Poster Presentation 50th International Society for the Study of the Lumbar Spine Annual Meeting 2024

The Efficacy of a TGF-β Inhibitor on the Biomechanical and Histological Properties of Paraspinal Muscles after Posterior Lumbar Spinal Surgery in a Rat Model (#238)

Shun Yamamoto 1 2 3 , Masoud Malakoutian 1 2 , Alexander Burden 1 2 , Iraj D Hasemi 1 2 , Keli Grant 4 , Alex Noonan 4 , Stephen HM Brown 4 , John Street 1 5 , Mitsuru Saito 3 , Thomas R Oxland 1 2 5
  1. Dept. Orthopaedics & Mechanical Engineering, University of British Columbia, Vancouver, British Columbia, Canada
  2. Orthopaedic and Injury Biomechanics Group, ICORD, Vancouver, British Columbia, Canada
  3. Dept. Orthopaedic Surgery, Jikei University School of Medicine, Minato-ku, Tokyo, Japan
  4. Dept. Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
  5. Dept. Orthopaedics, University of British Columbia, Vancouver, British Columbia, Canada

Introduction. Iatrogenic muscle damage is a frequent consequence of posterior spinal surgery [1]. A recent study in rats demonstrated an increase in the passive elastic modulus of the multifidus muscle fiber bundles coinciding with fibrotic changes at 13 weeks following spinal surgery [2]. The objective of this study was to investigate the efficacy of a muscle fibrosis inhibitor (i.e. TGF-β) on the post-surgical changes in the paraspinal muscles in a rat model at the early stage of 8 weeks following posterior lumbar spinal surgery. The study specifically addressed active muscle contraction, the passive elastic modulus, and histological changes in the paraspinal muscles. 

Materials and Methods. Fifteen Sprague-Dawley rats were randomized to three groups: a control group (Sham), a surgical injury group (SI), and a surgical injury plus treatment group (SI+T), with five rats per group. In the SI and SI+T groups, the multifidus were detached from the spine as normal surgical procedure, while the sham group received only a skin and fascia incision. The SI+T group was treated with a TGF-β inhibitor, whereas the SI group received a placebo (mouse IgG isotype control), both administered intraperitoneally at a dosage of 5mg/kg twice weekly. At the 8-week mark, muscle samples (approximately 6 fibers and 3 to 6 fiber bundles) from the multifidus and longissimus at L2 and L4 level, and psoas muscles were collected for biomechanical testing and histological examination for collagen type I deposition. The biomechanical testing included the measurement of both active specific force and passive elastic modulus, as described previously [3]. 

Results. For active properties, the study analyzed 175 muscle fibers (SI+T: 59, SI: 58, Sham: 58). For passive elastic modulus, 225 fibers (SI+T: 75, SI: 74, Sham: 76) and 311 fiber bundles (SI+T: 101, SI: 110, Sham: 100) were examined across the groups. The active specific force of the multifidus was highest for the sham group compared to the untreated injury group (SI) (Figure 1; p=0.0073). The passive elastic modulus of multifidus fibers was lowest in the SI group (Figure 2; p=0.001) while the multifidus fiber bundles in the SI+T group displayed a higher passive elastic modulus compared to the other groups (Figure 2; p=0.01). No significant differences were found in the longissimus and psoas muscles or in collagen type I deposition among the groups.

Conclusions. This study did not identify a consistent pattern in passive elastic modulus alterations or fibrosis following surgery, nor did it confirm a predictable effect of TGF-β inhibitor on the biomechanical properties of the paraspinal muscles. However, our results confirm that surgical injury impairs the active force of the multifidus muscle at 8 weeks post-surgery, aligning with previous observations of passive elastic modulus at 13 weeks post-operation [1].

Limitations.　Small sample size. Short term study.

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  1. 1. Derek TC et al. Eur Spine J. 2014 Feb;23(2):320-7.
  2. 2. Yamamoto S et al. Spine (Phila Pa 1976). 2021 Nov 1;46(21):E1125-E1135.
  3. 3. Malakoutian M et al. Eur Spine J. 2022 Sep;31(9):2383-2398.