Noradrenaline stimulates ATP release from DRG neurons by targeting β3 adrenoceptors as a factor of neuropathic pain

Abstract

Noradrenaline (NA), released in association with sympathetic nerve sprouting into the dorsal root ganglion (DRG) after peripheral nerve injury, may enhance neuropathic pain. ATP serves as a pain mediator; however, NA-regulated ATP mobilizations in the DRG is far from understanding. In the present study, we analyzed ATP mobilizations in acutely dissociated rat DRG neurons by recording single-channel currents through P2X receptor channels as an ATP biosensor in an outside-out patch-clamp configuration and by monitoring real-time enzymatic NADPH fluorescent imaging, and examined the role for beta(3) adrenoceptors in allodynia using an in vivo rat model. We show here that NA stimulates ATP release from DRG neurons as mediated via beta(3) adrenoceptors linked to G(s) protein involving PKA activation, to cause allodynia. This represents a fresh regulatory pathway for neuropathic pain relevant to noradrenergic transmission in the DRG.