Electric Current and Local Anesthetic Combination Successfully Treats Pain Associated With Diabetic Neuropathy
More than 24 million Americans have diabetes, and it is estimated that between 40% and 50% of these people will experience some form of nerve damage from their diabetes.1 Diabetic peripheral neuropathy (DPN) is a major cause of morbidity in patients, which is often manifested in the form of pain.
Considered the most distressing symptom of DPN, pain can be potentially disabling.2 Pharmacologic treatment of pain in patients with DPN includes tricyclic antidepressants, selective serotonin and norepinephrine reuptake inhibitors, and anticonvulsants.3 The only two drugs approved by the FDA for DPN are the antidepressant duloxetine (Cymbalta) and the anticonvulsant pregabalin (Lyrica). Patients with localized DPN may also try lidocaine patches (Lidoderm) or capsaicin before using a systemic medication.4
Despite advances in understanding the metabolic causes of neuropathy, treatments aimed at interrupting the pathological processes have been limited. What is known is that the first pathological change in the microvasculature is vasoconstriction, and as the disease progresses, neuronal dysfunction correlates closely with the development of vascular abnormalities, such as capillary basement membrane thickening and endothelial hyperplasia, which contribute to diminished oxygen tension and hypoxia.
Neuronal ischemia is a well-established characteristic of diabetic neuropathy (DN). Since all organs and systems are innervated, DN affects all peripheral nerves, including pain fibers, motor neurons, and autonomic nerves.
Available treatment options offer limited efficacy and potential side effects.5 Therefore, our approach was to combine bupivacaine with electrical stimulation. The bupivacaine is used to dilate capillaries and venules in the microcirculatory system, thereby causing increased circulation, which has been shown effective in various clinical studies to decrease pain in diabetic and nondiabetic patients.6 The electrical stimulation will provide both varied amplitudes and frequencies of electronic signals through computer-controlled, exogenously delivered specific parameter electroanalgesia.
While both bupivacaine and electrical stimulation are well studied, it is appropriate to further describe the difference between the electroanalgesia chosen versus standard electric current devices. Most electric current devices fall into a low frequency class with an amplitude modulation (AM) output of <2,000 Hz and 20 mAmp power. In these types of low-level machines, pain decrease is noted but there is no prolonged relief of pain.7 The device used in this study incorporates both AM, frequency modulation (FM), and AM/FM modes of stimulation to prevent accommodation. The device is currently in development and is not commercially available. A frequency range of 2,500 to 23,000 Hz with an energy delivery of up to 100 mAmp is possible. This allows for all of the benefits of medium frequency (2,000 to 100,000 Hz) stimulation, giving the patient the best possible chance for pain relief.
One hundred fourteen patients who had DPN-related pain were offered entry in this open-label trial. All study participants received a description of the treatment protocol and provided written informed consent to participate in the study. A total of 101 patients chose to complete the combined electric current and local anesthetic therapy protocol. The first patient enrolled in the trial in May 2008 and the last to enroll was in July 2010.
Of the 101 patients evaluated, there were 58 females and 43 males. The mean age of the study participants was 66.5 years old with a range of 31 to 87 years old. Patient ethnicity included 87% Caucasians, 9% Blacks, 4% Hispanics.
The entry criteria for this study were pain symptoms related to DPN. Figure 1 describes the primary and secondary pain characterized by each patient. Of the 101 patients enrolled, 67.6% had confirmed type 1 diabetes mellitus or type 2 diabetes, and 32.4% had prediabetes.
Out of the 101 patients, 60 received a baseline nerve conduction study (NCS) before their first treatment. Patients received a total of 12 electroanalgesia treatments, which were given 3 times per week (Monday, Wednesday, and Friday) for 4 weeks. The treatment duration was 25 minutes applied to either one or both feet, depending on where the neuropathy was present. During the first and third (Monday and Friday) treatment of each week, injections of 0.25% bupivacaine were performed using a 27-gauge needle. The injection sites were determined by the peripheral distribution of neuropathic pain. Up to four nerves were blocked in the same visit, including the sural, superficial peroneal, deep peroneal, saphenous, and posterior tibial.
Pre- and post-treatment pain assessments were given to each patient. The two assessments provided were the numeric rating system (NRS); and a quality of life pain questionnaire, which was administered either before or during treatment. The questionnaire measured and assessed quality of life–related items such as sleep, balance, walking, exercise, and participation in everyday activities creating a post-treatment score for each patient. At the conclusion of the study, if patients reported an incomplete response (defined as any pain score greater than 0 on the numeric rating scale) from the initial protocol, they were offered to complete a second course of therapy.
Of the 101 study participants, a subset of 60 were given a post–NCS to measure the effects of treatment on the function and ability of electrical conductance of the motor and sensory nerve.
The average pre-treated pain score on a scale of 0 to 10 was 5.39, and the average post-treatment score was 0.98, indicating an 81.8% reduction in symptoms. It is important to note that 31 of the 101 patients reported numbness as their primary symptom, which they did not define as pain, thereby entering an N/A when questioned by staff members. The above results interpret all N/A answers as a “0.” If we evaluate the 70 patients who did not report numbness as their primary symptom, the pre-treatment pain scores were 7.79, and the post-treatment pain score was 1.0, indicating an 87.2% reduction in symptoms.
The results in the first column of Table 1 identify the same 31 patients as those who did not receive an improvement in pain, but the patient response questionnaire captured their improvement in quality of life. Post-treatment quality of life benefits included improved pain-free sleeping, balance, walking, and enhanced ability to exercise—all of which were reported consistently across both genders.