Abstract
Background SSeCKS (Src SupprEssed C Kinase Substrate) is a proposed protein kinase C substrate/A kinase anchoring protein (AKAP)
that has recently been characterized in the rat peripheral nervous system. It has
been shown that approximately 40% of small primary sensory neurons contain SSeCKS-immunoreactivity
in a population largely separate from substance P (95.2%), calcitonin gene related
peptide (95.3%), or fluoride resistant acid phosphatase (55.0%) labeled cells. In
the spinal cord, it was found that SSeCKS-immunoreactive axon collaterals terminate
in the dorsal third of lamina II outer in a region similar to that of unmyelinated
C-, or small diameter myelinated Aδ-, fibers. However, the precise characterization
of the anatomical profile of the primary sensory neurons containing SSeCKS remains
to be determined. Here, immunohistochemical labeling at the light and ultrastructural
level is used to clarify the myelination status of SSeCKS-containing sensory neuron
axons and to further clarify the morphometric, and provide insight into the functional,
classification of SSeCKS-IR sensory neurons.
Methods Colocalization studies of SSeCKS with myelination markers, ultrastructural localization
of SSeCKS labeling and ablation of largely unmyelinated sensory fibers by neonatal
capsaicin administration were all used to establish whether SSeCKS containing sensory
neurons represent a subpopulation of unmyelinated primary sensory C-fibers.
Results Double labeling studies of SSeCKS with CNPase in the dorsal horn and Pzero in the
periphery showed that SSeCKS immunoreactivity was observed predominantly in association
with unmyelinated primary sensory fibers. At the ultrastructural level, SSeCKS immunoreactivity
was most commonly associated with axonal membrane margins of unmyelinated fibers.
In capsaicin treated rats, SSeCKS immunoreactivity was essentially obliterated in
the dorsal horn while in dorsal root ganglia quantitative analysis revealed a 43%
reduction in the number of SSeCKS-labeled cells. This attenuation is concomitant with
a decrease in fluoride-resistant acid phosphatase labeled fibers in the spinal cord
dorsal horn and small neuronal somata in sensory ganglia.
Conclusion These results demonstrate that SSeCKS is primarily localized within a distinct subpopulation
of small diameter, largely unmyelinated C-fiber primary sensory neurons putatively
involved in nociception.
