Activation of ATP-sensitive potassium channels antagonize nociceptive behavior and hyperexcitability of DRG neurons from rats

BACKGROUND: Nociceptive responses to noxious stimuli are initiated at peripheral nociceptor terminals. Ion channels play a vital role in pain signal initiation and conduction. Activation of K(ATP )channels has been implicated in mediating the analgesic effects of agents such as morphine. However, systematic studies regarding the effects of K(ATP )activators on nociception and neuronal excitability are scarce. RESULTS: In this study, we describe the antagonistic effects of K(ATP )activators pinacidil and diazoxide on nocifensive behavior induced by bradykinin (BK), thermo and mechanical stimuli, and the bradykinin-induced hyperexcitability of DRG neurons. We also found that K(ATP )activators can moderately activate K(ATP )in DRG neurons. Because the effects of K(ATP )activators can be reversed by the K(ATP )blocker glyburide, direct activation of K(ATP )is most likely the underlying mechanism. CONCLUSION: This systematic study clearly demonstrates that activation of K(ATP )could have significant modulatory effects on the excitability of sensory neurons and thus on sensory behaviors, such as nociception. K(ATP )activators can be evaluated clinically for the treatment of pain symptoms.