Rapid and Delayed Effects of Pulsed
Radiofrequency on Neuropathic Pain:
Electrophysiological, Molecular, and Behavioral
Evidence Supporting Long-Term Depression
Authors: Wen Yeong-Ray 
Published: January 2020

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
applicationsConclusion: 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)