Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
Gene/Protein
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Query: UMLS:C0151825 (
bone pain
)
3,118
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Crucial to the development and maintenance of pain sensations is neurotrophin receptor p75 (p75
NTR
), 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 p75
NTR
in the development of cancer-induced
bone pain
(CIBP). Therefore the present study examined whether p75
NTR
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 p75
NTR
and mTOR mRNA expression. Immunofluorescence analysis was performed to determine the coexpression of p75
NTR
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 p75
NTR
expression was significantly enhanced in the BDNF-treated primary DRG in the BDNF group.
In vivo
experiments determined that mTOR and p75
NTR
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 p75
NTR
-targeting small interfering RNA significantly decreased mTOR and p75
NTR
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/p75
NTR
/mTOR signaling may participate in nociceptive transmission in CIBP, suggesting a novel mechanism and potential therapeutic target for CIBP treatment and management.
...
PMID:Low-affinity neurotrophin receptor p75 of brain-derived neurotrophic factor contributes to cancer-induced bone pain by upregulating mTOR signaling. 3225 64
