Atorvastatin Prevents Neuroinflammation in Chronic Constriction Injury Rats through Nuclear NFκB Downregulation in the Dorsal Root Ganglion and Spinal Cord

Chu, Li-Wen; Wu, Pao‐Chu; Wu, Bin–Nan

doi:10.1021/acschemneuro.5b00032

Cited by 33 publications

(34 citation statements)

References 61 publications

(110 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Activated spinal glia were observed after oxaliplatin injection, and intrathecal injection of minocycline and fluorocitrate, which decrease the activation of astrocytes and microglia respectively, effectively attenuated neuropathic pain [22]. Activated glia are known to contribute to neuropathic pain by releasing pro-inflammatory cytokines such as IL-1β and TNF-α [13–15], and suppressing the activation of astrocytes and microglia down-regulated the expression of pro-inflammatory cytokines, which led to the alleviation of nerve injury-induced neuropathic pain [40, 41]. Intrathecal injection of pro-inflammatory cytokines such as IL-1β and TNF-α evoked hyperalgesia and allodynia in naive animals [42, 43].…”

Section: Discussionmentioning

confidence: 99%

Anti-allodynic effect of Buja in a rat model of oxaliplatin-induced peripheral neuropathy via spinal astrocytes and pro-inflammatory cytokines suppression

Jung

Lee

Kim

et al. 2017

BMC Complement Altern Med

View full text Add to dashboard Cite

BackgroundOxaliplatin, a widely used anticancer drug against metastatic colorectal cancer, can induce acute peripheral neuropathy, which is characterized by cold and mechanical allodynia. Activation of glial cells (e.g. astrocytes and microglia) and increase of pro-inflammatory cytokines (e.g. IL-1β and TNF-α) in the spinal cord play a crucial role in the pathogenesis of neuropathic pain. Our previous study demonstrated that Gyejigachulbu-Tang (GBT), a herbal complex formula, alleviates oxaliplatin-induced neuropathic pain in rats by suppressing spinal glial activation. However, it remains to be elucidated whether and how Buja (Aconiti Tuber), a major ingredient of GBT, is involved in the efficacy of GBT.MethodsCold and mechanical allodynia induced by an oxaliplatin injection (6 mg/kg, i.p.) in Sprauge-Dawley rats were evaluated by a tail immersion test in cold water (4 °C) and a von Frey hair test, respectively. Buja (300 mg/kg) was orally administrated for five consecutive days after the oxaliplatin injection. Glial activation in the spinal cord was quantified by immunohistochemical staining using GFAP (for astrocytes) and Iba-1 (for microglia) antibodies. The amount of spinal pro-inflammatory cytokines, IL-1β and TNF-α, were measured by ELISA.ResultsSignificant behavioral signs of cold and mechanical allodynia were observed 3 days after an oxaliplatin injection. Oral administration of Buja significantly alleviated oxaliplatin-induced cold and mechanical allodynia by increasing the tail withdrawal latency to cold stimuli and mechanical threshold. Immunohistochemical analysis showed the activation of astrocytes and microglia and the increase of the IL-1β and TNF-α levels in the spinal cord after an oxaliplatin injection. Administration of Buja suppressed the activation of spinal astrocytes without affecting microglial activation and down-regulated both IL-1β and TNF-α levels in the spinal cord.ConclusionsOur results indicate that Buja has a potent anti-allodynic effect in a rat model of oxaliplatin-induced neuropathic pain, which is associated with the inhibition of activation of astrocytes and release of pro-inflammatory cytokines in the spinal cord. Thus, our findings suggest that administration of Buja could be an alternative therapeutic option for the management of peripheral neuropathy, a common side-effect of oxaliplatin.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-017-1556-z) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Anti-allodynic effect of Buja in a rat model of oxaliplatin-induced peripheral neuropathy via spinal astrocytes and pro-inflammatory cytokines suppression

Jung

Lee

Kim

et al. 2017

BMC Complement Altern Med

View full text Add to dashboard Cite

show abstract

“… 13 – 15 Activation of NF-κB participated in nerve injury or inflammation-induced pathological pain. 16 , 17 Recent studies showed that NF-κB is also involved in chemotherapy-induced chronic pain. 8 , 9 However, whether activation of NF-κB p65 in DRG is involved in oxaliplatin-induced chronic pain is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of CX3CL1 mediated by NF-κB activation in dorsal root ganglion contributes to peripheral sensitization and chronic pain induced by oxaliplatin administration

et al. 2017

View full text Add to dashboard Cite

Painful peripheral neuropathy is a severe side effect in oxaliplatin therapy that compromises cancer patients' quality of life. However, its underlying pathogenic mechanisms remain largely unknown. Here, we found that intraperitoneal consecutive administration of oxaliplatin significantly increased excitability of small diameter dorsal root ganglion neurons and induced thermal hyperalgesia in rats. Furthermore, the CX3CL1 expression was significantly increased after oxaliplatin treatment, and intrathecal injection of a neutralizing antibody against CX3CL1 markedly attenuated the enhanced excitability of dorsal root ganglion neurons and thermal hyperalgesia. Importantly, the upregulated CX3CL1 is mediated by the NF-κB signaling pathway, as inhibition of NF-κB p65 activation with pyrrolidine dithiocarbamate or p65 siRNA inhibited the upregulation of CX3CL1, the enhanced excitability of dorsal root ganglion neurons, and thermal hyperalgesia induced by oxaliplatin. Further studies with chromatin immunoprecipitation found that oxaliplatin treatment increased the recruitment of NF-κB p65 to the CX3Cl1 promoter region. Our results suggest that upregulation of CX3CL1 in dorsal root ganglion mediated by NF-κB activation contributes to the peripheral sensitization and chronic pain induced by oxaliplatin administration.

show abstract

“…Inflammatory reactions are the primary cause of sequential damage associated with SCI, and inflammation is an important part of the acute SCI pathophysiological mechanism (24). SCI promotes a series of molecular biological events which lead to inflammatory cell activation, arising from circulatory system infiltration in spinal cord tissue, pro-inflammatory factors and neurotoxin release, and the generation of oxygen free radical and nitroso compounds which lead to cellular lesions (25). In the present study, it was demonstrated that sparstolonin B significantly decreased IL-18, IL-6, IL-1β, and IL-23 levels, and TNF-α and IFN-γ levels, in SCI rats.…”

Section: Discussionmentioning

confidence: 99%

Sparstolonin B attenuates spinal cord injury‑induced inflammation in rats by modulating TLR4‑trafficking

Yuan¹,

Zhang²,

Zhu³

et al. 2018

Mol Med Report

View full text Add to dashboard Cite

The present study used a spinal cord injury (SCI) model to evaluate whether sparstolonin B was able to prevent SCI, and to investigate the underlying signaling mechanism. Sparstolonin B attenuated the SCI‑induced Batto, Beattie and Bresnahan score and water content in rats. Sparstolonin B attenuated the mRNA expression of proinflammatory cytokines interleukin (IL)‑18, IL‑6, IL‑1β, and IL‑23, decreased the levels of tumor necrosis factor‑α and interferon‑γ, and decreased caspase‑3 activity and apoptosis regulator Bax protein expression in SCI rats. Similarly, sparstolonin B inhibited monocyte chemoattractant protein‑1 mRNA levels, and Toll‑like receptor (TLR) 4, myeloid differentiation primary response protein MyD88 (MyD88) and nuclear factor (NF)‑κB protein levels in SCI rats. The present results suggested that sparstolonin B may attenuate SCI‑induced inflammation and apoptosis in rats by modulating the TLR4/MyD88/NF‑κB signaling pathway.

show abstract

Atorvastatin Prevents Neuroinflammation in Chronic Constriction Injury Rats through Nuclear NFκB Downregulation in the Dorsal Root Ganglion and Spinal Cord

Cited by 33 publications

References 61 publications

Anti-allodynic effect of Buja in a rat model of oxaliplatin-induced peripheral neuropathy via spinal astrocytes and pro-inflammatory cytokines suppression

Anti-allodynic effect of Buja in a rat model of oxaliplatin-induced peripheral neuropathy via spinal astrocytes and pro-inflammatory cytokines suppression

Upregulation of CX3CL1 mediated by NF-κB activation in dorsal root ganglion contributes to peripheral sensitization and chronic pain induced by oxaliplatin administration

Sparstolonin B attenuates spinal cord injury‑induced inflammation in rats by modulating TLR4‑trafficking

Contact Info

Product

Resources

About