Abstract
Repeated nicotine administration has been associated with increased paradoxical sleep in rats and antinociceptive properties, whereas paradoxical sleep deprivation (PSD) elicits pronociceptive and inflammatory responses. Thus, we aimed to evaluate the effect of repeated nicotine administration and its withdrawal combined with PSD on pain sensitivity and inflammatory markers. Sixty adult male Wistar rats were subjected to repeated injections of saline (SAL) or nicotine (NIC) for 12 days or 7 days of nicotine followed by acute mecamylamine administration on day 8 to precipitate nicotine abstinence (ABST). On day 9, the animals were submitted to PSD for 72 h or remained in control condition (CTRL); on day 12, thermal pain threshold was assessed by the hot plate test. PSD significantly decreased the latency to paw withdrawal in all groups compared to their respective controls. ABST-PSD animals presented higher levels of interleukin (IL)-6 compared to all groups, except ABST-CTRL. After adjustment for weight loss, IL-6, IL-4 and tumor necrosis factor alpha, ABST-PSD was associated with the lowest pain threshold. Nicotine and IL-4 levels were predictors of higher pain threshold. Hyperalgesia induced by PSD prevailed over the antinociceptive action of nicotine, while the association between PSD and ABST synergistically increased IL-6 concentrations and decreased pain threshold.
Highlights
Repeated nicotine administration has been associated with increased paradoxical sleep in rats and antinociceptive properties, whereas paradoxical sleep deprivation (PSD) elicits pronociceptive and inflammatory responses
Considering that nicotine and PSD exert opposed effects on nociception, this work aimed to evaluate the effects of repeated nicotine administration and its withdrawal combined with PSD on pain sensitivity
On day 9, the animals were distributed into two conditions: normal sleep (CTRL) or 72 h of PSD, resulting in six experimental groups
Summary
Repeated nicotine administration has been associated with increased paradoxical sleep in rats and antinociceptive properties, whereas paradoxical sleep deprivation (PSD) elicits pronociceptive and inflammatory responses. We aimed to evaluate the effect of repeated nicotine administration and its withdrawal combined with PSD on pain sensitivity and inflammatory markers. Hyperalgesia induced by PSD prevailed over the antinociceptive action of nicotine, while the association between PSD and ABST synergistically increased IL-6 concentrations and decreased pain threshold. Acute nicotine administration has been reported to decrease both paradoxical sleep and slow-wave sleep in a dose-dependent manner[2]. We hypothesized that chronic nicotine treatment would at least partially counteract the effects of PSD on pain sensitivity in association with higher anti-inflammatory and lower pro-inflammatory cytokines levels. We aimed to investigate the independent predictors of pain threshold
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