The Important Role Of P2X₃ Receptor In Pain Of Neonatal Rats Development

The dorsal root ganglion and spinal dorsal horn play an important role in nociceptive information transmission from the periphery to central nervous system. More and more evidences suggest that the abnormal activation of neuron in DRG is necessary for the development and maintenance of pathological pain and hyperalgesia. A variety of nociceptive stimulus, such as peripheral and central nerve injury can induce the change of some important receptors, Substance P, NMDA and P2X3 receptor.The abnormal activation of some receptors can change the transmission of nociceptive inputs.ATP is an important neurotransmitter in nervous system and plays an important role in the transmission of nociceptive stimulus in DRG and spinal cord through binding with and acting on ATP-gated ionotropic P2X receptor. P2X3 receptor may modulate the nociception processes at peripheral and spinal cord levels. The P2X3 receptor mainly locates in the neurons which process the noxious stimulation. More and more evidences have shown that P2X3 receptor plays an important role in pain.This study will use some methods including ethology and morphology to study the important role of P2X3 receptor in the development of the nervous system and pain progress.Methods:1. Prepare the inflammatory pain model by injection of carrageenan in the subcutaneous of SD rat; and prepare the neuropathic pain model by the chronic constriction injury of sciatic nerve.2. Assay the pain threshold by thermal radiation and von Frey filament.3. Assay the expression of P2X3 receptor in DRG and spinal dorsal horn by IHC (immunohistochemistry).Results:1. After injection of carrageenan,thermal hyperalgesia and mechanical allodynia appeared in the neonatal and adult rats,and the change pattern of pain threshhold in neonatal and adult rats were similar.The TWL and PWT decreased obviously from 2h,descended to the lowest at 12h,then returned to the normal level after 72h.But the normal pain threshhold of neonatal rats increased with the development.2. In the normal growth of rats, the expression of P2X3 receptor decreased obviously. During the progress of inflammatory pain, the expression of P2X3 receptor dropped in 7, 14, 21 days postnatal rats, and the descent rate was obviously faster than the normal. While the expression of P2X3 receptor in adult rats DRG increased obviously,and reached the peach at 3 days after injection,after 7 days, it returned to the normal level.The expression of P2X3 receptor in 7 days postnatal rats'dorsal horn had no obvious changes after injection ,while the expression level firstly increased ,then declined to normal level in adult rats'dorsal horn.3. The change pattern of pain threshhold in neonatal and adult rats'neuropathic model was similar to the inflammatory pain model rats, but the injury progress last longer, and recovered slowly.4. The expression change pattern in neonatal and adult rats'neuropathic model was also similar to the inflammatory pain model rats. During the progress of neuropathic pain, the expression of P2X3 receptor dropped in 7, 14, 21 days postnatal rats, and the descent rate was obviously faster than the normal. While the expression of P2X3 receptor in adult rats DRG increased obviously,and reached the peach at 14 days after injury,after 28 days, it returned to the normal level.The expression of P2X3 receptor in 7 days postnatal rats'dorsal horn had no obvious changes after injection, while the expression level firstly increased, then declined to normal level in adult rats'dorsal horn.Conclusions:1. The pain threshold of neonatal rats increased with the maturation of nervous system. Injection of carrageenan in subcutaneous and the chronic compressed injury of sciatic nerve can induce hyperalgesia and pathological pain, and the pain threshold also dropped obviously, and then returned to the normal level.Compared with inflammatory pain, the progress of neuropathic pain lasted longer, and recovered slowly.2. The expression level of the P2X3 receptor in neonatal rats'DRG declined with growth, and played an important role in the development and maturation of nervous system. After inflammatory pain and neuropathic stimulous, the expression of the P2X3 receptor in neonatal rats'DRG dropped obviously, while increased in adult rats'DRG. P2X3 receptor played an important role in both inflammatory pain and neuropathic pain.The nervous system of neonatal rats was susceptible to noxious stimulation, and the structure and function can be changed after noxious stimulus.In summary, these results suggest that the expression of the P2X3 receptor plays an important role in inflammatory pain and neuropathic pain. Because the mechanism of pain is very complex, much further study is necessary, if we want to demonstrate the exact mechanism.