ArticleJournal of neuroinflammation2019
Targeting prokineticin system counteracts hypersensitivity, neuroinflammation, and tissue damage in a mouse model of bortezomib-induced peripheral neuropathy.
Article in Journal of neuroinflammation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- Bortezomib-induced gastrointestinal dysfunction, peripheral neuropathy and neuroimmune signalling are influenced by the gut microbiota in mice.Journal of neuroinflammation · 2026Article
- Neuronal toxicity and recovery from early bortezomib-induced neuropathy: blood-nerve barrier dysfunction without dorsal root ganglion damage.British journal of anaesthesia · 2026Article
- Gastrodin alleviates bortezomib-induced peripheral neuropathy by inhibiting NF-κB/NLRP3 pathway-mediated microglial inflammation.The Korean journal of pain · 2026Article
- Cytokine Dynamics in Bortezomib-Induced Peripheral Neuropathy: Challenges in Translating Preclinical Findings to Humans.Journal of the peripheral nervous system : JPNS · 2026Observational
- Reduced Neuroinflammation and Pain with a Functional Sourdough Bread Enriched with Legumes and Ancient Cereals in a Mouse Model of LPS-Induced Inflammation.International journal of molecular sciences · 2026Article
- Article
- Review
- Emerging role of macrophages in neuropathic pain.Journal of orthopaedic translation · 2025Review
- Bortezomib-induced peripheral neuropathy: from molecular mechanisms to clinical management.Frontiers in pharmacology · 2025Review
- The Prokineticin System in Inflammatory Bowel Diseases: A Clinical and Preclinical Overview.Biomedicines · 2023Review
- Therapeutic Potential of Targeting Prokineticin Receptors in Diseases.Pharmacological reviews · 2023Review
- Article
- Blocking prokineticin receptors attenuates synovitis and joint destruction in collagen-induced arthritis.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Article
- Animal models of chemotherapy-induced peripheral neuropathy for hematological malignancies: A review.Ibrain · 2023Review
- Non-Peptide Agonists and Antagonists of the Prokineticin Receptors.Current issues in molecular biology · 2022Review
- Role of inflammation and oxidative stress in chemotherapy-induced neurotoxicity.Immunologic research · 2022Review
- Osteoarthritis Pain in Old Mice Aggravates Neuroinflammation and Frailty: The Positive Effect of Morphine Treatment.Biomedicines · 2022Article
- Long-Term Treatment with Bortezomib Induces Specific Methylation Changes in Differentiated Neuronal Cells.Cancers · 2022Article
- Targeting Chemokines and Chemokine GPCRs to Enhance Strong Opioid Efficacy in Neuropathic Pain.Life (Basel, Switzerland) · 2022Review
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundNeuropathy is a dose-limiting side effect of many chemotherapeutics, including bortezomib. The mechanisms underlying this condition are not fully elucidated even if a contribution of neuroinflammation was suggested. Here, we investigated the role of a chemokine family, the prokineticins (PKs), in the development of bortezomib-induced peripheral neuropathy (BIPN), and we used a PK receptor antagonist to counteract the development and progression of the pathology.
methodsNeuropathy was induced in male C57BL/6J mice by using a protocol capable to induce a detectable neuropathic phenotype limiting systemic side effects. The presence of allodynia (both mechanical and thermal) and thermal hyperalgesia was monitored over time. Mice were sacrificed at two different time points: 14 and 28 days after the first bortezomib (BTZ) injection. At these times, PK system activation (PK2 and PK-Rs), macrophage and glial activation markers, and cytokine production were evaluated in the main station involved in pain transmission (sciatic nerve, DRG, and spinal cord), and the effect of a PK receptors antagonist (PC1) on the same behavioral and biochemical parameters was assessed. Structural damage of DRG during BTZ treatment and an eventual protective effect of PC1 were also evaluated.
resultsBTZ induces in mice a dose-related allodynia and hyperalgesia and a progressive structural damage to the DRG. We observed a precocious increase of macrophage activation markers and unbalance of pro- and anti-inflammatory cytokines in sciatic nerve and DRG together with an upregulation of GFAP in the spinal cord. At higher BTZ cumulative dose PK2 and PK receptors are upregulated in the PNS and in the spinal cord. The therapeutic treatment with the PK-R antagonist PC1 counteracts the development of allodynia and hyperalgesia, ameliorates the structural damage in the PNS, decreases the levels of activated macrophage markers, and prevents full neuroimmune activation in the spinal cord.
conclusionsPK system may be a strategical pharmacological target to counteract BTZ-induced peripheral neuropathy. Blocking PK2 activity reduces progressive BTZ toxicity in the DRG, reducing neuroinflammation and structural damage to DRG, and it may prevent spinal cord sensitization.
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