Abstract
Background: Repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex (PFC) and transcutaneous electrical nerve stimulation (TENS) have both been demonstrated as effective at alleviating neuropathic pain (NP). However, the comparative efficacy of these two neuromodulation techniques and the specific neural mechanisms underlying their effects remain unclear. Objective: This study aims to compare the efficacy of rTMS in the PFC and TENS in mitigating peripheral NP and to investigate the impact of rTMS on neuroinflammation. Methods: Eighteen adult male Sprague-Dawley rats were randomly divided into three groups: NP (chronic constriction injury [CCI] group, n = 6), rTMS (n = 6), and TENS (n = 6). rTMS was applied to the PFC, while TENS was applied to the right hind limb of the rats 1 week postoperatively. This treatment regimen was administered once daily, 5 days a week, for 4 consecutive weeks. The paw withdrawal mechanical threshold (PWMT) was measured to assess the pain-alleviating effects of rTMS and TENS. We further conducted enzyme-linked immunosorbent assays (ELISAs) to measure the levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) in the PFC and L4-L6 spinal cord to evaluate their impact on neuroinflammation. Additionally, we examined transient receptor potential vanilloid type 1 (TRPV1) expression in the PFC and the L4‒L6 spinal cord using western blotting and real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to explore the potential mechanisms involved. Hematoxylin and eosin (H&E) staining of the sciatic nerve was further performed to observe pathological changes. Results: Compared to the CCI group, both the rTMS and TENS groups exhibited a significant increase in PWMT, with the rTMS group demonstrating a notably greater PWMT than the TENS group. Furthermore, rTMS treatment triggered a significant decrease in IL-1β, IL-6, and TNF-α levels in the PFC and spinal cord, while TENS only decreased IL-1β expression in these regions. In both treatment groups, TRPV1 expression was significantly lower in the spinal cord, while H&E staining indicated improved pathological manifestations in the sciatic nerve. Conclusion: Both rTMS and TENS effectively ameliorated CCI-induced NP, with rTMS of the PFC showing superior performance. Both treatments reduced TRPV1 expression and suppressed neuroinflammation in the spinal cord, indicating that this may be one of the mechanisms through which they exert their therapeutic effects.