Sialylation Contributes To Hyperexcitability Of Injured Aα/β-Dorsal Root Ganglion Neurons In Rat

The increasing knowledge of neurophysiological mechanisms as the hyperexcitability of the injured primary sensory neurons is considered a key factor in the generating and maintaining of chronic pain, but the mechanisms of hyperexcitability need further clarification. As it is known that the injured neurons should increase their synthesis of some ion channels and other membrane proteins, and that the external domains of the proteins are sialylated, and the sialic acid carrying heavy negative charges, to form a "negative electrical halo" surrounding the injured neurons, which inspired us to believe that increased negative surface charges would reduce the net resting transmembrane potential (V_r) of the neurons and produce a depolarized hyperexcitation. As in our present studies, 1) By a HPLC-adaptation of the thiobarbituric acid assay, we measured the quantity of sialic acid over the DRG neurons of CCI rats, and found the increased sialic acid over the DRG neurons of CCI rats which showing hyperalgesia. 2) By intracellular recording technique, we have demonstrated the hyperexcitability of Aα/β dorsal root ganglion (DRG) neurons of rats following chronic constrictive injury (CCI), showing depolarizing shift of Vr, weaker intracellular stimulating threshold current (T_IC), increased duration and amplitude of action potential, and decreased duration and magnitude of afterhyperpolarization. 3) Moreover, the excitability of CCI DRG neurons was reduced substantially when the extracellular sialic acid was removed by neuraminidase, the V_R was increased and T_IC was almost doubled in CCI Aα/β-neurons, however desialylation had much less effect on V_r and T_IC of intact neurons and other indexes of all Aα/β-neurons. These results suggest that the increased negatively charged sialic acid residues over the injured DRG neurons contribute to the hyperexcitability by an electrostatic mechanism. Furthermore, we observed the effects of various cations on the electrophysiological properties of DRG neurons, we found that Ca²⁺, Mg²⁺, Ni²⁺ and Mn²⁺, probably under the mediation of the surface negative charges, inhibited the excitability of the DRG neurons especially the injured neurons. These observations prove further that surface charge mechanism play an important role in the generation and maintain of neuropathic pain.