Modulation of P2X receptors via adrenergic pathways in rat dorsal root ganglion neurons after sciatic nerve injury

The present study examined noradrenaline-induced modulation of ATP-evoked currents in dorsal root ganglion (DRG) neurons after sciatic nerve injury (transection). ATP (10 μM) generated fast/mixed type of whole-cell membrane currents, possibly as mediated via P2X3/P2X3-like receptors, and slow type of the currents, possibly as mediated via P2X2/3 receptors, in acutely dissociated L4/5 DRG neurons, without significant difference between sham and injury group. For sham group, noradrenaline (10 μM) enhanced fast/mixed type of ATP-evoked currents in ipsilateral DRG neurons, that is not inhibited by H-7, a broad inhibitor of protein kinases, but otherwise it had no effect on slow type of the currents. For injury group, noradrenaline (10 μM) significantly potentiated slow type of ATP-evoked currents in ipsilateral DRG neurons, that is abolished by H-7 or GF109203X, a selective inhibitor of protein kinase C (PKC), while it depressed fast/mixed type of the currents. In the analysis of real-time reverse transcription-polymerase chain reaction, an increase in the mRNAs for α1b, α2a, α2d, and β2 adrenergic receptors was found with the ipsilateral DRGs after sciatic nerve injury. Collectively, the results of the present study suggest that noradrenaline potentiates P2X2/3 receptor currents by activating PKC via α1 adrenergic receptors linked to Gq protein, perhaps dominantly α1b adrenergic receptors, in DRG neurons after sciatic nerve injury. This may account for a nociceptive pathway in response to noradrenergic sprouting after peripheral nerve injury.