Intrathecal xenogeneic chromaffin cell grafts reduce nociceptive behavior in a rodent tonic pain model

Autor: Y. Lazorthes, F. Tortosa, Brigitte Sallerin, Suzanne Jozan, C. Mascott, Mathieu Tafani, R.Y. Li, Jean-Christophe Sol, S. Larrue, F. Carraoue
Rok vydání: 2004
Předmět:
Male
Time Factors
Swine
Chromaffin Cells
Dopamine beta-Hydroxylase
Pharmacology
Rats
Sprague-Dawley

Cell therapy
Random Allocation
Catecholamines
Nicotinic Agonists
Cells
Cultured

Pain Measurement
Behavior
Animal

Morphine
Graft Survival
Chronic pain
Immunohistochemistry
Pain
Intractable

medicine.anatomical_structure
Neurology
medicine.drug
Narcotics
Nicotine
endocrine system
medicine.medical_specialty
Tyrosine 3-Monooxygenase
Enkephalin
Methionine

Blotting
Western

Transplantation
Heterologous

Subarachnoid Space
Developmental Neuroscience
Internal medicine
Chromogranins
medicine
Animals
Opioid peptide
Dose-Response Relationship
Drug

business.industry
medicine.disease
Rats
Transplantation
Disease Models
Animal

Endocrinology
Adrenal Medulla
Chromaffin cell
Catecholamine
Chromogranin A
Cattle
Intractable pain
business
Adrenal medulla
Zdroj: Experimental Neurology. 186:198-211
ISSN: 0014-4886
DOI: 10.1016/j.expneurol.2003.10.018
Popis: 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.
Databáze: OpenAIRE