Alterations of endogenous pain-modulatory system of the cerebral cortex in the neuropathic pain

Chen, Peng; Wang, Chen; Gong, Qihuang; Chai, Yang; Chen, Yunzhi; Song, Cuiwen; Wu, Yuanhua; Wang, Long

doi:10.1016/j.isci.2023.106668

Cited by 4 publications

(1 citation statement)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accordingly, elevated levels of p-IKBα were detected in the PFC and PAG of CCI mice that were inhibited by DADS and GYY4137, revealing the anti-inflammatory activity of these treatments, which can contribute to enhance the analgesic effects of CB2R agonists. It has been demonstrated that the excessive synthesis of inflammatory mediators induced by CCI produces a depletion of endogenous cannabinoids in the PFC and abnormal changes of endocannabinoid signaling during neuropathic pain [ 55 ]. Therefore, considering that the administration of ATB-352, a H 2 S donor, inhibits the enzymes involved in the degradation of the endogenous cannabinoids in the gut [ 56 ], we speculated that the reduction of the inflammatory responses produced by DADS and GYY4137 in the PFC and PAG of CCI mice might inhibit the enzyme monoacylglycerol lipase (MGL), involved in the degradation of 2-arachidonoyl glycerol (2-AG), resulting in the normalization of the low levels of this endocannabinoid in the brain, and thus explaining the enhancement of the analgesic effects of JWH-133 produced by DADS and GYY4137 during neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen Sulfide Interacting with Cannabinoid 2 Receptors during Sciatic Nerve Injury-Induced Neuropathic Pain

et al. 2023

View full text Add to dashboard Cite

Hydrogen sulfide (H2S) donors make opioids more effective in inhibiting nociception during inflammatory and neuropathic pain. We examined whether the analgesic, anxiolytic and/or antidepressant actions of the cannabinoid 2 receptor (CB2R) agonist, JWH-133, might be improved by pretreatment with H2S donors, DADS and GYY4137 in mice with sciatic nerve injury-provoked neuropathy (CCI). The reversion of the antinociceptive effects of these treatments with the CB2R antagonist, AM630, and the regulatory actions of H2S in the phosphorylation of NF-κB inhibitor alpha (IKBα) and in the brain-derived neurotrophic factor (BDNF), CB2R, Nrf2 and heme oxygenase 1 (HO-1) levels in prefrontal cortex (PFC), ventral hippocampus (vHIP) and periaqueductal gray matter (PAG), were examined. Data showed that the analgesic effects of JWH-133, systemically and locally administered, were improved by the DADS or GYY4137 pretreatment. The co-treatment of GYY4137 with JWH-133 also stopped anxiodepressive-like activities that concur with neuropathy. Our data likewise showed that both H2S donors normalized the inflammatory (p-IKBα), neurotrophic (BDNF) variations caused by CCI, increased the expression of CB2R and activated the Nrf2/HO-1 antioxidant pathway in PFC, v-HIP and/or PAG of animals with neuropathic pain. In addition, the blockade of the analgesia produced by high doses of DADS and GYY4137 with AM630 indicated the contribution of the endocannabinoid system in the effects of H2S during neuropathic pain, thus supporting the positive interaction between H2S and CB2R. Therefore, this study demonstrates the potential use of CB2R agonists combined with H2S donors as a possible treatment for peripheral nerve injury-caused neuropathic pain and the associated emotional disturbances.

show abstract

Section: Discussionmentioning

confidence: 99%

Hydrogen Sulfide Interacting with Cannabinoid 2 Receptors during Sciatic Nerve Injury-Induced Neuropathic Pain

et al. 2023

View full text Add to dashboard Cite

show abstract

Mahuang Fuzi Xixin decoction: A potent analgesic for neuropathic pain targeting the NMDAR2B/CaMKIIα/ERK/CREB pathway

Chai,

He,

Liang

et al. 2024

Heliyon

View full text Add to dashboard Cite

Analgesic effect of Dahuang Fuzi Decoction in neuropathic pain through inhibiting TNF-α and PI3K-AKT signaling

Qu,

Gong,

et al. 2024

Front. Neurosci.

View full text Add to dashboard Cite

BackgroundNeuropathic pain (NeP) presents considerable challenges in terms of effective management and significantly impacts the quality of life for affected patients. The current treatment options for NeP are limited, highlighting the need for alternative therapeutic approaches. Dahuang Fuzi Decoction (DF), a formula from traditional Chinese medicine, has shown potential in relieving pain symptoms associated with various types of NeP. However, the mechanisms through which DF exerts its effects remain largely unknown.MethodsIn this study, we employed ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS) to analyze the chemical composition of DF. A chronic sciatic nerve compression injury (CCI) rat mode was used to assess the analgesic efficacy of DF for NeP. Network pharmacology analysis was performed to identify the potential signaling pathways affected by DF.ResultsDF treatment significantly increased the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in CCI rats, indicating its analgesic effect. Network pharmacology analysis suggested that DF potentially modulated TNF-α and PI3K-AKT signaling pathways. Furthermore, DF treatment decreased the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in spinal cord tissues of CCI rats, suggesting an anti-inflammatory effect. Western blot analysis revealed that DF treatment reduced the expression of TNF-α, TNFR1, and phosphorylated forms of PI3K, AKT, IKKα/β, IKBα, and NF-κB in the spinal cord of CCI rats. Immunofluorescence analysis confirmed significant reductions in TNF-α and TNFR1 expression, as well as in AKT and NF-κB phosphorylation within astrocytes following DF administration.ConclusionOur findings characterize the chemical constituents of DF and elucidate its underlying mechanism for relieving NeP. The analgesic effect of DF involves the inhibition of TNF-α and PI3K-AKT signaling pathways, providing a potential therapeutic approach for NeP management.

show abstract

Alterations of endogenous pain-modulatory system of the cerebral cortex in the neuropathic pain

Cited by 4 publications

References 45 publications

Hydrogen Sulfide Interacting with Cannabinoid 2 Receptors during Sciatic Nerve Injury-Induced Neuropathic Pain

Hydrogen Sulfide Interacting with Cannabinoid 2 Receptors during Sciatic Nerve Injury-Induced Neuropathic Pain

Mahuang Fuzi Xixin decoction: A potent analgesic for neuropathic pain targeting the NMDAR2B/CaMKIIα/ERK/CREB pathway

Analgesic effect of Dahuang Fuzi Decoction in neuropathic pain through inhibiting TNF-α and PI3K-AKT signaling

Contact Info

Product

Resources

About