Primary afferent interactions: analysis of calcitonin gene-related peptide-immunoreactive terminals in contact with unlabeled and GABA-immunoreactive profiles in the monkey dorsal horn.

The present study analyses the relationship of calcitonin gene-related peptide (CGRP)-immunoreactive primary afferent terminals with unlabeled and GABA-immunoreactive profiles in the primate (Macaca fascicularis) dorsal horn. One-hundred CGRP-immunoreactive terminals located in the superficial dorsal horn were quantitatively analysed and all profiles in apposition or in synaptic contact with these terminals were categorized as either axon terminals or dendrites with or without vesicles. These profiles were then further classified as to whether they were GABA-immunoreactive. All of the CGRP-immunoreactive terminals demonstrated axodendritic interactions; in addition to dendrites without vesicles, approximately half of the CGRP-immunoreactive terminals had dendrites with vesicles as postsynaptic elements. Of the dendrites with vesicles, 25/53 were GABAergic but only 3/67 of the postsynaptic dendrites without vesicles were GABAergic. GABAergic vesicle-containing dendrites were the most prominent CGRP-GABAergic interaction. Axoaxonic and dendroaxonic interactions were a rare occurrence, thus the classical anatomical substrate for primary afferent depolarization involving GABA- and CGRP-immunoreactive terminals could not be substantiated. CGRP-GABAergic interactions often involved diadic and triadic arrangements. These findings are discussed in relation to previously described primary afferent synaptology, primary afferent-GABAergic interactions and spinal cord mechanisms for modulation of noxious input.