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Updated: Jun 13, 2026

Intracranial Pharmacotherapy and Pain Assays in Rodents
02:26

Intracranial Pharmacotherapy and Pain Assays in Rodents

Published on: April 9, 2019

Receptor and cell-type-specific mechanisms in mesocortical dopamine circuits gate chronic pain and comorbid

Ya-Qi Cai1, Xin-Yu Hou1, Guo-Hong Wang1

  • 1Department of Translational Neuroscience, Jing'an District Centre Hospital of Shanghai, State Key Laboratory of Brain Function and Disorders and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China.

Neuron
|June 11, 2026
PubMed

Insights

The mesocorticolimbic dopamine circuitry in the brain plays a role in chronic pain and depression. Targeting specific dopamine receptors (D1R and D2R) in the orbitofrontal cortex may offer new pain and depression treatment strategies.

Area of Science:

  • Neuroscience
  • Pain Research
  • Dopamine Signaling

Background:

  • The mesocorticolimbic dopamine (DA) system is linked to chronic pain and depression.
  • Specific receptor and circuit mechanisms underlying these conditions are not fully understood.

Purpose of the Study:

  • To investigate the role of orbitofrontal cortex (OFC) dopamine receptors (D1R and D2R) in mediating pain and depressive behaviors.
  • To explore the therapeutic potential of targeting the ventral tegmental area (VTA)-OFC pathway in a trigeminal neuralgia (TN) mouse model.

Main Methods:

  • Utilized a trigeminal neuralgia (TN) mouse model.
  • Investigated the effects of activating or blocking dopamine receptors (D1R, D2R) in the OFC.
  • Examined neuronal projections from the OFC to the laterodorsal tegmental nucleus (LDTg) and basolateral amygdaloid nucleus (BLA).

Main Results:

  • TN induced a hypodopaminergic state in the VTA-OFC circuit.
  • Activation of the VTA-DA-OFC pathway reduced both allodynia and anxiodepressive-like behaviors.
  • Selective blockade of D2Rs abolished pain relief, while D1R blockade abolished depression relief.
  • Targeting OFC D1R+ neurons improved depressive behaviors; targeting OFC D2+ neurons produced analgesia.

Conclusions:

  • OFC D1R- and D2R-expressing neurons independently mediate anxiodepression and allodynia.
  • Selective modulation of VTA-OFC dopamine pathways offers potential therapeutic strategies for distinct chronic pain symptoms.
Keywords:
basolateral amygdalachronic paincomorbidity of chronic pain and depression/anxietydepressiondopamine D1 receptordopamine D2 receptorlaterodorsal tegmental nucleusorbitofrontal cortexventral tegmental area

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