Section 1 Bone Tumours

**3**

**Chapter 1**

**Abstract**

**1. Introduction**

and Treatment

*Sonny Hermanus Johannes Sliepen*

the mechanism of action and current treatments.

**Keywords:** CIBP, NOP receptor, RANK/RANKL, NGF/TrkA, IL-6

Cancer induced bone pain (CIBP) is a big accompanying clinical problem of bone tumors with a high unmet medical need [1]. It is a debilitating form of different pain components that severely affects a patients' quality of life. The complex mechanism of CIBP largely involves the nervous system with transmembrane receptors and channels on the nerve fibers. Briefly, the nervous system consists of the central nervous system, i.e. the brain and the spinal cord, and the peripheral nervous system, i.e. the autonomic (unconscious, the para- and sympathetic nervous system) and somatic (conscious/voluntary) nervous system. A neuron is a nerve cell consisting of a cell body (soma), projections receiving input signals (the dendrites) and a single long arm away from the soma (the axon/fiber) that ends with the axon terminal (synapse). Axons contain a sheath of myelin that serves as isolation in a similar way as plastic around an electrical wire. Regarding the somatic nervous system, neurons with projections towards the spinal cord (afferent) respond to stimuli and are the sensory neurons. The neurons that respond to the brain and the signals from the spinal cord (efferent) are the motor neurons [2]. Pain is the defense mechanism against external factors that could cause tissue damage (a noxious stimuli) and nociception is detecting such stimulus. The

Bone Cancer Pain, Mechanism

The world health organization (WHO) has predicted a global amount of 19 million cancer cases by 2025. Breast, prostate and lung cancer are common cancer types and show metastasis in 60 to 84% of the cases, with 75 to 90% experiencing life-altering cancer-induced bone pain (CIBP), characterized by continuous, dull progressive pain with movement-induced incident peaks and random breakthrough spikes. Therefore, it is the most difficult pain condition to treat. CIBP is a unique type of pain with neuropathic and nociceptive components. Briefly, an invading tumor cell disturbs the healthy balance of the bone resulting in an acidic microenvironment, activating sensory fibers in the bone. The invaded tumor cell and adjacent stromal cells secrete mediators initiating an immune response with transcriptional signaling, resulting in increased cytokines and growth factors. Sensory nerve fibers are damaged and start to sprout, causing ectopic firing, and as tumors grow in size they activate mechanoreceptors. Aside from bisphosphonates and antibody therapy, CIBP is treated by a range of NSAIDs to strong opioids, but remains undertreated in one-third of cases. This chapter discusses the accompanying CIBP of bone tumors,
