P2X7 receptors in satellite glial cells mediate high functional expression of P2X3 receptors in immature dorsal root ganglion neurons

We immunostained DRGs of immature rats and found that P2X3Rs were expressed only in neurons and P2X7Rs were expressed only in SGCs. Western blot analyses indicated that P2X3R expression decreased while P2X7R expression increased with the age of rats. Electrophysiological studies showed that the number of DRG neurons responding to the stimulation of the P2XR agonist, α,β-meATP, was higher and the amplitudes of α,β-meATP-induced depolarizations were larger in immature DRG neurons. As a result, P2X3R-mediated flinching responses were much more pronounced in immature rats than those found in adult rats. When we reduced P2X7R expression with P2X7R-siRNA in postnatal and adult rats, P2X3R-mediated flinch responses were greatly enhanced in both rat populations.These results show that the P2X7R expression increases as rats age. In addition, P2X7Rs in SGCs exert inhibitory control on the P2X3R expression and function in sensory neurons of immature rats, just as observed in adult rats. Regulation of P2X7R expression is likely an effective way to control P2X3R activity and manage pain relief in infants.The DRG neuron is the first (primary) neuron in the somatosensory pathway relaying nociceptive (pain), itch and other sensory information from the skin or internal organs to the brain. The cell bodies (somata) of DRG neurons are densely packed in a DRG. Each neuronal soma is tightly wrapped by a layer of SGCs, which are often coupled with one another through gap junctions [1,2]. A neuronal soma with its surrounding SGCs is frequently enclosed by a connective tissue sheath and forms a distinct morphological unit [3]. There is no evidence that classical synaptic contacts exist between neuronal somata in DRGs [2]. We and others have shown that neuronal somata communicate bidirectionally with their surrounding SGCs in DRGs [4,5] and trigeminal ganglia [6]. The communication modulates the activity of somata thus affecting the afferent inputs into the spinal cord [4].Purinergic ionotr