Adrenal medullary transplants reduce formalin-evoked c-fos expression in the rat spinal cord

Abstract

Previous studies have indicated that adrenal medullary chromaffin cells transplanted into the spinal subarachnoid space can alleviate pain behaviors in several animal models. The goal of this study was to assess whether decreased activation of spinal dorsal horn neurons responsive to nociceptive stimuli may contribute to these antinociceptive effects. In order to address this, expression of neural activity marker c-fos in response to intraplantar formalin was evaluated in animals with intrathecal adrenal medullary or control striated muscle transplants. Adrenal medullary transplants significantly attenuated formalin-induced flinching behaviors in both acute and tonic phases of the formalin response, in comparison with control transplanted animals. Fos-like-immunoreactive (Fos-LI) cell numbers were markedly reduced in the dorsal horns of animals with adrenal medullary transplants in comparison to robust Fos-LI expression in control transplanted animals. This reduction was observed in both superficial and deep laminae of the dorsal horn, but the magnitude of the decrease was greatest in lamina V. Similar to reports using other antinociceptive treatments, some residual c-fos expression was observed, particularly in laminae I-II, in animals with adrenal medullary transplants. The results of these studies suggest that adrenal medullary transplants produce antinociception in part by inhibiting spinal dorsal horn neuronal activation in response to noxious stimuli.