Chronic sleep deprivation (CSD) has been related to more significant pain sensitivity. Chronic pain is defined as chronic suffering that lasts more than three months and affects 11-40% of the world’s population. Over a third of the population in the United States complains of sleep problems.
This statistic is even more concerning when one considers that patients suffering from chronic pain are more likely to have difficulty sleeping. Although clinical and epidemiological investigations have discovered a link between poor sleep and increased pain levels, the underlying mechanisms of this association remain unclear.
This study sought to fill this information gap by investigating the effect of NADA on the experience of pain during sleep disturbance. Alexandre et al. established a mouse model to study CSD. This paradigm enables the finding of significantly increased pain sensitivity, known as “CSD-induced hyperalgesia.”
The scientists determined that the thalamic reticular nucleus (TRN) may be the cause of pain in persons with CSD after researching the neurological foundations. Through its projections to the anteroposterior thalamus, the TRN was revealed to play an essential role in CSD-induced hyperalgesia. The TRN is the ultimate integrator when it comes to sensory processing, attention, arousal, and sleep spindle formation. Â
Chemogenetic stimulation of TRN neurons projecting to the anteroposterior part of the thalamus was found to attenuate CSD-induced hyperalgesia. However, inhibiting these neurons resulted in a higher pain response. The endocannabinoid NADA was decreased in the TRN following CSD, according to the results of a metabolic investigation.
Concurrently, activation of the CB1 receptor (endocannabinoid receptor 1) was attenuated. Local NADA injection into the TRN reduced CSD-induced hyperalgesia, revealing the endocannabinoid’s critical involvement in the pain response after sleep disturbance. The consequences of these results for medical practice are far-reaching.
The relationship between disrupted sleep, the TRN, and the endocannabinoid system provides a unique viewpoint on pain management. By concentrating on the endocannabinoid NADA, there may be chances to develop novel therapy strategies for patients experiencing discomfort due to sleep issues. Â
In conclusion, the findings of this study not only shed new light on the neural mechanisms by which sleep deprivation increases pain sensitivity but also suggest that the endocannabinoid system, and specifically NADA, may be targets for the development of effective pain management strategies. As the global prevalence of sleep disorders rises, we must understand more about the links between them. Â
Journal Reference Â
Ding, W., Yang, L., Shi, E., Kim, B., Low, S., Hu, K., … Shen, S. (2023). The endocannabinoid N-arachidonoyl dopamine is critical for hyperalgesia induced by chronic sleep disruption. Retrieved from https://www.nature.com/articles/s41467-023-42283-6Â
