Intrathecal allograft of chromaffin cells for intractable pain treatment: A model for understanding CNS tolerance mechanisms in humans

Abstract

GRAFTS of adrenal medulla tissue or chromaffin cells have been proposed for the treatment of Parkinson's disease and chronic pain. 1,2 It has been shown that transplanted chromaffin cells can release analgesic neuroactive substances, including catecholamines, opioid peptides, metenkephalin, somatostatin, and so on. 3,4 The subarachnoid space is a favored site for the allograft since the phenomenon of immunologic privilege is classically related to the central nervous system (CNS). 5 Despite this privilege phenomenon, grafts implanted in the CNS are not always tolerated, although the frequency of rejection is lower, for example, than that for skin-grafting. 6 The course of the local cellular immunologic response following the transplantation of xenogeneic or allogeneic grafts into the CNS have generally been followed in animal models. Few studies have been reported in this area on humans. Our study was carried out in an attempt to identify the cellular immune response in the cerebrospinal fluid (CSF) after intrathecal grafts of chromaffin cells recovered from brain dead donors for the treatment of chronic pain in end-stage cancer patients. Our study took place between June 1993 and April 1996, with the consent of the Regional Ethical Committee and the Regional People Protection Committee, Toulouse I, in accordance with French Bioethics Law. This study population comprised 12 end-stage cancer patients; 10 had received one graft only, and a second graft had been performed in 2 patients. All the patients experienced chronic cancer-related pain which had been treated orally first and then by intrathecally-administered morphine prior the start of the study. The intrathecally-administered morphine continued for the duration of the study. A very short course of cyclosporin was given during the first 2 weeks following the transplantation. This immunosuppressive treatment commenced on the day the graft was performed (day 0).