Intrathecal implants of bovine chromaffin cells alleviate mechanical allodynia in a rat model of neuropathic pain.
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.
Gene Therapy Center and Surgical Research Division, Centre Hospitalier Universitaire Vaudois, Lausanne University Medical School, Switzerland.
I
I
Décosterd
E
E
Buchser
N
N
Gilliard
J
J
Saydoff
A D
AD
Zurn
P
P
Aebischer
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D017690:Cell Transplantation; D019439:Chromaffin Cells / Q000502:physiology*; D004744:Enkephalin, Methionine / Q000378:metabolism; D008297:Male; D009479:Neuropeptides / Q000378:metabolism; D010146:Pain / Q000209:etiology / Q000473:pathology; D059408:Pain Management; D010147:Pain Measurement; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000473:pathology; D013116:Spinal Cord / Q000502:physiology*; D014183:Transplantation, Heterologous
D002395:Catecholamines; D009479:Neuropeptides; D004744:Enkephalin, Methionine