Update on cellular transplantation into the CNS as a novel therapy for chronic pain

Abstract

The transplantation of cells that secrete neuroactive substances with analgesic properties into the CNS is a novel method that challenges current approaches in treating chronic pain. This review covers pre-clinical and clinical studies from both allogeneic and xenogeneic sources. One cell source that has been utilized successfully is the adrenal chromaffin cell, since such cells constitutively release catecholamines, opioid peptides, and neurotrophic factors; release can be augmented with nicotine. Other graft sources include AtT-20 and B-16 cell lines which release enkephalins and catecholamines, respectively. For grafting in rodents, adrenal medullary tissue pieces are transplanted to the subarachnoid space. Chromaffin cell transplants can decrease pain sensitivity in normal rats using standard acute pain tests (paw-pinch, hot-plate, and tail-flick). In addition, transplants can restore normal pain thresholds in rodent models of chronic pain (formalin, adjuvant-induced arthritis, and sciatic-nerve tie) which closely similate the pathologies of human chronic pain conditions. Xenografts have been studied due to concerns that future application for human pain may be limited by donor availability. Despite immune privileges of the CNS, xenografts require at least short-term immunosuppression to obtain a viable graft. Cell encapsulation is one method of sustaining a xenograft (in rat and human hosts) while circumventing the need for immunosuppression. Clinical studies have been initiated for terminal cancer patients with promising results as assessed by markedly reduced narcotic intake, visual analog scale ratings, and increased CSF levels of catecholamines and met-enkephalin.