ArticleActa pharmacologica Sinica2021
D2 receptor activation relieves pain hypersensitivity by inhibiting superficial dorsal horn neurons in parkinsonian mice.
Article in Acta pharmacologica Sinica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed, 31 citations in OpenAlex.
- Enhanced substance P-NK1R signaling in the parabrachial-parasubthalamic pathway promotes hyperalgesia and affective aversion in neuropathic pain.Acta pharmacologica Sinica · 2026Article
- Nigra-Subthalamic Dopaminergic Circuitry Modulates and Represents Distinct Pain Modality in Physiological and Pain States in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Role of Serotonergic System in Parkinson's Disease-Related Pain.Neuroscience bulletin · 2026Review
- Novelty exploration-activated ensemble in the lateral hypothalamus confers analgesic and anxiolytic effects.Nature communications · 2026Article
- An attention-demanding hunting paradigm engages the superior colliculus-zona incerta circuit mediating analgesia in male mice.Nature communications · 2026Article
- Dysfunction of subthalamic dopaminergic circuitry contributes to anxiety- and depression-like behaviors in 6-OHDA lesion-induced hemiparkinsonian mice.Acta pharmacologica Sinica · 2025Article
- Pharmacological and Genetic Approaches to Downregulate FIS1 Mitigate Neuropathic Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- The Locus Coeruleus-Periaqueductal Gray GABAergic Projection Regulates Comorbid Pain and Depression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Excitatory projections from the nucleus reuniens to the medial prefrontal cortex modulate pain and depression-like behaviors in mice.PLoS biology · 2025Article
- Brainstem serotonin amplifies nociceptive transmission in a mouse model of Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Mouse spinal cord cellular mapping of dopamine D2 receptors-containing cells.Frontiers in neuroanatomy · 2025Article
- Activation and polarization of striatal microglia and astrocytes are involved in bradykinesia and allodynia in early-stage parkinsonian mice.Fundamental research · 2024Article
- MOTS-c is an effective target for treating cancer-induced bone pain through the induction of AMPK-mediated mitochondrial biogenesis.Acta biochimica et biophysica Sinica · 2024Article
- The anterior cingulate cortex controls the hyperactivity in subthalamic neurons in male mice with comorbid chronic pain and depression.PLoS biology · 2024Article
- Commentary: Gut dysbiosis in patients with chronic pain: a systematic review and meta-analysis.Frontiers in immunology · 2024Article
- PACAP/PAC1-R activation contributes to hyperalgesia in 6-OHDA-induced Parkinson's disease model rats via promoting excitatory synaptic transmission of spinal dorsal horn neurons.Acta pharmacologica Sinica · 2023Article
- A nigro-subthalamo-parabrachial pathway modulates pain-like behaviors.Nature communications · 2022Article
- Dopamine receptor D2 regulates GLUA1-containing AMPA receptor trafficking and central sensitization through the PI3K signaling pathway in a male rat model of chronic migraine.The journal of headache and pain · 2022Article
- Assessment of the anti-nociceptive effects of fetal ventral mesencephalic tissue allografts in a rat model of hemi-Parkinson's disease using fMRI.Frontiers in aging neuroscience · 2022Article
- Serotonergic Neurotransmission System Modulator, Vortioxetine, and Dopaminergic DMolecules (Basel, Switzerland) · 2021Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic pain is a common and undertreated nonmotor symptom in Parkinson's disease (PD). Although chronic pain is improved by L-dopa in some PD patients, the underlying mechanisms remain unclear. In this study, we established PD mice by unilateral microinjection of 6-OHDA in the medial forebrain bundle to investigate the contribution of spinal cord dopamine receptors to parkinsonian pain hypersensitivity. The von Frey filament tests and thermal pain tests revealed that these PD mice displayed decreased nociceptive thresholds in both hindpaws; intrathecal injection of L-dopa or apomorphine significantly increased the mechanical and thermal nociceptive thresholds, and the analgesic effect was mimicked by ropinirole (a D2 receptor agonist), but not SKF38393 (a D1/D5 receptor agonist), and blocked by sulpiride (a D2 receptor antagonist), but not SKF83566 (a D1/D5 receptor antagonist). Whole-cell recordings in lumber spinal cord slices showed that superficial dorsal horn (SDH) neurons in PD mice exhibited hyperexcitability, including more depolarized resting membrane potentials and more action potentials evoked by depolarizing current steps, which were mitigated by ropinirole. Furthermore, ropinirole inhibited the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in SDH neurons more strongly in PD mice than in control mice. However, sulpiride caused less disinhibition of sEPSCs in PD mice than in control mice. Taken together, our data reveal that pain hypersensitivity in PD mice is associated with hyperexcitability of SDH neurons, and both events are reversed by activation of spinal D2 receptors. Therefore, spinal D2 receptors can be promising therapeutic targets for the treatment of PD pain.
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