| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Research Abstract |
The P2X3 receptor is a ligand-gated cation channel activated by the binding 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 regulation of the P2X3 receptor in sensory ganglion neurons have been observed. The purpose of this study was t examine the precise regulation of P2X3 mRNA expression in primary sensory neurons after nerve injury.
We used two nerve injury models in the rat, the transection of the tibial and common peroneal nerves and the transection of the infraorbital nerve, and observed dorsal root ganglion (DRG) and trigeminal ganglion neurons, respectively. P2X3 mRNA in both neuron populations was detected by in situ hybridization with an oligonucleotide probe that was confirmed by Northern blot analysis. To identify axotomized neurons, we examined the expression of activating transcription factor 3 (ATF3), which
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is regarded as a neuronal-injury marker, using immunohistochemistry.
In the DRG, the mean percentage of P2X3 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 of P2X3 mRNA-labeled neurons in ATF3 immunoreactive (ir) neurons was 29.5% at 3 postoperative days, which gradually decreased to 11.2% at 28 days after injury. In the trigeminal ganglion, the mean percentage of P2X3 mRNA-labeled 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 P2X3 mRNA-labeled neurons was 25.3% at 1 postoperative day and was reduced to 6.1% at 28 postoperativ days.
The finding that P2X3 mRNA in ATF3-ir neurons decreased significantly after injury indicates that axotomized neurons decreased the expression of P2X3 mRNA, despite the increase in P2X3 mRNA relative to the total number of sensory ganglio neurons. These data strongly suggest that P2X3 mRNA expression increases in intact neurons and that P2X3 mRNA in intact neurons may play a role in the pathomechanism of post nerve injury in primary sensory neurons. Less
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