Glycosylation Of Primary Sensory Neuron Membrane Involves In The Neuropathic Chronic Pain

Background: Ectopic spontaneous discharge (ESD) of primary sensory neurons is recognized to be important for the generation or maintenance of neuropathic pain following the nerve injury. However, the mechanisms underlying ESD are not clearly understood. One possibility is that an accumulation of ion channels at both the site of injury and the cell body is responsible for the generation of ESD. It is known that a general feature of many membrane voltage-gated ion channels, particularly most voltage-gated sodium channels, is that they are heavily glycosylated, with a large fraction of carbohydrate in the form of sialic acid residues that usually carry a negative charge at physiological PH. These charges are expected to lie on the external domain of the channels and could influence the gating properties of the channels. Objectives and methods: The present study is undertaken to examine our hypothesis that with the accumulation of ion channels, increased sialic acids at the injury site or DRG somata result in a reduction of net transmembrane potential that evoke ESD in injured neurons. We test our hypothesis through the following means. 1. ESD originating from injury site or DRG somata of CCI rats was recorded using a teased fiber technique in 5th left dorsal root or sciatic nerve just proximal injury site. Divalent cations (Ca²⁺, Mg²⁺, Mn²⁺, Ni²⁺ and La³⁺), organic compounds with positive charges such as poy-lysine and hexamethonium were applied to adsorb the external membrane negative charges and changes of the rate of ESD were observed. To determine whether sialic acids residues contribute to the negative charges with which positively-charged agents interact, neuraminidase (2 U/ml) was used to remove sialic...