Transplants of adrenal medullary chromaffin cells reduce forelimb and hindlimb allodynia in a rodent model of chronic central pain after spinal cord hemisection injury.
In the majority of patients, spinal cord injury (SCI) results in abnormal pain syndromes in which non-noxious stimuli become noxious (allodynia). To reduce allodynia, it would be desirable to implant a permanent biological pump such as adrenal medullary chromaffin cells (AM), which secrete catecholamines and opioid peptides, both antinociceptive substances, near the spinal cord. We tested this approach using a recently developed a mammalian SCI model of chronic central pain, which results in development of mechanical and thermal allodynia. Thirty day-old male Sprague-Dawley rats were spinally hemisected at T13 and allowed 4 weeks for recovery of locomotor function and development of allodynia. Nonimmunosuppressed injured animals received either control-striated muscle (n = 7) or AM (n = 10) transplants. Nociceptive behavior was tested for 4 weeks posttransplant as measured by paw withdrawals to von Frey filaments, radiant heat, and pin prick stimuli. Hemisected animals receiving AM demonstrated statistically significant reductions in both fore- and hindlimb mechanical and thermal allodynia, but not analgesia, when compared to hemisected animals receiving striated muscle transplants (P < 0.05). Tyrosine hydroxylase immunoreactivity indicated prolonged transplant survival and production of catecholamines. HPLC analysis of cerebrospinal fluid samples from animals receiving AM transplants demonstrated statistically significant increases in levels of dopamine (sevenfold), norepinephrine (twofold), and epinephrine (threefold), compared to control values several weeks following transplant (P < 0.05). By 28 days posttransplant, however, antinociceptive effects were diminished. These results support the therapeutic potential of transplanted AM in reducing chronic central pain following spinal cord injury.
Department of Anatomy and Neurosciences, University of Texas Medical Branch, Galveston, Texas 77555-1069, USA.
B C
BC
Hains
K M
KM
Chastain
A W
AW
Everhart
D J
DJ
McAdoo
C E
CE
Hulsebosch
D000313:Adrenal Medulla / Q000166:cytology / Q000637:transplantation*; D000818:Animals; D002395:Catecholamines / Q000096:biosynthesis / Q000134:cerebrospinal fluid; D019439:Chromaffin Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D002851:Chromatography, High Pressure Liquid; D002908:Chronic Disease; D004195:Disease Models, Animal; D005552:Forelimb / Q000502:physiology; D006085:Graft Survival; D006614:Hindlimb / Q000502:physiology; D006930:Hyperalgesia / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology / Q000637:transplantation; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000134:cerebrospinal fluid / Q000503:physiopathology / Q000628:therapy*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002395:Catecholamines; D014446:Tyrosine 3-Monooxygenase