Cancer Pain Syndromes Craig D. Blinderman, MD, MA Co-Director, MGH Cancer Pain Clinic MGH Palliative Care Service

1. Cancer Pain Syndromes Craig D. Blinderman, MD, MA Co-Director, MGH Cancer Pain Clinic MGH Palliative Care Service

2. Objectives • Review the definition of pain and basic pathophysiology • Review the common causes of pain in cancer patients • Review approach to managing pain

3. Defining Pain • Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Merskey, H., Bogduk, N, ed. Classification of Chronic Pain, Second Edition. IASP Task Force on Taxonomy. 1994, IASP Press: Seattle. 209-214.

4. Taxonomy of Pain • Classification may be based on: • Anatomy • Body System • Temporal Characteristics • Severity • Etiology • Pathophysiology • Defined pain syndromes

5. Taxonomy of Pain • Clinically, it is useful to determine both the etiology and inferred pathophysiology in the assessment of the pain complaint, as this may suggest the use of specific therapies.

6. Taxonomy of Pain • Nociceptive • Somatic • Visceral • Neuropathic • Psychogenic • Idiopathic

7. Nociceptive Pain • Nociceptive somatic pain • Sustained predominantly by tissue injury or inflammation. • Described as sharp, aching, stabbing, throbbing or pressure-like. • Nociceptive visceral pain • Poorly localized; described as crampy pain (e.g. obstruction of hollow viscus), or as aching and stabbing (e.g. pain secondary to splenomegaly).

8. Neuropathic Pain • Sustained by abnormal somatosensory processing in the PNS or CNS. • Typically, described as “burning,” “shock-like,” “electrical.” • May be paroxysmal in nature. • On physical examination, patients may have allodynia (pain induced by non-painful stimuli) and hyperalgesia (increased perception of painful stimuli).

9. Psychogenic Pain • Refers to pain that is believed to be sustained predominantly by psychological factors. • Rare in the cancer population.

10. Idiopathic Pain • In the absence of evidence sufficient to label pain as either nociceptive or neuropathic, we may use the term “idiopathic.” • In patients with cancer, this term should lead to additional workup and a search for an underlying etiology and pathophysiology.

11. Basic Pathophysiology of Pain Transduction • Conversion of thermal, chemical, mechanical stimulus to electrical activity at nociceptor • Na channels Conduction • Passage of action potential along the first order neuron to dorsal horn of spinal cord Transmission • Transfer and modulation of input from one neuron to another • Substance P, Glutamate, Brain derived neurotropic factor • Inhibitory interneurons Perception • Awareness and meaning of pain Modulation • Descending pathways inhibit transmission of nociceptive impulses • e.g. Periaqueductal grey matter in midbrain-->nucleus raphae in medulla • Norepinephrine, serotonin, endogenous opioids

12. Peripheral and Central Pathways for Pain Ascending Tracts Descending Tracts Cortex • Modulation • Descending pathways inhibit transmission of nociceptive impulses • Perception • Awareness and meaning of pain • Transmission • Transfer and modulation of input from one neuron to another • Conduction • Passage of action potential along the first order neuron to dorsal horn of spinal cord • Transduction • Conversion of thermal, chemical, mechanical stimulus to electrical activity at nociceptor Thalamus Midbrain Pons Medulla Spinal Cord

13. Cancer Pain Syndromes

14. Syndrome: Definition • A temporal and qualitative convergence of symptoms and signs, which conforms to a recognized pattern • Associated with distinct etiologies, pathophysiologies, and prognostic and therapeutic implications

15. Cancer Pain Syndromes • Related to tumor involvement • Accounts for 78% of pain problems in inpatient cancer population and 62% of outpatient cancer population in MSKCC survey • Metastatic bone disease, hollow viscous involvement and nerve compression or infiltration are most common causes • Pain syndromes associated with cancer therapy • 19% of pain problems in inpatient population and 25% in outpatient population • Pain unrelated to cancer or therapy • Approx. 3% of inpatients have pain unrelated to their cancer and 10% in outpatient population • Generalized pain in a dying cancer patient Foley, KM. Pain syndromes in patients with cancer. Oxford Textbook of Palliative Medicine, 3rd Ed..

16. Cancer Pain Syndromes: Temporal Patterns • Temporal Classification • Acute • Chronic • Breakthrough Pain

17. Acute Cancer Pain • Defined by a recent onset and a natural history characterized by transience. • May or may not be associated with overt pain behaviors. • Usually caused by diagnostic or therapeutic interventions

18. Causes of Acute Cancer Pain Diagnostic Interventions Acute postoperative pain Therapeutic interventions Analgesic Techniques Associated with chemotherapy Associated with radiotherapy Acute pain associated with hormonal therapy Acute pain associated with immunotherapy Acute pain associated with infection

19. Chronic Cancer Pain • Persists for one month or more beyond the usual course of an acute illness or injury • Most commonly due to direct effects of the tumor • Other causes: • Due to cancer therapy (15-25%) • Pathology unrelated to either the cancer or its treatment (5-15%)

20. Causes of Chronic Cancer Pain • Related to tumor involvement • Bone pain syndromes • Headache and Facial Pain • Tumor involvement of the peripheral nervous system • Visceral pain syndromes • In neuroendocrine tumors with liver involvement this may be a major source of pain • Somatic soft tissue pain syndromes • Paraneoplastic pain syndromes • Pain syndromes associated with cancer therapy • Post-chemotherapy pain syndromes • Chronic pain associated with hormonal therapy • Chronic post-surgical pain syndromes • Chronic post-radiation pain syndromes

21. Therapeutic strategy for cancer pain Non-pharmacological Modalities Cognitive behavioral interventions Massage, Physical Therapy Acupuncture Cutaneous techniques Radiation Therapy Surgery Interventional procedures Anesthetic techniques Pharmacotherapy Non-opioid analgesics NSAIDs Acetaminophen Dipyrone Opioid analgesics Codeine Morphine Oxycodone Fentanyl Hydromorphone Methadone Levorphanol Adjuvant analgesics Anticonvulsants Antidepressants Local anesthetic agents GABA agonists NMDA antagonists Others

22. Summary • Cancer Pain may be due to the affects of the tumor on viscera, nerves, bones and soft tissue. • Acute and Chronic Pain syndromes may also be due to the treatment of cancer • Effective management of cancer pain requires recognizing syndromes and their inferred pathophysiology