Recently, it has been suggested that the M current, which in the mammalian nociceptors is mediated by heteromers of the Kv7 potassium channels family (Kv 7.2, 7.3 and 7.5), may play an important role in inflammatory and neuropathic pain (Passmore et al, J Neurosci, 2003). The M-current was measured in cultured rat DRG neurons as the current component deactivating during a repolarizing step from -20 mV to -50 mV in the whole-cell mode. Upon application of flupirtine(20 mM) the electrical threshold was significantly heightened (611.13 ± 93.61 pA compared to 280.13 ± 59.07 pA, n = 7, Student's paired t test, p = 0.018) and the repolarization time during the action potential was lowered (3.06 ± 0.42 ms compared to 2.56 ± 0.51 ms, n = 7, Student's paired t test, p = 0.022). Application of zinc pirythione (10 mM) has also raised the electrical threshold (467.5 ± 93.17 pA compared to 325.13 ± 116.77 pA, n = 7, Student's paired t test, p = 0.0018). Application of prostaglandin E₂ reduced M current deactivation amplitude from 170.07 ± 38.01 pA to 102.42 ± 17.30 pA (Student's paired t test, n = 7, p = 0.015). This suggests that prostaglandin E₂ as well as bradykinin via activation of G protein-coupled receptors and secondary messengers cascade modulate the M current, hence the mechanism described would play an important role in enhanced response to stimuli during inflammatory pain.