| Summary: | <p>Abstract</p> <p>Background</p> <p>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<sub>ATP </sub>channels has been implicated in mediating the analgesic effects of agents such as morphine. However, systematic studies regarding the effects of K<sub>ATP </sub>activators on nociception and neuronal excitability are scarce.</p> <p>Results</p> <p>In this study, we describe the antagonistic effects of K<sub>ATP </sub>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<sub>ATP </sub>activators can moderately activate K<sub>ATP </sub>in DRG neurons. Because the effects of K<sub>ATP </sub>activators can be reversed by the K<sub>ATP </sub>blocker glyburide, direct activation of K<sub>ATP </sub>is most likely the underlying mechanism.</p> <p>Conclusion</p> <p>This systematic study clearly demonstrates that activation of K<sub>ATP </sub>could have significant modulatory effects on the excitability of sensory neurons and thus on sensory behaviors, such as nociception. K<sub>ATP </sub>activators can be evaluated clinically for the treatment of pain symptoms.</p>
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