REGION-SPECIFIC ALTERATIONS IN A MALE MOUSE MODEL OF NEUROPATHIC PAIN INDUCED-DEPRESSION: TRANSCRIPTOMIC CHARACTERIZATION

Approximately 35% of patients with neuropathic pain also experience comorbid major depressive disorder (MDD). In this study, we aimed at studying dynamic molecular changes during the development of neuropathic pain and its associated behavioural consequences in six brain regions: the Basolateral Amygdala (BLA), Dorsal Raphe Nucleus, Habenula, Insular Cortex, Nucleus Accumbens, and Ventral Tegmental Area. Neuropathic pain was induced by implanting a polyethylene tube around the sciatic nerve in male mice. Behavioral characterization was performed using a battery of tests, including the Von Frey test, the Splash, and the Novelty suppressed feeding tests. We used RNA sequencing to track transcriptomic changes at different stages of the comorbidity development, with an initial time point (TP1) two weeks after surgery, during which the animals exhibited hypersensitivity, then developed depressive-like disorders after eight weeks (TP2) and recovered from their hypersensitivity while maintaining depressive-like phenotypes after twelve weeks (TP3). Sequencing data revealed time-dependent and region-specific alterations within the six chosen brain areas. Gene expression was most strongly correlated within the same region across the time-points than between the different brain regions. The number of differentially expressed genes (DEGs) was significantly higher at TP2 for all regions, except for the BLA, which showed a gradual increase of DEGs throughout the development of depressive disorders. Overall, these results indicate that the comorbidity between chronic pain and emotional disorders leads to dynamic transcriptomic alterations in various brain regions.