The environment presented by host tissue may influence cellular transplants in the CNS depending on injury or disease. Here we examined whether chronic pain alters cerebrospinal fluid (CSF), thereby enhancing the analgesic effect of transplanted adrenal cells. CSF samples were taken intracisternally from rats with neuropathic pain induced by chronic constriction injury of the sciatic nerve. The samples were applied to cultured bovine chromaffin-cell clusters while catecholamine release was measured by fast cyclic voltammetry. This caused marked and sustained elevations in catecholamine levels, compared to CSF from sham-operated controls, which were reversible by the nicotinic antagonist mecamylamine. These results suggest that chronic neuropathic pain produces increased CSF levels of secretogogues for chromaffin cells, and illustrates the importance of host microenvironmental factors in determining graft function. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.