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Mitochondrial Transplantation with Vitamin D Therapy Mitigates Paraspinal Muscle Atrophy and Neuropathic Pain Following Spinal Surgery

ABSTRACT: Chronic pain after spinal surgery (CPSS) is frequently accompanied by paraspinal muscle atrophy (PMA). This study aimed to explore the potential of mitochondrial transplantation and/or vitamin D (VitD) therapy to counteract PMA- and pain-associated mitochondrial dysfunction. Plasma-derived mitochondria (pMT) were collected from human blood samples. The structure, size, and purity of the pMT were verified, and their mitochondrial respiratory enzyme activity was analyzed. A 2-week rat model of CPSS was created at the fifth left lumbar vertebra through denervation and laminectomy. The rats were assigned to 5 groups, namely, pMT/VitD, pMT, VitD, surgery, and control and administered intramuscular pMT ± VitD injections. The effects elicited in each group were investigated after 2 weeks via muscle morphology measurement and comprehensive tissue analysis. Combined pMT and VitD treatments showed potential in alleviating surgery-induced muscle atrophy and modulating pain responses. Thus, pMT and/or VitD treatment restored muscle atrophy by modulating proteostasis, suppressing apoptosis, and increasing PGC1α levels.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE267096 | GEO | 2025/09/24

REPOSITORIES: GEO

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Project description:Belt electrode-skeletal muscle electrical stimulation (B-SES) involves the use of belt-shaped electrodes to simultaneously contract multiple muscle groups. Twitch contractions have been demonstrated to protect against denervation-induced muscle atrophy in rats, possibly via mitochondrial biosynthesis. In this study, we examined whether inducing tetanus contractions with B-SES suppresses muscle atrophy and identified the underlying molecular mechanisms. We evaluated the effects of acute (60 Hz, 5 min) and chronic (60 Hz, 5 min, every alternate day for 1 week) B-SES on the tibialis anterior (TA) and gastrocnemius (GAS) muscles in Sprague Dawley rats using belt electrodes attached to both ankle joints. In acute stimulation, a significant decrease in glycogen content in the left and right TA and GAS was observed, suggesting that B-SES causes simultaneous contractions in multiple muscle groups. B-SES also enhanced p70S6K phosphorylation, an indicator of the mechanistic target of rapamycin complex 1 activity. During chronic stimulations, rats were divided into control (CONT), denervation-induced atrophy (DEN), and DEN+electrically stimulated with B-SES (DEN＋ES) groups. After 7 days of treatment, muscle wet weight (n = 8-11 for each group) and muscle fiber cross-sectional area (CSA, n = 6 for each group) of the TA and GAS muscles were reduced in the DEN and DEN+ES groups compared to those in the CON group. The DEN+ES group showed significantly higher muscle weight and CSA than the DEN group. Although RNA-seq and pathway analysis suggested that mitochondrial and ribosome biogenesis are key events in this phenomenon, mitochondrial content showed no difference. In contrast, ribosomal RNA 28S and 45S (n = 6) levels in the DEN+ES group were higher than those in the DEN group. The mRNA levels of the muscle proteolytic molecules Atrogin-1 and MuRF1 were significantly higher in DEN than in CONT but were suppressed in DEN+ES. In conclusion, tetanic electrical stimulation of both ankles using belt electrodes was effective in preventing denervation-induced atrophy in multiple muscle groups. Unlike twitch contractions, ribosomal biosynthesis plays a key role in tetanic contractions to prevent muscle atrophy.

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Mitochondrial Transplantation with Vitamin D Therapy Mitigates Paraspinal Muscle Atrophy and Neuropathic Pain Following Spinal Surgery

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