title: Diabetic-induced increased sodium channel activity attenuated by tetracaine in sensory neurons in vitro.
abstract: 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.
authors.affiliation: Electrophysiology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar (Mohali) 160 062, Punjab, India.
authors.forename: Rathej
authors.initials: R
authors.lastname: Meerupally
authors.affiliation: Electrophysiology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar (Mohali) 160 062, Punjab, India. Electronic address: jnsingh@niper.ac.in.
authors.forename: Jitendra Narain
authors.initials: JN
authors.lastname: Singh
authors.affiliation: Electrophysiology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar (Mohali) 160 062, Punjab, India. Electronic address: sssharma@niper.ac.in.
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Sharma
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013748:Tetracaine / Q000494:pharmacology*
chemical_list: D000779:Anesthetics, Local; D015222:Sodium Channels; D013748:Tetracaine
keywords: Diabetic neuropathy; Dorsal root ganglion; Hyperglycemia; Pain perception; Voltage-gated sodium channel; Whole cell patch clamp