| Pain related to the underlying disease |
| Cancer progression (eg, new fracture at site of known bone metastases) |
| New onset of specific etiologies of pain (eg, neuropathic pain, skin ulceration, rectal tenesmus, myalgia) that are known to be less responsive to systemic opioids or opioid monotherapy |
| Psychological/spiritual pain related to the experience of an end stage illness (existential pain of impending death) |
| Opioid pharmacology/technical problems |
| Opioid tolerance (eg, rapid dose escalation with no analgesic effect) |
| Dose-limiting opioid toxicity (eg, sedation, delirium, hyperalgesia, nausea) |
| Poor oral absorption (for oral medications) or skin absorption (eg, transdermal patch adhesive failure) |
| Pump, needle, or catheter problems (intravenous, subcutaneous, or spinal opioids) |
| Pain unrelated to the primary disease process |
| Worsening of a preexisting noncancer pain syndrome (eg, diabetic neuropathy) |
| New noncancer pain syndrome (eg, dental abscess) |
| Other psychological problems |
| Depression, anxiety, somatization, hypochondria, factitious disorders |
| Dementia and delirium both can effect a patient's report of and experience of pain |
| Opioid substance use disorders or opioid diversion |
