Dynamics of Lateral Habenula-Ventral Tegmental Area Microcircuit on Pain-Related Cognitive Dysfunctions

doi:10.3390/neurolint15040082

Review

. 2023 Oct 27;15(4):1303-1319.

doi: 10.3390/neurolint15040082.

Dynamics of Lateral Habenula-Ventral Tegmental Area Microcircuit on Pain-Related Cognitive Dysfunctions

Ana Raquel Pereira^{1

2

3}, Mobina Alemi^{1

2

3}, Mariana Cerqueira-Nunes^{1

2

3

4}, Clara Monteiro^{1

2

3}, Vasco Galhardo^{1

2

3}, Helder Cardoso-Cruz^{1

2

3}

Affiliations

¹ Instituto de Investigação e Inovação em Saúde-Pain Neurobiology Group, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.
² Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.
³ Departamento de Biomedicina-Unidade de Biologia Experimental, Faculdade de Medicina, Universidade do Porto, Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal.
⁴ Programa Doutoral em Neurociências, Faculdade de Medicina, Universidade do Porto, Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal.

PMID: 37987455
PMCID: PMC10660716
DOI: 10.3390/neurolint15040082

Review

Dynamics of Lateral Habenula-Ventral Tegmental Area Microcircuit on Pain-Related Cognitive Dysfunctions

Ana Raquel Pereira et al. Neurol Int. 2023.

. 2023 Oct 27;15(4):1303-1319.

doi: 10.3390/neurolint15040082.

Authors

Ana Raquel Pereira^{1

2

3}, Mobina Alemi^{1

2

3}, Mariana Cerqueira-Nunes^{1

2

3

4}, Clara Monteiro^{1

2

3}, Vasco Galhardo^{1

2

3}, Helder Cardoso-Cruz^{1

2

3}

Affiliations

¹ Instituto de Investigação e Inovação em Saúde-Pain Neurobiology Group, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.
² Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.
³ Departamento de Biomedicina-Unidade de Biologia Experimental, Faculdade de Medicina, Universidade do Porto, Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal.
⁴ Programa Doutoral em Neurociências, Faculdade de Medicina, Universidade do Porto, Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal.

PMID: 37987455
PMCID: PMC10660716
DOI: 10.3390/neurolint15040082

Abstract

Chronic pain is a health problem that affects the ability to work and perform other activities, and it generally worsens over time. Understanding the complex pain interaction with brain circuits could help predict which patients are at risk of developing central dysfunctions. Increasing evidence from preclinical and clinical studies suggests that aberrant activity of the lateral habenula (LHb) is associated with depressive symptoms characterized by excessive negative focus, leading to high-level cognitive dysfunctions. The primary output region of the LHb is the ventral tegmental area (VTA), through a bidirectional connection. Recently, there has been growing interest in the complex interactions between the LHb and VTA, particularly regarding their crucial roles in behavior regulation and their potential involvement in the pathological impact of chronic pain on cognitive functions. In this review, we briefly discuss the structural and functional roles of the LHb-VTA microcircuit and their impact on cognition and mood disorders in order to support future studies addressing brain plasticity during chronic pain conditions.

Keywords: chronic pain; cognitive dysfunctions; lateral habenula; mood disorders; ventral tegmental area.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish this comprehensive review.

Figures

**Figure 1**
Intra-hemispheric representation of the lateral habenula and ventral tegmental area microcircuit inputs and outputs with their respective neurotransmitter systems. BLA, basolateral amygdala; LHb, lateral habenula; mPFC, medial prefrontal cortex; NAc, nucleus accumbens; RMTg, rostromedial tegmental area; and VTA, ventral tegmental area.

See this image and copyright information in PMC

References

1. Li J., Li Y., Zhang B., Shen X., Zhao H. Why depression and pain often coexist and mutually reinforce: Role of the lateral habenula. Exp. Neurol. 2016;284:106–113. doi: 10.1016/j.expneurol.2016.08.010. - DOI - PubMed
1. Li Y., Wang Y., Xuan C., Li Y., Piao L., Li J., Zhao H. Role of the Lateral Habenula in Pain-Associated Depression. Front. Behav. Neurosci. 2017;11:31. doi: 10.3389/fnbeh.2017.00031. - DOI - PMC - PubMed
1. Borsook D., Linnman C., Faria V., Strassman A.M., Becerra L., Elman I. Reward deficiency and anti-reward in pain chronification. Neurosci. Biobehav. Rev. 2016;68:282–297. doi: 10.1016/j.neubiorev.2016.05.033. - DOI - PubMed
1. Goutagny R., Loureiro M., Jackson J., Chaumont J., Williams S., Isope P., Kelche C., Cassel J.-C., Lecourtier L. Interactions between the lateral habenula and the hippocampus: Implication for spatial memory processes. Neuropsychopharmacology. 2013;38:2418–2426. doi: 10.1038/npp.2013.142. - DOI - PMC - PubMed
1. Jacinto L.R., Mata R., Novais A., Marques F., Sousa N. The habenula as a critical node in chronic stress-related anxiety. Exp. Neurol. 2017;289:46–54. doi: 10.1016/j.expneurol.2016.12.003. - DOI - PubMed

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[1] Li J., Li Y., Zhang B., Shen X., Zhao H. Why depression and pain often coexist and mutually reinforce: Role of the lateral habenula. Exp. Neurol. 2016;284:106–113. doi: 10.1016/j.expneurol.2016.08.010. - DOI - PubMed

[2] Li J., Li Y., Zhang B., Shen X., Zhao H. Why depression and pain often coexist and mutually reinforce: Role of the lateral habenula. Exp. Neurol. 2016;284:106–113. doi: 10.1016/j.expneurol.2016.08.010. - DOI - PubMed

[3] Li Y., Wang Y., Xuan C., Li Y., Piao L., Li J., Zhao H. Role of the Lateral Habenula in Pain-Associated Depression. Front. Behav. Neurosci. 2017;11:31. doi: 10.3389/fnbeh.2017.00031. - DOI - PMC - PubMed

[4] Li Y., Wang Y., Xuan C., Li Y., Piao L., Li J., Zhao H. Role of the Lateral Habenula in Pain-Associated Depression. Front. Behav. Neurosci. 2017;11:31. doi: 10.3389/fnbeh.2017.00031. - DOI - PMC - PubMed

[5] Borsook D., Linnman C., Faria V., Strassman A.M., Becerra L., Elman I. Reward deficiency and anti-reward in pain chronification. Neurosci. Biobehav. Rev. 2016;68:282–297. doi: 10.1016/j.neubiorev.2016.05.033. - DOI - PubMed

[6] Borsook D., Linnman C., Faria V., Strassman A.M., Becerra L., Elman I. Reward deficiency and anti-reward in pain chronification. Neurosci. Biobehav. Rev. 2016;68:282–297. doi: 10.1016/j.neubiorev.2016.05.033. - DOI - PubMed

[7] Goutagny R., Loureiro M., Jackson J., Chaumont J., Williams S., Isope P., Kelche C., Cassel J.-C., Lecourtier L. Interactions between the lateral habenula and the hippocampus: Implication for spatial memory processes. Neuropsychopharmacology. 2013;38:2418–2426. doi: 10.1038/npp.2013.142. - DOI - PMC - PubMed

[8] Goutagny R., Loureiro M., Jackson J., Chaumont J., Williams S., Isope P., Kelche C., Cassel J.-C., Lecourtier L. Interactions between the lateral habenula and the hippocampus: Implication for spatial memory processes. Neuropsychopharmacology. 2013;38:2418–2426. doi: 10.1038/npp.2013.142. - DOI - PMC - PubMed

[9] Jacinto L.R., Mata R., Novais A., Marques F., Sousa N. The habenula as a critical node in chronic stress-related anxiety. Exp. Neurol. 2017;289:46–54. doi: 10.1016/j.expneurol.2016.12.003. - DOI - PubMed

[10] Jacinto L.R., Mata R., Novais A., Marques F., Sousa N. The habenula as a critical node in chronic stress-related anxiety. Exp. Neurol. 2017;289:46–54. doi: 10.1016/j.expneurol.2016.12.003. - DOI - PubMed

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Dynamics of Lateral Habenula-Ventral Tegmental Area Microcircuit on Pain-Related Cognitive Dysfunctions

Affiliations

Dynamics of Lateral Habenula-Ventral Tegmental Area Microcircuit on Pain-Related Cognitive Dysfunctions

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Abstract

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