Proteomic Analysis of the Spinal Dorsal Horn in Mice with Neuropathic Pain After Exercise

Abstract

Purpose

Neuropathic pain (NP) is a chronic pain state with a complex etiology that currently lacks effective treatment in clinical practice. Studies have found that exercise training can alleviate NP hyperalgesia, but the specific mechanism remains unclear. Here, we sought to identify proteins and signaling pathways critical for mediating the effects of treadmill training on NP in a mouse model of spared nerve injury (SNI).

Methods

We used Tandem Mass Tag (TMT) technology for proteins and signaling pathways identification. Functional enrichment analyses were conducted using DAVID and Metascape software. Ingenuity pathway analysis was used to conduct functional annotation and analyze alterations in canonical pathways and molecular networks. Reverse transcription quantitative PCR (RT-qPCR) was used to confirm the results of proteomics analysis.

Results

A total of 270 differentially expressed proteins were screened in the detrained and trained groups (P ≤0.05). Enrichment and ingenuity pathway analysis revealed the effects of treadmill training on autophagy, cAMP-mediated signaling, calcium signaling and NP signaling in dorsal horn nerves. Treadmill training reduced the expression of Akt3, Atf2, Gsk3b, Pik3c3, Ppp2ca, and Sqstm1, and increased the expression of Pik3cb in the autophagic pathway.

Conclusion

Our results suggest that treadmill training may alleviate nociceptive hyperalgesia in NP mice by modulating the autophagic pathway, providing unique mechanistic insights into the analgesic effects of exercise.

Keywords:

• proteomic changes
• exercise
• neuropathic pain
• IPA
• passway analysis

Data Sharing Statement

The datasets used during the present study are available from the corresponding author upon reasonable request.

Ethics Approval

All experimental protocols were approved by Animal Use and Ethics Committee of the Second Hospital of Lanzhou University.

Acknowledgments

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This work was supported by grants from the Natural Science Foundation of Gansu Province of China (20JR10RA726, 21JR11RA178); and Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital (CY2022-QN-B01).