Cancer induced bone pain

Dr Catherine Urch
Lead Consultant in Palliative Medicine,
Imperial College Healthcare NHS Trust

Biography
Dr. Urch trained in Palliative Medicine at Trinity Hospice, moving to St. Thomas’ then Guy’s Hospital.  She then completed her PhD at UCL, investigating the development of pain pathways.  Her post-doctoral work has focused on the patho-physiology of the spinal cord pain pathways in cancer-induced bone pain.  As a consultant she has worked at UCLH, the Royal Marsden and Hospitals.  From 2004 she was consultant at Royal Brompton and St Mary’s Hospitals allowing her interest in SPC in non-malignant diseases and treatment of non-malignant pain to develop.  From 2009 she has been lead consultant and Hon SL at Imperial College, establishing a team across all three hospital sites, developing the undergraduate education curriculum and continuing laboratory based research at UCL.

Abstract
The understanding of the mechanisms of bone pain has developed hugely in the last 10 years or so.  From the concept that pain only arose once the periostium was breached, we have moved to an understanding of primary afferent transmission from within the bone itself.  An alteration in the preparation (demineralisation) of bones for immunocytochemistry allowed the presence of highly innervated bone trabeculae as well as the periostium to be revealed.  Neural innervation is predominately peptidergic C fibres and SNS which follow vascular channels and trabeculae to the bone marrow.  The C fibres have numerous receptors including TrkA / NGF, Bradykinin 1, endothelin A, acid sensing ion channels, P2X and many more.  Ready to sense, transduce and transmit any change in the bone milleau.  As can be seen from the above limited array altered pH, as around activated osteoclasts, inflammatory response and presence of dead cells will all stimulate C fibres.  The central response to primary afferent activation and the more interesting question as to inhibition of the majority of bone destruction has only recently explored.

Cancer induced bone pain (CIBP) will be discussed to illustrate the recent changes in understanding in bone pain.  Clinically CIBP is a common sequelae of disease progression.  Pain has been reported to occur in up to 80% of cases of metastatic bone disease, and correlates with reduced quality of life, increased depression, and reduced performance status.  Cancer induced bone pain (CIBP) is a clinical problem with reports of 50-90% of patients attending either outpatient pain clinics or requiring hospice admission reporting pain on movement.

One model for investigating bone pain is the limited cancer–induced-bone pain model.  The models are all reproducible, consistent and appear to parallel aspects of the clinical situation.  From these models investigations into the mechanisms (peripheral and central) of the pathophysiology have revealed startling results.  These models will be discussed as an example of somatic pain, illustrating the complexity and uniqueness of cancer pain.

Suggested reading:
Mantyh, P. W., Clohisy, D. R., Koltzenburg, M. and Hunt, S. P. Molecular mechanisms of cancer pain (2002) Nat Rev Cancer, 2, 201-9.

Portenoy, R. K. and Hagen, N. A. Breakthrough pain: definition, prevalence and characteristics (1990) Pain, 41, 273-281.

Urch, C. E., Donovan-Rodriguez, T. and Dickenson, A. H. Alterations in dorsal horn neurones in a rat model of cancer-induced bone pain (2003) Pain, 106, 347-56.

Urch, C. The pathophysiology of cancer-induced bone pain: current understanding. (2004) Palliative Medicine 18, 267-274

Watkins, L. R., Milligan, E. D. and Maier, S. F. Glial activation: a driving force for pathological pain (2001) Trends Neurosci, 24, 450-5.