Limited Changes in Spinal Lamina I Dorsal Horn Neurons following the Cytotoxic Ablation of Non-Peptidergic C-Fibers

Abstract

BackgroundNon-peptidergic nociceptive neurons are a sub-population of small diameter primary sensory neurons that comprise approximately 50 % of the C fiber population. Together with the peptidergic sub-population, they transmit nociceptive information from the periphery to the superficial dorsal horn of the spinal cord. Despite the numerous studies investigating the role of the non-peptidergic primary afferents, their role in normal nociception and in pain remains poorly understood. Our lab has previously demonstrated that, in rat models of neuropathic and inflammatory pain, there is a de novo expression of substance P receptors (NK-1r) by lamina I pyramidal projection neurons, a neuronal population that normally does not express these receptors.ResultsIn this study, we used a ribosomal toxin, saporin, conjugated to the lectin IB4 to selectively ablate the non-peptidergic nociceptive C fibers, to investigate if the loss of these fibers was enough to induce a change in NK-1r expression by lamina I projection neurons. IB4-saporin treatment led to the permanent ablation of the IB4-positive afferents but also to a small non-significant reduction in CGRP-positive afferents. An overall increase in immunoreactivity for the NK-1r was observed in lamina I projection neurons, however, the lack of non-peptidergic afferents did not increase the number of lamina I pyramidal projection neurons immunoreactive for the receptor.ConclusionsOur results demonstrate that the deletion of the non-peptidergic afferents, at the L4–L5 spinal levels, is not sufficient to trigger the de novo expression of NK-1r by projection pyramidal neurons but increases the expression of NK-1r in fusiform and multipolar projection neurons. Furthermore, our data suggest that a neuropathic component is essential to trigger the expression of NK-1r by pyramidal neurons.

Selective-cold output through a distinct subset of lamina I spinoparabrachial neurons

“…These observations raise the interesting possibility that cold-selective SPB neurons express Gria1, rather than Gria4, thereby enabling distinct types of synaptic plasticity. Previous studies have also suggested that coldselective (albeit random) lamina I neurons in cat are pyramidal [24], and lamina I pyramidal neurons have been shown to be negative for Tacr1-immunoreactivity in rat and monkey [2,43,44,54,55]. However, the idea that cold output neurons are pyramidal remains controversial since others have suggested that there is no relation between morphology and the expression of Tacr1 in rat lamina I projection neurons [47], and most pyramidal lamina I projection neurons expressed Fos after noxious stimuli [51,52].…”

Inhibiting endocytosis in CGRP+ nociceptors attenuates inflammatory pain-like behavior

“…AP2α2 is preferentially expressed in CGRP containing DRG neurons. Previous immunological labeling of AP2α2 in the superficial lamina of the rodent dorsal horn suggested a putative differential expression of AP2α2 in nociceptors 3,[17][18][19] . In order to resolve this, we probed mDRG neurons with antibodies against AP2α2 20 , CGRP, and an Alexa fluor-conjugated IB4.…”

Saporin from Saponaria officinalis as a Tool for Experimental Research, Modeling, and Therapy in Neuroscience

“…It was shown that elimination of these neurons by injection of IB4-saporin decreased sensitivity to noxious stimuli [ 72 ] and duration of mechanical hyperalgesia [ 73 ], however, quite unexpectedly this suppression of pain response was compensated at later stages and nociceptive threshold recovered [ 72 ]. Later on, it was shown that this compensation of IB4-saporin-induced loss of nociceptive fibers includes an increase in the surface expression of NK1 receptors in the subpopulation of spinal cord neurons that already expressed NK1 receptors ( Figure 2 B) [ 74 ]. Importantly, using this saporin-based toxin it was shown that GDNF is one of endogenous mediators that can activate IB4-binding nociceptors [ 75 ].…”