ArticleMolecular pain
Chemokine receptor CXCR4 activates the RhoA/ROCK2 pathway in spinal neurons that induces bone cancer pain.
Article in Molecular pain. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Molecular targets in bone cancer pain: a systematic review of inflammatory cytokines.Journal of molecular medicine (Berlin, Germany) · 2024Pooled it
- Inhibition of GPR4 Ameliorates Neuropathic Pain and Neuronal Ferroptosis via Regulation of Spinal RhoA/YAP Signaling in Rats.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- Review
- Pharmacological Management of Cancer Pain: Advances in Treatment Strategies and Drug Delivery Systems.Pharmaceutics · 2025Review
- Long noncoding RNA NONRATT007487.2 drives cancer-induced bone pain progression through direct interaction with CXCL1.The Korean journal of pain · 2025Article
- Exploring the Role of RhoA/ROCK Signaling in Pain: A Narrative Review.Aging and disease · 2025Review
- Mechanisms of Cancer-Induced Bone Pain.Journal of pain research · 2025Review
- The CXCL12/CXCR4 Axis: An Emerging Therapeutic Target for Chronic Pain.Journal of pain research · 2025Review
- Involvement of CXCL12/CXCR4 in CB2 receptor agonist-attenuated morphine tolerance in Walker 256 tumor-bearing rats with cancer pain.European journal of medical research · 2024Article
- Chemokine CXCL12 Activates CXC Receptor 4 Metastasis Signaling Through the Upregulation of a CXCL12/CXCR4/MDMX (MDM4) Axis.Cancers · 2024Article
- Effects of fasudil on glial cell activation induced by tooth movement.Progress in orthodontics · 2024Article
- Activation of RhoA/ROCK2 signaling by hypoxia-inducible factor 1α in promoting tumor growth and metastasis in human colon cancer.Journal of gastrointestinal oncology · 2024Article
- Mesenchymal stem cell transplantation plays a role in relieving cancer pain.Frontiers in pharmacology · 2024Review
- Article
- Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- CXCR4 antagonists disrupt leukaemia-meningeal cell adhesion and attenuate chemoresistance.British journal of haematology · 2023Article
- Article
- miR-301a Deficiency Attenuates the Macrophage Migration and Phagocytosis through YY1/CXCR4 Pathway.Cells · 2022Article
- Recent Advances in CXCL12/CXCR4 Antagonists and Nano-Based Drug Delivery Systems for Cancer Therapy.Pharmaceutics · 2022Review
- Identification of Potential mRNA Biomarkers in Milk Small Extracellular Vesicles of Enzootic Bovine Leukosis Cattle.Viruses · 2022Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChemokine receptor CXCR4 has been found to be associated with spinal neuron and glial cell activation during bone cancer pain. However, the underlying mechanism remains unknown. Furthermore, the RhoA/ROCK2 pathway serves as a downstream pathway activated by CXCR4 during bone cancer pain. We first validated the increase in the expressions of CXCR4, p-RhoA, and p-ROCK2 in the spinal dorsal horn of a well-characterized tumor cell implantation-induced cancer pain rat model and how these expressions contributed to the pain behavior in tumor cell implantation rats. We hypothesized that spinal blockade of the CXCR4-RhoA/ROCK2 pathway is a potential analgesic therapy for cancer pain management.
methodsAdult female Sprague-Dawley rats (body weight of 180-220 g) and six- to seven-week old female Sprague-Dawley rats (body weight of 80-90 g) were taken. Ascitic cancer cells were extracted from the rats (body weight of 80-90 g) with intraperitoneally implanted Walker 256 mammary gland carcinoma cells. Walker 256 rat mammary gland carcinoma cells were then injected (tumor cell implantation) into the intramedullary space of the tibia to establish a rat model of bone cancer pain.
resultsWe found increased expressions of CXCR4, p-RhoA, and p-ROCK2 in the neurons in the spinal cord. p-RhoA and p-ROCK2 were co-expressed in the neurons and promoted by overexpressed CXCR4. Intrathecal delivery of CXCR4 inhibitor Plerixafor (AMD3100) or ROCK2 inhibitor Fasudil abrogated tumor cell implantation-induced pain hypersensitivity and tumor cell implantation-induced increase in p-RhoA and p-ROCK2 expressions. Intrathecal injection of stromal-derived factor-1, the principal ligand for CXCR4, accelerated p-RhoA expression in naive rats, which was prevented by postadministration of CXCR4 inhibitor Plerixafor (AMD3100) or ROCK2 inhibitor Fasudil.
conclusionsCollectively, the spinal RhoA/ROCK2 pathway could be a critical downstream target for CXCR4-mediated neuronal sensitization and pain hypersensitivity in bone cancer pain, and it may serve as a potent therapeutic target for pain treatment.
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