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
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. 1. Introduction 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. Injury to median nerve, neuropeptide Y-like immunoreactive (NPY-LI) fibers are dramatically induced in the lesion side cuneate nucleus (CN), but not detected in the intact side [16]. Furthermore, given an electrical stimulation
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