Converging circuits between pain and depression: the ventral tegmental area as a therapeutic hub

Abstract

Chronic pain and depression are highly prevalent pathologies and cause a major socioeconomic burden to society. Chronic pain affects the emotional state of the individuals suffering from it, while depression worsens the prognosis of chronic pain patients and may diminish the effectiveness of pain treatments. There is a high comorbidity rate between both pathologies, which might share overlapping mechanisms. This review explores the evidence pinpointing a role for the ventral tegmental area (VTA) as a hub where both pain and emotional processing might converge. In addition, the feasibility of using the VTA as a possible therapeutic target is discussed. The role of the VTA, and the dopaminergic system in general, is highly studied in mood disorders, especially in deficits in reward-processing and motivation. Conversely, the VTA is less regarded where it concerns the study of central mechanisms of pain and its mood-associated consequences. Here, we first outline the brain circuits involving central processing of pain and mood disorders, focusing on the often-understudied role of the dopaminergic system and the VTA. Next, we highlight the state-of-the-art findings supporting the emergence of the VTA as a link where both pathways converge. Thus, we envision a promising part for the VTA as a putative target for innovative therapeutic approaches to treat chronic pain and its effects on mood. Finally, we emphasize the urge to develop and use animal models where both pain and depression-like symptoms are considered in conjunction.

Dopamine dynamics in chronic pain: music-induced sex-dependent behavioral effects in mice

“…The ability to quantify neurotransmitter release in a subsecond scale offers unprecedented opportunities to understand the neural mechanisms underlying different physiological and pathological processes (Scimemi and Beato 2009; Patriarchi et al 2020; 2018). We hypothesized that the effects of music in chronic pain conditions might be mediated, at least in part, by alterations in dopamine dynamics in the NAcc (Flores-García et al 2023). Accordingly, we investigated potential alterations in dopamine release over time following CFA injection and music exposure.…”

“…Possible mechanisms explaining the benefits of music listening on chronic pain and associated symptoms may involve the modulation of various neurotransmitter systems, including the serotoninergic and dopaminergic pathways (Papadakakis, Sidiropoulou, and Panagis 2019; Mavridis 2015; Moraes et al 2018a; Martikainen et al 2015; Ren et al 2021). In our recent review, we highlighted the convergence of mechanisms in chronic pain and depression, pointing the ventral tegmental area (VTA) as a potential therapeutical hub (Flores-García et al 2023). Chronic pain conditions are often associated with alterations in the mesolimbic pathway, in which dopaminergic VTA neurons project to the NAcc (Ren et al 2021; Kuner and Kuner 2021; Tanasescu et al 2016).…”

“…Nevertheless, the neurological mechanisms underlying the effects of music listening in reducing pain and associated comorbidities remain mostly unknown. As we recently reviewed, the mesolimbic system, connecting the ventral tegmental area (VTA) and the nucleus accumbens (NAcc), has gained attention in the intersection of pain and mood disorders (Flores-García et al 2023). Interestingly, listening to music has been shown to induce changes in neural activity, triggering the release of neurotransmitters such as dopamine or endogenous peptides in different brain areas, including the NAcc (Kuner and Kuner 2021; Martikainen et al 2015; Moraes et al 2018a; Mavridis 2015; Chanda and Levitin 2013; Ferreri et al 2019; Blood and Zatorre 2001; Salimpoor et al 2011).…”