Diabetic-induced increased sodium channel activity attenuated by tetracaine in sensory neurons in vitro.

The present study was aimed to explore correlation between the altered pain perception and Na(+) channel activity in diabetic animals as well as the effect of tetracaine on sensory neurons of diabetic rat. In streptozotocin-induced diabetic rats behavioral nociceptive parameters were assessed. The Na(+) current (INa) was obtained using whole-cell voltage-clamp configuration in dorsal root ganglion (DRG) neurons isolated from diabetic rat (in vitro). In addition, the effects of tetracaine on altered Na(+) channel activity associated with diabetes in small DRG neurons were evaluated. After induction of diabetes mechanical allodynia, thermal hyperalgesia and Na(+) channel activity were altered significantly in 4th and 6th week in relation to the control. Altered pain parameters were in correlation with increased INa in time-dependent manner. In comparison to age-matched control (-1.10±0.20nA) the INa was found to be -2.49±0.21nA at 4th week and -3.71±0.28nA at 6th week. The increased activity of Na(+) channels was blocked by tetracaine even in diabetic condition. The depression of the INa on tetracaine exposure was not sensitive to the voltage or time. The conductance curve shifted towards right around -8.0mV. The alterations in neuropathic pain associated with diabetes and Na(+) channel activity has been clearly correlated in time-dependent manner. The INa density was increased significantly with the progression of neuropathic pain. Local anesthetic, tetracaine potentially blocked the Na(+) channel activity in diabetic sensory neurons.

TRPM8-dependent shaking in mammals and birds.

Removing water from wet fur or feathers is important for thermoregulation in warm-blooded animals. The "wet dog shake" (WDS) behavior has been largely characterized in mammals but to a much lesser extent in birds. Although it is known that TRPM8 is the main molecular transducer of low temperature in mammals, it is not clear if wetness-induced shaking in furred and feathered animals is dependent on TRPM8. Here, we show that a novel TRPM8 agonist induces WDS in rodents and, importantly, in birds, similar to the shaking behavior evoked by water-spraying. Furthermore, the WDS onset depends on TRPM8, as we show in water-sprayed mice. Overall, our results provide multiple evidence for a TRPM8 dependence of WDS behaviors in all tested species. These suggest that a convergent evolution selected similar shaking behaviors to expel water from fur and feathers, with TRPM8 being involved in wetness sensing in both mammals and birds.