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

Abstract

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.

Yaobishu Regulates Inflammatory, Metabolic, Autophagic, and Apoptosis Pathways to Attenuate Lumbar Disc Herniation

“…The inhibition of the RAGE/STAT3 pathway in the DRG could alleviate persistent pain hypersensitivity caused by LDH [ 11 ]. Dexamethasone reduced the LDH levels by restoring the L-PGDS/PI3K/Akt pathway [ 15 ]. RvD1 might reduce LDH symptoms by regulating inflammatory mediators and the NF- κ B/p65 and p-ERK pathways [ 48 ].…”

“…At present, traditional Chinese medicine is commonly used clinically to treat LDH, such as Yaobitong capsule (different from Yaobishu decoction) [ 13 ] and Shentong Zhuyu decoction [ 14 ]. As previously described, dexamethasone compounds alleviate nerve root pain in LDH rats by inhibiting the inflammatory response of the DRG tissues [ 15 ]. Curcumin compounds inhibited LDH radiculopathy by reducing DRG inflammation and apoptosis [ 16 ].…”

IL‐17 in intervertebral disc degeneration: Mechanistic insights and therapeutic implications

“…Xu, Wang, et al, 2021). There is increasing evidence that this signaling pathway is closely associated with the occurrence and development of IDD (Ouyang et al, 2017, Shao et al, 2020, W. Xu, Ding, et al, 2021. Interestingly, recent work from our laboratory showed that treatment with recombinant IL-17 aggravates IDD by inhibiting NP cell autophagy via activation of the PI3K/Akt/ Bcl-2 pathway (He et al, 2020).…”

Biochemical and Structural Characteristics, Gene Regulation, Physiological, Pathological and Clinical Features of Lipocalin-Type Prostaglandin D2 Synthase as a Multifunctional Lipocalin

“…The PGE 2 -or bicuculline-induced allodynia is reproduced in L-Pgds gene KO mice by administration of subfemtomole amount of PGD 2 (Eguchi et al, 1999). In a rat lumbar disk herniation model with thermomechanical allodynia and degeneration of DRG, overexpression and knockdown of L-Pgds gene, respectively, attenuates and worsens the allodynia and tissue degradation (Xu et al, 2021).…”