Alteration of dorsal root ganglion P2X₃ receptor expression and function following spinal nerve ligation in the rat

Abstract.

One subtype of ATP-gated ion channel, the P2X₃ receptor, is expressed primarily on peripheral sensory neurons. While it is known that P2X₃ receptors can participate in certain forms of nociceptive signaling, their involvement in neuropathic pain transmission is not known. We have examined the expression and function of P2X₃ receptors in a rat spinal nerve ligation model of neuropathic pain. Fourteen days following L5/L6 spinal nerve ligation, the corresponding dorsal root ganglia (DRG) were removed from animals exhibiting mechanical allodynia, and these were studied using immunohistochemical and electrophysiological techniques. Using a polyclonal antibody to label the P2X₃ receptor, a significant reduction in neuronal P2X₃ immunoreactivity was observed in the ipsilateral (injured) L5 and L6 DRG following nerve ligation. In vitro electrophysiological analysis of acutely isolated DRG neurons revealed a similar decrease in functional P2X₃-containing receptors. In small diameter (22–25 µm) neurons, a significant reduction in the number of cells exhibiting a response to α,β-meATP was observed. However, a subset of small diameter neurons retained P2X₃ responses of equal amplitude to those recorded from naive and sham control DRG neurons. Interestingly, P2X₃ immunoreactivity and P2X₃-like responses were also detected in a subset of larger diameter (50 µm) neurons and the number and amplitude of these responses were unchanged after spinal nerve ligation. These results suggest that, while there appears to be a decrease in fast desensitizing P2X₃ receptors following L5/L6 nerve ligation injury, certain subsets of small and large DRG neurons maintain normal P2X₃ receptor expression and function. These remaining receptors may provide a P2X₃ receptor-mediated component to neuropathic pain.