VTA dopaminergic neurons involved in chronic spared nerve injury pain-induced depressive-like behavior

Abstract

Affective disorders, such as depression, are commonly associated with the development of chronic pain, but the underlying mechanisms still remain unclear. The dopaminergic system, located in the midbrain, is considered one of the regions where algesia and emotional processing overlap. This suggests a structural basis hypothesis for the comorbidity of chronic pain and depression, highlighting the interplay between nociceptive and affective processing. But there are more and more evidences show that somatic and head/facial pain involve different neuronal overlap. In previous study, the research show that VTA dopaminergic system involved in pIONT surgery induced depressive-like behaviors in mice. But there still no evidence shows if chronic somatic pain will induce depressive-like behaviors and which neuronal circle pathway is underly. In this study, we assessed depressive-like behaviors and performed artificial interference of VTA (ventral tegmental area) dopaminergic neurons in a mouse model of chronic peripheral neuropathic pain induced by the spared nerve injury (SNI) model. After a 4-week duration of hyperalgesia and allodynia resulting from SNI surgery, social withdraw and other depressive-like behaviors were observed in the SNI group. Furthermore, the dopaminergic cells’ excitability in VTA were significantly increased in SNI mice. The excitability alteration was improved play a key role in the development and modulation of the chronic peripheral neuropathic pain-induced depressive-like behaviors. It has been shown pain and affections have structural and functional circuits to interact with each other, therefore the neuroplastic changes and functional role of VTA dopaminergic neurons within these circuits may serve as potential targets for understanding and therapeutically addressing the development of depressive-like symptoms accompanied by prolonged pain syndromes in humans.