Alleviation of neuropathic pain symptoms by xenogeneic chromaffin cell grafts in the spinal subarachnoid space

Aldric T. Hama, Jacqueline Sagen

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


Recent data have suggested that adrenal medullary tissue allografts in the spinal cord subarachnoid space, by releasing catecholamines and opioid peptides, attenuate responses to various acute noxious stimuli and chronic pain-related behaviors. However, the application of this approach is limited by the low availability of allogeneic donor material. Alternatively, chromaffin cells from xenogeneic sources such as the bovine adrenal medulla are plentiful and simple to extract. The goal of this study was to evaluate the potential for bovine chromaffin cell xenografts in the rat spinal subarachnoid space to alleviate chronic pain. This was assessed in an animal model of neuropathic pain induced by loose ligation of the sciatic nerve, which resulted in allodynia, hyperalgesia, and skin temperature abnormalities. Two weeks after nerve injury, animals were implanted with either isolated bovine chromaffin cells or control bovine adrenal fibroblasts in the spinal subarachnoid space at the level of lumbar enlargement and immunosuppressed with cyclosporine A. In animals with chromaffin cell implants, but not fibroblast implants, both cold allodynia and thermal hyperalgesia were markedly reduced or eliminated as early as 1 week following implantation and hind paw skin temperature asymmetry was also normalized. These beneficial effects were maintained without decrement or apparent tolerance for the 9 week course of the symptomology. The analgesic effects of chromaffin cell grafts were partially attenuated following i.t. injection of naloxone and phentolamine separately and in combination, suggesting involvement of spinal opioid and α-adrenergic receptors. Following termination of behavioral studies, immunocytochemical analysis revealed robust survival of chromaffin cells in the implants. These results demonstrate that chromaffin cell xenografts may be effective in alleviating pain of neurogenic origin.

Original languageEnglish (US)
Pages (from-to)183-193
Number of pages11
JournalBrain research
Issue number1-2
StatePublished - Jul 18 1994
Externally publishedYes


  • Chromaffin cell
  • Hyperalgesia
  • Naloxone
  • Neural transplantation
  • Peripheral neuropathy
  • Phentolamine

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)


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