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

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; Guoping Feng; Shiqian Shen

doi:10.1038/s41467-023-42283-6

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

Nat Commun. 2023 Oct 25;14(1):6696. doi: 10.1038/s41467-023-42283-6.

Authors

Weihua Ding^#¹, Liuyue Yang^#¹, Eleanor Shi¹, Bowon Kim¹, Sarah Low¹, Kun Hu², Lei Gao¹, Ping Chen³, Wei Ding³, David Borsook⁴, Andrew Luo⁵, Jee Hyun Choi⁶, Changning Wang⁷, Oluwaseun Akeju¹, Jun Yang⁷, Chongzhao Ran⁷, Kristin L Schreiber⁸, Jianren Mao¹, Qian Chen^{9

10}, Guoping Feng¹¹, Shiqian Shen¹²

Affiliations

¹ Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
² Department of Pathology, Tuft University School of Medicine, Boston, MA, USA.
³ College of Science and Mathematics, University of Massachusetts Boston, Boston, MA, USA.
⁴ Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁵ Summer Intern Program of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, currently at Brandeis University, Boston, MA, USA.
⁶ Center for Neuroscience, Korea Institute of Science and Technology, Seoul, South Korea.
⁷ Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁸ Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁹ McGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
¹⁰ Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
¹¹ McGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA. fengg@mit.edu.
¹² Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. sshen2@mgh.harvard.edu.

^# Contributed equally.

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Dopamine* / pharmacology
Endocannabinoids*
Hyperalgesia
Mice
Receptor, Cannabinoid, CB1
Sleep
Thalamic Nuclei

Substances

Endocannabinoids
Dopamine
Receptor, Cannabinoid, CB1

Abstract

Publication types

MeSH terms

Substances

Grants and funding