Management of intractable cancer pain: from intrathecal morphine to chromaffin cell allograft

The durable effectiveness of intrathecal morphine administration is well es tablished for the management of intractable cancer pain, after failure of s ystemic opioids, secondary to the persistence of non-reversible undesirable side effects. Many patients are referred to late in the disease course. Th is conservative method to control pain of malignant origin must not be rese rved for last resort treatment for terminal patients. Intra-cerebro-ventric ular morphine administration is a very effective and generally safe method for controlling intractable cancer pain. Because of the chronic implantatio n of an intra-ventricular catheter this method is somewhat invasive. Its in dications remain a simple and effective alternative when the topography of nociceptive pain is diffuse or cephalic. In clinical practice, intrathecal and/or intra-cerebro-ventricular administration of opioids is limited by co st, the need for specialized maintenance and mechanical malfunctions if imp lantable drug delivery systems, or by the risk of bacterial contamination a nd ambulatory constraints when repeated daily injections via an intrathecal access port are used. To answer these limitations, cell therapy using intr athecal chromaffin cell allograft is a promising approach for the managemen t of cancer pain refractory to traditional drug therapy and pain lesion sur gery. The basic rationale and preclinical studies on experimental pain mode ls have enabled starting prospective clinical trials. Prior to transplantat ion, handling and preparation of the chromaffin tissue is critical for allo graft viability. The initial results of clinical trials with human chromaff in cell grafts from intractable cancer pain have reported long-lasting pain relief, in correlation with met-enkephalin release into the CSF. Convincin g evidence will require controlled studies. The limitations of this innovat ive cell therapy and especially the lack of human adrenal gland availabilit y point to the need for new sources of cells. Perspectives include xenogeni c or engineered cell lines.