Terminals In Superficial Dorsal Horn Research Articles

Presynaptic modulation of spinal nociceptive transmission by glial cell line-derived neurotrophic factor (GDNF).

The role of glial cell line-derived neurotrophic factor (GDNF) in nociceptive pathways is still controversial, as both pronociceptive and antinociceptive actions have been reported. To elucidate this role in the mouse, we performed combined structural and functional studies in vivo and in acute spinal cord slices where C-fiber activation was mimicked by capsaicin challenge. Nociceptors and their terminals in superficial dorsal horn (SDH; laminae I-II) constitute two separate subpopulations: the peptidergic CGRP/somatostatin+ cells expressing GDNF and the nonpeptidergic IB4+ neurons expressing the GFRα1-RET GDNF receptor complex. Ultrastructurally the dorsal part of inner lamina II (LIIid) harbors a mix of glomeruli that either display GDNF/somatostatin (GIb)-IR or GFRα1/IB4 labeling (GIa). LIIid thus represents the preferential site for ligand-receptor interactions. Functionally, endogenous GDNF released from peptidergic CGRP/somatostatin+ nociceptors upon capsaicin stimulation exert a tonic inhibitory control on the glutamate excitatory drive of SDH neurons as measured after ERK1/2 phosphorylation assay. Real-time Ca(2+) imaging and patch-clamp experiments with bath-applied GDNF (100 nM) confirm the presynaptic inhibition of SDH neurons after stimulation of capsaicin-sensitive, nociceptive primary afferent fibers. Accordingly, the reduction of the capsaicin-evoked [Ca(2+)]i rise and of the frequency of mEPSCs in SDH neurons is specifically abolished after enzymatic ablation of GFRα1. Therefore, GDNF released from peptidergic CGRP/somatostatin+ nociceptors acutely depresses neuronal transmission in SDH signaling to nonpeptidergic IB4+ nociceptors at glomeruli in LIIid. These observations are of potential pharmacological interest as they highlight a novel modality of cross talk between nociceptors that may be relevant for discrimination of pain modalities.

Kainate receptors in primary afferents to the rat gracile nucleus

In a previous work, we demonstrated that under weak paraformaldehyde fixation, kainate receptors (KR) (GluR5/6/7) are expressed in primary afferent terminals in superficial dorsal horn. We extended our study to primary afferents to the gracile nucleus; immunostaining for GluR5/6/7 in weakly fixed sections was in puncta of variable size. In double-stained sections, the majority of immunostained puncta colocalized with synaptophysin. Because of their large size and relations with smaller puncta, single-stained for synaptophysin, these terminals were presumed to be of dorsal column primary afferents. This was confirmed by anterograde labeling with cholera toxin B and with electron microscopy, which showed that GluR5/6/7 was present in terminals with morphology of primary afferents. These observations demonstrate that expression of presynaptic KR is a general feature of primary afferents with different functional properties.