TNF and neoplasm: The mechanism underlying pain flare is multifactorial and is thought to include localised inflammation caused by damage to tissues, leading to the release of cytokines such as tumour necrosis factor‐α (TNF‐α); interleukin‐1 (IL‐1) and prostaglandins; stimulation of the highly innervated periosteum; increased activation of osteoclasts; and tumour necrosis [33, 34].