Alteration in the voltage dependence of NMDA receptor channels in rat dorsal horn neurones following peripheral inflammation

1. It has been proposed that the activation of NMDA receptors and upregulation of protein kinase C (PKC) underlie the exaggerated and persistent pain experienced in the inflammatory state. However, there is no direct evidence to show that inflammation alters the function of NMDA receptors. 2. We examined the voltage-dependent properties of NMDA receptor channels in rat dorsal horn neurones that receive sensory inputs from an inflamed hindpaw. 3. Peripheral inflammation was induced by injections of complete Freund's adjuvant (CFA). Membrane currents were measured using the perforated patch-clamp technique. 4. After CFA treatment, the current-voltage relationship of NMDA receptor channels was shifted in the hyperpolarized direction. This resulted in enhanced NMDA responses at negative potentials. 5. The change was mediated by PKC because the voltage shift was blocked by the selective PKC inhibitors chelerythrine and bisindolymaleimide I. 6. Furthermore, the Mg²⁺ blockade of NMDA receptors was reduced. This reduction could account for the shift in the voltage dependence of NMDA receptor channels. 7. These results indicate that NMDA receptor channel characteristics in the dorsal horn are altered by inflammation, and that the changes observed could contribute to the hyperalgesia and allodynia associated with tissue injury.