Painful diabetic neuropathy (PDN) is a common complication of
diabetes mellitus and adversely affects the patients' quality of life. Evidence has accumulated that PDN is associated with hyperexcitability of peripheral nociceptive primary sensory neurons. However, the precise cellular mechanism underlying PDN remains elusive. This may result in the lacking of effective
therapies for the treatment of PDN. The phenolic
glucoside,
gastrodin, which is a main constituent of the Chinese herbal medicine Gastrodia elata Blume, has been widely used as an
anticonvulsant,
sedative, and
analgesic since ancient times. However, the cellular mechanisms underlying its
analgesic actions are not well understood. By utilizing a combination of behavioral surveys and electrophysiological recordings, the present study investigated the role of
gastrodin in an experimental rat model of STZ-induced PDN and to further explore the underlying cellular mechanisms. Intraperitoneal administration of
gastrodin effectively attenuated both the
mechanical allodynia and
thermal hyperalgesia induced by STZ injection. Whole-cell patch clamp recordings were obtained from nociceptive,
capsaicin-sensitive small diameter neurons of the intact dorsal root ganglion (DRG). Recordings from diabetic rats revealed that the abnormal hyperexcitability of neurons was greatly abolished by application of GAS. To determine which currents were involved in the antinociceptive action of
gastrodin, we examined the effects of
gastrodin on transient
sodium currents (I(
NaT)) and
potassium currents in diabetic small DRG neurons. Diabetes caused a prominent enhancement of I(
NaT) and a decrease of
potassium currents, especially slowly inactivating
potassium currents (I(AS)); these effects were completely reversed by GAS in a dose-dependent manner. Furthermore, changes in activation and inactivation kinetics of I(
NaT) and total
potassium current as well as I(AS) currents induced by STZ were normalized by GAS. This study provides a clear cellular basis for the peripheral
analgesic action of
gastrodin for the treatment of
chronic pain, including PDN.