Alteration of P2X1-6 receptor expression in retrograde Fluorogold-labeled DRG neurons from rat chronic neuropathic pain model

Accumulating evidence indicates that P2X receptors may serve an important role in pain and nociceptive sensations. However, recent studies of regulation of P2X receptor expression following nerve injury have produced variable or conflicting results. In the present study the alteration of expression of P2X1-6 receptor subunits in retrograde Flurorogold (FG)-labeled L4+L5 dorsal root ganglion (DRG) neurons were evaluated following unilateral chronic constriction injury (CCI) of the rat sciatic nerve using immunohistochemistry combined with a retrograde fluorescence-tracing method. It was demonstrated that there was no significant difference in the proportion of FG-labeled DRG neurons between the sham and CCI groups (P>0.5). The percentages of P2X1-immunoreactive (IR) and P2X2-IR FG-labeled DRG neurons were not significantly different between the sham and CCI groups (41.5±8.2 vs. 45.2±7.4% and 58.1±6.2 vs. 69.1±3.5%, P>0.05). The percentages of P2X3-IR and P2X6-IR FG-labeled DRG neurons significantly increased in the CCI group compared with the sham group (51.6±4.1 vs. 28.5±3.4% and 41.8±2.2 vs. 22.6±3.3%, P>0.01). By contrast, the percentage of P2X4-IR FG-labeled DRG neurons significantly decreased in the CCI group compared with the sham group (29.4±3.3 vs. 45.0±3.7%, P<0.01). The P2X5-IR positive FG-labeled neurons were not detected in the CCI and sham groups. The results of the present study provided the first evidence regarding the regulation of the expression of the P2X1-6 receptor in sensory neurons being directly associated with chronic nerve injury in rats and also suggest that compared with the P2X3 receptor, the P2X2/3 heteromeric receptor is not the major receptor involved in peripheral neuropathic pain sensation. In addition, the possible functional role of P2X6 receptors in peripheral neuropathic pain requires further investigation.