Analgesic effects of adrenal chromaffin cell transplants

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DESCRIPTION (provided by applicant): Transplantation of same species (allogeneic) chromaffin cells from the adrenal gland to the central nervous system has been widely shown to produce profound analgesia. This was first demonstrated in rats, but the technique has also successfully alleviated pain in more than 35 cancer patients. After spinal transplant, these patients show a distinct increase in spinal fluid levels of endogenous opioids and catecholamines, with a robust analgesic effect. The effects last many months and are accompanied by a definite inhibition in the development of tolerance to exogenous opiate analgesic drugs, a common problem with these patients. Thus transplantation of allogeneic chromaffin cell graft clearly shows potential as a means of treating chronic, intractable pain. Unfortunately, transplantation of allogeneic chromaffin cells has limitations similar to other transplants, e.g., the availability of suitable human tissue. To meet this challenge, xenogeneic (cross-species) transplants have demonstrated clear analgesic effects in rodents. However, there are significant roadblocks in transferring this method to humans. Earlier work indicates that purification of bovine or porcine cells minimizes rejection potential in rats. Preliminary work also indicates that embedding cells in a collagen matrix may improve their viability and analgesic potential. However, prior to attempting cross-species transplants in humans, it is critical to examine these effects in detail in species that are much closer to man immunologically and neurophysiologically, namely nonhuman primates. Thus, the work proposed here entails investigations designed to optimize the analgesic potential of xenogeneic chromaffin cells when transplanted into primates. The experiments will determine, in vitro, the effects of seeding cells in collagen matrices on the viability, integrity, and rejection potential of purified chromaffin cells. In vivo experiments will take these preparations to monkeys, investigating cell-dose dependence and collagen matrix effects on the analgesic efficacy of xenogeneic transplants. In this way, we hope to move much closer to the capability of treating patients with severe chronic pain with a novel treatment that is long-lasting and not only does not precipitate tolerance, but also appears to impede its development.