Weihua Ding Liuyue Yang Eleanor Shi Bowon Kim Sarah Low Kun Hu Lei Gao Ping Chen Wei Ding David Borsook Andrew Luo Choi, Ji Hyun Changning Wang Oluwaseun Akeju Jun Yang Chongzhao Ran Kristin L. Schreiber Jianren Mao Qian Chen Guoping Feng Shiqian Shen 2024-01-12T06:33:18Z 2024-01-12T06:33:18Z 2023-11-22 2023-10 2041-1723 https://pubs.kist.re.kr/handle/201004/79791 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. English Nature Publishing Group The endocannabinoid N-arachidonoyl dopamine is critical for hyperalgesia induced by chronic sleep disruption Article 10.1038/s41467-023-42283-6 1 Nature Communications, v.14, no.1 Nature Communications 14 1 Y scie scopus 001096436800011 Multidisciplinary Sciences Science & Technology - Other Topics Article THALAMIC RETICULAR NUCLEUS PAIN NEURONS SENSITIVITY INSOMNIA ACCUMULATION RESTRICTION DEPRIVATION CONNECTIONS HOMEOSTASIS