Pulsed Radiofrequency Application Reduced Mechanical Hypersensitivity and Microglial Expression in Neuropathic Pain Model

Park, Hea-Woon; Ahn, Sungjin; Son, Jo-Young; Kim, Su-Jeong; Hwang, Se Jin; Cho, Yun-Woo; Lee, Dong Gyu

doi:10.1111/j.1526-4637.2012.01453.x

Cited by 31 publications

(45 citation statements)

References 39 publications

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“…Tanaka et al demonstrated that PRF of the rat sciatic nerve significantly reduces mechano-allodynia induced by resiniferatoxin (Tanaka et al 2010), Aksu et al found that PRF significantly decreases mechanohyperalgesia in rabbits after tight ligation of the sciatic nerve (Aksu et al 2010), and Perret et al reported that PRF to the DRG decreases allodynia in rats with chronic constriction injury (CCI) to the L5 spinal nerve (Perret et al 2011). In rats with L5 spinal nerve ligation (SNL), Park et al found that PRF decreases mechanohypersensitivity (Park et al 2012). Despite confirmed efficacy in multiple neuropathic pain models and clinical studies, the anti-nociceptive mechanisms of PRF remain unclear.…”

Section: Introductionmentioning

confidence: 96%

Pulsed Radiofrequency Treatment Enhances Dorsal Root Ganglion Expression of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels in a Rat Model of Neuropathic Pain

2015

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Pulsed radiofrequency (PRF) treatment is a minimally invasive technique with multiple therapeutic applications. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel mediating Ih may regulate neuropathic pain signaling. This study aimed to determine whether PRF suppresses neuropathic pain by altering HCN channel expression in dorsal root ganglion (DRG) neurons. Male Sprague Dawley rats with sciatic nerve chronic constriction injury (CCI) were randomly assigned to PRF (n = 60) and sham control (n = 60) groups, respectively. On postoperative day 7 (D07), PRF or sham treatment was delivered to the proximal sciatic nerve for 8 min. Behavioral tests were performed before surgery (D0), on D07, and on D1, D7, and D14 after PRF or sham treatment. HCN1 and HCN2 expression levels in the DRG were examined by immunohistochemistry and Western blot. The results showed that thermal hyperalgesia, mechano-allodynia, and mechano-hyperalgesia were lower, and DRG expression levels of HCN1 and HCN2 higher, in the PRF group compared with sham control animals (all P < 0.05 at D14). In conclusion, PRF can upregulate HCN channel expression in the DRG of rats with sciatic nerve CCI. How this regulation of Ih in nociceptive afferents contributes to the suppression of neuropathic pain by PRF remains to be determined.

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Section: Introductionmentioning

confidence: 96%

Pulsed Radiofrequency Treatment Enhances Dorsal Root Ganglion Expression of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels in a Rat Model of Neuropathic Pain

2015

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“…In an L5 spinal nerve ligation neuropathic pain model in the rat, PRF attenuated mechanical allodynia for more than 32 days after a single PRF treatment at 25 V for 2 min adjacent to DRG [17]. Furthermore, PRF application at 45 V for 3 min on DRG yielded a reduction of mechanical hypersensitivity in rats with L5 spinal nerve ligation (SNL) and transaction [36]. In our study, immediate PRF was effective in alleviating the SNI-induced neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

Association between extracellular signal-regulated kinase expression and the anti-allodynic effect in rats with spared nerve injury by applying immediate pulsed radiofrequency

et al. 2015

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BackgroundThe application of pulsed radiofrequency (PRF) close to the dorsal root ganglia, or peripheral nerves, has been demonstrated to be effective for the treatment of chronic neuropathic pain conditions. The goal of this study was to investigate the analgesic effect of immediate PRF treatment after nerve injury and its possible cellular alterations in the dorsal horn of the spinal cord in rats with spared nerve injury (SNI).MethodsNeuropathic pain was achieved in a SNI neuropathic pain model by ligating and cutting the common peroneal and tibial branches of the left sciatic nerve, leaving the sural nerve intact. Wistar rats were divided into four groups that received different treatments, i.e., SNI and PRF for 6 min at 45 V (SNI + PRF-45 V), at 60 V (SNI + PRF-60 V), SNI alone, and sham groups. After the SNI surgery, each rat was immediately given the PRF treatment (500 kHz, rate of 2 Hz, 20 ms duration, temperature below 42 °C) on the left sciatic nerve 0.3–0.4 cm proximal to the injured site. The behavioral measurements included mechanical allodynia and cold allodynia of the ipsilateral hind paw and were performed during the 28 days that followed the SNI surgery and PRF treatment. Total extracellular signal-regulated kinase 1 and 2 (ERK1/2) and phospho-ERK1/2 were measured using Western blot in the ipsilateral spinal cord from animals in the different groups.ResultsThe three groups of rats with nerve injuries manifested a lower paw withdrawal threshold (PWT) in the behavioral measurement of mechanical allodynia and a shorter painful-behavior duration in the cold allodynia test over 28 days. Mechanical allodynia measurement showed that both the PRF-45 V and PRF-60 V treatment groups exhibited a more prominent antiallodynic effect than did the SNI group from days 1 to 28 after surgery. Similarly, in comparison with the SNI group, both the SNI + PRF-45 V and SNI + PRF-60 V groups had significant inhibition on the cold allodynia measurement from days 1 to 28 after surgery. Furthermore, the activation of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) in the ipsilateral spinal dorsal horn of SNI rats was effectively inhibited in the SNI + PRF-45 V and SNI + PRF-60 V groups for 28 days after surgery.ConclusionsImmediate PRF application on the proximal nerve injury site provided a significant inhibition of neuropathic pain formation, accompanied by the inhibition of ERK activation.

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“…Various experimental neuropathic pain models show the pain-relieving effect of PRF on mechanical hypersensitivity, and sometimes on thermal allodynia [79][80][81][82][83][84] (Table 1). …”

Section: Behavioral Studiesmentioning

confidence: 99%

“…85 The latter pathways are known to be involved in the modulation of neuropathic pain. 82,85,86 A critical factor in behavioral pain assessment in these experimental animal studies and their use for clinical translation is the problem of evoked and reflexive assessments. This method of assessment clearly differs from clinical assessment of pain sensitivity in humans and may partially explain the relatively limited translation of experimental animal findings into clinical breakthroughs.…”

Section: Behavioral Studiesmentioning

confidence: 99%

“…Future research should systematically analyze the experimental effects of PRF on these distinct cellular-molecular processes underlying radicular pain. Currently, most experimental studies on PRF in radicular and neuropathic pain have focused on optimization of the behavioral pain-relieving effect of PRF based on finite and discrete anatomic locations, on temporal features, and on the use of different pulse stimulation-parameters 82,88,89. …”

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confidence: 99%

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Pulsed Radiofrequency

Boxem

Huntoon

Zundert

et al. 2014

Regional Anesthesia and Pain Medicine

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Radicular pain is an important health care problem, with only limited evidence-based treatments available. Treatment selection should ideally target documented pathophysiological pathways. In herniated discs, a sequence in the inflammatory cascade can be observed that initiates and maintains increased nociceptive signal input. Inflammatory mediators including tumor necrosis factor α are released from the nucleus pulposus and the degenerating peripheral nerve, which, in turn, induces production of neurotrophins like nerve growth factor and brain-derived neurotrophic factor. Neurotrophins interfere not only with the generation of ectopic firing of nociceptive neurons in the dorsal root ganglion but also with the excitability and sensitization of neuronal transmission in the dorsal spinal horn. Radicular pain is further characterized by the electrophysiological spreading of the afferent nociceptive input over different spinal nerve roots. Both the complex pathophysiological pathways involved and the spreading of the nociceptive signal make radicular pain difficult to treat. Pulsed radiofrequency (PRF) is considered an option in treatment of radicular pain. To understand and increase the efficiency of PRF interventional treatments in radicular pain, both in vitro and in vivo studies aiming at elucidating part of the mechanism of action of PRF are described. Potential factors that may improve the efficacy of PRF treatment in radicular pain are discussed.

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Pulsed Radiofrequency Application Reduced Mechanical Hypersensitivity and Microglial Expression in Neuropathic Pain Model

Abstract: Our result demonstrated that the mechanical hypersensitivity, induced by L5 SNL, was attenuated by a PRF procedure on the ipsilateral DRG. This analgesic effect may be associated with an attenuation of the microglial activation in the dorsal horn.

Cited by 31 publications

References 39 publications

Pulsed Radiofrequency Treatment Enhances Dorsal Root Ganglion Expression of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels in a Rat Model of Neuropathic Pain

Pulsed Radiofrequency Treatment Enhances Dorsal Root Ganglion Expression of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels in a Rat Model of Neuropathic Pain

Association between extracellular signal-regulated kinase expression and the anti-allodynic effect in rats with spared nerve injury by applying immediate pulsed radiofrequency

Pulsed Radiofrequency

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