The pathophysiology of cancer-induced bone pain: current understanding

Cancer-induced bone pain (CIBP) is a common clinical problem. Although treatment has been revolufionised in the past 10 years with the introduction of bisphosphonates, pain arising spontaneously or from movement, remains a leading cause of unresolved pain in many patients. Until recently little was understood about the peripheral and central mechanisms of bone pain. Insight into the mechanisms of osteoblast and osteoclast activation, via receptor activator for nuclear factor kappaB (BANK) dependent and independent mechanisms and a re-evaluation of primary afferent terminals within bone have led to a suggestion that CIBP may be a mixture of inflammatory and neuropathic stimuli. The recently published animal model of localised but progressive bone destruction has allowed greater insight into the peripheral and dorsal horn pathophysiology, which hitherto was precluded. Immunocytochemical markers of neurotransmitters and receptors indicate that CIBP has unique characteristics, unlike neuropathy or inflammation. Evidence for an increased excitability within the dorsal horn, and especially Lamina I, and possible mechanisms underlying this unique pain state will be discussed.