Although opioids are widely prescribed for chronic pain due to fibromyalgia (FM), the effects of opioid medications on the activity of the central nervous system (CNS) and on reward behavior and clinical outcomes have not been determined for this indication. Current evidence strongly suggests that altered activity in the brain and spinal cord contributes to the chronicity of FM symptoms, and opioids are known to produce similar changes in CNS activity. Thus, the central hypothesis is that opioids exacerbate existing alterations in pain and reward processes in the CNS in individuals with FM. To test this hypothesis, the proposal includes clinical neuroimaging research projects and a comprehensive training plan that Dr. Katherine Martucci, Ph.D., will conduct under the guidance of expert mentors, advisors and collaborators at Stanford University (Drs. Sean Mackey, Brian Knutson, Jodie Trafton, and Gary Glover). During the K99 mentored training phase (Years 1-2;
Aims 1 & 2), Dr. Martucci will conduct a clinical research study using brain and spinal cord functional magnetic resonance imaging (fMRI) to measure differences between individuals with FM who take opioids and individuals with FM who do not.
Aim 1 will determine the effect of opioids on levels of pain and spinal cord activity in FM.
Aim 2 will determine the effect of opioids on the brain's reward systems and reward behavior in FM. This phase will include a training program in advanced CNS neuroimaging analysis, brain reward processes, opioid therapy, clinical research, advanced statistics, and responsible research conduct. It will also include training in lab management, mentoring, and teaching through didactic courses at Stanford University and from established mentors. During the R00 independent research phase (Years 3-5;
Aim 3), Dr. Martucci will conduct a longitudinal clinical study of individuals with FM, both opioid-dependent and opioid-nave, to determine changes in pain, symptoms, and CNS activity in FM over time. The projects and training of the initial mentored K99 training phase will effectively prepare Dr. Martucci to conduct the projects proposed for the later independent R00 phase. Together, these projects will provide a more complete picture of the effects of opioid medications in FM and will fill the critical knowledge gaps of inherent risks of neurobiological changes and altered behavior and psychology that occur when prescribing opioids. This proposal requests support for Dr. Martucci to receive additional training in order to enhance and expand her current level of graduate and postdoctoral research expertise in neurobiology of pain processing and chronic pain research. This will enable her to successfully transition to an independent R01-funded, faculty- level principal investigator and to achieve her long-term goal of establishing an independent research lab focused on neurological and behavioral alterations in chronic pain.
Opioids are considered generally not effective for the treatment of FM; however, they are still prescribed to up to an estimated 40% of this patient population. It is currently unknown whether opioids cause negative effects on CNS function, brain reward systems, and long-term clinical outcomes in individuals with FM. The proposed projects will determine how opioids impact pain, reward behavior, and brain function in FM and will lead to the development of new methods to determine appropriateness of prescribing opioids to individuals with FM.