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Papers of the Week

Papers: 21 Oct 2023 - 27 Oct 2023

2023 Oct 25

Nat Commun




The endocannabinoid N-arachidonoyl dopamine is critical for hyperalgesia induced by chronic sleep disruption.


Ding W, Yang L, Shi E, Kim B, Low S, Hu K, Gao L, Chen P, Ding W, Borsook D, Luo A, Choi JH, Wang C, Akeju O, Yang J, Ran C, Schreiber KL, Mao J, Chen Q, Feng G, Shen S


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.