Spinal Interferon Regulatory Factor 8 and Brain-derived Neurotrophic Factor in the Prefrontal Cortex are Involved in Pain-induced Depression Relief via Ultrasound-guided Pulsed Radiofrequency in a Rat Spared Nerve Injury Model.

BACKGROUND

Pain-depression comorbidity has become a great burden to individuals and society. Nevertheless, the mechanisms underlying comorbid diseases have still not been fully revealed. Ultrasound-guided pulsed radiofrequency (PRF) on peripheral nerves, which produces remarkable analgesia via high-frequency electromagnetic energy, has become a main, minimally invasive treatment for chronic neuropathic pain.

OBJECTIVES

The aim of this study was to explore the effect of ultrasound-guided PRF on the sciatic nerve of spared nerve injury (SNI) rats to relieve pain-induced depression.

STUDY DESIGN

Experimental trial in rats.

SETTING

The research took place in the Laboratory of The First Affiliated Hospital of Wenzhou Medical University.

METHODS

Sixty male Wistar rats were randomly divided into a sham group, an SNI group, an SNI + free-PRF group, and an SNI + PRF group. Ultrasound-guided PRF was applied to the sciatic nerve on day 7 after SNI. The basal paw mechanical withdrawal threshold (PMWT) was evaluated as a measure for pain-related behavior, and a  sucrose preference test was performed as a measure for depression-related behavior. The expression levels of spinal interferon regulatory factor 8 (IRF8) and of brain-derived neurotrophic factor (BDNF) in the prefrontal cortex (PFC) were also studied on days 21 and 42.

RESULTS

The results showed that the PMWT was significantly decreased in rats following SNI operation; the decreased levels of PMWT were reversed in the SNI + PRF group after the application of PRF on the sciatic nerve on day 7. There were no statistically significant differences among the groups in the sucrose preference rate on day 21 after SNI operation. The sucrose preference rate on day 42 was higher in the SNI + PRF group than in the SNI + free-PRF group. Western blot and reverse transcription polymerase chain reaction also demonstrated that ultrasound-guided PRF on the sciatic nerve downregulated overexpression of spinal IRF8 and increased the levels of BDNF in the PFC.

LIMITATIONS

This study was performed using only an SNI rat model which cannot represent all rodent neuropathic pain models. Only the short-term effectiveness of ultrasound-guided PRF on the sciatic nerve of SNI rats was investigated. The BDNF changes of other important brain areas were not taken into consideration in this study.

CONCLUSIONS

These findings suggest that ultrasound-guided PRF on sciatic nerve could alleviate pain-induced depression. The mechanisms of this treatment may be involved in the downregulated spinal IRF8 and the increased BDNF in PFC.