Targeting the chemokine ligand 2–chemokine receptor 2 axis provides the possibility of immunotherapy in chronic pain

Liu, Shan; Lan, Xiao-Bing; Tian, Miaomiao; Zhu, Chunhao; Ma, Lin; Yang, Jia-Mei; Du, Juan; Zheng, Ping; Liu, Ning

doi:10.1016/j.ejphar.2023.175646

Cited by 2 publications

(2 citation statements)

References 193 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…C-C chemokine receptors regulate biological processes such as cell migration, proliferation, and inflammation response. C-X-C motif chemokine ligand 10 (CXCL10/IP10) has been widely reported to be elevated in the plasma of COVID-19 ( 58 ), and targeting the chemokine ligand 2-chemokine receptor 2 axis provides potential for immunotherapy in chronic pain ( 59 ). Finally, utilizing a potential causal model analysis, we identified causal components in the genetic correlation between COVID-19 and chronic pain, consistent with the previous Mendelian randomization study by Zhao ( 60 ).…”

Section: Discussionmentioning

confidence: 99%

Genetic overlap and causality between COVID-19 and multi-site chronic pain: the importance of immunity

Chen,

Liu,

Zhang

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

BackgroundThe existence of chronic pain increases susceptibility to virus and is now widely acknowledged as a prominent feature recognized as a major manifestation of long-term coronavirus disease 2019 (COVID-19) infection. Given the ongoing COVID-19 pandemic, it is imperative to explore the genetic associations between chronic pain and predisposition to COVID-19.MethodsWe conducted genetic analysis at the single nucleotide polymorphism (SNP), gene, and molecular levels using summary statistics of genome-wide association study (GWAS) and analyzed the drug targets by summary data-based Mendelian randomization analysis (SMR) to alleviate the multi-site chronic pain in COVID-19. Additionally, we performed a latent causal variable (LCV) method to investigate the causal relationship between chronic pain and susceptibility to COVID-19.ResultsThe cross-trait meta-analysis identified 19 significant SNPs shared between COVID-19 and chronic pain. Coloc analysis indicated that the posterior probability of association (PPH4) for three loci was above 70% in both critical COVID-19 and COVID-19, with the corresponding top three SNPs being rs13135092, rs7588831, and rs13135092. A total of 482 significant overlapped genes were detected from MAGMA and CPASSOC results. Additionally, the gene ANAPC4 was identified as a potential drug target for treating chronic pain (P=7.66E-05) in COVID-19 (P=8.23E-03). Tissue enrichment analysis highlighted that the amygdala (P=7.81E-04) and prefrontal cortex (P=8.19E-05) as pivotal in regulating chronic pain of critical COVID-19. KEGG pathway enrichment further revealed the enrichment of pleiotropic genes in both COVID-19 (P=3.20E-03,Padjust=4.77E-02,hsa05171) and neurotrophic pathways (P=9.03E-04,Padjust =2.55E-02,hsa04621). Finally, the latent causal variable (LCV) model was applied to find the genetic component of critical COVID-19 was causal for multi-site chronic pain (P=0.015), with a genetic causality proportion (GCP) of was 0.60.ConclusionsIn this study, we identified several functional genes and underscored the pivotal role of the inflammatory system in the correlation between the paired traits. Notably, heat shock proteins emerged as potential objective biomarkers for chronic pain symptoms in individuals with COVID-19. Additionally, the ubiquitin system might play a role in mediating the impact of COVID-19 on chronic pain. These findings contribute to a more comprehensive understanding of the pleiotropy between COVID-19 and chronic pain, offering insights for therapeutic trials.

show abstract

Section: Discussionmentioning

confidence: 99%

Genetic overlap and causality between COVID-19 and multi-site chronic pain: the importance of immunity

Chen,

Liu,

Zhang

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Additionally, BMS-741672 is in the second phase of clinical trials for patients with diabetic neuropathic pain; however, no study results have yet been posted [239]. Targeting CCR2 through siRNA, blocking antibodies, or small-molecule antagonists may provide new therapeutic possibilities for managing neuropathic pain [240]. The available literature suggests that the pharmacological modulation of spinal neuroimmunological interactions via CCR2 may represent a new strategy for effective polytherapy with opioids in patients suffering from neuropathic pain; however, better pharmacological tools are needed.…”

Section: Ccr2mentioning

confidence: 99%

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

Pawlik

Mika

2023

Molecules

View full text Add to dashboard Cite

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.

show abstract

Targeting the chemokine ligand 2–chemokine receptor 2 axis provides the possibility of immunotherapy in chronic pain

Cited by 2 publications

References 193 publications

Genetic overlap and causality between COVID-19 and multi-site chronic pain: the importance of immunity

Genetic overlap and causality between COVID-19 and multi-site chronic pain: the importance of immunity

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

Contact Info

Product

Resources

About