Clinical evidence that ketmaine (an NMDA inhibitor) may reverse analgesic tolerance to opioids in cases of intractable cancer pain

Tolerance to the analgesic effects of morphine complicates the management of patients with cancer pain, as the necessity for increasing doses of opioids predisposes the patient to intolerable side effects such as nausea, constipation and sedation. Recent work by Dickenson (1994) and others has provided evidence for an involvement of the N – methyl –D - aspartate (NMDA) receptor in inflammatory pain, neuropathic pain, allodynia and ischaemic pain. The co-administration of NMDA inhibitors such as Ketamine and Dextromethorphan with opioids has been demonstrated by Tiseo et al (1994) and others to reverse the development of tolerance to the analgesic effects of morphine in rodents. Limited clinical application of these findings is evident from the literature. This paper will describe 2 recent cases of intractable cancer pain at our hospital where systemic co-administration of morphine and ketamine resulted in greatly reduced opioid requirements, a corresponding decrease in opioid induced side effects, and satisfactory patient outcomes. Further application of this combination is planned, and its significance in chronic pain as well as cancer pain warrants further investigation.