Effects of Pre-emptive Lidocaine Treatment and Diabetes on Rats Following Median Nerve Injury

• Main Authors: Chi-Te Lin, 林至德
• Other Authors: 呂俊宏
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/23006345388948645368

博士 === 國立臺灣大學 === 解剖學暨生物細胞學研究所 === 98 === Part 1. Effects of pre-emptive lidocaine treatment on rats following median nerve injury ABSTRACT Following peripheral nerve injury, lidocaine application has been demonstrated to suppress injury discharges. However, there is very little information about the effects of lidocaine pre-treatment. The aim of the present study was to examine the effects of pre-treatment with lidocaine on injury discharges of the nerve, and neuropeptide Y (NPY) and c-Fos expression in the cuneate nucleus (CN) after median nerve transection (MNT). Rats received either saline or 1%, 5%, or 10% lidocaine applied topically to the median nerve before nerve transection. Electrophysiological recording was used to examine the changes in injury discharges of the nerve at post-injection, transection, pre- and post-electrical stimulation stages in the different groups. Sequential immunohistochemistry was also used to identify the number of NPY-like immunoreactive (NPY-LI) fibers and c-Fos-LI cells in the corresponding CN. An increasing frequency of injury discharges was observed at all stages in the pre-saline group, which were suppressed by lidocaine pre-treatment in a dose-dependent manner. Lidocaine pre-treatment also attenuated the number of injury-induced NPY-LI fibers and c-Fos-LI neurons within the CN in a dose-dependent manner. Furthermore, expression of c-Fos-LI neurons in the CN was significantly reduced by an NPY receptor antagonist, indicating that NPY modulated c-Fos expression following MNT. In chronic constriction injury (CCI) model, lidocaine pre-treatment dose dependently delayed and attenuated the development of mechanical allodynia within a 28-day period and also reduced the number of c-Fos-LI neurons within the CN. In addition, the mean number of c-Fos-LI neurons in the CN was significantly negative correlated to the sign of mechanical allodynia following CCI. These data suggest that suppressing injury discharges with lidocaine pre-treatment effectively prevent morphological changes in the CN and attenuate neuropathic pain following median nerve injury. Furthermore, the expression of c-Fos in the CN may be regarded as the scale of mechanical allodynia in rat treated with median nerve injury. Part 2. Effects of diabetes on rats following median nerve injury ABSTRACT In this study we examined the temporal changes in neuropeptide Y (NPY) expression in dorsal root ganglion (DRG) neurons and cuneate nucleus (CN) in streptozotocin (STZ)-induced diabetic rats with or without median nerve transection (MNT). Numerous NPY-like immunoreactive (NPY-LI) neurons and fibers were detected in the DRG and CN in the diabetic MNT (DMNT) rats respectively, but not in those with diabetes alone. Following MNT, the time-course of NPY expression pattern in the diabetic DRG and CN was similar and both peaked at 2 weeks, which was earlier than that in the non-diabetic MNT rats. Consequently, the expression of neurotrophin-3 (NT-3) immunoreactivity in DRG neurons was coincidentally decreased and reached the nadir at 2 weeks in the diabetic MNT rats, which was also earlier than that in the non-diabetic MNT rats. Following electrical stimulation of the transected nerve, the number of NPY-LI fibers became attenuated and the induced c-Fos-LI cells concurrently appeared in the ipsilateral CN. In the diabetic CN, the number of c-Fos-LI cells also peaked at 2 weeks after MNT, which was consistent with the temporal pattern of changes in NPY expression. The results suggest that in diabetes, MNT induced NPY expression via the reduction of NT-3, and electrical stimulation of the injured median nerve evoked the release of NPY and accordingly more c-Fos-LI cells were identified in the CN. Furthermore, this study demonstrated early NPY and c-Fos expression in the diabetic rats after MNT, suggesting that the development of neuropathic signs may be advanced in hyperglycemic rats.