Benedict Alter, MD, PhD
Systems Neuroscience of Pain and Pain Relief
Dr. Alter is Assistant Professor and Director of Translational Pain Research in the Division of Pain Medicine. His research explores how the brain modulates pain and how endogenous pain dampening systems can be systematically leveraged for novel pain therapies. Specific projects elucidate basic research questions on the systems neuroscience level, translational questions bringing basic knowledge towards novel treatments, and clinical questions aimed at understanding how pain modulatory systems change in chronic pain.
Mechanisms and Translational Application of Endogenous Analgesia
International Anesthesia Research Society; Funding Period: 2020-2021; PI: Benedict Alter, MD, PhD
Dr. Alter previously investigated “offset analgesia,” which is defined as a reduction in subjective pain intensity if a noxious stimulus is preceded by a stronger stimulus and is thought to arise from endogenous pain inhibition in the central nervous system, reflecting “endogenous analgesia.” In a cohort of healthy volunteers, he found that offset analgesia can be contingently paired with cues in a training paradigm, such that following training, the cues themselves are analgesic. This represents a novel experimental paradigm to study placebo analgesia and suggests that offset analgesia arises from changing motivational states during a noxious stimulus. Supporting this model, in a related study, he found evidence of an opposing “onset hyperalgesia” in a cohort of healthy volunteers. Intriguingly, there is an inverse correlation between offset analgesia and onset hyperalgesia across participants in this sample. Overall, these findings relate offset analgesia and onset hyperalgesia to other forms of central modulation of pain and is consistent with offset analgesia and onset hyperalgesia representing behavioral correlates of bidirectional descending inhibitory and excitatory pathways projecting from midbrain to the spinal cord dorsal horn.
Integrating Brain and Behavioral Measures of Endogenous Analgesia to Personalize Treatment in Chronic Pain Management
Brain Biomarker of Endogenous Analgesia in Patients with Chronic Knee Pain, American Academy of Pain Medicine, Funding Period: 2020-2021; PI: Benedict Alter, MD, PhD
Although endogenous analgesia strongly modulates acute pain in the lab, the relevance of endogenous analgesia for patient outcomes is less well known. The most commonly used assessments of endogenous analgesia in patients are limited by technical aspects, expense, and accessibility, preventing their widespread use and resulting in a knowledge gap in how endogenous analgesia impacts patient outcomes and treatment response. The goal of the current project is to define changes in endogenous analgesia in patients with chronic pain using novel brain and behavioral tools, including functional near-infrared spectroscopy (fNIRS) and offset analgesia. FNIRS allows cost-effective measurement of activity-dependent cortical hemodynamic changes in an ambulatory, clinic based setting. Offset analgesia allows measurement at a single body site and is mechanistically-distinct from the most commonly-used measure of endogenous analgesia, conditioned pain modulation. The overall hypothesis is that heterogeneity in endogenous analgesia, measured with offset analgesia and fNIRS, contributes to variability in treatment responses. For example, deficits in endogenous analgesia may limit responses to certain treatments. Identifying subgroups of patients with varying endogenous analgesia capacity may allow personalization of chronic pain management.
Improving Clinical Trials and Pain Management Practice with Biosignatures of Chronic Pain and Treatment Response
In a given chronic pain diagnosis, it is likely that variation in patient characteristics has a strong effect on treatment outcome. With mentorship and collaboration from Dr. Ajay Wasan, Dr. Alter has explored multiple ways to feasibly capture this variability for clinical use. First, he examined the feasibility and reliability of a bedside quantitative sensory testing battery in post-herpetic neuralgia. Second, the impact of patient-reported pain characteristics has been explored, specifically examining the importance of pain distribution over the body. Patterns of body map selection could be identified through cluster analysis of research registry data. Clusters based on this body map data alone have distinct pain characteristics and outcomes, suggesting that the bodily distribution of pain may itself predict outcome responses. Finally, “real world” outcomes data from pain interventions for chronic knee pain have been examined by combining research registry data and electronic medical record (EMR) review. Together, sensory phenotyping and bioinformatic signatures show promise in feasibly identifying sub-groups of chronic pain patients, which may optimally respond to different chronic pain treatments.