Calcitonin gene-related peptide dynamics in rat dorsal root ganglia and spinal cord following different sciatic nerve injuries

Abstract

We examined calcitonin gene-related peptide (CGRP) expression dynamics in the dorsal root ganglia (DRGs) and spinal cords of adult rats subjected to one of the following three types of unilateral sciatic nerve injury: crush (SNC), ligation (SNL), or transection combined with subsequent neurorrhaphy (SNT). Following SNC, CGRP immunoreactivity (IR) was increased in ipsilateral primary sensory neurons of L4–L5 DRGs, laminae I–II and spinal motoneurons; an area of CGRP-labeled fibers in ipsilateral laminae III–V was also increased in size following SNC. CGRP up-regulation exhibited a distinct temporospatial pattern and expression levels had returned to baseline levels by the end of the 28-day test period. Similar to SNC, SNT also resulted in an increase of CGRP-IR in these areas, though to a slightly lesser degree in the three latter areas. By contrast SNL, which is associated with complete blockade of axonal transport, induced a sustained decrease in CGRP-IR in primary sensory neurons of L4–L5 DRGs and superficial laminae (I–IIo), as well as in an ipsilateral area occupied by CGRP-labeled fibers. Interestingly, SNL did not affect CGRP-IR in spinal motoneurons, but did result in an accumulation of nerve growth factor (NGF) distal to ligature that was apparent as early as 1 day post-injury and persisted throughout the experimental period. These findings indicate that the nature of peripheral nerve injury has an impact on CGRP expression dynamics and that the response involves target tissues in vivo. Our results have important implications for elucidating the mechanisms of nerve regeneration.