Differential regulation of P2X(3) mRNA expression by peripheral nerve injury in intact and injured neurons in the rat sensory ganglia

The P2X(3) receptor is a ligand-gated cation channel activated by the bindi ng of extracellular adenosine 5'-triphosphate (ATP), an agent that has been suggested to have a role in the nociceptive pathway after tissue and nerve injury. After peripheral nerve injury, both down regulation and up regulat ion of the P2X(3) receptor in sensory ganglion neurons have been observed. The purpose of this study was to examine the precise regulation of P2X(3) m RNA expression in primary sensory neurons after nerve injury. We used two n erve injury models in the rat, the transection of the tibial and common per oneal nerves and the transection of the infraorbital nerve, and observed do rsal root ganglion (DRG) and trigeminal ganglion neurons, respectively. P2X (3) mRNA in both neuron populations was detected by in situ hybridization w ith an oligonucleotide probe that was confirmed by Northern blot analysis. To identify axotomized neurons. we examined the expression of activating tr anscription factor 3 (ATF3). which is regarded as a neuronal-injury marker, using immunohistochemistry. In the DRG, the mean percentage of P2X(3) mRNA -labeled neurons relative to the total number of neurons increased from 32. 7% in the naive rats to 42.7% at 3 days after injury. The mean percentage o f P2X(3) mRNA-labeled neurons in ATF3 immunoreactive (ir) neurons was 29.5% at 3 postoperative days, which gradually decreased to 11.2% at 28 days aft er injury. In the trigeminal ganglion, the mean percentage of P2X(3) mRNA-l abeled neurons was 36.9% at 3 days after injury, versus 26.0% in the naive rats. In the ATF3-ir neurons, the mean percentage of P2X(3) mRNA-labeled ne urons was 25.3% at 1 postoperative day and was reduced to 6.1% at 28 postop erative days. The finding that P2X(3) mRNA in ATF3-ir neurons decreased sig nificantly after injury indicates that axotomized neurons decreased the exp ression of P2X(3) mRNA, despite the increase in P2X(3) mRNA relative to the total number of sensory ganglion neurons. These data strongly suggest that P2X(3) mRNA expression increases in intact neurons and that P2X(3) mRNA in intact neurons may play a role in the pathomechanism of post-nerve injury in primary sensory neurons. (C) 2001 International Association for the Stud y of Pain. published by Elsevier Science B.V. All rights reserved.