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

Abstract

Summary: The synaptic relationships between primary afferent central endings containing substance P (SP) and calcitonin gene-related peptide (CGRP) and GABAergic internenrons 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 immunoreactivity was separate or co-localized in small roundish, slender, sinuous or large scalloped (fan-like) terminals with closely packed round agranular synaptic vesides of various sizes and few large dense core vesides 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 nodceptive primary afferents transmit pain stimuli to intrinsic inhibitory internenrons, thereby modulating nodceptive information via a postsynaptic circuit.

Increase in CGRP- and nNOS-immunoreactive neurons in the rat trigeminal ganglion after infusion of an NO donor

“…The granular structures are reminiscent of intracellular stores such as endoplasmic reticulum or Golgi apparatus. Neuropeptides such as CGRP are thought to be stored in, transported by and released from large vesicles with or without dense cores (42)(43)(44)(45). Thus, an alternative explanation for the increase in numbers of immunoreactive neurons may be an opening of these intracellular stores caused by infusion of the NO donor, so that more neurons gain sufficient immunoreactivity to be detected by immunofluorescence.…”

Inflammatory mediator-induced modulation of GABAA currents in human sensory neurons

“…Particularly important is the gating of afferent input to the spinal cord. While data from rodent models also suggest that post-synaptic inhibitory circuitry in the spinal cord dorsal horn is likely to be important for regulation of nociceptive threshold, particularly in the presence of injury, available electrophysiological, pharmacological and morphological data suggest that pre-synaptic inhibition of afferent input is the dominant mechanism for inhibition of somatosensory input into the CNS (Eccles et al, 1962, Eccles et al, 1963, Nishi et al, 1974, Mokha et al, 1983, Hiura et al, 1998, Reeve et al, 1998, Rudomin and Schmidt, 1999, Bae et al, 2000, Olave et al, 2002, Sutherland et al, 2002, Sokal and Chapman, 2003, Vesselkin et al, 2003, Weng and Dougherty, 2005). Virtually all dorsal root ganglion (DRG) neurons from rat respond to GABA with a rapidly activating, bicuculline-sensitive anion current (Oyelese et al, 1995, Zhu et al, 2012a).…”

Nonselective innervation of lamina I projection neurons by cocaine‐ and amphetamine‐regulated transcript peptide (CART)‐immunoreactive fibres in the rat spinal dorsal horn

“…One of the most characteristic features of these terminals is the coexistence of small densely packed vesicles and variable number of large dense-core vesicles (DiFiglia et al, 1982;Carlton et al, 1987;Alvarez et al, 1993;Hiura et al, 1998). It has been shown that these axons form synaptic contacts mainly on dendrites, but axosomatic arrangements also appear frequently both in lamina I and II (DiFiglia et al, 1982;Carlton et al, 1987;Hayes & Carlton, 1992;Alvarez et al, 1993;Ribeiro-da-Silva, 1995;Hiura et al, 1998).…”