Relationship of Substance P- and CGRP-immunoreactive Central Endings of the Primary Afferent Neurons to GABAergic Interneurons in the Guinea Pig Suhstantia Gelatinosa

Abstract

The synaptic relationships between primary afferent central endings containing substance P (SP) and calcitonin gene-related peptide (CGRP) and GABAergic interneurons in the guinea pig substantia gelatinosa of the lumbar spinal dorsal horn were studied. The pre-embedding PAP method was used for detection of GABA and the post-embedding double immunogold labeling method for SP and CGRP detection. Immunogold particles specific for SP and CGRP were mainly localized separately or together in large synaptic vesicles devoid of dense cores. SP and CGRP immnnoreactivity was separate or co-localized in small roundish, slender, sinuous or large scalloped (fan-like) terminals with closely packed round agranular synaptic vesicles of various sizes and few large dense core vesicles and mitochondria, which are thought to be capsaicin-sensitive primary afferent terminals. These SP- and CGRP-immunoreactive boutons make presynaptic or symmetric contacts with GABAergic dendrites and soma. These findings suggest that the central endings of nociceptive primary afferents transmit pain stimuli to intrinsic inhibitory interneurons, thereby modulating nociceptive information via a postsynaptic circuit.