Kinin B2 Receptor Mediates Cisplatin-Induced Painful Peripheral Neuropathy by Intracellular Kinase Pathways and TRPA1 Channel Sensitisation

Becker, Grace Vieira; Fialho, Maria Fernanda Pessano; Oliveira, Sara Marchesan

doi:10.3390/ph16070959

Cited by 4 publications

(2 citation statements)

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“…In this sense, recent studies using pharmacological antagonism and genetic manipulation have demonstrated the contribution of kinin B 1 and B 2 receptors to the painful behaviours of cisplatin-induced peripheral neuropathy [54]. Furthermore, it was observed that PLC and protein kinase C epsilon (PKCε) intracellular signalling pathways downstream from the kinin B 2 receptor activation are involved in the transient receptor potential ankyrin 1 (TRPA1) channel sensitization, contributing to the painful behaviours caused by cisplatin in mice [55]. Thus, kinin receptor antagonists present themselves as promising pharmacological strategies for treating cisplatin-induced peripheral neuropathy (Figure 2).…”

Section: Role Of G Protein-coupled Receptors In Cisplatin-induced Per...mentioning

confidence: 99%

“…In addition to genetic approaches, pharmacological tools suggest the involvement of TRPA1 and TRPV1 in cisplatin-induced pain behaviours. For example, the pharmacological inhibition of the TRPA1 channel (using the A967079 antagonist) reduced the mechanical and cold allodynia induced by cisplatin in mice, while a TRPA1 agonist (allyl isothiocyanate) at a subnociceptive dose enhanced these behaviours [55]. Furthermore, cisplatin-induced mechanical hypersensitivity was inhibited by silencing TRPA1 and TRPV1 through the intraplantar administration of a membrane-impermeable lidocaine analogue (QX-314) together with TRPV1 agonist (capsaicin) or with TRPA1 agonist, allyl isothiocyanate (AITC) [81].…”

Section: Role Of Ion Channels In Cisplatin-induced Peripheral Neuropathymentioning

confidence: 99%

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G Protein-Coupled Receptors and Ion Channels Involvement in Cisplatin-Induced Peripheral Neuropathy: A Review of Preclinical Studies

Becker,

Atuati,

Oliveira

2024

Cancers

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Cisplatin is a platinum-based chemotherapy drug widely used to treat various solid tumours. Although it is effective in anti-cancer therapy, many patients develop peripheral neuropathy during and after cisplatin treatment. Peripheral neuropathy results from lesions or diseases in the peripheral somatosensory nervous system and is a significant cause of debilitation and suffering in patients. In recent years, preclinical studies have been conducted to elucidate the mechanisms involved in chemotherapy-induced peripheral neuropathic pain, as well as to promote new therapeutic targets since current treatments are ineffective and are associated with adverse effects. G-protein coupled receptors and ion channels play a significant role in pain processing and may represent promising targets for improving the management of cisplatin-induced neuropathic pain. This review describes the role of G protein-coupled receptors and ion channels in cisplatin-induced pain, analysing preclinical experimental studies that investigated the role of each receptor subtype in the modulation of cisplatin-induced pain.

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Section: Role Of G Protein-coupled Receptors In Cisplatin-induced Per...mentioning

confidence: 99%

Section: Role Of Ion Channels In Cisplatin-induced Peripheral Neuropathymentioning

confidence: 99%

G Protein-Coupled Receptors and Ion Channels Involvement in Cisplatin-Induced Peripheral Neuropathy: A Review of Preclinical Studies

Becker,

Atuati,

Oliveira

2024

Cancers

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An emerging aspect of cancer neuroscience: A literature review on chemotherapy-induced peripheral neuropathy

Tao,

Chen,

Zeng

et al. 2025

Cancer Letters

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The analgesic effects of Yu-Xue-Bi tablet (YXB) on mice with inflammatory pain by regulating LXA4-FPR2-TRPA1 pathway

Liu,

Zhang,

Zhu

et al. 2024

Chin Med

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Background Oxylipins including lipoxin A4 (LXA4) facilitate the resolution of inflammation and possess analgesic properties by inhibiting macrophage infiltration and transient receptor potential (TRP) protein expression. Yu-Xue-Bi Tablet (YXB) is a traditional Chinese patent medicine used to relieve inflammatory pain. Our previous research has shown that the analgesic effect of YXB is related to inhibiting peripheral inflammation and regulating macrophage infiltration, but the mechanism is not yet clear. The purpose of this study is to explore the mechanisms of YXB on mice models with Complete Freund’s Adjuvant (CFA)-induced inflammatory pain from the perspective at the resolution of inflammation. Methods Mechanical allodynia thresholds and heat hypersensitivity were measured using the Von Frey test and the hot plate test respectively. The open field test and the tail suspension test were employed to measure anxiety and depressive behaviors respectively. The expression of CD68+ and the proportion of F4/80+CD11b+ cells were measured by immunofluorescence staining and flow cytometry. The expression of transient receptor potential ankyrin 1(TRPA1) was measured by immunofluorescence staining and western blotting. Oxylipins omics analysis provided quantitative data on oxylipins in the paws, and enzyme linked immunosorbent assay (ELISA) was used to measure the levels of LXA4 there. Immunofluorescence staining was used to perform the expression of Leukotriene A4 hydroxylase (LTA4H) in the paws of mice. The impact of injecting the formyl peptide receptor 2(FPR2) antagonist WRW4 and the TRPA1 agonist AITC into the left paws was observed, focusing on the expression of mechanical allodynia thresholds, the expression of CD68+, TRPA1 in the paws, and Calcitonin gene-related peptide (CGRP) in the L5 spinal dorsal horn. Results YXB elevated mechanical allodynia thresholds, alleviated heat hypersensitivity and anxiety and depressive behaviors in CFA mice. It significantly reduced the number of CD68+ and proportion of F4/80+CD11b+ within the paws, thereby decreasing macrophage infiltration. Additionally, it diminished the expression of TRPA1 in the paws and TRPV1 in the DRG, leading to an inhibition of peripheral sensitization. Through quantitative analysis, it was found that YXB could modulate DHA-derived oxylipins and LXA4. ELISA results indicated that YXB elevated the levels of LXA4 and inhibited the expression of LAT4H in the paws. Furthermore, the pro-resolution and analgesic effects of YXB were hindered after administration of the FPR2 antagonist. Compared with the AITC group, YXB showed no significant improvement in anti-inflammatory and analgesic effects. Conclusions YXB can regulate the oxylipins of paws in CFA mice to promote the resolution of inflammation. The LXA4-FPR2-TRPA1 pathway is a key mechanism for the resolution of inflammation and analgesic effects.

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Kinin B2 Receptor Mediates Cisplatin-Induced Painful Peripheral Neuropathy by Intracellular Kinase Pathways and TRPA1 Channel Sensitisation

Cited by 4 publications

References 73 publications

G Protein-Coupled Receptors and Ion Channels Involvement in Cisplatin-Induced Peripheral Neuropathy: A Review of Preclinical Studies

G Protein-Coupled Receptors and Ion Channels Involvement in Cisplatin-Induced Peripheral Neuropathy: A Review of Preclinical Studies

An emerging aspect of cancer neuroscience: A literature review on chemotherapy-induced peripheral neuropathy

The analgesic effects of Yu-Xue-Bi tablet (YXB) on mice with inflammatory pain by regulating LXA4-FPR2-TRPA1 pathway

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