Role of TRPV4-P2X7 Pathway in Neuropathic Pain in Rats with Chronic Compression of the Dorsal Root Ganglion

Fan, Xiaoping; Wang, Chuanwei; Han, Junting; Ding, Xinli; Tang, Shaocan; Ning, Liping

doi:10.1007/s11064-021-03352-8

Cited by 13 publications

(6 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CBGA has antioxidant, antibacterial, neuromodulator and neuroprotective effects [ 69 ] while being an effective modulator of TRPV 1, TRPV 3 and TRPV4 channels [ 70 ]. Members of TRPV and TRPM subfamilies have high expression levels in neurons mediating neuropathic pain [ 71 , 72 , 73 , 74 ]. Interestingly, members of the TRPM families are expressed in the hippocampus and basal ganglia, brain structures that display a significant loss of neurons at the initial stages of the development of neurodegenerative diseases, such as Alzheimer’s disease.…”

Section: Discussionmentioning

confidence: 99%

Acute Toxicity and Pharmacokinetic Profile of an EU-GMP-Certified Cannabis sativa L. in Rodents

Filipiuc,

Ştefănescu,

Solcan

et al. 2023

Pharmaceuticals

View full text Add to dashboard Cite

The conundrum of Cannabis sativa’s applications for therapeutical purposes is set apart by the hundreds of known and commercially available strains, the social, cultural and historical context, and the legalization of its use for medical purposes in various jurisdictions around the globe. In an era where targeted therapies are continuously being developed and have become the norm, it is imperative to conduct standardized, controlled studies on strains currently cultivated under Good Manufacturing Practices (GMP) certification, a standard that guarantees the quality requirements for modern medical and therapeutic use. Thus, the aim of our study is to evaluate the acute toxicity of a 15.6% THC: <1% CBD, EU-GMP certified, Cannabis sativa L. in rodents, following the OECD acute oral toxicity guidelines, and to provide an overview of its pharmacokinetic profile. Groups of healthy female Sprague-Dawley rats were treated orally with a stepwise incremental dose, each step using three animals. The absence or presence of plant-induced mortality in rats dosed at one step determined the next step. For the EU GMP-certified Cannabis sativa L. investigated, we determined an oral LD50 value of over 5000 mg/kg in rats and a human equivalent oral dose of ≈806.45 mg/kg. Additionally, no significant clinical signs of toxicity or gross pathological findings were observed. According to our data, the toxicology, safety and pharmacokinetic profile of the tested EU-GMP-certified Cannabis sativa L. support further investigations through efficacy and chronic toxicity studies in preparation for potential future clinical applications and especially for the treatment of chronic pain.

show abstract

Section: Discussionmentioning

confidence: 99%

Acute Toxicity and Pharmacokinetic Profile of an EU-GMP-Certified Cannabis sativa L. in Rodents

Filipiuc,

Ştefănescu,

Solcan

et al. 2023

Pharmaceuticals

View full text Add to dashboard Cite

show abstract

“…HC067047, a selective inhibitor of TRPV4, was purchased from MerkExpress (SML0143). HC067047 (0.1 mg/kg, 20 µL) was dissolved in 10% DMSO and administered by intrathecal injection [ 31 ]. We intrathecally injected either Bobcat339 or HC067047 for 7 consecutive days.…”

Section: Methodsmentioning

confidence: 99%

TET1-TRPV4 Signaling Contributes to Bone Cancer Pain in Rats

Niu

Liu

et al. 2023

Brain Sciences

View full text Add to dashboard Cite

Bone cancer pain (BCP) is excruciating for cancer patients, with limited clinical treatment options and significant side effects, due to the complex and unclear pathogenesis of bone cancer pain. Peripheral sensitization in dorsal root ganglion (DRG) neurons is a recognized cellular mechanism for bone cancer pain. The pathological mechanism of chronic pain is increasingly being affected by epigenetic mechanisms. In this study, we unbiasedly showed that the DNA hydroxymethylase ten-eleven translocation 1 (TET1) expression was significantly increased in the L4–6 DRG of BCP rats and ten-eleven translocation 2 (TET2) expression did not change significantly. Notably, TET1 inhibition by intrathecal injection of Bobcat339 (a TET1 inhibitor) effectively relieved mechanical hyperalgesia in BCP rats. Peripheral sensitization in chronic pain relies on the activation and overexpression of ion channels on neurons. Here, we demonstrated that TRPV4, one of the transient receptor potential ion channel family members, was significantly elevated in the L4–6 DRG of BCP rats. In addition, TRPV4 inhibition by intrathecal injection of HC067047 (a TRPV4 inhibitor) also significantly attenuated mechanical hyperalgesia in BCP rats. Interestingly, we found that TET1 inhibition downregulated TRPV4 expression in the L4–6 DRG of BCP rats. As a result, these findings suggested that TET1 may contribute to bone cancer pain by upregulating TRPV4 expression in the L4–6 DRG of BCP rats and that TET1 or TRPV4 may become therapeutic targets for bone cancer pain.

show abstract

“…[38][39][40][41] In satellite glial cells, P2X7R functions in the extracellular signal-regulated kinase 1 (ERK) signaling pathway to mediate the pain response and is modulated by the transient receptor potential vanilloid receptors 1 and 4 (TRPV1 and TRPV4). [42][43][44] Wu et al 45 recently established a chronic compression injury model and uncovered a novel transcriptional mechanism where BDNF prompts P2X7R expression in dorsal root ganglion neurons. Besides its presence in brain cells, P2X7R is also expressed in the salivary gland epithelium, with heightened expressed in patients afflicted with primary desiccation syndrome.…”

Section: Diverse Localization Of P2x7rmentioning

confidence: 99%

“…Importantly, it is intricately linked to the pain response 38–41 . In satellite glial cells, P2X7R functions in the extracellular signal‐regulated kinase 1 (ERK) signaling pathway to mediate the pain response and is modulated by the transient receptor potential vanilloid receptors 1 and 4 (TRPV1 and TRPV4) 42–44 . Wu et al 45 .…”

Section: An Overview Of P2x7rmentioning

confidence: 99%

Involvement of microglial P2X7 receptor in pain modulation

Zhang,

Gao,

Zhang

et al. 2023

CNS Neurosci Ther

View full text Add to dashboard Cite

BackgroundPain is a rapid response mechanism that compels organisms to retreat from the harmful stimuli and triggers a repair response. Nonetheless, when pain persists for extended periods, it can lead to adverse changes into in the individual’s brain, negatively impacting their emotional state and overall quality of life. Microglia, the resident immune cells in the central nervous system (CNS), play a pivotal role in regulating a variety of pain‐related disorders. Specifically, recent studies have shed light on the central role that microglial purinergic ligand‐gated ion channel 7 receptor (P2X7R) plays in regulating pain. In this respect, the P2X7R on microglial membranes represents a potential therapeutic target.AimsTo expound on the intricate link between microglial P2X7R and pain, offering insights into potential avenues for future research.MethodsWe reviewed 140 literature and summarized the important role of microglial P2X7R in regulating pain, including the structure and function of P2X7R, the relationship between P2X7R and microglial polarization, P2X7R‐related signaling pathways, and the effects of P2X7R antagonists on pain regulation.ResultsP2X7R activation is related to M1 polarization of microglia, while suppressing P2X7R can transfer microglia from M1 into M2 phenotype. And targeting the P2X7R‐mediated signaling pathways helps to explore new therapy for pain alleviation. P2X7R antagonists also hold potential for translational and clinical applications in pain management.ConclusionsMicroglial P2X7R holds promise as a potential novel pharmacological target for clinical treatments due to its distinctive structure, function, and the development of antagonists.

show abstract

Role of TRPV4-P2X7 Pathway in Neuropathic Pain in Rats with Chronic Compression of the Dorsal Root Ganglion

Cited by 13 publications

References 51 publications

Acute Toxicity and Pharmacokinetic Profile of an EU-GMP-Certified Cannabis sativa L. in Rodents

Acute Toxicity and Pharmacokinetic Profile of an EU-GMP-Certified Cannabis sativa L. in Rodents

TET1-TRPV4 Signaling Contributes to Bone Cancer Pain in Rats

Involvement of microglial P2X7 receptor in pain modulation

Contact Info

Product

Resources

About