Abstract
The ventral tegmental area (VTA) is one of the main brain regions harboring dopaminergic (DA) neurons, and plays important roles in reinforcement and motivation. Recent studies have indicated that DA neurons not only respond to rewarding stimuli, but also to noxious stimuli. Furthermore, VTA DA neurons undergo plasticity during chronic pain. Lateral and medial VTA neurons project to different brain areas, and have been characterized via their distinct electrophysiological properties. In this study, we characterized electrophysiological properties of lateral and medial VTA DA neurons using DAT-cre reporter mice, and examined their plasticity during neuropathic pain states. We observed various DA subpopulations in both the lateral and medial VTA, as defined by action potential firing patterns, independently of synaptic inputs. Our results demonstrated that lateral and medial VTA DA neurons undergo differential plasticity after peripheral nerve injury that leads to neuropathic pain. However, these changes only reside in specific DA subpopulations. This study suggests that lateral and medial VTA DA neurons are differentially affected during neuropathic pain conditions, and emphasizes the importance of subpopulation specificity when targeting VTA DA neurons for treatment of neuropathic pain.
Highlights
Dopaminergic (DA) neurons within the ventral tegmental area (VTA) play an important role in the regulation of appetitive stimuli, anxiety, aversion and pain [1,2,3,4,5]
We find that only specific subtypes of medial and lateral dopaminergic VTA undergo injury-induced changes in their electrophysiological properties, suggesting that chronic pain states are associated with altered neuronal plasticity in specific DA neuron populations in the VTA
The spared nerve injury (SNI) model was validated by pain behavioural tests (Additional file 2: Figure S2), using a different set of mice than the ones used for electrophysiology test, to avoid putative CNS changes that might be induced by acute noxious stimuli
Summary
Dopaminergic (DA) neurons within the ventral tegmental area (VTA) play an important role in the regulation of appetitive stimuli, anxiety, aversion and pain [1,2,3,4,5]. It has been suggested that pain relief is signaled as reward via VTA DA neurons [6]. VTA DA neurons are directly activated by noxious stimuli [7]. Recent studies revealed plasticity of VTA dopamine neurons during neuropathic pain, expressed as decreased excitability [8, 9]. Noxious stimuli, such as footshocks, induce phasic firing in only specific subpopulations of VTA DA neurons [6, 7]. If not all existing studies reported plasticity in VTA DA neurons in chronic pain conditions as a whole population. They receive inputs from, and project to a number of brain regions, including the nucleus accumbens (NAc), the medial prefrontal cortex (mPFC), and
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
