The pain associated with bone cancer is often difficult to manage. It is relatively unresponsive to opioid therapy, which indicates that a neuropathic and/or tumorigenic component is involved. Nerve growth factor (NGF) is known to influence inflammatory and neuropathic pain, and anti-NGF therapy has been shown to alleviate both of these. Sevcik et al. have investigated the effects of a novel NGF-sequestering antibody on a mouse model of bone cancer, and propose two mechanisms for its pain-relieving effects.

As expected, the antibody produced a significant decrease in ongoing and movement-evoked pain behaviours in the mouse model. However, the authors found that this pain decrease was not the result of changes in disease progression, sympathetic innervation or infiltration of macrophages to the bone.

They propose that anti-NGF therapy could have an impact on bone cancer pain in more ways than one. NGF is involved in many processes that increase nociceptive signalling, and reductions in several of these processes were seen in the mouse model in response to anti-NGF therapy. For example, the anti-NGF antibody reduced both the upregulation of dynorphin, which is involved in chronic pain, and the expression of activating transcription factor 3 (ATF3), which is upregulated in response to neuronal injury.

Furthermore, the anti-hyperalgesic effects of anti-NGF therapy could be partially attributed to the fact that almost all sensory innervation of bone is provided by nociceptors that express calcitonin gene-related peptide (CGRP) and tyrosine kinase receptor A (TrkA), which are susceptible to blockade by anti-NGF therapies.

The next step will be to investigate whether such therapies can produce safe and effective pain relief in humans.