A1 Adenosine Receptor Activation Inhibits P2X3 Receptor–Mediated ATP Currents in Rat Dorsal Root Ganglion Neurons

Abstract

Purinergic signaling is involved in multiple pain processes. P2X3 receptor is a key target in pain therapeutics, while A1 adenosine receptor signaling plays a role in analgesia. However, it remains unclear whether there is a link between them in pain. The present results showed that the A1 adenosine receptor agonist N 6 -cyclopentyladenosine (CPA) concentration-dependently suppressed P2X3 receptor-mediated and α,β-methylene-ATP (α,β-meATP)-evoked inward currents in rat dorsal root ganglion (DRG) neurons.CPA signi cantly decreased the maximal current response of α,β-meATP, as shown a downward shift of its concentration-response curve. The CPA-induced suppression was independent on the clampingvoltageof the membrane. Inhibition of ATP currents by CPA was completely prevented by the A1 adenosine receptor antagonist KW-3902, and disappeared after the intracellular dialysis of either the G i/oprotein inhibitor pertussis toxin, the adenylate cyclase activator forskolin, or the cAMP analog 8-Br-cAMP.Morover, CPA suppressed the membrane potential depolarization and action potential burst induced by α,β-meATP in DRG neurons. Finally, CPA relieved α,β-meATP-induced nociceptive behaviors in rats by activating peripheral A1 adenosine receptors in dose-dependent manner. These results indicated that CPA inhibited P2X3 receptor activity in rat primary sensory neurons by activating A1 adenosine receptors, G i/oproteins and intracellular cAMP signaling, revealing a novel peripheral mechanism underlying its analgesic effect.

The Underlying Mechanisms of Sleep Deprivation Exacerbating Neuropathic Pain

“…Most of the anti-injury sensory effects of adenosine depend on A1R activation. 138 In a mouse model of acute postoperative pain, nociceptive hyperalgesia occurs through the involvement of reduced peripheral and central A1Rs. 139 In another report, to elucidate the effect of adenosine on pain signaling, intrathecal adenosine injections were tested in two types of neuropathic pain (spinal cord compression and chronic constriction of the sciatic nerve) and in postoperative pain (plantar incision).…”