Objective: 

According to existing paradigm, homomeric P2X3 receptors (expressed almost exclusively in the sensory neurons) play especially important role in the nociception. In this study we have examined the effect of m-opioids on the currents generated by P2X3 receptors in the neurons from DRG of rat.

Methods: 

Acutely isolated or cultured for 12–24 hours neurons from dorsal root ganglia (DRG) of rat were studied using conventional patch clamp techniques and rapid application method.

Results: 

In approximately every fifth of the examined small sensory neurons demonstrating functional P2X3 receptors the inward currents elicited by their activation was effectively blocked by m-opioid agonist leu-enkephalin (IC50 close to 10 nM). We have found that pretreatment of the neuron with naloxon causes approximately ten-fold increase in the sensitivity of P2X3 receptor-induced current to the blocking action of opioids (IC50 decreases to 1 nM). Cross reactions of P2X3 receptors to rapid successive applications of opioids and naloxone indicate at the possibility of multiple states of opioid receptors.

Conclusions: 

P2X3 receptors in a fraction of small (putatively nociceptive) sensory neurons of rat are under inhibitory control of opioid receptors. The effectiveness of this control is strongly modulated by pre-treatment with naloxone. This effect can serve as at least partial explanation for the well-known phenomenon of functional naloxone-induced supersensitivity to opioids.