Stereological analysis of galanin and CGRP synapses in the dorsal horn of neuropathic primates

The present study investigates the nature of the galanin (GAL) increase and the calcitonin gene-related peptide (CGRP) decrease in the dorsal horn following peripheral nerve injury. These two peptides are known to colocalize in primary afferent terminals. Primates which had a tight ligation of the L7 spinal nerve demonstrated a variety of neuropathic symptoms 2 weeks postsurgery, including mechanical and cold allodynia, and heat hyperalgesia. Computer-enhanced image analyses of L7 spinal cord sections demonstrated an increase in GAL immunostaining and a decrease in CGRP immunostaining in the experimental compared to the control dorsal horn. Stereological analyses demonstrated that neither the numbers of GAL-labeled synapses nor the numbers or diameters of the dense-core vesicles in each GAL terminal changed after the lesion. However, there was a significant increase in the number of GAL-labeled glial cell bodies and processes on the experimental side, which accounted for the increased staining density observed at the light microscopic level. In contrast, the number of CGRP-labeled terminals was decreased on the experimental side, accounting for the decreased staining density seen at the light level. Thus, the decrease in number of CGRP synapses combined with the stable number of GAL synapses suggests that many GAL terminals no longer colocalize with CGRP after peripheral nerve lesion. This may indicate increased antinociceptive activity after nerve lesions. If so, there is less of a morphologic and more of a functional and chemical plasticity for GAL than may be presently envisioned. The possible role of GAL in neuropathic pain is discussed.