| First Author | Old EA | Year | 2014 |
| Journal | J Clin Invest | Volume | 124 |
| Issue | 5 | Pages | 2023-36 |
| PubMed ID | 24743146 | Mgi Jnum | J:212753 |
| Mgi Id | MGI:5582119 | Doi | 10.1172/JCI71389 |
| Citation | Old EA, et al. (2014) Monocytes expressing CX3CR1 orchestrate the development of vincristine-induced pain. J Clin Invest 124(5):2023-36 |
| abstractText | A major dose-limiting side effect associated with cancer-treating antineoplastic drugs is the development of neuropathic pain, which is not readily relieved by available analgesics. A better understanding of the mechanisms that underlie pain generation has potential to provide targets for prophylactic management of chemotherapy pain. Here, we delineate a pathway for pain that is induced by the chemotherapeutic drug vincristine sulfate (VCR). In a murine model of chemotherapy-induced allodynia, VCR treatment induced upregulation of endothelial cell adhesion properties, resulting in the infiltration of circulating CX3CR1(+) monocytes into the sciatic nerve. At the endothelial-nerve interface, CX3CR1(+) monocytes were activated by the chemokine CX3CL1 (also known as fractalkine [FKN]), which promoted production of reactive oxygen species that in turn activated the receptor TRPA1 in sensory neurons and evoked the pain response. Furthermore, mice lacking CX3CR1 exhibited a delay in the development of allodynia following VCR administration. Together, our data suggest that CX3CR1 antagonists and inhibition of FKN proteolytic shedding, possibly by targeting ADAM10/17 and/or cathepsin S, have potential as peripheral approaches for the prophylactic treatment of chemotherapy-induced pain. |
