Background & Aims

Cancer pain animal models have been intensively researched in order to identify adequate study animal models that match the pain experienced by human cancer patients. These models can be classified into two categories: Non-bone cancer pain models and bone cancer pain models. Although bone cancer pain is the most severe type of chronic pain, the underlying mechanism and relationship between physiological and anatomical pain are yet unclear. The SJSA-1 cell line (formerly OsA-CL) was established in 1982 from the primary tumor of a patient diagnosed with primitive multipotential sarcoma of the femur. The SJSA-1 cell line has been employed in cancer research, however detailed facts about its use in an animal model of cancer pain are not readily available in the search results. The aims is to discover the best way for creating an animal model of cancer pain using the SJSA-1 cell line, which will aid researchers in recommendation for bone cancer pain animal model.

Methods

In this study 100k, 300k, 600k SJSA-1 cell line in 10 mcl PBS planted into male Wistar Rattus norvegicus. The rats were dissected at the proximal lateral region of the femoral trochanter. Then the dental burs were used to make a hole in the femoral bone until reached the intramedullary area. The cancer cells were prepared separately and injected immediately. After the cells were injected, the wound was stitched with surgical suture. Immunosuppressive medicine was given for 7 days intramuscularly. On days 7, 10, 13, 15, 18, and 21, rats’ pain levels were monitored with Ugo Basile® SRL’s electronic von Frey filament. Testing began with the normal leg and progressed to the leg that had cancer cells. X-ray of the femoral bone were checked to reveal lytic process or sunburst appearance which portrayed osteosarcoma. The animals were sacrificed on day 21, femoral bone was taken to examine the pathological structure using HE stained.

Results

3 rats died in the group of 600k cells throughout 21 days of observation, while 5 rats (41.7%) had lytic appearance in X-Ray on day 21st. The von Frey test results in 100k and 300k cancer cells revealed no significant difference in pain level even after 21 days of observation, which was supported by X-ray results that showed only bone inflammation & improved on the 7th day after the immunosuppressive medication was stopped. Each week (days 14 and 21), the group with 100k and 300k cells saw just a 20% and 57.1% rise in inflammation (increased opacity) on bone X-rays. After receiving 600k cells, 7 rats developed nodules in the soft tissue of their foot. On the 14th day, the rats with 600k cancer cells had a lytic app. on X-ray, and there was a significant difference in pain intensity by Von Frey filament with a p value of less than 0.05 on day 13. The pathological structure of the femur displayed a demineralized bone when stained with HE in the 600k group.

Conclusions

In this study, pain model rats with 600k SJSA-1 cancer cells, which might cause bone inflammation and lysis, ultimately leading to cancer. The von Frey test and radiological imaging showed no statistically significant difference between animals injected with less than 300k. The radiological image of the femoral bones in 100k cells group revealed minimal inflammation, but the bones injected with 300k cells were inflamed/opaque on day 7 but healed 7 days later. This is consistent with the pathologic histology of numerous femur bone, demonstrating that in the intramedullary cell replace with osteosarcoma cell. The model’s shortcoming is that it only addresses mechanical analgesia; more study is still being conducted for thermal analgesia, immunological suppression, and metastasis.

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Presenting Author

Herdiani Sulistyo Putri

Poster Authors

Herdiani Sulistyo Putri

MD., FIP.

Doctoral Program in Biomedical Science at Faculty of Medicine, Universitas Airlangga

Lead Author

Nancy Margarita Rehatta

Prof.

Department of Anesthesiology and Reanimation, Airlangga University

Lead Author

Suharjono Suharjono (Prof. MS.

Apt. PhD)

Department of Pharmacy Practice, Faculty of Pharmacy, Universitas Airlangga

Lead Author

Ira Sari Yudaniayanti (Vet. M.P.

PhD)

Department of Clinical Veterinary, Faculty of Veterinary Medicine, Universitas Airlangga

Lead Author

Archie Arman Dwiyatna (MD)

Department of Anesthesiology and Reanimation, Faculty of Medicine, Universitas Airlangga

Lead Author

Faiz Muhammad Ammar (MD)

Department of Anesthesiology and Reanimation, Faculty of Medicine, Universitas Airlangga

Lead Author

Ahsin Fikri (MD)

Department of Anesthesiology and Reanimation, Faculty of Medicine, Universitas Airlangga

Lead Author

Topics

  • Trial Design