| SSeCKS (s&barbelow;rc s&barbelow;uppre&barbelow;ssed C&barbelow; k&barbelow;inase s&barbelow;ubstrate) is a proposed protein kinase C substrate that has been localized in the peripheral and central nervous system. In this study, approximately 40% of small primary sensory neurons in the DRG contain SSeCKS-immunoreactivity with many of these cells devoid of SP (4.8%), CGRP (4.7%), or FRAP reactivity (45.0%). In the spinal cord, SSeCKS-immunoreactive axon collaterals terminate in the dorsal third of lamina IIouter suggesting that these fibers are unmyelinated C-, or small diameter myelinated Aδ-, fibers. Additionally, capsaicin treatment essentially obliterated SSeCKS immunoreactivity in the dorsal horn. Quantitative analysis of dorsal root ganglia revealed a 43% reduction in the number of SSeCKS-labeled cells. These results suggest that SSeCKS is localized within a distinct subpopulation of small diameter, unmyelinated C-fiber afferents involved in nociception and polymodal sensory neurotransmission. As SSeCKS-containing neurons and their axonal processes develop from E17 to aged (2 yrs old) stages, it is apparent that these neurons follow the normal developmental pattern of unmyelinated C-fiber primary afferents. Small diameter SSeCKS-containing neurons in the DRG of the rat also contain a small (18.2%) subpopulation that express the high affinity NGF receptor trkA and 13.6% express the low affinity NGF receptor p75NTR. Immunoreactivity for SSeCKS and trkA or p75NTR in the dorsal horn of the spinal cord is limited to the superficial dorsal horn and visibly reflects the overlapping populations in the DRG. It is hypothesized that SSeCKS may be localized within a novel subpopulation of small diameter, unmyelinated C-fiber afferents. The characterization of SSeCKS-containing primary sensory afferent modality and connectivity can be described indirectly by classification based on neurochemistry and neurotrophic receptors specific to this class of primary afferents. The findings reported here in conjunction with the fact that SSeCKS is a PKC substrate suggest that, in neurons, SSeCKS may have a role as a possible mediator in the inflammatory response during hyperalgesic or chronic pain states. |
