BASIC SCIENCE RESEARCH ARTICLE

Loss of astrocytic A1 adenosine receptor is involved in a chemotherapeutic agent–induced rodent model of neuropathic pain

Lin Liu MD

Department of Pain, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, China

Contribution: Formal analysis, Investigation, Methodology, Software, Writing - original draft

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Lingjie Xia MD,

Lingjie Xia MD

Department of Pain, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, China

Contribution: Data curation, Formal analysis, Funding acquisition, Investigation

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Yao Cui MD,

Corresponding Author

Yao Cui MD

[email protected]

orcid.org/0000-0002-7067-6511

Department of Oncology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, China

Correspondence

Yao Cui, Department of Oncology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou 450003, China.

Email: [email protected]

Contribution: Formal analysis, Funding acquisition, Project administration, Validation, Visualization, Writing - review & editing

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Lin Liu MD,

Lin Liu MD

Department of Pain, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, China

Contribution: Formal analysis, Investigation, Methodology, Software, Writing - original draft

Search for more papers by this author

Lingjie Xia MD,

Lingjie Xia MD

Department of Pain, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, China

Contribution: Data curation, Formal analysis, Funding acquisition, Investigation

Search for more papers by this author

Yao Cui MD,

Corresponding Author

Yao Cui MD

[email protected]

orcid.org/0000-0002-7067-6511

Department of Oncology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, China

Correspondence

Yao Cui, Department of Oncology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou 450003, China.

Email: [email protected]

Contribution: Formal analysis, Funding acquisition, Project administration, Validation, Visualization, Writing - review & editing

Search for more papers by this author

First published: 06 March 2023

https://doi.org/10.1002/mus.27812

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Abstract

Introduction/Aims

Oxaliplatin is a commonly used platinum chemotherapy drug, whereas peripheral neurotoxicity is a widely observed adverse reaction lacking a satisfactory therapeutic strategy. Different adenosine receptors underlying the common neuropathic phenotype play different roles through varied pathophysiological mechanisms. In this study, we investigated the role of adenosine receptor A1 (A1R) in oxaliplatin-induced neuropathic pain and its potential use in an effective therapeutic strategy.

Methods

We established an oxaliplatin-induced neuropathic pain model simulating the mode of chemotherapy administration and observed the related neuropathic behavioral phenotype and implicated mechanisms.

Results

Five weekly injections of oxaliplatin for 2 weeks induced a severe and persistent neuropathic pain phenotype in mice. A1R expression in the spinal dorsal horn decreased during this process. Pharmacological intervention against A1R verified its importance in this process. Mechanistically, the loss of A1R expression was mainly attributed to its decreased expression in astrocytes. Consistent with the pharmacological results, the oxaliplatin-induced neuropathic pain phenotype was blocked by specific therapeutic interventions of A1R in astrocytes via lentiviral vectors, and the expression of glutamate metabolism–related proteins was upregulated. Neuropathic pain can be alleviated by pharmacological or astrocytic interventions via this pathway.

Discussion

These data reveal a specific adenosine receptor signaling pathway involved in oxaliplatin-induced peripheral neuropathic pain, which is related to the suppression of the astrocyte A1R signaling pathway. This may provide new opportunities for the treatment and management of neuropathic pain observed during oxaliplatin chemotherapy.

CONFLICT OF INTEREST STATEMENT

The authors have no conflicts of interest to disclose.

Open Research

DATA AVAILABILITY STATEMENT

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Volume67, Issue5

May 2023

Pages 417-426

Loss of astrocytic A1 adenosine receptor is involved in a chemotherapeutic agent–induced rodent model of neuropathic pain

Abstract

Introduction/Aims

Methods

Results

Discussion

CONFLICT OF INTEREST STATEMENT

Open Research

DATA AVAILABILITY STATEMENT

REFERENCES

References

Information

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Loss of astrocytic A1 adenosine receptor is involved in a chemotherapeutic agent–induced rodent model of neuropathic pain

Abstract

Introduction/Aims

Methods

Results

Discussion

CONFLICT OF INTEREST STATEMENT

Open Research

DATA AVAILABILITY STATEMENT

REFERENCES

References

Related

Information