Pulsed Radiofrequency Reduced Neuropathic
Pain Behavior in Rats Associated with
Upregulation of GDNF Expression
Authors: Fang Luo 
Published: February 2021

Background: Pulsed radiofrequency (PRF) is a novel nondestructive interventional technique for
the treatment of neuropathic pain (NP). However, this intervention is still lack of relevant regulation
and the mechanism of action is insofar not clear. Historically, most studies have reported that PRF
can relieve reduce hyperalgesia in multiple NP animal models by acting on the dorsal root ganglion.
However, a few recent studies have shown that PRF can effectively treat hyperalgesia in pain models
by a direct application on injured peripheral nerves.
Objectives: To observe changes in pain behavior and the pathology of the sciatic nerve (SN) after
applying PRF at the ligation site in a chronic constriction injury (CCI) rat model and to investigate the
effect of PRF on the expression of glia cell line-derived neurotrophic factor (GDNF) in nervous tissue.
Study Design: A randomized, experimental trial.
Setting: Experimental Animal Center, Beijing Tiantan Hospital, Capital Medical University.
Methods: Thirty-six adult Sprague-Dawley rats were randomly divided into 3 groups: Sham-Sham
(SS), CCI-Sham (CS), and CCI-PRF (CP). The right SNs of the rats in the CS and CP groups were
ligated to create a CCI model. For the SS group, the right SN was separated without ligation. On the
14th fourteenth day after surgery, PRF treatment was applied at the ligation site of the SN for the
rats in the CP group using a 45 V output voltage at 42°C for 3 minutes. The electrode was placed in
rats in the SS and CS groups without electricity applied. The hindpaw withdrawal threshold (HWT)
and thermal withdrawal latency (TWL) were measured at various time points before and after the
treatments in each group. Optical microscopic scores and electron microscopic observation were
given to the right SN ligation sites of the rats in each group 14 days after the treatment . Meanwhile,
the GDNF expression levels in the ligation site of the SN and in the L4-L6 spinal cord segments were
determined for each group by enzyme-linked immunosorbent assay (ELISA).
Results: Fourteen days after PRF treatment, the HWT and TWL values in the CP group were significantly
increased compared to those of the CS group (P < 0.01). Under the optical microscope, the axonal number,
axonal diameter, and myelin sheath thickness in the CP group were significantly increased compared to
those of the CS group 14 days after PRF treatment (P < 0.01). Under the electron microscope, the
degeneration at the SN ligation site was significantly improved in the CP group compared to the CS
group. The GDNF expression levels at the ligation site of the SN and the L4-L6 spinal segments in the
CP and CS groups were increased compared to those of the SS group (P < 0.01). In addition, the GDNF
expression in the CP group was significantly higher than that in the CS group (P < 0.01).
Limitations: GDNF expression was only measured at day 14 after the treatment rather than at
various time points during the experiment.
Conclusions: The findings suggest that the application of PRF at the impaired SN relieved reduced
the CCI-induced NP by through regulating the upregulation of the GDNF expression in the nervous
tissues.
Key words: Pulsed radiofrequency, chronic constriction injury, sciatic nerve, spinal cord, hind paw
withdrawal threshold, thermal withdrawal latency, optical microscopic, electron microscope, glia cell
line-derived neurotrophic factor, enzyme-linked immunosorbent assay