Open Access

Low‑affinity neurotrophin receptor p75 of brain‑derived neurotrophic factor contributes to cancer‑induced bone pain by upregulating mTOR signaling

  • Authors:
    • Xiao‑Wen Meng
    • Xiao‑Hong Jin
    • Xiang Wei
    • Li‑Na Wang
    • Jian‑Ping Yang
    • Fu‑Hai Ji
  • View Affiliations

  • Published online on: October 14, 2019     https://doi.org/10.3892/etm.2019.8097
  • Pages: 4379-4387
  • Copyright: © Meng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Crucial to the development and maintenance of pain sensations is neurotrophin receptor p75 (p75NTR), the low affinity receptor of brain‑derived neurotrophic factor (BDNF). This receptor is widespread among dorsal root ganglion (DRG) neurons and the spinal cord. Few reports have demonstrated the specific role of p75NTR in the development of cancer‑induced bone pain (CIBP). Therefore the present study examined whether p75NTR contributed to CIBP by upregulating mammalian target of rapamycin (mTOR) signaling. A CIBP rat model was induced and reverse transcription‑quantitative polymerase chain reaction was employed to determine p75NTR and mTOR mRNA expression. Immunofluorescence analysis was performed to determine the coexpression of p75NTR and mTOR in DRG neurons, as well as the spinal cord. Von Frey filaments were used to measure the 50% likelihood of paw withdrawal thresholds (PWTs). Spontaneous pain was assessed by ambulatory score. The results demonstrated that compared with the control group, mTOR activation in primary cultured DRG neurons was significantly increased. In addition, mTOR and p75NTR expression was significantly enhanced in the BDNF‑treated primary DRG in the BDNF group. In vivo experiments determined that mTOR and p75NTR levels were increased in the CIBP rats compared with the sham group. PWT, in response to mechanical stimulation, was significantly lower compared with that in sham rats and the ambulatory score was significantly higher than that in sham rats. Finally, intrathecal injection of a p75NTR‑targeting small interfering RNA significantly decreased mTOR and p75NTR expression levels in DRG neurons and the spinal cord of CIBP rats, as well as partially reversing the decline in PWTs and the increase in ambulatory score. In conclusion, the present study determined that the activation of BDNF/p75NTR/mTOR signaling may participate in nociceptive transmission in CIBP, suggesting a novel mechanism and potential therapeutic target for CIBP treatment and management.

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December 2019
Volume 18 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

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APA
Meng, X., Jin, X., Wei, X., Wang, L., Yang, J., & Ji, F. (2019). Low‑affinity neurotrophin receptor p75 of brain‑derived neurotrophic factor contributes to cancer‑induced bone pain by upregulating mTOR signaling. Experimental and Therapeutic Medicine, 18, 4379-4387. https://doi.org/10.3892/etm.2019.8097
MLA
Meng, X., Jin, X., Wei, X., Wang, L., Yang, J., Ji, F."Low‑affinity neurotrophin receptor p75 of brain‑derived neurotrophic factor contributes to cancer‑induced bone pain by upregulating mTOR signaling". Experimental and Therapeutic Medicine 18.6 (2019): 4379-4387.
Chicago
Meng, X., Jin, X., Wei, X., Wang, L., Yang, J., Ji, F."Low‑affinity neurotrophin receptor p75 of brain‑derived neurotrophic factor contributes to cancer‑induced bone pain by upregulating mTOR signaling". Experimental and Therapeutic Medicine 18, no. 6 (2019): 4379-4387. https://doi.org/10.3892/etm.2019.8097