Impact of chronic nicotine on the development and maintenance of neuropathic hypersensitivity in the rat

Abstract

These findings demonstrate that chronic nicotine produces a stable, long-lasting, mechanical hypersensitivity that exacerbates mechanical sensitivity resulting from peripheral nerve injury. The mechanism of this may involve an increase in spinal neuronal activity and apoptosis.

Increased spinal dynorphin contributes to chronic nicotine-induced mechanical hypersensitivity in the rat

“…As mentioned above, we have previously reported on chronic nicotine-induced mechanical hypersensitivity and our current results support our earlier findings [14]. In contrast, most previous studies have focused on the impact of chronic nicotine on thermal sensitivity.…”

“…Our previous studies indicate that chronic administration of 8.6 mg/kg/day produces plasma nicotine and cotinine concentrations similar to those found in moderately heavy smokers [14]. Although lower doses of chronic nicotine have been shown to produce thermal antinociception [34], chronic administration of 1 mg/kg/day and 0.4 mg/ kg/day nicotine failed to alter mechanical sensitivity to pressure (unpublished observations).…”

“…Paw withdrawal measurements were performed on days 5 and 14 post-osmotic pump implantation. On day 14 post-pump implantation, paw withdrawal thresholds of rats receiving 8.6 mg/kg/ day nicotine were measured at least 1 hour prior to the intrathecal administration of undiluted polyclonal anti-dynorphin A [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] antiserum (Oncogene, San Diego, CA) or normal rabbit serum (NRS). Paw withdrawal thresholds were measured by an observer blinded to treatment at 30 and 60 minutes post-dynorphin antiserum/NRS administration.…”

“…Repeated exposure of rats to cigarette smoke increases tail flick latencies and reduces paw withdrawal thresholds to von Frey filaments [1]. Recently, our laboratory has reported that chronic nicotine increases the sensitivity of normal rats to mechanical pressure and compounds nerve injury-induced mechanical hypersensitivity following peripheral nerve injury [14].…”

“…Although the mechanism of chronic nicotine-induced mechanical hypersensitivity is unknown, the transcription factor, cAMP response element binding protein (CREB), is phosphorylated in the spinal cords of chronic nicotine-treated rats [14]. A considerable amount of evidence has accumulated to demonstrate the importance of prolonged CREB activation in central sensitization [21] and a number of pain-related genes are upregulated by pCREB including the immediate early gene c-fos [16], brain-derived neurotrophic factor (BDNF) [4], calcitonin gene-related peptide (CGRP) [8], the neurokinin 1 receptor [2], and prodynorphin [16].…”