Contribution of the P2X4 Receptor in Rat Hippocampus to the Comorbidity of Chronic Pain and Depression

Li, Lin; Zou, Yuting; Liu, Baoe; Yang, Runan; Yang, Jingjian; Sun, Minghao; Li, Zijing; Xu, Xiaoxiao; Li, Guilin; Liu, Shuangmei; Greffrath, Wolfgang; Treede, Rolf‐Detlef; Liang, Shangdong

doi:10.1021/acschemneuro.0c00623

Cited by 21 publications

(27 citation statements)

References 43 publications

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“…Subcortical structures including the hippocampus and basal ganglia have been implicated in chronic pain [ 52 ]. The hippocampus is a key region for memory and learning, which are important aspects of chronic pain and depression [ 53 ] and relevant to their co-occurrence [ 53 , 54 ]. TN patients have been reported to exhibit higher depression and anxiety scores than HCs [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Gray matter volume reduction with different disease duration in trigeminal neuralgia

et al. 2021

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Purpose Structural magnetic resonance imaging is widely used to explore brain gray and white matter structure in trigeminal neuralgia (TN) but has yielded conflicting findings. This study investigated the relationship between disease duration as a clinical feature of TN and changes in brain structure. Methods We divided 49 TN patients into three groups (TN1–TN3) based on disease duration (TN1 = 1.1 ± 0.7 (0–2) years, TN2 = 4.8 ± 1.5 (3–7) years, TN3 = 15.1 ± 5.5 (10–30) years). We used voxel-based morphometry (VBM) to compare the gray matter volume (GMV) across groups and between TN patients and 18 matched healthy control subjects. Results The TN1 group showed reduced GMV of pain-related regions in the cerebellum; the TN2 group showed reduced GMV in the thalamus and the motor/sensory cortex; and the TN3 group showed reduced GMV in the emotional and reward circuits compared with healthy controls. Similar brain regions, including bilateral hippocampi, caudate, left insular cortex, and medial superior frontal cortex, were affected in TN2 and TN3 compared with TN1. Conclusion Disease duration can explain differences in structural alterations—especially in pain-related brain regions—in TN. These results highlight the advanced structural neuroimaging method that are valuable tools to assess the trigeminal system in TN and may further our current understanding of TN pathology.

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Section: Discussionmentioning

confidence: 99%

Gray matter volume reduction with different disease duration in trigeminal neuralgia

et al. 2021

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“…The DEGs were mainly distributed in tissues of the circulatory system, immune system, and neurologic system, consistent with the fact that MDD patients usually Frontiers in Psychiatry 10 frontiersin.org harbor coronary artery disease (29). In our study, the most typical tissues were cardiomyocytes, lymphoma Burkitt, CD33+ myeloid, pineal, and Dorsal Root Ganglion, which might imply the probable reasons for clinical manifestations in MDD, such as repeated infection, circadian rhythm disorder and feeling pain (30,31).…”

Section: Discussionmentioning

confidence: 61%

Identification of potential Mitogen-Activated Protein Kinase-related key genes and regulation networks in molecular subtypes of major depressive disorder

Chen¹,

Lu²,

Zeng³

et al. 2022

Front. Psychiatry

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BackgroundMajor depressive disorder (MDD) is a heterogeneous and prevalent mental disorder associated with increased morbidity, disability, and mortality. However, its underlying mechanisms remain unclear.Materials and methodsAll analyses were conducted based on integrated samples from the GEO database. Differential expression analysis, unsupervised consensus clustering analysis, enrichment analysis, and regulation network analysis were performed.ResultsMitogen-activated protein kinase (MAPK) signaling pathway was identified as an associated pathway in the development of MDD. From transcriptional signatures, we classified the MDD patients into two subgroups using unsupervised clustering and revealed 13 differential expression genes between subgroups, which indicates the probably relative complications. We further illustrated potential molecular mechanisms of MDD, including dysregulation in the neurotrophin signaling pathway, peptidyl-serine phosphorylation, and endocrine resistance. Moreover, we identified hub genes, including MAPK8, TP53, and HRAS in the maintenance of MDD. Furthermore, we demonstrated that the axis of miRNAs-TFs-HRAS/TP53/MAPK8 may play a critical role in MDD.ConclusionTaken together, we demonstrated an overview of MAPK-related key genes in MDD, determined two molecular subtypes, and identified the key genes and core network that may contribute to the procession of MDD.

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“…The mechanism by which P2X4 activation after surgery causes PND is unclear. Recent studies have shown the activation of P2X4-mediated NLRP3 inflammasome signaling in multiple models [32], including the hippocampus of rats with comorbidities of chronic pain and depression [33]. Emerging evidence has shown that NLRP3 inflammasome is closely related to the neuroinflammation of postoperative cognitive dysfunction [34].…”

Section: Discussionmentioning

confidence: 99%

Role of P2X4/NLRP3 Pathway-Mediated Neuroinflammation in Perioperative Neurocognitive Disorders

Yuan

et al. 2022

Mediators of Inflammation

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Several studies have demonstrated that neuroinflammation is the key to perioperative neurocognitive disorders (PND); however, the specific mechanism postsurgery and anesthesia has not yet been fully clarified. The present study is aimed at exploring the effects of P2X4/NLRP3 signaling pathway in neuroinflammation and cognitive impairment after surgery. 12–14-month-old male C57BL/6 mice undergoing open tibial fracture surgery by sevoflurane anesthesia were administered P2X4R inhibitor 5-BDBD or saline was intraperitoneally for 3 consecutive days after surgery. Then, the animals were subjected to Morris water maze test or sacrificed to collect the hippocampus. The level of P2X4R and NLRP3 was estimated by Western blot, the activation of microglia was detected via immunohistochemistry, and the expression of TNF-α, IL-1β, and IL-6 was quantified by enzyme-linked immunosorbent assay. These results indicated that tibial surgery caused cognitive impairment, increased the expression of P2X4R and NLRP3, and aggravated the neuroinflammation and microglia activation. However, intraperitoneal injection of 5-BDBD attenuated these effects. In conclusion, these findings indicated that the P2X4/NLRP3 pathway might be involved in the pathophysiology of PND.

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Contribution of the P2X4 Receptor in Rat Hippocampus to the Comorbidity of Chronic Pain and Depression

Cited by 21 publications

References 43 publications

Gray matter volume reduction with different disease duration in trigeminal neuralgia

Gray matter volume reduction with different disease duration in trigeminal neuralgia

Identification of potential Mitogen-Activated Protein Kinase-related key genes and regulation networks in molecular subtypes of major depressive disorder

Role of P2X4/NLRP3 Pathway-Mediated Neuroinflammation in Perioperative Neurocognitive Disorders

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