Prostate cancer is unique in that bone is often the only clinically detectable site of
metastasis. Prostate
tumors that have metastasized to bone frequently induce bone
pain which can be difficult to fully control as it seems to be driven simultaneously by inflammatory, neuropathic, and tumorigenic mechanisms. As
nerve growth factor (
NGF) has been shown to modulate inflammatory and some
neuropathic pain states in animal models, an
NGF-sequestering antibody was administered in a prostate model of
bone cancer where significant bone formation and bone destruction occur simultaneously in the mouse femur. Administration of a blocking antibody to
NGF produced a significant reduction in both early and late stage
bone cancer pain-related behaviors that was greater than or equivalent to that achieved with acute administration of 10 or 30 mg/kg of
morphine sulfate. In contrast, this
therapy did not influence
tumor-induced bone remodeling, osteoblast proliferation, osteoclastogenesis,
tumor growth, or markers of sensory or sympathetic innervation in the skin or bone. One rather unique aspect of the sensory innervation of bone, that may partially explain the
analgesic efficacy of anti-
NGF therapy in relieving
prostate cancer-induced bone
pain, is that nearly all nerve fibers that innervate the bone express trkA and p75, and these are the receptors through which
NGF sensitizes and/or activates nociceptors. The present results suggest that anti-
NGF therapy may be effective in reducing
pain and enhancing the quality of life in patients with prostate
tumor-induced
bone cancer pain.