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. 2021 Jan;21(1):64-74.
doi: 10.1111/papr.12934. Epub 2020 Aug 8.

Dexamethasone Suppresses Radicular Pain Through Targeting the L-PGDS/PI3K/Akt Pathway in Rats With Lumbar Disc Herniation

Weixing Xu  1 , Weiguo Ding  1 , Hongfeng Sheng  1 , Di Lu  1 , Xinwei Xu  1 , Bin Xu  1
Affiliations

Dexamethasone Suppresses Radicular Pain Through Targeting the L-PGDS/PI3K/Akt Pathway in Rats With Lumbar Disc Herniation

Weixing Xu et al. Pain Pract. 2021 Jan.

Abstract

Purpose: Lumbar disc herniation (LDH) is a frequently occurring disease with unknown etiology, which makes treatment a challenge. The aim of this study was to analyze the effects of dexamethasone on LDH and elucidate the underlying mechanisms.

General methods: An LDH rat model was established by nucleus pulposus implantation. The activity of the lipocalin type prostaglandin D synthase (L-PGDS)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) axis was evaluated by Western blotting. Paw withdrawal threshold and paw withdrawal latency were assessed by the Von Frey hairs method and the thermal dolorimeter of Hargreaves, respectively. The 21-point Basso-Beattie-Bresnahan scale was used to assess the locomotor function of rats. Pathological changes in the affected region were analyzed by hematoxylin-eosin staining. Immunofluorescence was used to measure the expression of microtubule-associated protein (MAP-2).

Findings: Lumbar disc herniation markedly increased thermo-mechanical allodynia and induced dorsal root ganglion (DRG) degeneration by inactivating the L-PGS/PI3K/Akt pathway. Dexamethasone restored the L-PGDS/PI3K/Akt pathway and relieved LDH-induced thermo-mechanical allodynia. Furthermore, overexpression and knockdown of L-PGDS respectively attenuated and worsened LDH-triggered thermo-mechanical allodynia and tissue degeneration by modulating the PI3K/Akt pathway. Pretreatment with dexamethasone partially abrogated the effect of L-PGDS knockdown through PI3K/Akt activation.

Conclusions: Dexamethasone relieves LDH-mediated radicular pain by exerting anti-inflammatory effects and reducing the suppression of L-PGDS induced by LDH. Meanwhile, the activity of the PI3K/Akt pathway was decreased, possibly due to the attenuated inflammation induced by dexamethasone. Our results revealed the underlying mechanism of dexamethasone, which might be helpful in reducing the side effects of dexamethasone and provide more focused therapy in LDH.

Keywords: dexamethasone; lipocalin type prostaglandin D synthase; lumbar disc herniation; phosphatidylinositol 3-kinase; protein kinase B.

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References

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