2010 — 2011 |
Martucci, Katherine Theresa |
F31Activity Code Description: To provide predoctoral individuals with supervised research training in specified health and health-related areas leading toward the research degree (e.g., Ph.D.). |
Alterations in Temporal Aspects of Pain Processing and Modulation @ Wake Forest University Health Sciences
DESCRIPTION (provided by applicant): Despite the severity and frequency of chronic pain, current medicine lacks diagnostic tools for treatment selection to consistently and effectively alleviate pain on an individual basis. The symptoms of hyperalgesia and allodynia are helpful for clinical diagnoses, however, more subtle temporal changes in sensitivity may also represent important diagnostic endpoints. Painful aftersensations, the abnormal persistence in pain long after the end of a tactile / thermal stimulus, are frequently observed in chronic pain and may be related to altered temporal processing of nociceptive information due to disrupted pain modulation. In order to better understand how nociceptive processing is temporally altered in clinical states, a combination of psychophysical and fMRI studies will examine healthy subjects and CRPS (complex regional pain syndrome) patients to address the following specific aims: Aim 1: To identify temporal alterations in pain perception as a consequence of central sensitization. Aim 2: To identify neuropharmacological substrates supporting temporal processing of noxious stimuli. Aim 3: To identify neurophysiological correlates of temporally altered pain perception in chronic pain. Offset analgesia is a phenomenon that may represent the dynamic engagement of endogenous anti- nociceptive mechanisms during the processing of temporal dimensions of noxious stimuli. Assessment of offset analgesia and subjects/patients responses to acute painful heat stimuli with variable durations and slow fall rates will allow us to elucidate how temporal aspects of pain processing are altered in states of central sensitization (capsaicin-heat sensitization and chronic pain) and pharmacological manipulation (opioid agonist and antagonist). We will then correlate these changes in psychophysical responses to observed physiological abnormalities using functional imaging of cortical and subcortical regions with BOLD (blood oxygenation level dependent) and ASL (arterial spin labeling) fMRI designs. The proposed research in this fellowship application aims to resolve the lack in understanding of pain mechanisms and how nociceptive processing is dramatically altered in chronic pain patients. The investigation of mechanisms that support temporal processing of noxious information may contribute to and improve clinical assessment and treatment of pathological pain states.
|
0.97 |
2015 — 2021 |
Martucci, Katherine Theresa |
K99Activity Code Description: To support the initial phase of a Career/Research Transition award program that provides 1-2 years of mentored support for highly motivated, advanced postdoctoral research scientists. R00Activity Code Description: To support the second phase of a Career/Research Transition award program that provides 1 -3 years of independent research support (R00) contingent on securing an independent research position. Award recipients will be expected to compete successfully for independent R01 support from the NIH during the R00 research transition award period. |
The Impact of Opioids On Chronic Pain: Clinical Research and Career Training in Spinal Cord Fmri and Brain Reward Systems
? DESCRIPTION (provided by applicant): 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-naïve, 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.
|
1 |