Rapid and Delayed Effects of Pulsed Radiofrequency on Neuropathic Pain: Electrophysiological, Molecular, and Behavioral Evidence Supporting Long-Term Depression

2017 · Benefit · Low evidence

← Research stream

BenefitLow evidencePaper 1352

Study snapshot

Publicationmanual · 2017

Study typeanimal

Reported directionBenefit

Evidence ratingLow

Abstract

Rapid and Delayed Effects of Pulsed Radiofrequency on Neuropathic Pain: Electrophysiological, Molecular, and Behavioral Evidence Supporting Long-Term Depression Huang RY, Liao CC, Tsai SY, Yen CT, Lin CW, Chen TC, Lin WT, Chang CH, Wen YR.Rapid and Delayed Effects of Pulsed Radiofrequency on Neuropathic Pain: Electrophysiological, Molecular, and Behavioral Evidence Supporting Long-Term Depression. Pain Physician. 2017 Feb;20(2):E269-E283. Abstract BACKGROUND: Pulsed radiofrequency (PRF) has been widely employed for ameliorating clinical neuropathic pain. How PRF alters electrophysiological transmission and modulates biomolecular functions in neural tissues has yet to be clarified. We previously demonstrated that an early application of low-voltage bipolar PRF adjacent to the dorsal root ganglion (DRG) reduced acute neuropathic pain in animals. By contrast, the present study investigated how PRF alters postsynaptic sensitization to produce early and delayed effects on neuropathic pain. OBJECTIVES: Our objective was to test the hypothesis that a 5-minute session of PRF could rapidly produce selective long-term depression (LTD) on C-fiber-mediated spinal sensitization and sustain the effect through the long-lasting inhibition of injury-induced ERK-MAPK activation. This may explain the prolonged analgesic effect of PRF on chronic neuropathic pain. STUDY DESIGN: Experiments were conducted on both normal rats and neuropathic pain rats that received spinal nerve ligation (SNL) 8 days prior. SETTING: An animal laboratory in a medical center of a university in Taiwan. METHODS: We first compared changes in field potentials in the L5 superficial spinal dorsal horn (SDH) that were evoked by conditioning electrical stimuli in the sciatic nerve in male adult rats before (as the baseline) and after PRF stimulation for at least 2 hours. Bipolar PRF was applied adjacent to the L5 DRG at an intensity of 5 V for 5 minutes, whereas the control rats were treated with sham applications. The electrophysiological findings were tested for any correlation with induction of spinal phospho-ERK (p-ERK) in normal and neuropathic pain rats. We then investigated the delayed effect of PRF on SNL-maintained pain behaviors for 2 weeks as well as p-ERK in SDH among the control, SNL, and PRF groups. Finally, potential injury in the DRGs after PRF stimulation was evaluated through behavioral observations and ATF-3, a neuronal stress marker. RESULTS: In the evoked field-potential study, the recordings mediated through A- and C-afferent fibers were identified as A-component and C-component, respectively. PRF significantly reduced the C-components over 2 hours in both the normal and SNL rats, but it did not affect the A-components. In the SNL rats, the C-component was significantly depressed in the PRF group compared with the sham group. PRF also inhibited acute p-ERK induced by mechanical nociception in both the control and SNL rats. For a longer period, PRF ameliorated SNL- maintained mechanical allodynia for 10 days and thermal analgesia for 14 days, and it significantly reduced late ERK activation within spinal neurons and astrocytes 14 days afterward. Moreover, PRF in the normal rats did not alter basal withdrawal thresholds or increase the expression and distribution of ATF-3 in the DRGs. LIMITATIONS: Several issues should be considered before translating the animal results to clinical applications. CONCLUSIONS: Low-voltage bipolar PRF produces LTD through selective suppression on the C-component, but not on the A-component. It also inhibits ERK activation within neurons and astrocytes in SDHs. The findings suggest that PRF alleviates long-lasting neuropathic pain by selectively and persistently modulating C-fiber- mediated spinal nociceptive hypersensitivity.Key words: Pulsed radiofrequency (PRF), dorsal root ganglion (DRG), neuropathic pain, ERK activation, evoked field potential, ATF-3, long-term depression (LTD), spinal nerve ligation (SNL). ncbi.nlm.nih.gov Excerpt The specially designed bipolar system has been described previously (27,29). The stimulation electrode was inserted into the left L5 foraminal canal, whereas the reference electrode was placed in contact with the surrounding non-neural tissues. The electrodes were connected to a PXI-5402 Function Generator (National Instruments, Austin, TX) to generate RF pulses with the following parameter settings based on clinical settings: 2-Hz biphasic trains with 500-kHz RF waves, 25-ms train width, and oscillating amplitudes at an intensity of ± 2.5 V. The PRF duration was 300 seconds. The control group received an electrode placement without electricity as a sham stimulation.

Machine Enhanced Logic

AI evidence extraction

Structured fields below were generated from the paper’s abstract and metadata to make the evidence easier to inspect. Automated extraction may be incomplete or incorrect; verify important details against the original paper.

Study typeanimal

Effect directionbenefit

PopulationMale adult rats (normal and neuropathic pain model rats with spinal nerve ligation 8 days prior)

Sample sizeNot supplied

ExposureRF · 500 MHz · 5 minutes (300 seconds)

Evidence strengthLowConfidence: 78% · Peer reviewed: yes

Main findings

Bipolar PRF (5 V for 5 minutes) applied adjacent to the L5 DRG significantly reduced C-fiber-mediated (C-component) evoked field potentials for over 2 hours in both normal and SNL rats, without affecting A-components. PRF inhibited acute p-ERK induced by mechanical nociception and reduced late ERK activation 14 days later; in SNL rats it ameliorated mechanical allodynia for 10 days and thermal analgesia for 14 days. In normal rats, PRF did not alter basal withdrawal thresholds or increase ATF-3 in DRGs.

Outcomes measured

Spinal dorsal horn (L5 SDH) evoked field potentials (A- and C-components)
Spinal phospho-ERK (p-ERK) / ERK-MAPK activation in neurons and astrocytes
Mechanical allodynia (pain behavior)
Thermal analgesia (pain behavior)
DRG injury/stress marker ATF-3 expression and distribution
Basal withdrawal thresholds

Limitations

Sample size not stated in provided abstract
Authors note issues should be considered before translating animal results to clinical applications

View raw extracted JSON

{
  "study_type": "animal",
  "exposure": {
    "band": "RF",
    "source": "pulsed radiofrequency adjacent to dorsal root ganglion (DRG)",
    "frequency_mhz": 500,
    "sar_wkg": null,
    "duration": "5 minutes (300 seconds)"
  },
  "population": "Male adult rats (normal and neuropathic pain model rats with spinal nerve ligation 8 days prior)",
  "sample_size": null,
  "outcomes": [
    "Spinal dorsal horn (L5 SDH) evoked field potentials (A- and C-components)",
    "Spinal phospho-ERK (p-ERK) / ERK-MAPK activation in neurons and astrocytes",
    "Mechanical allodynia (pain behavior)",
    "Thermal analgesia (pain behavior)",
    "DRG injury/stress marker ATF-3 expression and distribution",
    "Basal withdrawal thresholds"
  ],
  "main_findings": "Bipolar PRF (5 V for 5 minutes) applied adjacent to the L5 DRG significantly reduced C-fiber-mediated (C-component) evoked field potentials for over 2 hours in both normal and SNL rats, without affecting A-components. PRF inhibited acute p-ERK induced by mechanical nociception and reduced late ERK activation 14 days later; in SNL rats it ameliorated mechanical allodynia for 10 days and thermal analgesia for 14 days. In normal rats, PRF did not alter basal withdrawal thresholds or increase ATF-3 in DRGs.",
  "effect_direction": "benefit",
  "limitations": [
    "Sample size not stated in provided abstract",
    "Authors note issues should be considered before translating animal results to clinical applications"
  ],
  "evidence_strength": "low",
  "confidence": 0.78,
  "peer_reviewed_likely": "yes",
  "keywords": [
    "pulsed radiofrequency",
    "PRF",
    "radiofrequency",
    "dorsal root ganglion",
    "DRG",
    "neuropathic pain",
    "spinal nerve ligation",
    "SNL",
    "ERK",
    "p-ERK",
    "MAPK",
    "evoked field potential",
    "C-fiber",
    "long-term depression",
    "LTD",
    "ATF-3"
  ],
  "suggested_hubs": [
    {
      "slug": "pain-therapy-prf",
      "weight": 0.9,
      "reason": "Animal study of pulsed radiofrequency applied near DRG for neuropathic pain outcomes."
    }
  ]
}

AI can be wrong. Always verify against the paper.

AI-extracted fields are generated from the abstract and metadata and may be incomplete or incorrect. This material is for informational purposes and is not medical advice.

Identifiers and source

DOI: Not supplied
PubMed: Not supplied

Read the original paper →

Related papers

← Back to the Research Library