by Massachusetts General Hospital

CSD induces hyperalgesia. a Experimental diagram of the sleep deprivation experiment and behavioral testing. b Sample EEG recording using wireless EEG recording. Brown line-EEG trace. Gray line-EMG trace. A representative sleep attempt on EEG and EMG traces during sleep deprivation. Lower panel: time-frequency representation of an EEG signal (spectrogram) showing increased slow activity (0.5–4 Hz) during a manually detected sleep attempt. c Duration of non-REM sleep during the sleep deprivation session (7 am–1 pm; n = 4 mice; Day 0 vs day 1, 3, 5 p < 0.0001) and during the representative sleep opportunity period (1 pm–3 pm, Day 0 vs day 1 p = 0.0033; Day 0 vs day 3 p = 0.0002; Day 0 vs day 5 p < 0.0001). One-way ANOVA indicated a statistically significant difference. Tukey’s post hoc test. **p < 0.01, *** p < 0.001, ****p < 0.0001. d Total cumulative sleep time over 24 h (7 am-7 am; n = 3 mice; Day 0 vs day 5 p = 0.03). Two-sided paired t test, *p < 0.05. e Facial mechanical withdrawal threshold (Sham vs CSD at day 3 p = 0.0003, day 5 p = 0.0003), hindpaw mechanical withdrawal threshold (Sham vs CSD at day 3 p = 0.0039, day 5 p < 0.0001), and hindpaw thermal withdrawal latency (Sham vs CSD at day 3 p = 0.0003, day 5 p < 0.0001) at the indicated time points. Testing was performed within 1 h after the CSD session. (Sham n = 8 mice, CSD n = 16). Two-way ANOVA indicated that the differences in behavioral parameters between the two groups were statistically significant. The Bonferroni post hoc test indicated that the differences at the indicated time points were significant. Data are presented as mean ± SEM, **p < 0.01, ***p < 0.001, ****p < 0.0001. Source data are provided as a Source Data file. EEG electroencephalogram, EMG Electromyography, NREM non-rapid eye movement. Credit: Nature Communications (2023). DOI: 10.1038/s41467-023-42283-6

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.

More information: Weihua Ding et al, The endocannabinoid N-arachidonoyl dopamine is critical for hyperalgesia induced by chronic sleep disruption, Nature Communications (2023). DOI: 10.1038/s41467-023-42283-6

Provided by Massachusetts General Hospital