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. 2024 Jun 29;25(13):7199.
doi: 10.3390/ijms25137199.

Intramuscular Pulsed Radiofrequency Upregulates BNDF-TrKB Expression in the Spinal Cord in Rats as an Alternative Treatment for Complicated Pain

Cheng-Loong Liang  1 , Cheng-Yo Yen  2 , Hao-Kuang Wang  1 , Yu-Duan Tsai  1 , Cien-Leong Chye  1 , Kuo-Wei Wang  3
Affiliations

Intramuscular Pulsed Radiofrequency Upregulates BNDF-TrKB Expression in the Spinal Cord in Rats as an Alternative Treatment for Complicated Pain

Cheng-Loong Liang et al. Int J Mol Sci. .

Abstract

Two cases of complicated pain exist: posterior screw fixation and myofascial pain. Intramuscular pulsed radiofrequency (PRF) may be an alternative treatment for such patients. This is a two-stage animal study. In the first stage, two muscle groups and two nerve groups were subdivided into a high-temperature group with PRF at 58 °C and a regular temperature with PRF at 42 °C in rats. In the second stage, two nerve injury groups were subdivided into nerve injury with PRF 42 °C on the sciatic nerve and muscle. Blood and spinal cord samples were collected. In the first stage, the immunohistochemical analysis showed that PRF upregulated brain-derived neurotrophic factor (BDNF) in the spinal cord in both groups of rats. In the second stage, the immunohistochemical analysis showed significant BDNF and tropomyosin receptor kinase B (TrkB) expression within the spinal cord after PRF in muscles and nerves after nerve injury. The blood biomarkers showed a significant increase in BDNF levels. PRF in the muscle in rats could upregulate BDNF-TrkB in the spinal cord, similar to PRF on the sciatica nerve for pain relief in rats. PRF could be considered clinically for patients with complicated pain and this study also demonstrated the role of BDNF in pain modulation. The optimal temperature for PRF was 42 °C.

Keywords: brain-derived neurotrophic factor; intercellular adhesion molecule 1; muscle; myofascial pain syndrome; posterior spinal instrumentation; pulsed radiofrequency treatment; tropomyosin receptor kinase B; vascular endothelial growth factor.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
BDNF expression in spinal cord after pulsed radiofrequency on muscle and sciatic nerve. (A) Increased BDNF expression in the gray matter of spinal cord after PRF on muscle. The rats underwent a PRF procedure on the muscles of lower limbs at 42 °C or 58 °C or a sham operation; 40× and 400× magnification. Quantification of BDNF-positive stained area in each group. One-way ANOVA followed by post Tukey test was used for statistical analysis to compare control and treated groups. * p < 0.05 for 42 °C RF result that was significantly different from control and ** p < 0.01 for 58 °C RF result that was significantly different from control treatments. (B) BDNF expression in spinal cord after pulsed frequency on sciatica nerve. The rats underwent a PRF procedure on the sciatic nerve at 42 °C or 58 °C or a sham operation; 40× and 400× magnification. Comparison of the percentage of BDNF-positive stained area between groups. One-way ANOVA followed by post Tukey test was used for statistical analysis to compare control and treated groups. * p < 0.05 for 42 °C RF result that was significantly different from control and ** p < 0.01 for 58 °C RF result that was significantly different control treatments.
Figure 2
Figure 2
Analysis of BDNF and ICAM-1 levels in blood (in the first and second stages). (A) There was a significant elevation in BDNF levels in both groups in the muscle groups. (B) There was a significant elevation in BDNF levels in both groups in the SCN groups. (C) There was no significant elevation in ICAM-1 levels in both groups. (D) The nerve injury group demonstrated significantly different expression levels at all time points when compared to the control group (p < 0.05, asterisk “*”). The muscle group also exhibited higher expression at 10 days and 14 days when compared to the control group (p < 0.05, symbel “#≠”). Noticeably, no significance difference between the nerve and muscle groups was observed at all time points. * Indicates p < 0.05 verus basline within one group. # Indicates p < 0.05 between nerve and no treatment groups at the time point. ≠ Indicates p < 0.05 between muscle and no treatment groups at the time point.
Figure 3
Figure 3
Immunohistochemistry of BDNF, S100, PGP9.5, and VEGF expression in muscle after pulsed radiofrequency at different temperatures. Seven days after PRF, the ablated muscles were harvested and processed for immunohistochemistry. Microscopic images show the elevation in BDNF, S100, PGP9.5, and VEGF expression around the probe (40× magnification). The arrows (↑) show the path of the PRF probe and the star (★) shows the tip of the probe.
Figure 4
Figure 4
BDNF and TrkB expression in spinal cord after pulsed radiofrequency in muscle in the second stage. Increased BDNF expression in the gray matter of spinal cord after PRF. The rats underwent PRF procedure at 42 °C on the muscles of lower limbs or on nerve , 40× and 400× magnification. Quantification of BDNF stained area (400×) are expressed as mean ± SEM. *** p < 0.001 compared with control group (one-way ANOVA followed by Tukey-Kramer post hoc test). Increased TrkB expression in the gray matter of spinal cord after PRF. The rats underwent PRF procedure at 42 °C on the muscles of lower limbs or on nerve. Quantification of TrkB stained area (400×) are expressed as mean ± SEM. * p < 0.05 compared with control group (one-way ANOVA followed by Tukey-Kramer post hoc test).
Figure 5
Figure 5
Von Frey test for pain behavior. The von Frey test showed a significant pain reduction in the PRF groups when comparing to the control group ( * p < 0.05, ** p < 0.01, *** p < 0.001).
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