Pulsed radiofrequency inhibited activation of spinal mitogen‐activated protein kinases and ameliorated early neuropathic pain in rats

Abstract

Background: Pulsed radiofrequency (PRF) has been widely used to treat chronic pain, but the effectiveness and mechanisms in preventing early neuropathic pain have not been well explored. Even fewer knowledge is available in its impact on glia-mediated nociceptive sensitization. This study aims to elucidate the modulation of PRF on nerve injury-induced pain development and activation of spinal mitogen-activated protein kinases (MAPKs). Methods: In a rat spinal nerve ligation (SNL) model, a low-volt PRF treatment was applied to the L5 dorsal root ganglion after nerve injury. Nociceptive behaviours were measured by von Frey and heat withdrawal tests at multiple time points. MAPK activations, including p-ERK and p-p38, as well as TNF-á level in the spinal dorsal horn were assessed and the cell types that expressed MAPK activation were identified by double immuno fluorescence staining.Results: We found that SNL promptly induced neuropathic pain in the affected hind limb for over 1 week as well as increased p-ERK and p-p38 in the spinal dorsal horn. PRF significantly attenuated SNL-induced mechanical allodynia and thermal hyperalgesia for 5–7 days. PRF also inhibited ERK and p38 activations, which were found majorly located within neurons and microglia, respectively. Besides, PRF significantly suppressed expression of TNF-á in the spinal dorsal horn throughout the course. Conclusions: Low-volt PRF significantly ameliorated SNL-induced acute pain. Inferentially, PRF may inhibit spinal sensitization by down-regulating spinal MAPK activations and activation-mediated cytokine release.We demonstrated that early PRF treatment in acute nerve injury helps to ameliorate neuropathic pain development.

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

“…Similarly, Lin et al . demonstrated that PRF inhibited ERK activation, which was detected on the third day after surgery [39]. Taken together, our results strongly suggest that immediate PRF treatment regulates ERK-mediated mechanisms in the spinal dorsal horn of SNI rats, which in turn reduces SNI-induced neuropathic pain.…”

“…Lin et al . found that early PRF treatment suppressed the levels of proinflammatory cytokines via neuromodulation and immune modulation, such as the downregulation of spinal MAPK (ERK) activation [39]. Therefore, we assumed that an immediate or early PRF intervention may result in less neuroinflammation compared with a delayed PRF intervention.…”

“…Accumulating evidence shows that the activation of MAPKs (p38, ERK, and JNK) can induce the synthesis of proinflammatory/pronociceptive mediators via distinct molecular and cellular mechanisms, resulting in the enhancement and prolongation of pain. Another study indicated that early application of PRF adjacent to the DRG significantly diminished nerve ligation-induced mechanical allodynia for 7 days and thermal hyperalgesia on postoperative days 3–7 by downregulating p38 and ERK activation [39]. However, the long-term effect of PRF on analgesia remains unknown.…”

Effects of Pulsed-radiofrequency Electrical Stimulation on the Rat with Detrusor overactivity

“…Andre'E aptly pointed out, using different stimulation parameters on different nerve were an important issue for clinical to treat detrusor overactivity [7]. Our research team recently used pulsed radio-frequency (PRF) electrical stimulation to successfully inhibit C-fiber excitatory responses and obstruct the pain conduction signal, the effect can maintain for 3-6 months [8,9]. To the best of our knowledge, few studies explored the feasibility of PRF electrical stimulation in the treatment of detrusor overactivity.…”

Effects of pulsed-radiofrequency neuromodulation on the rat with overactive bladder

“…We previously reported that pulsed radiofrequency (PRF) electrical stimulation can successfully inhibit C‐fiber afferent responses and block pain conduction signals for 3‐6 months …”