Introduction
Lumbar spinal stenosis (LSS) is the major cause of back pain and radicular pain that disturb usual ambulatory activities. Repetitive peripheral magnetic stimulation (rPMS) is a non-invasive peripheral stimulation tool that evokes muscle contractions and stimulates sensory nerve fibers. Use of this instrument has been increased in humans for a variety of clinical and scientific applications. This research aimed to evaluate possibility of therapeutic efficacy of high frequency (20Hz) rPMS in a LSS rat model by assessing mechanical allodynia and thermal hyperalgesia representing LSS pain mechanism. Also, cellular mechanism of anti-nociceptive effect was assessed with transient receptor potential vaniloid (TRPV), matrix metalloproteinases (MMPs), and inflammatory expressions since alteration of these were suggested to be critically involved in development of neuropathic pain.
Methods
The subject rats were randomly assigned to the following three groups: sham-operated control group (Sham), LSS-induced disease model group (LSS), and LSS-induced and treated with rPMS group (LSS+rPMS). The LSS rat models were induced by compression of silicone blocks in lumbar 4/5 spinal nerve roots. Sham group was only exposed lumbar 4/5 spinal nerve roots. The rPMS (Remed Co., Ltd) was given from 7 days after LSS induction, with 40 trains of 5 seconds, interstimulus interval at 20 Hz and inter-train interval of 55 seconds on L4-L5 spinal segment for 14 consecutive days. Thermal and mechanical sensitivities were measured using paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) with von Frey test on both hind paws and thermal withdrawal latency (TWL) in hot plate test before surgery and 3, 7, 14, and 21 days after the surgery (D-1, D3 to D21). The mRNA expression of TRPV4, TRPV1, MMP2, MMP9, TNF-α, and TGF-β in spinal cord were measured by using quantitative real-time PCR from D14 model. SPSS V18 was used for analyses.
Results
PWT, PWL, and TWL in the LSS-induced rat model were lowered by upregulated thermal and mechanical sensitivities from D3 (Ps <0.05). However, LSS+rPMS group showed attenuation of mechanical and thermal allodynia by elevating PWT and PWL from D14 to D21, and elevating TWL at D21 (Ps <0.05), while LSS group sustained low values of those (Fig. 2). Gene expressions of TRPV4, MMP2, MMP9, TNF-α, and TGF-β were upregulated by LSS-induction in the spinal cord tissue compared to Sham control, which means inflammatory response by LSS (Ps <0.05). However, TRPV4, MMP2, TNF-α, and TGF-β were down regulated in LSS+rPMS group, which indicate alleviation of inflammatory status in the spinal cord (Ps <0.05) (Fig 3).
Conclusion
Overall, this study suggested therapeutic effect of high-frequency rPMS administration in LSS with ameliorated neurobehavioral findings and downregulated TRPV4 and inflammatory markers which were elevated by LSS.
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Figure 1. Lumbar spinal stenosis (LSS) modeling: placement of silicon block for induction of LSS
Figure 2. Thermal and mechanical sensitivities assessment of the lumbar spinal stenosis (LSS) induced model. rPMS were administrated about L4-L5 spinal segment for 14 consecutive days. Results are presented as mean±SEM (n=6 in each group). ** denotes significant difference (Ps <0.01) compared to Sham group and + and ++ denotes significant difference (Ps <0.05, Ps <0.01) compared to LSS group. (A) and (B) were measured using von Frey test to assess the mechanical sensory thresholds and latencies of the bilateral hind paws. (C) was measured using hot plate test to assess the thermal sensory latency of the hind paw. Repeated measured ANOVA and ANOVA tests were used.
Figure 3. Effect of rPMS on mRNA expressions of TRPV1, TRPV4, MMP2, MMP9, TNF-α and TGF-β in spinal cord after lumbar spinal stenosis. Results are presented as mean±SEM of 4 animals per group. * and ** denote significant difference (Ps < 0.05, Ps <0.01) from Sham group. + and ++ denote significant difference (Ps < 0.05, Ps <0.01) from LSS group. ANOVA test was used for analysis.
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