Abstract
Bone cancer pain (BCP) profoundly impacts patient's quality of life, demanding more effective pain management strategies. The aim of this systematic review was to investigate the role of inflammatory cytokines as potential molecular targets in BCP. A systematic search for animal rodent models of bone cancer pain studies was conducted in PubMed, Scopus, and Web of Science. Methodological quality and risk of bias were assessed using the SYRCLE RoB tool. Twenty-five articles met the inclusion criteria, comprising animal studies investigating molecular targets related to inflammatory cytokines in BCP. A low to moderate risk of bias was reported. Key findings in 23 manuscripts revealed upregulated classic pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17, IL-18, IL-33) and chemokines in the spinal cord, periaqueductal gray, and dorsal root ganglia. Interventions targeting these cytokines consistently mitigated pain behaviors. Additionally, it was demonstrated that glial cells, due to their involvement in the release of inflammatory cytokines, emerged as significant contributors to BCP. This systematic review underscores the significance of inflammatory cytokines as potential molecular targets for alleviating BCP. It emphasizes the promise of targeted interventions and advocates for further research to translate these findings into effective therapeutic strategies. Ultimately, this approach holds the potential to enhance the patient's quality of life.