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 (I-Na) 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 Na+ in time-dependent manner. In comparison to age-matched control (-1.10 +/- 0.20 nA) the I-Na was found to be -2.49 +/- 0.21 nA at 4th week and -3.71 +/- 0.28 nA at 6th week. The increased activity of Na+ channels was blocked by tetracaine even in diabetic condition. The depression of the I-Na on tetracaine exposure was not sensitive to the voltage or time. The conductance curve shifted towards right around -8.0 mV. The alterations in neuropathic pain associated with diabetes and Na+ channel activity has been clearly correlated in time-dependent manner. The I-Na density was increased significantly with the progression of neuropathic pain. Local anesthetic, tetracaine potentially blocked the Na+ channel activity in diabetic sensory neurons. (C) 2014 Elsevier Inc. All rights reserved.