UCI Scientists Discover Pathway Blocking Transition from Acute to Chronic Pain

PainRelief.com Interview with:

Daniele Piomelli PhD Distinguished Professor, Anatomy & Neurobiology Louise Turner Arnold Chair in Neurosciences Joint Appointment, Biological Chemistry and Pharmacology School of Medicine Director, Center for the Study of Cannabis University of California, Irvine
Dr. Piomelli

Daniele Piomelli PhD
Distinguished Professor, Anatomy & Neurobiology
Louise Turner Arnold Chair in Neurosciences
Joint Appointment, Biological Chemistry and Pharmacology
School of Medicine
Director, Center for the Study of Cannabis
University of California, Irvine

PainRelief.com: What is the background for this study?

Response: The pain caused by physical trauma or by surgery can disappear in a relatively short time — or linger for months or even years. In some cases, for example after open heart surgery, the percent of people who develop persistent pain can be as high as 40%. Breast and knee surgery, among others, have similar outcomes. We still don’t understand how acute pain after an injury becomes chronic.  

PainRelief.com: What are the main findings?

Response: Our study in mice shows that tissue injury starts a chain of molecular events which culminates, exactly three days later, in a radical switch in the metabolism of the spinal cord. Spinal cord neurons, which normally use large amounts of energy produced by the mitochondria (cellular organelles), now turn to a different metabolic pathway called glycolysis. This switch is needed to cope with the injury, but comes at a cost: glycolysis produces only a small amount of energy, and neurons need a lot of it. Lack of energy makes the neurons sick and this causes them to become hyperexcited (which causes persistent pain). The metabolic switch is controlled by an enzyme called NAAA. We found that when we administer drugs that block NAAA only once three days after tissue injury we can prevent both the metabolic switch in spinal cord and the conversion of acute pain to chronic.  

PainRelief.com: What should readers take away from your report?

Response: The transition to chronic pain may be preventable by a relatively short treatment with a NAAA inhibitor. These agents are not clinically approved yet, but our study should encourage efforts to develop them into clinical drugs.   

PainRelief.com: What recommendations do you have for future research as a result of this work?

Response: We need to understand better what molecular changes occur in the nervous system after an injury, and how such changes can lead to the chronification of pain. One important take home message from our study is that after an injury every day brings new molecular changes in the spinal cord, and that some of these changes are critical for the transition to persistent pain states.

Citation: Reference: “NAAA-regulated lipid signaling governs the transition from acute to chronic pain” 22 October 2021, Science Advances.
DOI: 10.1126/sciadv.abi8834

This work was funded by grants R41NS106999, R42DA033683 and DA041229 from the National Institutes of Health.

Disclosures: We invented the first NAAA inhibitors and our University holds patents that protect these molecules and their use. 

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