Peripheral Mechanism of Cancer-Induced Bone Pain

Yang, Yachen; Yang, Wei; Zhang, Ruofan; Wang, Yanqing

doi:10.1007/s12264-023-01126-6

Cited by 7 publications

(1 citation statement)

References 152 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most patients with metastatic bone cancer experience severe pain. The molecular mechanisms by which bone metastasis generates pain are only beginning to be understood ( Figure 1 ) [ 59 , 60 , 61 , 62 ]. Cancer cells create their own acidic microenvironment [ 62 , 63 , 64 ].…”

Section: Trpv1 In Cancer Pain: Molecular Mechanismsmentioning

confidence: 99%

Targeting TRPV1 for Cancer Pain Relief: Can It Work?

Szallasi

2024

Cancers

View full text Add to dashboard Cite

Chronic intractable pain affects a large proportion of cancer patients, especially those with metastatic bone disease. Blocking sensory afferents for cancer pain relief represents an attractive alternative to opioids and other drugs acting in the CNS in that sensory nerve blockers are not addictive and do not affect the mental state of the patient. A distinct subpopulation of sensory afferents expresses the capsaicin receptor TRPV1. Intrathecal resiniferatoxin, an ultrapotent capsaicin analog, ablates TRPV1-expressing nerve endings exposed to the cerebrospinal fluid, resulting in permanent analgesia in women with cervical cancer metastasis to the pelvic bone. High-dose capsaicin patches are effective pain killers in patients with chemotherapy-induced peripheral neuropathic pain. However, large gaps remain in our knowledge since the mechanisms by which cancer activates TRPV1 are essentially unknown. Most important, it is not clear whether or not sensory denervation mediated by TRPV1 agonists affects cancer progression. In a murine model of breast cancer, capsaicin desensitization was reported to accelerate progression. By contrast, desensitization mediated by resiniferatoxin was found to block melanoma growth. These observations imply that TRPV1 blockade for pain relief may be indicated for some cancers and contraindicated for others. In this review, we explore the current state of this field and compare the analgesic potential of TRPV1 antagonism and sensory afferent desensitization in cancer patients.

show abstract

Section: Trpv1 In Cancer Pain: Molecular Mechanismsmentioning

confidence: 99%

Targeting TRPV1 for Cancer Pain Relief: Can It Work?

Szallasi

2024

Cancers

View full text Add to dashboard Cite

show abstract

Targeted therapy: P2X3 receptor silencing in bone cancer pain relief

Jiang,

Liu,

Zhang

et al. 2024

J Biochem & Molecular Tox

View full text Add to dashboard Cite

Bone cancer pain remains a significant clinical challenge, often refractory to conventional treatments. The upregulation of the P2X3 receptor in the dorsal root ganglia has been implicated in the pathogenesis of bone cancer pain. This study aimed to elucidate the role of the P2X3 receptor in this context and assess the therapeutic potential of receptor silencing. Utilizing a rat model with Walker 256 cells to simulate bone cancer pain, researchers conducted molecular analyses, including semi‐quantitative RT‐PCR and Western Blot, to investigate P2X3 receptor expression in the dorsal root ganglia. Results demonstrated a marked increase in P2X3 receptor levels in the dorsal root ganglia of the bone cancer pain model. Targeted silencing of the P2X3 receptor using specific shRNA delivered via lentiviral vectors significantly reduced pain sensitivity, underscoring the receptor's potential as a valuable therapeutic target. In addition, a comprehensive gene expression analysis leveraging the GEO data set GSE249443 was performed to explore the underlying biological pathways linked to bone cancer pain. This analysis provided insights into the intricate interplay between bone cancer pain and associated biological processes, offering a deeper understanding of the mechanisms involved in pain modulation and progression. In conclusion, this research identifies the P2X3 receptor as a critical molecular target for mitigating bone cancer pain. The selective silencing of the P2X3 receptor emerges as a promising and innovative therapeutic strategy, presenting novel avenues for managing bone cancer pain and potentially revolutionizing treatment approaches in this challenging domain.

show abstract