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

Abstract

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 P2X 3/P2X 3-like receptors, and slow type of the currents, possibly as mediated via P2X 2/3 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 α 1b, α 2a, α 2d, and β 2 adrenergic receptors was found with the ipsilateral DRGs after sciatic nerve injury. Collectively, the results of the present study suggest that noradrenaline potentiates P2X 2/3 receptor currents by activating PKC via α 1 adrenergic receptors linked to G q protein, perhaps dominantly α 1b 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.