Ultrastructural features of the colocalization of calcitonin gene related peptide with substance P or somatostatin in the dorsal horn of the spinal cord

Abstract

Calcitonin gene related peptide (CGRP), substance P (SP), and somatostatin (SOM) are probably the three most important sensory neuropeptides. However, in contrast to CGRP immunoreactivity (IR), SP- and SOM-IR occur also in neurons intrinsic to the dorsal horn. Colocalization of either SP- or SOM-IR with CGRP-IR is, therefore, strongly suggestive of a primary sensory origin. In this study, high resolution double-labelling immunocytochemistry was applied to detect CGRP/SP and CGRP/SOM colocalizations in axonal boutons of the rat superficial dorsal horn. Most boutons colocalizing CGRP-IR and SP-IR were not part of synaptic glomeruli. However, 15% of such boutons represented the central varicosities of type I synaptic glomeruli. CGRP-IR was always present in the small proportion of type I glomeruli central boutons that displayed SOM-IR. In a study in the cat combining double-labelling immunocytochemistry with intracellular injection of electrophysiologically characterized neurons, we found that nociceptive neurons received numerous synapses from varicosities colocalizing SP-IR and CGRP-IR. In contrast, non-nociceptive neurons almost completely lacked synaptic input from boutons colocalizing both immunoreactivities. This study confirms that fibres colocalizing SP-IR and CGRP-IR probably play a major role in spinal nociceptive mechanisms.