Research Article: Pre-Emptive Treatment of Lidocaine Attenuates Neuropathic Pain and Reduces Pain-Related Biochemical Markers in the Rat Cuneate Nucleus in Median Nerve Chronic Constriction Injury Model

Date Published: November 24, 2012

Publisher: Hindawi Publishing Corporation

Author(s): Chi-Te Lin, Yi-Ju Tsai, Hsin-Ying Wang, Seu-Hwa Chen, Tzu-Yu Lin, June-Horng Lue.


This study investigates the effects of lidocaine pre-emptive treatment on neuropathic pain behavior, injury discharges of nerves, neuropeptide Y (NPY) and c-Fos expression in the cuneate nucleus (CN) after median nerve chronic constriction injury (CCI). Behavior tests demonstrated that the pre-emptive lidocaine treatment dose dependently delayed and attenuated the development of mechanical allodynia within a 28-day period. Electrophysiological recording was used to examine the changes in injury discharges of the nerves. An increase in frequency of injury discharges was observed and peaked at postelectrical stimulation stage in the presaline group, which was suppressed by lidocaine pre-emptive treatment in a dose-dependent manner. Lidocaine pretreatment also reduced the number of injury-induced NPY-like immunoreactive (NPY-LI) fibers and c-Fos-LI neurons within the CN in a dose-dependent manner. Furthermore, the mean number of c-Fos-LI neurons in the CN was significantly correlated to the NPY reduction level and the sign of mechanical allodynia following CCI.

Partial Text

Pre-emptive analgesia is broadly used in clinical practice for relieving postoperation pain and preventing the subsequent development of chronic neuropathic pain after surgery [1, 2]. In chronic constriction injuries (CCIs) of rat sciatic nerves [3], neuropathic pain behavior was also relieved by pre-emptive treatment of MK-801 [4], nociceptin [5], or lidocaine [6], but little is known about the effect of pre-emptive analgesia on neuropathic pain behavior after median nerve CCI. Attenuating ectopic discharges, originating from the damaged nerves [7, 8] and/or their dorsal root ganglia (DRG) [9], were considered to be one of the pre-emptive analgesia mechanisms to relieve neuropathic pain. Topical or systemic application of local anesthetics has been reported to attenuate ectopic discharges [9, 10]. Clinical studies have also indicated that neuropathic pain is alleviated by application of local anesthetics to the painful target areas [11, 12]. Lidocaine is a local anesthetic that produces a transient analgesic effect in humans affected by neuropathic and postoperative pain [13, 14]. Local pretreatment of lidocaine effectively suppresses injury discharges induced by median nerve transection (MNT) [15], but lack of evidence regarding the median nerve CCI model.

The experiments were inspected and approved by the National Science Council Committee and the Animal Center Committee, College of Medicine, National Taiwan University, Taiwan (IACUCA Approval no. 20030114 and no. 20080267). Ethical guidelines from the International Association for the Study of Pain [23] were followed in the use of animals. Animals were housed under approved circumstances with a 12/12 h light/dark cycle with food and water available ad libitum.

The results of the present study demonstrate the attenuation of TH and reduction of injury discharges following CCI on median nerves by lidocaine pretreatment. Correspondingly, both the level of the injury-induced NPY fibers and the number of injury-induced c-Fos-LI cells in the CN at four weeks after medina nerve CCI were also dose-dependently reduced by lidocaine pretreatment. These results provide a possible mechanism in that the suppression of injury discharges by lidocaine pretreatment not only relieves neuropathic pain but also attenuates the NPY and c-Fos expressions in the CN after CCI.

Our results suggest that lidocaine pre-treatment dose-dependently suppressed injury discharges development to attenuate NPY expression after median nerve injury. This in turn significantly reduces the NPY release to decrease the transmitting of TH to the thalamus and c-Fos expression in the CTNs.