Journal of Pain Research (Mar 2023)
Proteomic Analysis of the Spinal Dorsal Horn in Mice with Neuropathic Pain After Exercise
Abstract
Jie Bai,1 Jingyu Zhang,1 Li Zhou,2 Yufang Hua1 1Department of Anesthesiology, Lanzhou University Second Hospital, Lanzhou, People’s Republic of China; 2Department of Pediatric Digestive, Gansu Provincial Maternity and Child-Care Hospital/Gansu Provincial Central Hospital, Lanzhou, People’s Republic of ChinaCorrespondence: Yufang Hua, Department of Anesthesiology, Lanzhou University Second Hospital, Lanzhou, 730030, People’s Republic of China, Tel +86 139 1903 2553, Email [email protected]: 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
