Project Summary / Abstract Although opioids are prescribed for chronic pain due to fibromyalgia, scientific understanding of the effects of opioid medications on central nervous system (CNS) activity and reward behavior is limited. Current evidence strongly suggests that altered brain and spinal cord activity contributes to the chronicity of fibromyalgia symptoms, and opioids produce similar changes in CNS activity. To determine the longitudinal effects of opioids on CNS activity in fibromyalgia, the proposal includes clinical neuroimaging research projects that build upon preliminary research and training completed by Dr. Martucci during the K99 phase of her award. During the R00 independent research phase of her award, Dr. Martucci will conduct a longitudinal clinical research study of fibromyalgia patients, both opioid-dependent and opioid- naïve, to determine how changes in chronic pain, accompanying symptoms, and CNS activity over time relate to fibromyalgia disease progression both in the presence of and not in the presence of continued opioid use. The study aims will be conducted via two projects. Project #1 will extend preliminary research investigating cervical spinal cord activity and the effects of opioids in patients with fibromyalgia in a longitudinal study (over 1 year). Project #2 will extend preliminary research investigating reward behavior and brain reward systems and the effects of opioids in patients with fibromyalgia in a longitudinal study (over 1 year). Additional goals of the projects will be to replicate initial findings (from the K99 phase) in a large and independent cohort of fibromyalgia patients from a different region of the United States and to identify potential influences of participant demographics and socioeconomic status on fibromyalgia symptoms, spinal cord activity, reward processing, and opioid effects. Together, these projects will provide a more complete picture of the neurophysiological effects of opioid medications in fibromyalgia and will fill critical knowledge gaps related to potential risks of neurobiological changes and altered psychology and behavior that may occur when prescribing opioids.