Mimicking opioid analgesia in cortical pain circuits.

Autor:	James JG; Dept. of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., McCall NM; Dept. of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Hsu AI; Dept. of Biobehavioral Health Sciences, School of Nursing, and Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Dept. of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA., Oswell CS; Dept. of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Salimando GJ; Dept. of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Mahmood M; Dept. of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Wooldridge LM; Dept. of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Wachira M; Dept. of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Jo A; Dept. of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Sandoval Ortega RA; Dept. of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Wojick JA; Dept. of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Beattie K; Dept. of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Farinas SA; Dept. of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Chehimi SN; Dept. of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Rodrigues A; Dept. of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Ejoh LL; Dept. of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Kimmey BA; Dept. of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Lo E; Dept. of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Azouz G; Dept. of Physiology and Biophysics, University of California Irvine, CA, USA., Vasquez JJ; Dept. of Physiology and Biophysics, University of California Irvine, CA, USA., Banghart MR; Dept. of Neurobiology, School of Biological Sciences, University of California San Diego, CA, USA., Creasy KT; Dept. of Biobehavioral Health Sciences, School of Nursing, and Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Beier KT; Dept. of Physiology and Biophysics, University of California Irvine, CA, USA., Ramakrishnan C; CNC Program, Stanford University, Stanford, CA, USA., Crist RC; Dept. of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Reiner BC; Dept. of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Deisseroth K; CNC Program, Stanford University, Stanford, CA, USA.; Dept. of Bioengineering, Stanford University, Stanford, CA, USA.; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.; Dept. of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA, USA., Yttri EA; Dept. of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA.; Neuroscience Institute, Carnegie Mellon University, Pittsburgh, PA, USA., Corder G; Dept. of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Dept. of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Dept. of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Apr 29. Date of Electronic Publication: 2024 Apr 29.
DOI:	10.1101/2024.04.26.591113
Abstrakt:	The anterior cingulate cortex plays a pivotal role in the cognitive and affective aspects of pain perception. Both endogenous and exogenous opioid signaling within the cingulate mitigate cortical nociception, reducing pain unpleasantness. However, the specific functional and molecular identities of cells mediating opioid analgesia in the cingulate remain elusive. Given the complexity of pain as a sensory and emotional experience, and the richness of ethological pain-related behaviors, we developed a standardized, deep-learning platform for deconstructing the behavior dynamics associated with the affective component of pain in mice-LUPE (Light aUtomated Pain Evaluator). LUPE removes human bias in behavior quantification and accelerated analysis from weeks to hours, which we leveraged to discover that morphine altered attentional and motivational pain behaviors akin to affective analgesia in humans. Through activity-dependent genetics and single-nuclei RNA sequencing, we identified specific ensembles of nociceptive cingulate neuron-types expressing mu-opioid receptors. Tuning receptor expression in these cells bidirectionally modulated morphine analgesia. Moreover, we employed a synthetic opioid receptor promoter-driven approach for cell-type specific optical and chemical genetic viral therapies to mimic morphine's pain-relieving effects in the cingulate, without reinforcement. This approach offers a novel strategy for precision pain management by targeting a key nociceptive cortical circuit with on-demand, non-addictive, and effective analgesia. Competing Interests: Competing interests. G.C, K.D., C.R. and G.J.S. are inventors on a provisional patent application through the University of Pennsylvania and Stanford University regarding the custom sequences used to develop, and the applications of mMORp and hMORp constructs (patent application number: 63/383,462 462 ‘Human and Murine Oprm1 Promotes and Uses Thereof’).
Databáze:	MEDLINE
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