Changing pattern Of C-FOS expression in spinal cord neurons after electrical stimulation of the chronically injured sciatic nerve in the rat

Abstract

Immunocytochemical technique was used to study the distribution of c-FOS protein immunoreactive cells in the spinal cord and gracile nuclei 2 h after electrical stimulation of the sciatic nerve in ketamine/xylazine/acepromazine-anesthetized adult rats. Quantitative examination of the c-fos-labeled cells in the spinal cord laminae was made in unoperated and sham operated controls, after sciatic nerve transection without electrical stimulation, and after electrical stimulation at C-fiber or Aα/β-fiber intensity, both in normal animals and at various survival times after chronic sciatic nerve injury (transection and ligation) or crush. Unoperated animals showed very few c-fos-labeled cells, and sham operated controls showed labeled cells located mainly outside the sciatic nerve projection territory. A small increase in number of c-fos protein positive cells was seen after sciatic nerve transection without electrical stimulation. Stimulation of the normal sciatic nerve at C-fiber intensity resulted in c-fos protein-positive cells within the sciatic projection territory in the ipsilateral dorsal horn. Labeled cells were seen in all spinal cord laminae except lamina IX, with the vast majority in lamina I and outer lamina II. No labeled cells were seen in the gracile nucleus. Stimulation at Aα/β fiber intensity resulted in no or only a very small number of c-fos-positive neurons. Electrical stimulation of the injured sciatic nerve at C-fiber intensity, using the uninjured contralateral side as control, resulted in significant decreases in c-fos-immunoreactive cells in lamina I plus the outer portion of lamina II at 12 and 39 days survival after injury. A non-significant decrease was seen in these laminae also after 21 days. Significant increases were seen in laminae III and IV at 21 days. Decreases in laminae V, VI and more ventral laminae were significant at 21 and 39 days after injury. At longer survival times, the difference between the normal and injured side seen weeks after injury tended to disappear. Stimulation at Aα/β fiber intensity 21 days after injury resulted in increases in the numbers of labeled cells in ipsilateral laminae II, III and IV and in the gracile nucleus. Sciatic nerve stimulation after crush injury resulted in more variable side differences, with tendencies for the same alterations as those noted after chronic transection-ligation. The results indicate that the morphological, biochemical and physiological alterations in primary sensory central endings and second order neurons which have earlier been demonstrated after peripheral nerve injury are accompanied by time-dependent changes in the activation pattern among spinal cord neurons after stimulation of the injured nerve.