Analgesia induced by transplantation of encapsulated tumor cells secreting beta-endorphin.

Abstract

The purpose of this study was to assess whether xenogeneic tumor cells immunologically isolated in polymer capsules could survive and continue to reduce pain when transplanted into the cerebrospinal fluid (CSF) of rats. The mouse tumor cell lines AtT-20 and gene-transfected Neuro2A, which secrete beta-endorphin, were enclosed in polymer capsules at a density of 5 x 10(6) cells/ml and transplanted into the spinal CSF space of the occipitoatlantal junction in male Sprague-Dawley rats. The analgesiometric tests (tail pinch, hot plate, and electrical stimulation) showed that the five rats with encapsulated AtT-20 or Neuro2A (eight rats) were significantly less sensitive to pain after transplantation than the eight control animals (analysis of variance; p < 0.05). The analgesia induced by encapsulated cells secreting beta-endorphin could be attenuated by the opiate antagonist naloxone, which suggested the involvement of opiate in mediating this response. Morphological study revealed that the cells in polymer capsules survived 1 month after transplantation in the CSF space. In vitro experiments with cultured capsules showed that both encapsulated AtT-20 and Neuro2A secrete peptide for 1 month. The results of this study suggest that immunologically isolated xenogeneic tumor cells can secrete opiate in the CSF space, and this method may be applied to the treatment of cancer pain.