Neurobiological Mechanisms to Alleviate Comorbid Pain and Obesity
Abstract
Our proposal responds to the FY22 CPMRP Investigator Initiated Research Award Focus Area: Investigating relationships between pain and its co-morbidities that can contribute to the development/progression of chronic pain. Unfortunately, after deployment, many Veterans face new battles: chronic pain and comorbid obesity. These conditions frequently occur together, significantly reduce quality and length of life, and Veterans are more likely to develop them than the general population. There is no cure, and current medications to alleviate pain are problematic because they cause weight gain. An optimal treatment would be to provide pain control with an agent that also enhances body weight management. So far, this goal has not been reached because of our limited knowledge of how the brain controls both pain and feeding. A potential candidate to simultaneously relieve pain and support weight loss is the peptide Neurotensin. Studies show that Neurotensin acts in the brain to reduce feeding and promote weight loss. Neurotensin relieves pain when it is injected into a particular brain area called the periaqueductal gray (PAG). We want to understand whether Neurotensin can simultaneously reduce pain and body weight, which would be optimal for treating comorbid chronic pain and obesity. Our exciting new evidence points to ways that Neurotensin could simultaneously reduce pain and body weight. We show that artificially activating a specific group of Neurotensin-expressing neurons in the hypothalamus that communicate to the PAG reduces pain, motivation to feed and body weight. The aim of this research proposal is to determine whether this brain Neurotensin system can reduce both pain and obesity at the same time and how it does so. The Neurotensin system can’t easily be studied in humans. Instead, we generated novel reagents to test how the brain Neurotensin system works in normal weight and obese laboratory mice. These will enable us to, for the first time, identify the exact Neurotensin targets to alleviate pain and reduce motivation to eat, without detrimental side effects. We will also and identify the best Neurotensin-based drugs that can reduce pain and body weight and may be suited for treating comorbid chronic pain and obesity. Potential persons with chronic pain that may be helped are individuals suffering from comorbid chronic pain and obesity, including the large population of affected Veterans. Potential Clinical Application: Uncovering the common mechanism in the brain by which chronic pain and obesity co-occur will identify the best way to use the Neurotensin system for alleviating pain and obesity. We will also test existing Neurotensin-based drugs known to provide analgesia, determine what cells they regulate, and find most promising drugs or approaches for treating pain and obesity. Projected Time to Person-Related Outcome: The projected time to patient outcome is difficult to estimate given that this is a basic research proposal. Since the common mechanism in the brain that underlies both pain and body weight control is unknown, this proposal may open a new area of investigation prior to direct impact. Via our studies we may identify a very promising drug candidate or biological target to treat both chronic pain and obesity in our animal models, but translating animal research findings to human benefits takes time and will be the focus of future work. However, since there is an active drug-design effort centered on Neurotensin, our findings could have rapid impact on the selection of current preclinical drugs and/or design of new ones capable of alleviating chronic pain and obesity in the future.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310579
Entities
People
- Gina Leinninger
Organizations
- Michigan State University
- United States Army