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• W4377029212 abstract "<b>Abstract ID 24304</b> <b>Poster Board 233</b> <b>Objective</b> Cancer metastasis to bone is a major contributor to neuropathic pain onset in patients and affects up to 66% of those in late-stage cancer. Many preclinical cancer pain models utilize patient derived cancer cell lines and to avoid a host immune response, are implanted into immunocompromised rodents. This approach discounts the importance of a healthy and intact immune response in cancer and cancer pain therapeutic drug development. To address this, we expanded upon previous literature (Wacnik et al., 2001) and developed a host-derived cancer pain mouse model produced by implantation of murine fibrosarcoma cells into the calcaneus bone. <b>Methods</b> NCTC 2472 murine fibrosarcoma cells were grown to 80% confluency, and a density of 2 × 10⁵ cells/10 μL was injected into the right calcaneus bone of adult male and female C3H/HeJ mice. Injection of PBS into other mice served as a sham control. The von Frey assay was utilized to assess tumor-induced mechanical allodynia. Expulsion of acetone on the paw and recording the time spent responding was used to measure cold allodynia. Thermal hotplate latencies were used to assess thermal hyperalgesia. <b>Results</b> Sarcoma implanted mice exhibited mechanical allodynia as early as 3 days post-implantation and lasted until day 13 post-implantation. Between males and females, the severity of allodynia was not different, despite a differential tumor volume increase. Despite the presence of mechanical allodynia, in both male and female mice there was no measurable onset of thermal hyperalgesia nor cold allodynia among sarcoma implanted subjects. Sham subjects did not exhibit mechanical allodynia, thermal hyperalgesia, or cold allodynia. Because tumor volume and von Frey responses were consistent from day 3 to day 8 post-implantation, these days were chosen to test analgesics. The prototypical opioid agonist morphine (1.78, 3.2, 5.6, 10 mg/kg, i.p.) dose-relatedly reversed tumor-induced mechanical allodynia. The ED₅₀ of morphine to reverse cancer pain was 3.302 (2.979 – 3.661) mg/kg. Mitragynine, the most prevalent alkaloid found in the natural product kratom, (17.8, 32, 56, 100 mg/kg, i.p.) also dose-relatedly reversed tumor-induced mechanical allodynia. The ED₅₀ of mitragynine to reverse cancer pain was 47.589 (42.833 – 52.872) mg/kg. <b>Conclusions</b> Sarcoma implantation resulted in mechanical allodynia, which was dose relatedly reversed by the prototypical opioid agonist morphine as well as the kratom alkaloid mitragynine. The use of a host-derived cancer pain mouse model produced by implantation of murine fibrosarcoma cells into the calcaneus bone allows for novel pain therapeutic assessment in immune-intact animals. This approach will aid in identification of promising analgesic therapeutic options for patients experiencing cancer-induced peripheral neuropathy. This work was supported by the National Institute on Drug Abuse DA25267 and DA48353" @default.
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• W4377029212 date "2023-05-18" @default.
• W4377029212 modified "2023-09-29" @default.
• W4377029212 title "Characterization of a Mouse Model of Neuropathic Pain Induced by Calcaneus Implantation of NCTC 2472 Mouse Sarcoma Cells" @default.
• W4377029212 doi "https://doi.org/10.1124/jpet.122.243040" @default.
• W4377029212 hasPublicationYear "2023" @default.
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