PainRelief.com Interview with:
Shiqian Shen, M.D.
–Anesthesia & Crit. Care, Massachusetts General Hospital
Associate Professor of Anaesthesia
–Harvard Medical School
Physician Investigator (Cl)
–Anesthesia, Critical Care and Pain Medicine, Mass General Research Institute
PainRelief.com: What is the background for this study? Would you describe the function of NADA?
Response: Both sleep disorders and chronic pain are very prevalent among adults. For example, about one third of U.S. adults report some level of sleep disturbance. Both common life experience and medial research strongly suggest that sleep deprivation leads to heightened pain experience/perception. However, the mechanisms of this link are not entirely clear. Hence we decide to study this important question.
NADA, N-arachidonoyl dopamine was first discovered to be an agonist for the Cannabinoid Receptor 1 and it was found in the brain of animals. It belongs to the endocannabinoid family. Additionally, NADA also belongs to the endovanilloid family. Administration of NADA to rodents produces a wide variety of behavioral changes, including behaviors mimicking the physiological paradigms association with cannabinoids. However, its physiological function is not well characterized.
What are the main findings?
Response: Using a previously established mouse model of sleep deprivation, we found that a brain region -thalamic reticular nucleus was linked the heightened pain sensitivities induced by chronic sleep deprivation (‘CSD-induced hyperalgesia’). Thalamic reticular nucleus is well known for its integrative functions in sleep and sensory modulation. For example, it is a critical modulatory center for information flowing between the thalamus and the cerebral cortex.
A screening of metabolites revealed that the level of NADA was decreased in the thalamic reticular nucleus following chronic sleep deprivation. In line with this, cannabinoid receptor 1 activities were also decreased following chronic sleep deprivation. Supplementation of NADA alleviated CSD-induced hyperalgesia. From a circuitry standpoint, the projections from the thalamic reticular nucleus to the ventroposterior portion of the thalamus mediated these effects.
PainRelief.com: What should readers take away from your report?
Response: Chronic pain is a multi-dimensional condition with somatosensory, cognitive, and affective aspects. Sleep disruption can both lead to and result from chronic pain, promoting a vicious cycle between the two. Understanding the mechanisms through which sleep disruption, a common comorbid condition of pain, promote exaggerated pain sensitivities will inform better and safer pain treatment.
PainRelief.com: What recommendations do you have for future research as a result of this study?
Response: The thalamic reticular nucleus has great heterogeneity in its topological projections and cellular types. We want to understand how these different types of cells coordinate to output a collective influence on sleep and pain.
From a clinical standpoint, we want to translate what we learned in animal studies to develop treatment modalities that could break the vicious cycle between chronic pain and sleep loss.
PainRelief.com: Is there anything else you would like to add? Any disclosures?
Response: Endocannabinoids are small molecules produced by our body that bind to cannabinoid receptors to exert their functions. Whether NADA itself or any natural products can be safely used by humans to treat pain induced by sleep loss are unknown.
No financial disclosures.
Citation: Weihua Ding, Liuyue Yang, Eleanor Shi, Bowon Kim, Sarah Low, Kun Hu, Lei Gao, Ping Chen, Wei Ding, David Borsook, Andrew Luo, Jee Hyun Choi, Changning Wang, Oluwaseun Akeju, Jun Yang, Chongzhao Ran, Kristin L. Schreiber, Jianren Mao, Qian Chen, Guoping Feng, Shiqian Shen. The endocannabinoid N-arachidonoyl dopamine is critical for hyperalgesia induced by chronic sleep disruption. Nature Communications, 2023; 14 (1) DOI: 10.1038/s41467-023-42283-6
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Last Updated on October 26, 2023 by PainRelief.com