Urinary N telopeptide levels in predicting the anti-nociceptive responses of zoledronic acid and paclitaxel in a rat model of bone metastases

Gui,Qi; Xu,Chengcheng; Li,Dapeng; Zhuang,Liang; Xia,Shu; Yu,Shiying

doi:10.3892/mmr.2015.3948

Urinary N telopeptide levels in predicting the anti-nociceptive responses of zoledronic acid and paclitaxel in a rat model of bone metastases

Authors:
- Qi Gui
- Chengcheng Xu
- Dapeng Li
- Liang Zhuang
- Shu Xia
- Shiying Yu
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Affiliations: Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China, Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Published online on: June 17, 2015 https://doi.org/10.3892/mmr.2015.3948
Pages: 4243-4249
Copyright: © Gui et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The present study investigated the hypothesis that urinary levels of N telopeptide (NTx) can be used to predict the anti‑nociceptive responses of zoledronic acid and paclitaxel on bone metastases in a rat model. Rats were implanted with intra‑femur Walker 256 carcinoma cells or control solution, and were treated with either normal saline, zoledronic acid or paclitaxel on the 10th day following surgery. Mechanical allodynia was recorded and the urine collagen‑crosslinked NTx values were measured prior to, and 7, 14 and 21 days following the injections. Bone sections and osteoclasts were stained on the 14th day (4 days post‑injection). Furthermore, the mRNA and protein expression levels of c‑fos in the spinal cord and acid‑sensing ion channel 3 (ASIC3) in the dorsal root ganglion (DRG) were analyzed. The mechanical allodynia of rats was attenuated from day 14 in the zoledronic acid group and from day 21 in the paclitaxel group. A positive correlation was observed between the anti‑nociceptive responses of zoledronic acid and paclitaxel, and the urinary levels of NTx (r=0.619; P<0.001). The mRNA levels of c‑fos in the spinal cord and ASIC3 in the DRG in the zoledronic acid group were reduced 14 and 21 days after inoculation, and this reduction was observed in the paclitaxel group 21 days after inoculation. Low dose paclitaxel was observed to have a weaker anti‑nociceptive effect on bone cancer pain, with a later‑onset, compared with zoledronic acid. The results suggested that urinary levels of NTx may predict the anti‑nociceptive responses of zoledronic acid and paclitaxel in a rat model of bone metastases.

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