Impaired Ventrolateral Periaqueductal Gray-Ventral Tegmental area Pathway Contributes to Chronic Pain-Induced Depression-Like Behavior in Mice

Lee, Ming Tatt; Peng, Wei‐Hao; Wu, Cheng-Chun; Kan, Hung‐Wei; Wang, Dengwu; Teng, Yang D.; Ho, Yu-Cheng

doi:10.1007/s12035-023-03439-z

Cited by 4 publications

(3 citation statements)

References 56 publications

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“…However, despite the high comorbidity between both pathologies in humans ( Goldberg and McGee, 2011 ; Cherif et al, 2020 ; Cohen et al, 2021 ) and the extensive clinical data that relate them ( Lampl et al, 2016 ; Roughan et al, 2021 ; Zhou et al, 2021 ; Voute et al, 2023 ), only a few preclinical studies have addressed them together. Of note, these studies generally coincide in suggesting that afferents from the PAG or the parabrachial nucleus (PBN), the dorsal raphe nucleus (DRN) or the BNST directly or indirectly control dopaminergic activity in the VTA efferent regions, such as the NAcc and PFC ( Waung et al, 2019 ; Yang et al, 2021 ; Zhang et al, 2021 ; Lee et al, 2023 ). Hence, the VTA seems to be critical in translating painful stimuli into aversive or depressive-like behaviors.…”

Section: Converging Mechanisms Between Pain and Depression In The Vtamentioning

confidence: 97%

“…Thus, the ablation of lPBN to substantia nigra pars reticulata glutamatergic neurons was enough to reduce pain-mediated inhibition of dopamine release in mice ( Coizet et al, 2010 ; Yang et al, 2021 ). Interestingly, one of the reports that addressed chronic pain and depression together ( Lee et al, 2023 ) used a spinal nerve ligation (SNL) mouse model. This model resulted in a dysregulation of the glutamatergic transmission from PAG into the VTA.…”

Section: Converging Mechanisms Between Pain and Depression In The Vtamentioning

confidence: 99%

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

Flores-García,

Rizzo,

Garçon-Poca

et al. 2023

Front. Pharmacol.

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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.

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Section: Converging Mechanisms Between Pain and Depression In The Vtamentioning

confidence: 97%

Section: Converging Mechanisms Between Pain and Depression In The Vtamentioning

confidence: 99%

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

Flores-García,

Rizzo,

Garçon-Poca

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Conversely, treatment with antidepressant drugs reduces immobility behavior and prevents the activation of PAG neurons ( Lino-de-Oliveira et al, 2006 ). Both chronic restraint stress and chronic pain have been shown to diminish glutamatergic neuron activity in the VLPAG, while the latter also weakens the VLPAG-ventral tegmental area (VTA) circuit, which may contribute to the observed co-occurrence of pain and depression ( Peng et al, 2022 ; Lee et al, 2023 ).…”

Section: Main Functional Characteristics and Mechanisms Of Pagmentioning

confidence: 99%

The contribution of periaqueductal gray in the regulation of physiological and pathological behaviors

Zhang,

Zhu,

et al. 2024

Front. Neurosci.

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Periaqueductal gray (PAG), an integration center for neuronal signals, is located in the midbrain and regulates multiple physiological and pathological behaviors, including pain, defensive and aggressive behaviors, anxiety and depression, cardiovascular response, respiration, and sleep-wake behaviors. Due to the different neuroanatomical connections and functional characteristics of the four functional columns of PAG, different subregions of PAG synergistically regulate various instinctual behaviors. In the current review, we summarized the role and possible neurobiological mechanism of different subregions of PAG in the regulation of pain, defensive and aggressive behaviors, anxiety, and depression from the perspective of the up-down neuronal circuits of PAG. Furthermore, we proposed the potential clinical applications of PAG. Knowledge of these aspects will give us a better understanding of the key role of PAG in physiological and pathological behaviors and provide directions for future clinical treatments.

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Ameliorative effect of α-tocopherol and tocotrienol-rich palm oil extract on menopause-associated mood disorder in ovariectomized mice

Liang,

Kow,

Lee

et al. 2024

Biochemical and Biophysical Research Communications

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Impaired Ventrolateral Periaqueductal Gray-Ventral Tegmental area Pathway Contributes to Chronic Pain-Induced Depression-Like Behavior in Mice

Cited by 4 publications

References 56 publications

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

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

The contribution of periaqueductal gray in the regulation of physiological and pathological behaviors

Ameliorative effect of α-tocopherol and tocotrienol-rich palm oil extract on menopause-associated mood disorder in ovariectomized mice

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