• Weixing Xu, Weiguo Ding, Hongfeng Sheng, Di Lu, Xinwei Xu, and Bin Xu.
• Department of Orthopaedics, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China.
• Pain Pract. 2021 Jan 1; 21 (1): 64-74.

PurposeLumbar 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 MethodsAn 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).FindingsLumbar 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.ConclusionsDexamethasone 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.© 2020 World Institute of Pain.

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