Persistent At-Level Thermal Hyperalgesia and Tactile Allodynia Accompany Chronic Neuronal and Astrocyte Activation in Superficial Dorsal Horn following Mouse Cervical Contusion Spinal Cord Injury

The purpose of this study was to examine the beneficial effects of electroacupuncture (EA) on neuropathic pain evoked by spinal cord injury (SCI) and determine the underlying molecular mechanisms of these effects. SCI was induced in rats. Behavioral tests were performed to examine pain responses induced by mechanical and thermal stimulation. Western blot analysis was used to measure the protein expression of phosphorylated mammalian target of rapamycin (p-mTOR), mTOR-mediated phosphorylated ribosomal protein S6 kinase beta-1 (p-S6K1), and phosphorylated eukaryotic translation initiation factor 4E-binding protein 1 (p-4E-BP1) in the superficial dorsal horn of the spinal cord. We showed that SCI increased the expression of p-mTOR, p-S6K1, and p-4E-BP1. The EA intervention attenuated the upregulation of mTOR signaling and alleviated mechanical and thermal pain responses in SCI rats. Blocking spinal mTOR by intrathecal injection of rapamycin also inhibited mechanical and thermal pain. In addition, blocking spinal phosphorylated phosphatidylinositide 3-kinase (p-PI3K) pathway attenuated p-mTOR pathways and mechanical and thermal hyperalgesia in SCI rats. EA also decreased the enhanced p-PI3K in the superficial dorsal horn of SCI rats. In conclusion, findings revealed specific signaling pathways that lead to neuropathic pain in response to SCI, including activation of PI3K-mTOR signaling. Further, results link the beneficial role of EA in alleviating SCI-induced neuropathic pain to its effect on these molecular mechanisms.

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Cervical spinal cord injury-induced neuropathic pain in male mice is associated with a persistent pro-inflammatory macrophage/microglial response in the superficial dorsal horn

Experimental Neurology ◽

10.1016/j.expneurol.2021.113757 ◽

2021 ◽

pp. 113757

Author(s):

Eric V. Brown ◽

Aditi Falnikar ◽

Nicolette Heinsinger ◽

Lan Cheng ◽

Carrie E. Andrews ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Neuropathic Pain ◽

Dorsal Horn ◽

Cervical Spinal Cord ◽

Superficial Dorsal Horn ◽

Male Mice ◽

Cord Injury ◽

Microglial Response ◽

Inflammatory Macrophage

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Photobiomodulation Promotes Repair Following Spinal Cord Injury by Regulating the Transformation of A1/A2 Reactive Astrocytes

Frontiers in Neuroscience ◽

10.3389/fnins.2021.768262 ◽

2021 ◽

Vol 15 ◽

Author(s):

Xuankang Wang ◽

Zhihao Zhang ◽

Zhijie Zhu ◽

Zhuowen Liang ◽

Xiaoshuang Zuo ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Growth Factor ◽

Motor Function ◽

Function Analysis ◽

Reactive Astrocytes ◽

Male Rats ◽

Dependent Manner ◽

Astrocyte Activation ◽

Cord Injury

After spinal cord injury (SCI), reactive astrocytes can be classified into two distinctive phenotypes according to their different functions: neurotoxic (A1) astrocytes and neuroprotective (A2) astrocytes. Our previous studies proved that photobiomodulation (PBM) can promote motor function recovery and improve tissue repair after SCI, but little is known about the underlying mechanism. Therefore, we aimed to investigate whether PBM contributes to repair after SCI by regulating the activation of astrocytes. Male rats subjected to clip-compression SCI were treated with PBM for two consecutive weeks, and the results showed that recovery of motor function was improved, the lesion cavity size was reduced, and the number of neurons retained was increased. We determined the time course of A1/A2 astrocyte activation after SCI by RNA sequencing (RNA-Seq) and verified that PBM inhibited A1 astrocyte activation and promoted A2 astrocyte activation at 7 days postinjury (dpi) and 14 dpi. Subsequently, potential signaling pathways related to A1/A2 astrocyte activation were identified by GO function analysis and KEGG pathway analysis and then studied in animal experiments and preliminarily analyzed in cultured astrocytes. Next, we observed that the expression of basic fibroblast growth factor (bFGF) and transforming growth factor-β (TGF-β) was upregulated by PBM and that both factors contributed to the transformation of A1/A2 astrocytes in a dose-dependent manner. Finally, we found that PBM reduced the neurotoxicity of A1 astrocytes to dorsal root ganglion (DRG) neurons. In conclusion, PBM can promote better recovery after SCI, which may be related to the transformation of A1/A2 reactive astrocytes.

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