Intrathecal implants of microencapsulated xenogenic chromaffin cells provide a long-term source of analgesic substances

Abstract

Adrenal medullary chromaffin cells secrete several neuroactive substances including catecholamines and opioid peptides that produce analgesic effects in the central nervous system. This study was designed to investigate whether intrathecal microencapsulated chromaffin cells could release analgesic materials producing antiallodynic effects on the chronic neuropathic pain in rats induced by chronic constriction injury (CCI) of the sciatic nerve. Prior to intrathecal implantation, chromaffin cells were encapsulated with alginate and poly-L-lysine to protect them from the host immune system. Behavior tests were performed before CCI, 1 week later, and at 4, 7, 14, 21, 28 days postimplantation. At the end of study, we performed cerebrospinal fluid (CSF) collection and implant retrieval. We observed that intrathecal implantation of encapsulated xenogenic chromaffin cells reduced the mechanical and cold allodynia in a model of neuropathic pain. CSF levels of catecholamines and metenkephalin in the rats that received implants were higher than the controls. In addition, we observed chronic survival of implants. These results suggested that intrathecal microencapsulated chromaffin cells may represent a new approach to chronic neuropathic pain management.