How Do You Determine If a Patient has Opioid-Induced Hyperalgesia?
Chronic opioid exposure can lead to opioid tolerance or opioid-induced hyperalgesia. They are two distinct phenomena that make pain difficult to control. Clinical differentiation between opioid tolerence and opioid-induced hyperalgesia can be challanging.
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Dalia H. Elmofty
Case
Question
A 40-year-old Caucasian female with metastatic rectal cancer underwent an abdominoperineal resection with posterior vaginectomy and flap reconstruction. She had undergone several rounds of chemotherapy and radiation before the procedure. The patient complains of severe, constant, rectal pain, worse with bowel movements and sitting. She is taking morphine sulfate extended release 200 mg twice daily. Because of sudden, severe onset of pelvic pain and right foot drop, she has been hospitalized. Computed tomographic scan revealed extensive spread of cancer in the abdominal and pelvic cavity with tumor compressing the lumbosacral plexus. Surgery, chemotherapy, and radiation were no longer options. Efforts to control her pain with escalating doses of oral and intravenous opioids were unsuccessful. Because of this lack of efficacy, a decision was made to begin a trial of intrathecal infusion with morphine, which was titrated over several days without pain relief. Additional oral and intravenous hydromorphone was administered for breakthrough pain. Over the next 24 h, her pain continued to escalate. At this point, she was receiving 30 mg per day of intrathecal morphine. Her pain and suffering were extreme. She complained of whole body pain, accompanied by episodes of agitation and confusion. You suspect that the patient may be suffering from opioid-induced hyperalgesia. You recommend reducing the opioid dosage and starting a sub-anesthetic, low-dose ketamine infusion because, as an N-methyl-D-aspartate (NMDA) receptor antagonist, it may offset the hyperalgesia. Your hospice/palliative care colleague believes this is a case of opioid-induced tolerance and prefers to continue to escalate the dose of intrathecal morphine. He states that there is insufficient evidence to support the existence of opioid-induced hyperalgesia in humans.
Does opioid-induced hyperalgesia exist or is it a hypothetical phenomenon? PRO: The history of medicine considers the existence of opioid-induced hyperalgesia. In the 1870s, Sir Thomas Clifford Allbutt, an English physician, questioned the benefits of intravenous morphine for pain control. He said, “Does morphia tend to encourage the very pain it pretends to relieve?” Opioid-induced hyperalgesia has become an area of interest, and more research is being conducted to understand the disorder. In this paradoxical phenomenon, the intensity of pain is increased rather than decreased in response to opioid administration. Hyperalgesia is defined by the International Association for the Study of Pain as increased pain from a normally painful stimulus. Allodynia is pain from a stimulus that does not normally provoke pain. Both hyperalgesia and allodynia indicate a hypersensitized state in patients with opioid-induced hyperalgesia. Studies have shown the existence of hyperalgesia in postoperative pain, cancer pain, chronic nonmalignant pain, and in experiments on healthy subjects [1]. CON: Evidence to support opioid-induced hyperalgesia in humans is insufficient. In the st
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