Painful Diabetic Neuropathy

Diabetes affects more than 30 million people in the United States and is a leading cause of morbidity. Over 25% diabetics also suffer from debilitating painful diabetic neuropathy in the lower legs and feet. This pain can be severe, difficult to control, and have a significant negative impact on quality of life. Opioid medications have historically been a mainstay of treatment for this pain, despite the risks. As the death toll from the U.S. opioid epidemic continues to rise, the need for quality alternative non-opioid medications to treat pain becomes more urgent. One of these potential medications is Low-Dose Naltrexone (LDN). This drug is reported to work by enhancing the body's natural pain relieving mechanisms and decreases inflammation by targeting specific cells called microglia which have been shown to influence chronic pain. LDN has been shown to be a safe medication with minimal side effects. Its efficacy has been demonstrated in other painful conditions but has never been fully studied for treating painful diabetic neuropathy. The goal of this randomized, placebo-controlled trial is to determine if LDN is effective for treating the pain caused by diabetic neuropathy. LDN's mechanism of action is well suited to treating painful diabetic neuropathy, and LDN shows significant promise as a safe, non-opioid alternative that can decrease pain and improve quality of life for those suffering from this painful condition.

Peripheral arterial disease (PAD) affects over 230 million adults worldwide and is a highly morbid, costly, and disabling condition. Ischemic leg pain drives disability in PAD patients and results from oxygen supply-demand mismatch, autonomic dysfunction, and muscle breakdown. This leg pain, which is unresponsive to traditional pharmacotherapy, limits the patient's tolerance to exercise, which is an important disease-modifying intervention. Spinal cord stimulation is a well-established therapy for medically intractable pain, including painful diabetic neuropathy (PDN) and ischemic pain, but is not part of the standard-of-care for PAD despite limited promising clinical data. Early studies used first-generation, tonic stimulation devices, but with these it was impossible to perform sham-controlled trials to test the treatment. Since then, new types of waveform treatments, including high-frequency spinal cord stimulation (SCS), have been shown to be more effective in the treatment of intractable pain. While high-frequency SCS is approved for PDN treatment, it has never been tested in the treatment of claudication pain from PAD. This study will enroll up to 15 participants between the ages of 19 and 89 who have PAD and PDN and are successfully implanted with a permanent SCS. Twelve weeks after SCS implantation, participants will receive two weeks of stimulation and two weeks of sham intervention, in random starting order. Blood flow, blood pressure, skin oxygen levels, and participant reported pain int the lower extremities will be assessed before SCS implantation, 12 weeks after SCS implantation and during each of the treatment periods. Participants will also complete a quality of life survey at the same time points. Comparisons of these measurements with the baseline and post-implantation measurements to determine the effects of SCS.

This study relies on the use of a smartphone application (SOMA) that the investigators developed for tracking daily mood, pain, and activity status in acute pain, chronic pain, and healthy controls over four months.The primary goal of the study is to use fluctuations in daily self-reported symptoms to identify computational predictors of acute-chronic pain transition, pain recovery, and/or chronic pain maintenance or flareups. The general study will include anyone with current acute or chronic pain, while a smaller sub-study will use a subset of patients from the chronic pain group who have been diagnosed with chronic low back pain, failed back surgery syndrome, or fibromyalgia. These sub-study participants will first take part in one in-person EEG testing session while completing simple interoception and reinforcement learning tasks and then begin daily use of the SOMA app. Electrophysiologic and behavioral data from the EEG testing session will be used to determine predictors of treatment response in the sub-study.

The purpose of the present study is to evaluate the role of peripheral afferent input for spontaneous pain in painful diabetic polyneuropathy