C-fiber structure varies with location in peripheral nerve

Recent advances in regeneration and pain research have revealed gaps in the understanding of normal C-fiber anatomy. In the rat PNS, C-fiber axons assemble into Remak bundles, but beyond this, features of C-fiber organization are not defined. Systematic sampling and quantitation reveals that Remak bundles exiting from the L5 dorsal root ganglion (DRG) contain large numbers of axons, for example, 56% of unmyelinated axons were in bundles of >20 axons. This is different from distal nerve segments such as the hindpaw plantar nerve where the median number of axons per bundle is 3. The cross-sectional area of unmyelinated axons in dorsal root was homogeneous near the DRG but variability in axonal area increased near the spinal cord (p = 0.00001) and the mean axonal area was unchanged. Unmyelinated axons in peripheral nerve were almost always isolated from one another by Schwann cell processes; however, in dorsal root 7% to 9% of unmyelinated axons were immediately adjacent within pockets containing 2 or more axons. Remak bundles in the distal peripheral nerve clustered with other Remak bundles. We observe that multiple unmyelinated axons are juxtaposed within the C-fiber/Remak bundle and that the close association of afferent axons may have important functional implications.