Impact of inflammatory disease on the nerve microenvironment

Abstract

The peripheral nervous system (PNS) has a distinctive anatomic organization that may contribute to its unique physiology as well as vulnerability to certain types of disease. The enclosure of bundles of myelinated and unmyelinated fibers by a semi-rigid and semi-permeable connective tissue sheath creates physiological compartments that are served by transperineurial and intrafascicular vessels but are devoid of lymphatic channels. Unlike tissues drained by lymphatics, interstitial fluid in the PNS flows from proximal to distal regions, propelled by positive endoneurial fluid pressure (EFP). There is a proximo-distal gradient from the dorsal root ganglia and roots to the extraganglionic nerves where the pressure is significantly lower [1]. EFP in the ganglia and roots is nearly twice as high as in the extraganglionic nerves. From the higher pressure in spinal fluid to the relatively low pressure in the sciatic fluid, a downward gradient continues until the nerve ending. At that point, the perineurium terminates as an ensheathing sleeve, and the normal slightly negative interstitial fluid pressure of the extraneural interstitium prevails. This gradient continues into the lymphatic channels where negative fluid pressure is greatest. The endoneurial microenvironment is sensitive to