Editor-in-Chief: Kenneth D. Candido, MD
Opioid-induced hyperalgesia (OIH) is a condition of nociceptive sensitization caused by exposure to opioids, which is characterized by a paradoxical response whereby patients receiving opioids for the treatment of pain actually become more sensitive to pain as a direct result of opioid therapy. There is increasing evidence showing OIH presents a clinical challenge in acute, chronic, and cancer pain settings. Both clinical and animal studies have shown that glutamate N-methyl-D-aspartate (NMDA) receptors may play a key role in OIH, and pre-application of ketamine, an NMDA receptor antagonist, or a co-administration of ketamine and opioids, can prevent OIH. However, no reports have shown if ketamine can reverse OIH once it occurs.
We present a case of a 56-year-old male with a past medical history of DM-2 with severe peripheral neuropathy, recurrent osteomyelitis of the left foot, hypertension, dyslipidemia, chronic neck and right arm pain due to cervical spondylosis, status post 4 times of cervical discectomy, and fusion surgeries for cervical radiculopathy. He was prescribed to high doses of opioids (morphine 60 mg, orally every 8 hours and hydrocodone/acetaminophen 10/325 mg, as needed up to 4 times daily) for approximately 10 years. He underwent left below-knee amputation due to uncontrolled osteomyelitis. The patient had worsening stump pain with an increasing dose of opioids and phantom pain on post-operative day one, and he developed OIH, diagnosed as escalating pain reports with every opioid dose increase. A ketamine infusion (loading dose of 10 mg IV bolus, then 20 mg/hour IV infusion) was used after total cessation of opioid use for post-operative analgesia for 3 consecutive days and the patient recovered from his obvious OIH, with his stump pain and phantom pain well-controlled by opioid administration on post-operative day 5.
In our case, the blockage of NMDA receptors by ketamine might quickly restore the balance between opioid-dependent analgesic systems and NMDA-dependent pronociceptive systems by deactivation of the latter, which may help the patient recover from OIH rapidly. While it is possible that ketamine may help facilitate patients’ recovery from OIH in addition to its ability to prevent OIH, this clinical observation must be tested in future prospective studies.
Key words: Opioids, ketamine, opioid-induced hyperalgesia, phantom pain, post-amputation, post-operative