Pulsed radiofrequency for chronic pain: In vitro evidence of an electroporation mediated calcium uptake

Mercadal, Borja; Vicente, Rubén; Ivorra, Antoni

doi:10.1016/j.bioelechem.2020.107624

Cited by 7 publications

(5 citation statements)

References 51 publications

(57 reference statements)

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“…29,32 The only other study related to PRF exposure in healthy cells showed that the administration of 2 Hz PRF to kidney embryonic cells resulted in a moderate Ca 2+ influx, which was thought to be due to the electroporation process. 30,33 Differences in cell type might explain why this was observed in kidney cells, but not in our study with neurons since neurons have a minimum limit of stimulus strength to trigger an action potential (AP) due to Ca 2+ influx. 34 In addition to Ca 2+ influx, this study also elaborates on the effect of PRF on the Δψm since it is related to Ca 2+ influx and energy generation in neurons.…”

Section: Discussionmentioning

confidence: 68%

Pulsed Radiofrequency 2 Hz Preserves the Dorsal Root Ganglion Neuron Physiological Ca2+ Influx, Cytosolic ATP Level, Δψm, and pERK Compared to 4 Hz: An Insight on the Safety of Pulsed Radiofrequency in Pain Management

Laksono,

Siswagama,

Nery

et al. 2023

JPR

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Background: Pulsed radiofrequency (PRF) is beneficial for radicular pain and is commonly administered at pulse frequencies of 2 or 4 Hz. However, its effects on healthy neurons have not yet been widely studied. This study aims to determine the effect of PRF at 2 Hz and 4 Hz on the physiology of healthy dorsal root ganglion (DRG) neurons. Methods: An in vitro experimental study was conducted using DRG neuron cultures divided into three groups. Control cells received no treatment, one cell group received 20 ms 2 Hz PRF for 360 s, and one cell group received a 4 Hz PRF 10 ms pulse for 360 s with similar energy. Ca 2+ influx, mitochondrial membrane potential (Δψm), cytosolic Adenosine triphosphate (ATP), and phosphorylated extracellular signal-regulated kinase (pERK) levels were measured. The data were analyzed using the One-Way ANOVA variance with α=5%. Results: DRG neurons exposed to PRF 2 Hz did not experience a significant change in Ca 2+ influx, whereas PRF 4 Hz caused a significant decrease in Ca 2+ influx compared to the basal level. PRF at 2 Hz did not cause a change in Δψm, whereas PRF at 4 Hz caused a significant decrease in Δψm (p<0.05). Both 2 and 4 Hz PRF resulted in a significant elevation in cytosolic ATP concentration, but the 2 Hz PRF had a higher cytosolic ATP than the 4 Hz group (p<0.05). Both 2 and 4 Hz did not show a significant difference in pERK intensity with respect to the control (p>0.05), indicating that there was no significant neuron activation. Conclusion: Both frequencies did not significantly activate DRG neurons, but with similar energy delivery, PRF 2 Hz preserved the physiological properties of healthy neurons better than PRF 4 Hz did. A 2 Hz PRF is the preferred frequency in clinical applications for neuron-targeted therapy.

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Section: Discussionmentioning

confidence: 68%

Pulsed Radiofrequency 2 Hz Preserves the Dorsal Root Ganglion Neuron Physiological Ca2+ Influx, Cytosolic ATP Level, Δψm, and pERK Compared to 4 Hz: An Insight on the Safety of Pulsed Radiofrequency in Pain Management

Laksono,

Siswagama,

Nery

et al. 2023

JPR

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“…These reported mechanisms help to elucidate how PRF inhibits the transmission of pain signals in a biological pathway. However, the biophysical mechanisms by which this electric field may act are not clearly elucidated yet [ 6 ]. One of the main effects reported after a PRF treatment is the increase in cytosolic free calcium concentration, an important messenger involved in both short and long-term cellular processes.…”

Section: Pulsed Radiofrequency: Mechanisms Of Actionmentioning

confidence: 99%

“…One of the main effects reported after a PRF treatment is the increase in cytosolic free calcium concentration, an important messenger involved in both short and long-term cellular processes. This mechanism could link PRF effects to a direct consequence on electric fields [ 6 ].…”

Section: Pulsed Radiofrequency: Mechanisms Of Actionmentioning

confidence: 99%

“…PRF creates an electromagnetic field with the aim of functionally disrupting the neuronal membrane, which modulates gene expression, affecting the release of cytokines [ 5 ]. The application of PRF is based on the delivery of a train of sinusoidal electrical bursts (5–20 ms length) in the radiofrequency range (500 kHz) at a repetitive rate of a few hertz (2–5 Hz) [ 6 ] ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

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The Mechanism of Action between Pulsed Radiofrequency and Orthobiologics: Is There a Synergistic Effect?

Jorge¹,

Huber²,

Rodrigues³

et al. 2022

IJMS

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Radiofrequency energy is a common treatment modality for chronic pain. While there are different forms of radiofrequency-based therapeutics, the common concept is the generation of an electromagnetic field in the applied area, that can result in neuromodulation (pulsed radiofrequency—PRF) or ablation. Our specific focus relates to PRF due to the possibility of modulation that is in accordance with the mechanisms of action of orthobiologics. The proposed mechanism of action of PRF pertaining to pain relief relies on a decrease in pro-inflammatory cytokines, an increase in cytosolic calcium concentration, a general effect on the immune system, and a reduction in the formation of free radical molecules. The primary known properties of orthobiologics constitute the release of growth factors, a stimulus for endogenous repair, analgesia, and improvement of the function of the injured area. In this review, we described the mechanism of action of both treatments and pertinent scientific references to the use of the combination of PRF and orthobiologics. Our hypothesis is a synergic effect with the combination of both techniques which could benefit patients and improve the life quality.

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“…PRF can also increase the levels of brain-derived neurotrophic factor and glial cell-derived neurotrophic factor, decrease the level of calcitonin gene-related peptide, and increase the expression of β-endorphin precursors (Hailong et al, 2018;Ren et al, 2018). Recent research results reveal that PRF induces a mild electroporation effect, causing a calcium uptake in the mechanism of chronic pain treatment (Mercadal et al, 2020). SF-36 is a very popular instrument for evaluating healthrelated quality of life, and it can be used to evaluate PHN patients' physical and mental health after PRF treatment.…”

Section: Figure 4 | (1-3)mentioning

confidence: 99%

CT-Guided Pulsed Radiofrequency at Different Voltages in the Treatment of Postherpetic Neuralgia

et al. 2020

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BackgroundPostherpetic neuralgia (PHN) is a form of long-lasting neuropathic pain that can severely affect patients’ quality of life. Pulsed radiofrequency (PRF) has been proven to be effective in treating PHN, but the optimal radiofrequency parameters are still not well defined. This retrospective study aimed to compare the efficacy and safety of CT-guided PRF at three different voltages for the treatment of PHN patients.MethodsThis study included 109 patients with PHN involving the thoracic dermatome who were treated in the Department of Pain Management of Shengjing Hospital, China Medical University, from January 2017 to May 2019. They were divided into three groups based on the PRF voltage used: group A (45 V), group B (55 V), and group C (65 V). The PRF therapy (voltage 45, 55, and 65 V) was performed in all patients by targeting the thoracic dorsal root ganglion. After surgery, patients were followed at 3 days, 1 month, 3 months, 6 months, and 12 months. Observation at each follow-up included basic patient characteristics, visual analog scale (VAS), 36-Item Short Form Health Survey (SF-36) scores, patient satisfaction, complications, and side effects.ResultsVisual analog scale scores decreased and SF-36 scores increased for all patients in the three groups at each post-operative time point (1, 3, 6, and 12 months; all P < 0.01). Pain relief, improvement in quality of life, and overall satisfaction were more significant for patients in group C than for those in groups A and B at the 3-, 6-, and 12-month follow-ups (all P < 0.05). Patients in group B had lower VAS scores and higher overall satisfaction levels than those in group A (both P < 0.01). A small number of patients from each group (n ≤ 3) experienced mild intraoperative and post-operative complications, which bore no relationship with group assignment (all P > 0.05). At post-operative day 3, patients in group C had skin numbness affecting a larger area than patients in the other two groups (both P < 0.05), but the differences were no longer statistically significant at day 30 after the operation. All patients experienced a drop in numbness area of more than 30% after surgery.ConclusionCompared with PFR at 45 and 55 V, PFR at 65 V had superior efficacy in treating PNH, with a favorable safety profile.

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Pulsed radiofrequency for chronic pain: In vitro evidence of an electroporation mediated calcium uptake

Cited by 7 publications

References 51 publications

Pulsed Radiofrequency 2 Hz Preserves the Dorsal Root Ganglion Neuron Physiological Ca2+ Influx, Cytosolic ATP Level, Δψm, and pERK Compared to 4 Hz: An Insight on the Safety of Pulsed Radiofrequency in Pain Management

Pulsed Radiofrequency 2 Hz Preserves the Dorsal Root Ganglion Neuron Physiological Ca2+ Influx, Cytosolic ATP Level, Δψm, and pERK Compared to 4 Hz: An Insight on the Safety of Pulsed Radiofrequency in Pain Management

The Mechanism of Action between Pulsed Radiofrequency and Orthobiologics: Is There a Synergistic Effect?

CT-Guided Pulsed Radiofrequency at Different Voltages in the Treatment of Postherpetic Neuralgia

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