Department of Palliative Medicine, Marshfield Clinic, Marshfield, WI. A history of an escalating chronic intractable pain in a patient with cryoglobulinemia, vasculitis, and severe cutaneous ulcerations is presented. A strategy of progressive, multi-agent, N-methyl-D-aspartate-receptor (NMDA-R) blockade that resulted in adequate pain control and a three-fold reduction in opioid consumption is described. Diagnostic process of neuropathic pain and the role of NMDA-R in the development of hyperalgesia are briefly reviewed. Thereafter, existing clinical literature describing the use of Ketamine, a major NMDA-R antagonist for management of malignant pain, is reviewed. Lastly, evidence-based original protocol for intravenous adjuvant Ketamine analgesia for severe cancer pain is presented. PMID: 17525784 [PubMed - in process]