Antihyperalgesic effects induced by the IL-1 receptor antagonist anakinra and increased IL-1beta levels in inflamed and osteosarcoma-bearing mice.
Based on the well established involvement of IL-1beta in inflammatory hyperalgesia, we have assessed the possible role played by IL-1beta in a murine model of bone cancer-induced pain. With this aim, we measured IL-1beta levels at the region of the tibia and the spinal cord in mice bearing a tibial osteosarcoma induced by the inoculation of NCTC 2472 cells, and we tested whether the IL-1 receptor antagonist, anakinra, inhibits some hypernociceptive reactions evoked by the neoplastic injury. Parallel experiments were performed in mice with a chronic inflammatory process (intraplantar injection of complete Freund's adjuvant, CFA). IL-1beta levels were increased in the tibial region of osteosarcoma-bearing mice and in the paws of inflamed mice. To a lesser extent, the content of IL-1beta in the spinal cord was also augmented in both situations. Osteosarcoma-induced thermal hyperalgesia was inhibited by 30 and 100 mg/kg of systemic anakinra, but only 300 mg/kg prevented inflammatory thermal hyperalgesia. Mechanical hyperalgesia induced by the osteosarcoma was blocked by 100 and 300 mg/kg of anakinra, whereas a partial reversion of inflammatory mechanical hyperalgesia was induced by 300 mg/kg. Anakinra, intrathecally administered (1 and 10 microg) did not modify hyperalgesia of either origin. Besides, both tumoral and inflammatory mechanical allodynia remained unaltered after the administration of anakinra. In conclusion, some hyperalgesic symptoms observed in this model of bone cancer are mediated by the peripheral release of IL-1beta and may be inhibited by antagonists of type I IL-1 receptors with a similar or greater potency than symptoms produced by inflammation.
Baamonde
Ana
A
Laboratorio de Farmacología, Facultad de Medicina, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, C/Julián Clavería 6, 33006 Oviedo, Asturias, Spain. arbaiza@uniovi.es
Curto-Reyes
Verdad
V
Juárez
Lucía
L
Meana
Alvaro
A
Hidalgo
Agustín
A
Menéndez
Luis
L
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001859:Bone Neoplasms / Q000150:complications* / Q000378:metabolism; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005620:Freund's Adjuvant; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D007249:Inflammation / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism; D007278:Injections, Spinal; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D012516:Osteosarcoma / Q000150:complications* / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation; D011312:Pressure; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1; D005620:Freund's Adjuvant; D015232:Dinoprostone