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Purinergic signaling: a potential therapeutic target for depression and chronic pain

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Abstract

The comorbid mechanism of depression and chronic pain has been a research hotspot in recent years. Until now, the role of purinergic signals in the comorbid mechanism of depression and chronic pain has not been fully understood. This review mainly summarizes the research results published in PubMed during the past 5 years and concludes that purinergic signaling is a potential therapeutic target for comorbid depression and chronic pain, and the purinergic receptors A1, A2A, P2X3, P2X4, and P2X7and P2Y6, P2Y1, and P2Y12 may be important factors. The main potential pathways are as follows: A1 receptor-related G protein-dependent activation of introverted K+ channels (GIRKs), A2A receptor-related effects on the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and MAPK/nuclear factor-κB (NF-κB) pathways, P2X3 receptor-related effects on dorsal root ganglia (DRG) excitability, P2X4 receptor-related effects on proinflammatory cytokines and inflammasome activation, P2X7 receptor-related effects on ion channels, the NLRP3 inflammasome and brain-derived neurotrophic factor (BDNF), and P2Y receptor-related effects on the phospholipase C (PLC)/inositol triphosphate (IP3)/Ca2+ signaling pathway. We hope that the conclusions of this review will provide key ideas for future research on the role of purinergic signaling in the comorbid mechanism of depression and chronic pain.

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Funding

This work was supported by grants (Nos. 81861138042, 81870574, 81570735, and 31560276) from the National Natural Science Foundation of China.

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  1. Yuting Zou and Runan Yang contributed equally to this work.

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  1. Neuropharmacology Laboratory of Physiology Department, Basic Medical School, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China

    Runan Yang, Lin Li, Xiumei Xu & Shangdong Liang

  2. First Clinical Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China

    Yuting Zou

  3. Jiangxi Provincial Key Laboratory of Autonomic Nervous Function and Disease, Nanchang, Jiangxi, 330006, People’s Republic of China

    Runan Yang, Lin Li, Xiumei Xu & Shangdong Liang

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Zou, Y., Yang, R., Li, L. et al. Purinergic signaling: a potential therapeutic target for depression and chronic pain. Purinergic Signalling 19, 163–172 (2023). https://doi.org/10.1007/s11302-021-09801-x

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