Protectin DX Attenuates Lumbar Radicular Pain of Non-compressive Disc Herniation by Autophagy Flux Stimulation via Adenosine Monophosphate-Activated Protein Kinase Signaling.

Qing-Xiang Zhao,Si-Cong Wang,Song Xue,Zhen-Xin Cao,Yi-Hao Wang,Tao Sun

doi:10.3389/fphys.2021.784653

Abstract

Background: Neuroinflammation plays a crucial role in initiating and sustaining lumbar radicular pain (LRP). Protectin DX (PDX) has been experimentally verified to possess pro-resolving properties and anti-inflammatory effects. This study aimed to observe the analgesic effects of PDX and its potential mechanisms in LRP rats with non-compressive lumbar disc herniation (NCLDH).Method: Only male rats were selected to avoid gender-related interferences. Rat models of NCLDH were established, and rats were randomly divided into four groups: the sham group, the vehicle group, the PDX (10 ng PDX) group, and the PDX (100 ng PDX) group. Changes in the mechanical withdrawal threshold and thermal withdrawal latency were observed for 7 days. The mRNAs of pro-inflammatory and anti-inflammatory mediators were evaluated via real-time polymerase chain reaction, whereas western blot and immunohistochemistry were separately conducted to assess the expression levels of autophagy-related proteins and adenosine monophosphate-activated protein kinase (AMPK) signaling.Results: Intrathecal delivery of PDX reduced interleukin (IL)-6 and IL-1β mRNA levels and facilitated mRNA transcription of transforming growth factor-β1, with attenuation of mechanical and thermal hyperalgesia in LRP rat models. With the application of nucleus pulposus to the dorsal root ganglion, autophagy flux and AMPK signaling were severely disrupted in the spinal dorsal horns, and intrathecal treatment with PDX could dose-dependently restore the dysfunction of autophagy flux and AMPK signaling.Conclusion: These data suggest that PDX possesses pro-resolving properties and exerts potent analgesic effects in LRP by affecting autophagy flux via AMPK signaling.

Highlights

Lumbar radicular pain (LRP), commonly secondary to protruded nucleus pulposus (NP), has been cited as the most frequent form of chronic pain disorder (Jensen et al, 2019)
With the application of nucleus pulposus to the dorsal root ganglion, autophagy flux and adenosine monophosphateactivated protein kinase (AMPK) signaling were severely disrupted in the spinal dorsal horns, and intrathecal treatment with Protectin DX (PDX) could dosedependently restore the dysfunction of autophagy flux and AMPK signaling
These data suggest that PDX possesses pro-resolving properties and exerts potent analgesic effects in LRP by affecting autophagy flux via AMPK signaling

Summary

Introduction

Lumbar radicular pain (LRP), commonly secondary to protruded nucleus pulposus (NP), has been cited as the most frequent form of chronic pain disorder (Jensen et al, 2019). A wealth of clinical evidence supported the theory that mechanical compression was frequently associated with the pathophysiology of LRP. At present increasing preclinical studies (Huang et al, 2018a; Wang et al, 2020) have revealed that neuroinflammation caused by NP could directly provoke LRP, even with a lack of nerve root compression. The presumption of inflammation on the pathophysiology of LRP has presented an effective treatment strategy for this disorder (Kennedy et al, 2018). This study aimed to observe the analgesic effects of PDX and its potential mechanisms in LRP rats with non-compressive lumbar disc herniation (NCLDH)

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Results

Conclusion