TRANSPLANTS OF IMMUNOLOGICALLY ISOLATED XENOGENEIC CHROMAFFIN CELLS PROVIDE A LONG-TERM SOURCE OF PAIN-REDUCING NEUROACTIVE SUBSTANCES

Adrenal medullary chromaffin cells are a potential source of neuroacti ve substances for transplantation into the CNS to alleviate neurochemi cal deficits. In particular, work in our laboratory has suggested that adrenal medullary transplants in the spinal subarachnoid space can al leviate pain by providing sustained local delivery of catecholamines a nd opioid peptides. One of the major limitations for clinical applicat ion of neural transplantation is the availability of donor material in sufficient quantities. This limitation may be overcome by the use of xenogeneic donors if long-term graft rejection can be prevented. The p urpose of this study was to assess whether xenogeneic chromaffin cells immunologically isolated by semipermeable membranes could survive and continue to reduce pain when transplanted into the CNS. Isolated bovi ne chromaffin cells were encapsulated by semipermeable polymer membran es and implanted into the rat spinal subarachnoid space. Pain sensitiv ity was assessed at several intervals up to 3 months following implant ation. Results indicated that encapsulated bovine chromaffin cell impl ants, but not empty control capsules, could repeatedly reduce pain sen sitivity with nicotine stimulation for the duration of the study. This response was dose related, indicating that pharmacologic integrity of the transplanted chromaffin cells is retained. The analgesia induced by encapsulated chromaffin cell implants could be attenuated by the op iate antagonist naloxone and the alpha-adrenergic antagonist phentolam ine, suggesting the involvement of both opioid peptides and catecholam ines in mediating this response. In addition, in vitro neurochemical s tudies of recultured capsules revealed sustained release of Met-enkeph alin and catecholamines from encapsulated cells 3 months following imp lantation into the spinal subarachnoid space. The results of this stud y suggest that immunologically isolated xenogeneic cells can provide a long-term source of neuroactive substances for the alleviation of pai n.