Temporal Multi-Omic Exploration of the Ventral Tegmental Area in Chronic Pain and Passive Coping Behaviors
Description
The comorbidity of chronic pain and mood disorders poses a clinical challenge involving neurobiological mechanisms within key brain regions like the ventral tegmental area (VTA). We employed a multidisciplinary approach in male mice, combining proteomics, phosphoproteomics, and lipidomics with behavioral and immunohistochemical analyses in a neuropathic pain model. Our findings reveal a temporal evolution of the VTA molecular landscape: an early signature related to metabolic reallocation followed by a late maladaptive state characterized by shifts in energy metabolism and cytoskeletal remodeling. This late maladaptive state involved stoichiometric remodeling of Kv7 potassium channel subunits and depletion of the endocannabinoid 2-arachidonoylglycerol (2-AG), coinciding with passive coping behavior. Pharmacological administration of 2-AG or potentiation of Kv7 channel function reversed pain-induced passive coping. Together, these findings delineate a temporal molecular evolution in the VTA and validate 2-AG and Kv7 systems as regulatory nodes linking chronic pain to the emergence of passive coping behaviors. The uploaded data includes confocal images from immunohistochemical experiments focused on the VTA, targeted lipidomic data from the same region, and associated behavioral measurements.
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Institutions
- University of ArizonaArizona, Tucson