D-Cycloserine for the Treatment of Chronic, Refractory Low Back Pain

Chronic pain is common and affects millions of people in the United States, resulting in a marked deterioration in physical and emotional functioning and quality of life. Chronic back pain (CBP) is the most common form of chronic pain, and its high prevalence reflects the fact that no effective and safe treatments for CBP exist. Non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are widely used to treat CBP, yet well-designed studies have failed to show long-term efficacy in CBP. Furthermore, both drug classes are associated with major safety warnings, focused on the potential for death and abuse. Therefore, the need for a non-opioid medication to treat pain is clear and reflected in one of the Fiscal Year 2016 Peer Reviewed Medical Research Program (PRMRP) Areas of Encouragement, namely “Non- opioid Pain Management”. Our proposal is responsive to the specific objective of “Research on treatments for chronic pain management, particularly for complex patients (i.e., chronic, high-utilization polypharmacy patients)”, which is typical of many of the individuals who suffer with CBP. Previous research by our group has demonstrated that chronic pain differs in many ways from acute pain, particularly with regard to how it is processed in the brain, what parts of the brain are activated (parts responsible for emotion, mood) and how pain is managed. Animal studies of chronic pain identified several compounds that specifically interfered with brain pathways in chronic pain, resulting in less pain and pain behavior. Based on these findings, our group undertook a pilot study of one of these compounds, D-cycloserine (DCS), a drug currently marketed in the United States to treat tuberculosis but which also has effects on the brain. This study in 41 individuals with CBP demonstrated efficacy similar in magnitude to that of NSAIDs and opioids but without their associated side effects. The goal of this proposal is first and foremost to determine in a larger group of people with CBP the extent and duration of pain relief resulting from treatment with DCS. This will be accomplished by undertaking a randomized, placebo-controlled trial of DCS, lasting for 24 weeks. We will also investigate how DCS affects brain activity, utilizing brain magnetic resonance imaging (MRI) scans. And from the results of the brain scans and questionnaires people complete during the study regarding their pain and behavior, we will develop a new questionnaire that will be able to predict who will respond to DCS treatment. We will also carefully assess the safety of DCS by following side effects reported by study participants. This proposal can have a significant impact on people with CBP and potentially on people with any type of chronic pain, relieving their pain and improving their ability to function. This may be of particular significance to groups like the military in which back pain is a common condition, often arising from some aspect of their activity and leading to an inability to return to previous responsibilities. Importantly, pain relief will be accomplished without the dangerous and limiting side effects of the currently available treatments. Furthermore, results from this study will allow the development of a clinical tool to predict who will respond to DCS treatment, and thus this study has the potential to introduce personalized medicine – the right drug for the right person - for the first time to the pain field.