Pulsed radiofrequency effects on the lumbar ganglion of the rat dorsal root: a morphological light and transmission electron microscopy study at acute stage

Abstract

Since the dorsal root ganglia represent the first structure of pain modulation, they are the target of the newest therapies of neuropathic pain. Between these, pulsed radiofrequency (PRF) has been described among the promising non-invasive methods. Although the results encourage the clinical use of this procedure, their mechanism of action is still unclear. Aim of our study was to analyze acute effects of PRF on the rat lumbar ganglion and on nervous fibres running inside it. Clinical works describe PRF treatment as a technique without any visible neurological deficit. The few disposable histological works are contractictory: some describe no signs of cellular damage and some demonstrate visible intracellular modifications. A total of 20 male Wistar rats were deeply anesthesized. Ten were positioned in a stereotactic system, and exposed to PRF at 2 Hz for 30 s after exposition of paravertebral muscles and positioning of a stimulation needle on left L4 ganglion. The other ten were used as controls. After 1 h, the left dorsal root ganglions L3, L4, L5 of the 20 animals were explanted, fixed in 2.5% Karnowsky solution and prepared for light and transmission electron microscopy. At light microscopy no differences between treated and control animals were observed; at transmission electron microscopy, instead, it was possible to observe that T gangliar cells contained an abnormal abundant smooth reticulum with enlarged cisternae and numerous vacuoles; myelinated axons presented pathological features and their myelin coverage was not adherent. Instead, unmyelinated axons appeared normal in shape and dimension and the Schwann cells surrounding it had intact plasmamembrane. Our results, obtained at acute stage, reveal that the PRF procedure should destroy the myelin envelope of nervous fibres. Further future studies, at chronic stage, should give other information on the prognosis of the myelinic damage.

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

“…It is thought to occur via a neuromodulatory effect that interferes with sensory neuron-specific molecules and gene expression involved in neuropathic pain development [36]. In other studies, RF stimulation at DRG altered synaptic transmission and cell morphology and induced Fos expression in the superficial dorsal horn, which suggests that this type of stimulation increases spinal neuron activity [18–20, 40]. The expression of ERK in DRG and the dorsal horn has been suggested to be a major target of mitogen-activated protein kinases (MAPKs) in the treatment of neuropathic pain.…”

Radiofrequency Treatments for Neuropathic Pain: Review and New Approaches

“…Furthermore, histological analyses revealed changes in neuronal morphology following PRF (Erdine et al, 2009;Erdine et al, 2005;Podhajsky et al, 2005;Protasoni et al, 2009;Tun et al, 2009), which may alter the electronic properties of sensory neurons and potentially interrupt normal afferent signaling to the spinal cords.…”

“…These studies reported increased c-Fos expression in the dorsal horn (Higuchi et al, 2002;Van Zundert et al, 2005), increased expression of activating transcription factor 3 (Hamann et al, 2006), and morphological changes in the DRG or the peripheral nerve (Erdine et al, 2009;Erdine et al, 2005;Podhajsky et al, 2005;Protasoni et al, 2009;Tun et al, 2009). …”

“…Secondary effects on the nervous system after PRF application have been studied in animal models (Erdine et al, 2009;Erdine et al, 2005;Hamann et al, 2006;Higuchi et al, 2002;Podhajsky et al, 2005;Protasoni et al, 2009;Tun et al, 2009;Van Zundert et al, 2005). These studies reported increased c-Fos expression in the dorsal horn (Higuchi et al, 2002;Van Zundert et al, 2005), increased expression of activating transcription factor 3 (Hamann et al, 2006), and morphological changes in the DRG or the peripheral nerve (Erdine et al, 2009;Erdine et al, 2005;Podhajsky et al, 2005;Protasoni et al, 2009;Tun et al, 2009).…”

Pulsed Radiofrequency

“…Conversely, RF at 67°C resulted in significant changes, for example, mitochondrial degeneration and a loss of nuclear membrane integrity. 75,76 An effect was seen on myelinated nerve fibers after the application of RF or PRF on the sciatic nerve. Radiofrequency resulted in severe WD of the distal peripheral nerve, in contrast to the PRF group, where only changes in myelin configuration were observed.…”