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 p ain syndromes in which nonnoxious stimuli become noxious (allodynia). To re duce allodynia, it would be desirable to implant a permanent biological pum p such as adrenal medullary chromaffin cells (AM), which secrete catecholam ines and opioid peptides, both antinociceptive substances, near the spinal cord. We tested this approach using a recently developed a mammalian SCI mo del of chronic central pain, which results in development of mechanical and thermal allodynia. Thirty day-old male Sprague-Dawley rats were spinally h emisected at T13 and allowed 4 weeks for recovery of locomotor function and development of allodynia. Nonimmunosuppressed injured animals received eit her control-striated muscle (n = 7) or AM (n = 10) transplants. Nociceptive behavior was tested for 4 weeks posttransplant as measured by paw withdraw als to von Frey filaments, radiant heat, and pin prick stimuli. Hemisected animals receiving AM demonstrated statistically significant reductions in b oth 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 trans plant survival and production of catecholamines. HPLC analysis of cerebrosp inal fluid samples from animals receiving AM transplants demonstrated stati stically significant increases in levels of dopamine (sevenfold), norepinep hrine (twofold), and epinephrine (threefold), compared to control values se veral weeks following transplant (P < 0.05). By 28 days posttransplant, how ever, antinociceptive effects were diminished. These results support the th erapeutic potential of transplanted AM in reducing chronic central pain fol lowing spinal cord injury, (C) 2000 Academic Press.