Summary: Researchers discovered how sleep deprivation can exacerbate pain. Their study demonstrates that a neurotransmitter, N-arachidonoyl dopamine (NADA), decreases in a brain region called the thalamic reticular nucleus (TRN) due to sleep loss.
By administering NADA to this region, they reduced the increased pain sensitivity in mice. The findings suggest that targeting the endocannabinoid system could provide relief for those suffering from pain due to sleep disruption.
Key Facts:
- Chronic sleep disruption leads to heightened pain sensitivity through decreased N-arachidonoyl dopamine (NADA) in the thalamic reticular nucleus.
- Administering NADA to the TRN in mice reduced the exaggerated pain sensitivity resulting from sleep deprivation.
- Both the cannabinoid receptor 1 and NADA play crucial roles in the pain sensitivity linked to sleep loss.
Source: Mass General
People often experience headaches and body pain after a lack of sleep, but the mechanisms behind this phenomenon are unclear.
A new study led by investigators at Massachusetts General Hospital (MGH), a founding member of Mass General Brigham (MGB) and published in Nature Communications reveals that a certain chemical messenger, or neurotransmitter, plays a major role.
Through experiments conducted in mice, the researchers found that the heightened pain sensitivity than can result from chronic sleep disruption (CSD)—or CSD-induced hyperalgesia—involved signaling from a part of a brain known as the thalamic reticular nucleus (TRN).
Analyses of metabolites showed that the level of N-arachidonoyl dopamine (NADA), a type of neurotransmitter called an endocannabinoid, decreased in the TRN as a result of sleep deprivation.
Activity of the cannabinoid receptor 1, which is involved in controlling pain perception, also decreased in the thalamic reticular nucleus after CSD.
Administering NADA to the TRN reduced CSD-induced hyperalgesia in mice.
This beneficial effect of administered NADA could be countered by blocking the cannabinoid receptor 1, suggesting that both the receptor and NADA play a role in pain sensitivity due to sleep deprivation.
“We provide a mechanism as to how sleep disruption leads to exaggerated pain, suggesting that harnessing the endocannabinoid system might break the vicious cycle between pain and sleep loss,” says co–senior author Shiqian Shen, MD, the clinical director of MGH’s Tele Pain Program.
Additional authors include 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, and co–senior author Guoping Feng (MIT).
About this sleep and pain research news
Author: Brandon Chase
Source: Mass General
Contact: Brandon Chase – Mass General
Image: The image is credited to Neuroscience News
Original Research: Open access.
“The endocannabinoid N-arachidonoyl dopamine is critical for hyperalgesia induced by chronic sleep disruption” by Shiqian Shen et al. Nature Communications
Abstract
The endocannabinoid N-arachidonoyl dopamine is critical for hyperalgesia induced by chronic sleep disruption
Chronic pain is highly prevalent and is linked to a broad range of comorbidities, including sleep disorders. Epidemiological and clinical evidence suggests that chronic sleep disruption (CSD) leads to heightened pain sensitivity, referred to as CSD-induced hyperalgesia.
However, the underlying mechanisms are unclear. The thalamic reticular nucleus (TRN) has unique integrative functions in sensory processing, attention/arousal and sleep spindle generation.
We report that the TRN played an important role in CSD-induced hyperalgesia in mice, through its projections to the ventroposterior region of the thalamus.
Metabolomics revealed that the level of N-arachidonoyl dopamine (NADA), an endocannabinoid, was decreased in the TRN after CSD. Using a recently developed CB1 receptor (cannabinoid receptor 1) activity sensor with spatiotemporal resolution, CB1 receptor activity in the TRN was found to be decreased after CSD. Moreover, CSD-induced hyperalgesia was attenuated by local NADA administration to the TRN.
Taken together, these results suggest that TRN NADA signaling is critical for CSD-induced hyperalgesia.
