open access

Vol 11, No 1 (2017)
Review paper
Published online: 2017-09-20
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Bone pain in cancer patients — what is known about its pathomechanisms?

Renata Zajączkowska, Wojciech Leppert, Jerzy Wordliczek
Medycyna Paliatywna w Praktyce 2017;11(1):17-23.

open access

Vol 11, No 1 (2017)
Review articles
Published online: 2017-09-20

Abstract

Bone is after lung and liver the third most common site of metastatic disease in cancer patients. Many cancer types including breast, prostate, lung, and kidney have a strong predilection to metastasize to bones, which induce pain, pathologic skeletal fractures, spinal instability and compression of the spinal cord or others structures of nervous system, hypercalcemia, decreased mobility and increased mortality. Bone cancer pain is a kind of chronic pain with unique and complicated pathophysiology with both a nociceptive and neuropathic component. The nociceptive component of cancer bone pain is driven by the release of pronociceptive substances produced by tumor and their stromal cells, acidosis caused by bone-destroying osteoclasts, and mechanical destabilization and fracture of the bone. The neuropathic component of cancer bone pain is induced by tumor cell growth which injures and destroys structures of nervous system and distal ends of nerve fibers that normally innervate the bone, by release factors that sensitize and activate bone nociceptors, and release growth factors that drive pathological ectopic sprouting of both sensory and sympathetic nerve fibers and neuroma formation. These newly sprouted nerve fibers which can be observed in the periosteum, mineralized bone, and marrow have a unique morphology, organization, and a high density that is never observed in normal bone. All described mechanisms contribute to peripheral and central sensitization observed in cancer patient with bone metastases.

Abstract

Bone is after lung and liver the third most common site of metastatic disease in cancer patients. Many cancer types including breast, prostate, lung, and kidney have a strong predilection to metastasize to bones, which induce pain, pathologic skeletal fractures, spinal instability and compression of the spinal cord or others structures of nervous system, hypercalcemia, decreased mobility and increased mortality. Bone cancer pain is a kind of chronic pain with unique and complicated pathophysiology with both a nociceptive and neuropathic component. The nociceptive component of cancer bone pain is driven by the release of pronociceptive substances produced by tumor and their stromal cells, acidosis caused by bone-destroying osteoclasts, and mechanical destabilization and fracture of the bone. The neuropathic component of cancer bone pain is induced by tumor cell growth which injures and destroys structures of nervous system and distal ends of nerve fibers that normally innervate the bone, by release factors that sensitize and activate bone nociceptors, and release growth factors that drive pathological ectopic sprouting of both sensory and sympathetic nerve fibers and neuroma formation. These newly sprouted nerve fibers which can be observed in the periosteum, mineralized bone, and marrow have a unique morphology, organization, and a high density that is never observed in normal bone. All described mechanisms contribute to peripheral and central sensitization observed in cancer patient with bone metastases.

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Keywords

bone pain, treatment, pathophysiology, bone metastases

About this article
Title

Bone pain in cancer patients — what is known about its pathomechanisms?

Journal

Palliative Medicine in Practice

Issue

Vol 11, No 1 (2017)

Article type

Review paper

Pages

17-23

Published online

2017-09-20

Bibliographic record

Medycyna Paliatywna w Praktyce 2017;11(1):17-23.

Keywords

bone pain
treatment
pathophysiology
bone metastases

Authors

Renata Zajączkowska
Wojciech Leppert
Jerzy Wordliczek

References (21)
  1. Zhu XC, Zhang JL, Ge CT, et al. Advances in cancer pain from bone metastasis. Drug Des Devel Ther. 2015; 9: 4239–4245.
  2. Delaney A, Fleetwood-Walker SM, Colvin LA, et al. Translational medicine: cancer pain mechanisms and management. Br J Anaesth. 2008; 101(1): 87–94.
  3. Roodman GD. Mechanisms of bone metastasis. N Engl J Med. 2004; 350(16): 1655–1664.
  4. Buga S, Sarria JE. The management of pain in metastatic bone disease. Cancer Control. 2012; 19(2): 154–166.
  5. Porter A, David M. Palliative care for bone, spinal cord, brain and liver metastases. W: Gunderson LL, Tepper JE red. Clinical radiation oncology Elsevier. ; 2007: 437–457.
  6. Smith HS. Painful bone metastases. Ann Palliat Med. 2012; 1: 14–31.
  7. Greenberg AJ, Rajkumar SV, Therneau TM, et al. Relationship between initial clinical presentation and the molecular cytogenetic classification of myeloma. Leukemia. 2014; 28(2): 398–403.
  8. Middlemiss T, Laird BJA, Fallon MT. Mechanisms of cancer-induced bone pain. Clin Oncol (R Coll Radiol). 2011; 23(6): 387–392.
  9. Li BT, Wong MH, Pavlakis N. Treatment and Prevention of Bone Metastases from Breast Cancer: A Comprehensive Review of Evidence for Clinical Practice. J Clin Med. 2014; 3(1): 1–24.
  10. Portenoy RK, Forbes K, Lussier D, et al. Difficult pain problems: an integrated approach. In: Doyle D, et al. ed. Oxford textbook of palliative medicine. Oxford University Press;, Oxford 2004: 438–458.
  11. Colvin L, Fallon M. Challenges in cancer pain management--bone pain. Eur J Cancer. 2008; 44(8): 1083–1090.
  12. Falk S, Dickenson AH. Pain and nociception: mechanisms of cancer-induced bone pain. J Clin Oncol. 2014; 32(16): 1647–1654.
  13. Dushyanthen S, Cossigny DAF, Quan GMY. The osteoblastic and osteoclastic interactions in spinal metastases secondary to prostate cancer. Cancer Growth Metastasis. 2013; 6: 61–80.
  14. Mantyh PW. Bone cancer pain: from mechanism to therapy. Curr Opin Support Palliat Care. 2014; 8(2): 83–90.
  15. Yoneda T, Hiasa M, Nagata Y, et al. Acidic microenvironment and bone pain in cancer-colonized bone. BoneKEy Reports. 2015; 4.
  16. Jimenez-Andrade JM, Bloom AP, Stake JI, et al. Pathological sprouting of adult nociceptors in chronic prostate cancer-induced bone pain. J Neurosci. 2010; 30(44): 14649–14656.
  17. Bloom AP, Jimenez-Andrade JM, Taylor RN, et al. Breast cancer-induced bone remodeling, skeletal pain, and sprouting of sensory nerve fibers. J Pain. 2011; 12(6): 698–711.
  18. Wordliczek J, Zajaczkowska R. Mechanisms in Cancer Pain. Cancer Pain. 2013: 47–70.
  19. Mantyh WG, Jimenez-Andrade JM, Stake JI, et al. Blockade of nerve sprouting and neuroma formation markedly attenuates the development of late stage cancer pain. Neuroscience. 2010; 171(2): 588–598.
  20. Wordliczek J, Zajączkowska R. Mechanizmy bólu u chorego na nowotwór. In: Wordliczek J, Dobrogowski J. ed. TYTUŁ. PZWL, Warszawa : 641–661.
  21. Leppert W, Nowakowska E. Rola radioterapii w leczeniu objawów zaawansowanej choroby nowotworowej. Med Paliat Prakt. 2008; 2: 33–47.

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