Intrathecal xenogeneic chromaffin cell grafts reduce nociceptive behavior in a rodent tonic pain model.
Adrenal medullary chromaffin cells synthetize and secrete a combination of pain-reducing neuroactive compounds including catecholamines and opioid peptides. Previous reports have shown that implantation of chromaffin cells into the spinal subarachnoid space can reduce both acute and chronic pain in several animal models. We recently demonstrated that human chromaffin cell grafts in the cerebrospinal fluid (CSF) could alleviate intractable cancer pain after failure of systemic opiates. However, wider application of this approach was limited by the limited availability of allogeneic donor material. Alternatively, chromaffin cells from xenogeneic sources such as bovine adrenal medulla were successful in the experimental treatment of pain, but recent concern over risk of prion transmission precluded use of bovine grafts in human clinical trials. The objective of the present study was to investigate the possibility of developing a new xenogeneic porcine source of therapeutic chromaffin cells because this strategy is currently considered the safest for transplantation in man. In the present study, we report the isolation and the characterization of primary porcine chromaffin cells (PCC) compared to bovine cells. We show, for the first time, that these cells grafted in the rat subarachnoid space can attenuate pain-related behaviors as assessed by the formalin test, a model of tonic pain. Moreover, in addition to behavioral studies, immunohistochemical analysis revealed robust survival of chromaffin cells 35 days after transplantation. Taken together, these results support the concept that porcine chromaffin cells may offer an alternative xenogeneic cell source for transplants delivering pain-reducing neuroactive substances.
Sol
J C
JC
Laboratory of Pain and Cell Therapy, Rangueil Medical School, 31062 Toulouse, Cedex, France. jc_sol@hotmail.com
Sallerin
B
B
Larrue
S
S
Li
R Y
RY
Jozan
S
S
Tortosa
F
F
Mascott
C
C
Carraoue
F
F
Tafani
M
M
Lazorthes
Y
Y
D000313:Adrenal Medulla / Q000166:cytology; D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western / Q000379:methods; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000637:transplantation*; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism; D004195:Disease Models, Animal; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004744:Enkephalin, Methionine / Q000378:metabolism; D006085:Graft Survival / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009020:Morphine / Q000627:therapeutic use; D009294:Narcotics / Q000627:therapeutic use; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D010148:Intractable Pain / Q000628:therapy*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013346:Subarachnoid Space; D013552:Swine; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000379:methods; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002395:Catecholamines; D053379:Chromogranin A; D002864:Chromogranins; D009294:Narcotics; D018722:Nicotinic Agonists; D004744:Enkephalin, Methionine; D009538:Nicotine; D009020:Morphine; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase