Neurotensin Alleviates Chronic Pain after Spinal Cord Injury by Modulating Dopaminergic Neuron Activity in the Ventral Tegmental Area

Abstract

Background: Neurotensin (NT), an endogenous neuropeptide, plays a crucial role in modulating dopaminergic transmission. Dopaminergic drugs may serve as an effective therapy against chronic pain, a frequent adverse symptom observed in spinal cord injury (SCI) patients. Therefore, we aimed to investigate whether the mechanism of NT for chronic pain after SCI involves the modulation of dopaminergic neuronal activity. Methods: The SCI rat model was used with or without NT administration based on the experimental design. Ultrasonic vocalizations (USVs) and von Frey filaments were performed to assess the effect of NT on pain behavior in SCI rats. Dopaminergic neuron firing and bursting within the ventral tegmental area (VTA) were examined using electrophysiology. Furthermore, the dopamine D2 receptor (D2DR) was quantified using quantitative real-time polymerase chain reaction and immunohistochemistry. Results: Significant spontaneous and induced pain could be observed in SCI rats along with a decrease in dopaminergic neuron firing and bursting activities as well as upregulation of D2DR expression (p < 0.001). Importantly, NT treatment significantly alleviated pain symptoms and promoted dopaminergic neuron firing and bursting activities in SCI rats (p < 0.001). Additionally, NT treatment diminished D2DR mRNA level and positive expression in SCI rats (p < 0.001). Conclusion: NT alleviates expression level of D2DR and activates dopaminergic firing and bursting activities in the VTA region, thereby relieving SCI-induced chronic pain.