CXCR3 signalling partially contributes to the pathogenesis of neuropathic pain in male rodents

Li, Kai; Tan, Yong-Hui; Feng, Shi‐Yang; Fu, Kai‐Yuan

doi:10.1111/joor.13262

Cited by 4 publications

(2 citation statements)

References 36 publications

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“…Study have exhibited that CXCR3 knockout mice had a high tolerance to SNI-induced NPP. And the occurrence time of mechanical pain sensitivity will be delayed (Li et al, 2021). In addition, there is increasing evidence that proinflammatory factors and chemokines can be synthesized and secreted by spinal cord neurons and dorsal root ganglion (He et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Demethylase FTO promotes neuropathic pain development via regulating the m6A methylation levels of CXCR3

Wang

Zhao

2022

Acta Biochim Pol

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Objective: Neuropathic pain (NPP) is an indirect or direct pain caused by somatic sensory nervous system dysfunction or primary injury, which is considered to be one of the most serious public health problems. This study aimed to investigate the role of adiposity-associated protein (FTO) in NPP. Materials and Methods: Sciatic nerve injury (SNI) treatment was performed to establish an NPP model in vivo. The qRT-PCR and western blot assays were conducted to measure the relative mRNA and protein expressions. Additionally, the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) of the mice were measured on days 0, 1, 3, 5, 7, and 14. The m6A level of CXCR3 was determined with Methylated RNA immunoprecipitation (MeRIP) assay and the inflammatory factor expressions were determined with Elisa kits. Results and Discussion: The FTO and CXCR3 expressions were up-regulated and the METTL14 expression was down-regulated in SNI mice. FTO-silenced increased the m6A and decreased the mRNA levels of CXCR3 in SNI mice. Furthermore, FTO-silenced decreased the mRNA stability of the CXCR3. Besides, in the SNI mice, FTO-silenced increased the PWL and PWT, and decreased the TNF-α, IL-1β, and IL-6 levels. While over-expressed CXCR3 inverted the FTO-silenced effects. Conclusions: Knockdown of FTO relieved the NPP progression via triggering the demethylation of CXCR3, thereby down-regulating the CXCR3expression.

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Section: Discussionmentioning

confidence: 99%

Demethylase FTO promotes neuropathic pain development via regulating the m6A methylation levels of CXCR3

Wang

Zhao

2022

Acta Biochim Pol

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“…Published data suggest that CXCL11 plays an important role in the first phase of the development of pain [28,167]. Intrathecal administration induces quick but shortterm hypersensitivity in naive mice [28].…”

Section: Chemokines In Neuropathic Painmentioning

confidence: 99%

Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain

Pawlik

Mika

2023

Molecules

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Neuropathic pain is a debilitating condition that affects millions of people worldwide. Numerous studies indicate that this type of pain is a chronic condition with a complex mechanism that tends to worsen over time, leading to a significant deterioration in patients’ quality of life and issues like depression, disability, and disturbed sleep. Presently used analgesics are not effective enough in neuropathy treatment and may cause many side effects due to the high doses needed. In recent years, many researchers have pointed to the important role of chemokines not only in the development and maintenance of neuropathy but also in the effectiveness of analgesic drugs. Currently, approximately 50 chemokines are known to act through 20 different seven-transmembrane G-protein-coupled receptors located on the surface of neuronal, glial, and immune cells. Data from recent years clearly indicate that more chemokines than initially thought (CCL1/2/3/5/7/8/9/11, CXCL3/9/10/12/13/14/17; XCL1, CX3CL1) have pronociceptive properties; therefore, blocking their action by using neutralizing antibodies, inhibiting their synthesis, or blocking their receptors brings neuropathic pain relief. Several of them (CCL1/2/3/7/9/XCL1) have been shown to be able to reduce opioid drug effectiveness in neuropathy, and neutralizing antibodies against them can restore morphine and/or buprenorphine analgesia. The latest research provides irrefutable evidence that chemokine receptors are promising targets for pharmacotherapy; chemokine receptor antagonists can relieve pain of different etiologies, and most of them are able to enhance opioid analgesia, for example, the blockade of CCR1 (J113863), CCR2 (RS504393), CCR3 (SB328437), CCR4 (C021), CCR5 (maraviroc/AZD5672/TAK-220), CXCR2 (NVPCXCR220/SB225002), CXCR3 (NBI-74330/AMG487), CXCR4 (AMD3100/AMD3465), and XCR1 (vMIP-II). Recent research has shown that multitarget antagonists of chemokine receptors, such as CCR2/5 (cenicriviroc), CXCR1/2 (reparixin), and CCR2/CCR5/CCR8 (RAP-103), are also very effective painkillers. A multidirectional strategy based on the modulation of neuronal–glial–immune interactions by changing the activity of the chemokine family can significantly improve the quality of life of patients suffering from neuropathic pain. However, members of the chemokine family are still underestimated pharmacological targets for pain treatment. In this article, we review the literature and provide new insights into the role of chemokines and their receptors in neuropathic pain.

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The Role of CXCR3 in Nervous System‐Related Diseases

Wang,

Guo,

Jia

et al. 2024

Mediators of Inflammation

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Inflammatory chemokines are a group of G‐protein receptor ligands characterized by conserved cysteine residues, which can be divided into four main subfamilies: CC, CXC, XC, and CX3C. The C‐X‐C chemokine receptor (CXCR) 3 and its ligands, C‐X‐C chemokine ligands (CXCLs), are widely expressed in both the peripheral nervous system (PNS) and central nervous system (CNS). This comprehensive literature review aims to examine the functions and pathways of CXCR3 and its ligands in nervous system‐related diseases. In summary, while the related pathways and the expression levels of CXCR3 and its ligands are varied among different cells in PNS and CNS, the MPAK pathway is the core via which CXCR3 exerts physiological functions. It is not only the core pathway of CXCR3 after activation but also participates in the expression of CXCR3 ligands in the nervous system. In addition, despite CXCR3 being a common inflammatory chemokine receptor, there is no consensus on its precise roles in various diseases. This uncertainty may be attributable to distinct inflammatory characteristics, that inflammation simultaneously possesses the dual properties of damage induction and repair facilitation.

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CXCR3 signalling partially contributes to the pathogenesis of neuropathic pain in male rodents

Cited by 4 publications

References 36 publications

Demethylase FTO promotes neuropathic pain development via regulating the m6A methylation levels of CXCR3

Demethylase FTO promotes neuropathic pain development via regulating the m6A methylation levels of CXCR3

Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain

The Role of CXCR3 in Nervous System‐Related Diseases

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