Alteration of dorsal root ganglion P2X sub(3) receptor expression and function following spinal nerve ligation in the rat

• Published in: Experimental brain research 2002-12, Vol.147 (4), p.511-519
• Main Authors: Kage, K, Niforatos, W, Zhu, C I, Lynch, KI, Honore, P, Jarvis, MI
• Format: Article
• Language: English
• ISSN: 0014-4819
• DOI: 10.1007/s00221-002-1263-x

One subtype of ATP-gated ion channel, the P2X sub(3) receptor, is expressed primarily on peripheral sensory neurons. While it is known that P2X sub(3) 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 P2X sub(3) 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 P2X sub(3) receptor, a significant reduction in neuronal P2X sub(3) 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 P2X sub(3)-containing receptors. In small diameter (22-25 mu m) neurons, a significant reduction in the number of cells exhibiting a response to alpha , beta -meATP was observed. However, a subset of small diameter neurons retained P2X sub(3) responses of equal amplitude to those recorded from naive and sham control DRG neurons. Interestingly, P2X sub(3) immunoreactivity and P2X sub(3)-like responses were also detected in a subset of larger diameter (50 mu m) 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 P2X sub(3) receptors following L5/L6 nerve ligation injury, certain subsets of small and large DRG neurons maintain normal P2X sub(3) receptor expression and function. These remaining receptors may provide a P2X sub(3) receptor-mediated component to neuropathic pain.