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. Ascending Tracts Descending Tracts Cortex Midbrain Medulla Spinal Cord Thalamus Pons Peripheral and Central Pathways for Pain 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

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 a)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 b)Pain syndromes associated with cancer therapy 19% of pain problems in inpatient population and 25% in outpatient population c)Pain unrelated to cancer or therapy Approx. 3% of inpatients have pain unrelated to their cancer and 10% in outpatient population d)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