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Cancer Pain – Causes & Challenges

Cancer Pain – Causes & Challenges. The Inflammatory Nature of Cancer Pain Pawandeep Brar Palliative Care Physician Temmy Latner Centre for Palliative Care Mount Sinai Hospital . Objectives . Mechanisms of Cancer Pain Inflammatory Markers Role in Cancer Pain . Mechanisms of Cancer Pain.

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Cancer Pain – Causes & Challenges

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  1. Cancer Pain – Causes & Challenges The Inflammatory Nature of Cancer Pain PawandeepBrar Palliative Care Physician TemmyLatner Centre for Palliative Care Mount Sinai Hospital

  2. Objectives • Mechanisms of Cancer Pain • Inflammatory Markers Role in Cancer Pain

  3. Mechanisms of Cancer Pain • Clinical questions do arise though when one considers the mechanisms of cancer pain: • Why are only 25% of bone metastases painful? • Why do patients with similar disease present with very different pain? • Why doesn’t every patient respond to opioids?

  4. Mechanisms of Cancer Pain • Need to think of mechanisms of: • Inflammation-local, CNS • Neuropathy, CNS changes • Visceral/Somatic • Also need to think of: • Cancer treatment related pain particularly CIPN • Co-morbidities • Psychosocial Factors • Genetic factors

  5. Cytokines and Cancer Pain • Progression of cancer  variety of local changes, including chemotaxis of immune cells (e.g. macrophages, T cells, dendritic cells) & production of pro-inflammatory agents • Several of these agents play major roles in cell proliferation, angiogenesis, invasion & metastases

  6. Cytokines and Cancer Pain • Included are pro-inflammatory cytokine gene products that can be pro-nociceptive as well • Tumour necrosis factor • Interleukins • metalloproteases

  7. Tumor Necrosis Factor • TNFα • Considerable evidence of its role in pain • Initiates cascade of inflammatory responses • Produced by tumours hyperalgesia& nocioceptorsensitization neuronal discharge in DRG & adjacent neurons

  8. Tumor Necrosis Factor • Increased Levels of TNF play a role in bony mets pain and neuropathic pain • Activates channels that stimulate an acidic environment of bone mets • Increase TNF levels associated with overall neuronal hyperexcitability and increase neuropathic pain

  9. Interleukins • Interleukin-1β • Produced by macrophages, glial cells, sympathetic & sensory neurons • Also produced by tumour cells • Increased Interleukin 1B levels • Increase dorsal horn excitablility • Inhibition of tonic neurons • Contribute to central sensitization associated with chronic pain

  10. Interleukins • IL 6 • Involved in generation of neuropathic pain • Directly regulates sensitivity of nocioceptors

  11. Metalloproteases • Metalloproteases • roles in neuroinflammation and are involved in a wide range of CNS diseases • Matrix metalloproteases (MMP) family of enzymes expressed by malignant cells • Facilitate tumour invasion, metastasis, angiogenesis • MMPs implicated in neuropathic pain particularly CINP

  12. How does this change current pain management strategies? • Reality that we have no specific treatments to target cytokines in pain • What all this tells us is that cancer pain is complex & mostly an inflammatory event • Specific drugs being developed to counter effects of cytokines on pain & tumor growth

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