Elsevier

Brain Research Bulletin

Volume 155, February 2020, Pages 19-28
Brain Research Bulletin

Review
The role and pharmacological properties of the P2X7 receptor in neuropathic pain

https://doi.org/10.1016/j.brainresbull.2019.11.006Get rights and content

Highlights

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    Further clarified the structure and the function of P2X7R gene.

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    Further discussed and summarized the pathogenesis of NPP.

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    Provided some data of P2X7R antagonists for the treatment of NPP in future.

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    Provided up-to-date data support for the intrinsic link between P2X7R and NPP.

Abstract

Neuropathic Pain (NPP) is caused by direct or indirect damage to the nervous system and is a common symptom of many diseases. Clinically, drugs are usually used to suppress pain, such as (lidocaine, morphine, etc.), but the effect is short-lived, poor analgesia, and there are certain dependence and side effects. Therefore, the investigation of the treatment of NPP has become an urgent problem in medical, attracting a lot of research attention. P2X7 is dependent on Adenosine triphosphate (ATP) ion channel receptors and has dual functions for the development of nerve damage and pain. In this review, we explored the link between the P2X7 receptor (P2X7R) and NPP, providing insight into the P2X7R and NPP, discussing the pathological mechanism of P2 X7R in NPP and the biological characteristics of P2X7R antagonist inhibiting its over-expression for the targeted therapy of NPP.

Section snippets

The gene structure of P2X7R

P2X7R is the latest P2X subtype, and is trimer that dependent on ATP non-selective cation channel, which differ from other P2X subtypes (1–6) (Boyce and Swayne, 2017; Arandjelovic et al., 2012). Initially, the P2X7R is recognized in macrophages and lymphocytes, and is associated with apoptosis and inflammatory response (He et al., 2017; Jiang et al., 2017; Di Virgilio et al., 2017). Later, it was found that the mRNA and protein of P2X7R were also expressed in spinal cord, brain, skeletal

P2X7R electrophysiology and involved in signaling pathways

P2X7R is activated by binding to ATP, causing a conformational change of the protein molecule and opening the pore on cell membrane, leading to increased sodium, calcium influx and potassium outflow, triggering the changes in cell membrane potential, thereby affecting related signaling pathways (Faria et al., 2017; Kasuya et al., 2017; Kopp et al., 2017). In addition, it also alters the activities of some protein molecules (enzymes and protein kinases) involved in process of signal

The antagonists and pharmacological properties of P2X7R

P2X7 has been reported to play a key role in many disease processes, such as autoimmune diseases (Savio and Coutinho-Silva, 2016; Faliti et al., 2019), inflammation (Crabbé et al., 2019; Ozen et al., 2019), neurodegenerative diseases (Janssen and Mach, 2019), tumor (Bergamin et al., 2019), chronic pain (Bernier et al., 2018), etc. Therefore, selecting the effective antagonists of P2X7R to inhibit its over-expression will be a drug target for the treatment of some diseases. There have been a lot

The role of P2X7R in nervous system

P2X7R are mainly distributed in glial cells, ganglia (Bennett et al., 2009; Tsuda and Inoue, 2007). Under physiological conditions, low expression of P2X7R does not cause damage in the nervous system, under pathological conditions, such as neurodegeneration, neuroinflammation, brain ischemia, hypoxia, etc. P2X7R is activated, and tissue damage is increased (Kaiser et al., 2016; Yiangou et al., 2006). In the past, there has been controversy about whether P2X7R are expressed in neurons and

The pathological mechanism of NPP

NPP is a condition caused by direct or indirect damage, primary or secondary damage, dysfunction, and transient disturbance in the central or peripheral nervous system, there is still a feeling of pain after the noxious stimulation is eliminated, mainly characterized by pain sensitivity, allodynia, sensation or absence, and spontaneous pain (Seixas et al., 2016; Vadivelu et al., 2019; Yang et al., 2017). In recent years, with the continuous study of the pathological mechanism of NPP, it has

P2X7R and neuropathic pain

A large number of studies have shown that P2X7R is closely related to neuronal activation, neurosensitization, pain transmission and neuroinflammation (Honore et al., 2006; Apolloni et al., 2014; Bernier et al., 2018; Yang et al., 2016). The relationship between P2X7R and NPP is more reported in the peripheral nervous system (Bravo et al., 2015; Turtle et al., 2018). After sciatic nerve injury, the expression level of P2X7R was significantly increased, induced allergic pain and hyperalgesia (Yu

Conclusion

NPP is a common syndrome of most diseases in clinical, mainly due to damage to the nervous system, resulting in pain sensation, seriously affecting the life quality of patients. Therefore, using effective methods to alleviate NPP and relieving the suffering of patients, attracting wide attention of researchers. Due to the pathological mechanism of NPP is complex, drugs are often used to relieve pain in clinical, but the effect of treatment is poor. The role of P2X7R in occurrence of NPP has

Declaration of Competing Interest

There is on conflict of interests.

Acknowledgments

This study was performed by Wen-jun Zhang and fully supported by professor Zhengming Zhu. These studies were supported by grants from the National Natural Science Foundation of China (8156100154, 81760418 and 81260190), the Natural Science Foundation of Jiangxi Province (20181BBG70015 and 20181BAB205061).

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