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Intrathecal implants of adrenal chromaffin cells are known to release analgesic substances such as catecholamines and opioid peptides. In the present study, bovine chromaffin cells were encapsulated in a permselective polymer membrane which protects the cells from the host immune system and allows grafting of xenogeneic cells without immunosuppression. The effects of such implants were evaluated on the pain behavior resulting from a chronic constrictive injury (CCI) of the rat sciatic nerve. Sprague-Dawley rats with a unilateral lesion were implanted in the lumbar subarachnoid space and tested for mechanical/thermal allodynia and hyperalgesia. A significant reduction in pain was observed after mechanical non-nociceptive stimulation in animals implanted with chromaffin cells. Furthermore, these animals showed decreased signs of spontaneous pain. However, response to thermal non-noxious stimuli or to painful mechanical stimuli was not significantly decreased. Abundant clusters of viable chromaffin cells intensely labeled with the anti-tyrosine hydroxylase antibodies were observed in the retrieved implants. These results establish the analgesic efficacy of intrathecal encapsulated chromaffin cells in a chronic pain model of nerve injury. Immunoprotected allo- or xenogeneic chromaffin cells acting as 'mini pumps' continuously delivering neuroactive substances could be a useful therapy for patients suffering from neuropathic pain.
Andrea Serino, Robert Leeb, Oliver Alan Kannape, Skander Mensi, Sylvain Cardin, Fabien Bourban, Alexis Dorier
Douglas Hanahan, Nadine Fournier, Krisztian Homicsko, Mélanie Louise Tichet, Agnieszka Alicja Chryplewicz, Jeremy Gilles Louis Guillot, Simge Yücel, Mohammad Sadegh Saghafinia, Inti Zlobec, Yuqing Xie, Dalya Ataca, Qiqun Zeng, Fleuriane Marie Tryskele Laurene Gallean, Peng Zhang, Lucine Christe