Alterations in the distribution of stimulus-evoked c-fos in the spinal cord after neonatal peripheral nerve injury in the rat

Neonatal peripheral nerve injury results in a significant rearrangement of the central terminals of surviving axotomized and adjacent intact primary a fferents in the dorsal horn of the spinal cord. This study investigates the ability of these afferents to make functional contacts with dorsal horn ce lls, using c-Sos expression as a marker of synaptic activation. Graded elec trical stimulation at A- or C-fiber strength of either the neonatally axoto mized sciatic nerve or the adjacent uninjured saphenous nerve was performed in adult rats. Stimulation of the contralateral uninjured nerve served as a control. Quantitative examination of the number and distribution of c-fos -labeled cells in the spinal cord laminae was performed. Electrical stimula tion of the previously axotomized sciatic nerve at A-fiber intensity result ed in many labeled profiles in laminae I-V of the lumbar spinal cord on the experimental as compared to the contralateral side. Electrical stimulation of uninjured saphenous nerve or saphenous-nerve-innervated skin (using pin electrodes) at A-fiber intensity did not evoke c-fos. Stimulation of the s aphenous nerve at C-fiber intensity, however, resulted in a significant inc rease in the number and distribution of c-fos-labeled profiles in laminae I -V on the experimental side as compared to the contralateral control side. The results show that the distribution of c-fos-expressing cells after neon atal nerve injury is compatible with the previously demonstrated distributi on of sprouting of primary afferents belonging to an uninjured nerve adjace nt to an injured nerve, and that the surviving axotomized afferents are cap able of transmitting signals to postsynaptic cells. These findings indicate that A beta afferent stimulation of injured but not uninjured afferents el icits c-Sos expression in postsynaptic cells. This may reflect an injury-in duced maintenance of a normal developmental process whereby A beta stimulat ion elicits c-fos in dorsal horn neurons. (C) 2000 Elsevier Science B.V. Al l rights reserved.