low (2 Hz) or high (100 Hz) frequencies alone. It implies that the stimulation frequency played an important role in TENS treatment.

Experimental study has demonstrated that electrical stimulation could improve endoneurial blood flow and normalize deficits in nerve conduction velocity. Several clinical studies showed that a good clinical response with improvement of peripheral circulation was achieved in the stimulated field, and that may be related to the increased endogenous opioid-like substances (e.g. endorphins, encephalin) within the central nervous system, which inhibit the transmission of painful stimuli by closing the 'gate' to pain transmission by C fibres.

Somers DL and Somers MF. Treatment of neuropathic pain in a patient with diabetic neuropathy using transcutaneous electrical nerve stimulation applied to the skin of the lumbar region. Physical Therapy 1999; 79: 767-775.

For several reasons, such an alternative electrode placement might be desirable when TENS is used to treat people with painful diabetic neuropathy.

First, large diameter myelinated nerve fibers may be damaged in the painful extremities of people with severe diabetic neuropathy. Because activation of large-diameter myelinated nerve fibers is believed to be the mechanism by which high-frequency TENS produces analgesia the modality may be more effective for people with severe neuropathy if it is delivered through undamaged peripheral nerves.

Another reason to consider not placing the electrodes on the painful extremity is the concern for integument integrity. Because vascular insufficiency so often affects the extremities of people with diabetes skin breakdown is a common occurrence and an important concern. Although there is no evidence that TENS causes skin breakdown, the most prevalent side effect of TENS when used for pain relief is skin irritation.

Consequently, it may be desirable to avoid placing the TENS electrodes on an involved extremity of a person with diabetes. Such a strategy also may be prudent when diabetic neuropathy results in diminished pain and temperature sensation, a frequent occurrence in the affected limb of people with diabetic neuropathy.

Following 20 minutes of TENS on the first day of treatment, the patient reported a 38% reduction in intensity of pain. After 17 days, the patient reported no pain following 20 minutes of TENS and that she could sleep through the night.

Wikstrom SO, Svedman P, Svensson H, Tanweer AS. Effect of transcutaneous nerve stimulation on microcirculation in intact skin and blister wounds in healthy volunteers. Scand J Plast Reconst Hand Surg 1999; 33: 195-201.

The mean blood flow increased by 40% during low frequency TENS and by 12% during high frequency TENS.

The microcirculatory blood flow, measured as red blood cell velocity (RBC-V) in 5–14 individual capillaries in each wound, was assessed before and during 45 minutes of TENS (2 Hz and 100 Hz). Mean RBC-V increased by 23% during low frequency TENS (n = 6) and by 17% during high frequency TENS (n = 8).

Khalil Z, Merhi M. Effects of aging on neurogenic vasodilator responses evoked by transcutaneous electrical nerve stimulation: relevance to wound healing. Journal of Gerontology 2000; 55A (60): B257-B263.

Using the healing endpoint as the time when full wound contraction occurred, the active group required 14.7 +/- 0.2 days for complete healing, a significant improvement over the sham group (21.8 +/- 0.3 days).

We contend that low-frequency TENS can improve the vascular response of old rats. In addition, wound healing in aged rats can be accelerated by peripheral activation of sensory nerves at low-frequency electrical stimulation parameters.