Neuropathic pain is refractory to conventional analgesics. Thus, the mechanism of neuropathic pain in rats with left L5 spinal nerve transection was reexamined. The patch-clamp technique was used on the isolated bilateral L5 dorsal root ganglion neurons. When rats exhibited established neuropathic pain, only the neurons with the diameter of 40-50 um (Abeta neurons) on the ipsilateral side showed a significantly larger density of an inward current at <–80 mV (Ih current) than that on the contralateral side. Ivabradine—an Ih current inhibitor—inhibited Ih currents in these neurons on both the sides in a similar concentration-dependent manner, with an IC50 of ~3 uM. Moreover, the oral administration of ivabradine significantly alleviated the neuropathic pain on the ipsilateral side. An inhibitor of adenylyl cyclase or an antagonist of prostanoid EP4 receptors (CJ-023423) inhibited ipsilateral, but not contralateral Ih currents in these neurons. Furthermore, the intrathecal administration of CJ-023423 significantly attenuated neuropathic pain on the ipsilateral side. Thus, ivabradine and/or CJ-023423 may be a lead compound for the development of novel therapeutics against neuropathic pain.

To: 要旨(抄録)