Elsevier

Brain Research

Volume 900, Issue 2, 11 May 2001, Pages 261-267
Brain Research

Research report
Effects of rapid eye movement (REM) sleep deprivation on pain sensitivity in the rat

https://doi.org/10.1016/S0006-8993(01)02320-4Get rights and content

Abstract

The relationship between pain and sleep seems to be reciprocal: if pain may interrupt or disturb sleep, poor sleep can also influence pain perception. However the influence of sleep disturbances on pain sensitivity remain poorly investigated. The aim of this study was to assess the effect of REM sleep deprivation on the reaction of rats subjected to different noxious stimuli. In each experiment 16 Wistar male rats were randomly assigned to two groups: controls (n=8), and REM sleep deprived rats (n=8). REM sleep deprivation was elicited using the ‘inverted flower pot’ technique. Four different experiments were performed to assess the sensitivity to mechanical (vocalization threshold in paw pressure), thermal (tail withdrawal latency in hot water immersion), electrical (envelope of 2nd peep in tail shock test) and chemical (analgesic behavior in formalin test) noxious stimuli. All experiments were performed over a 5-day period with baseline (day 1, day 2) in a dry environment and REM sleep deprivation (day 3, day 4 and day 5) in a wet environment. Under wet conditions, vocalization threshold in the paw pressure test (−20%, P=0.005), and tail withdrawal latency in the hot water immersion test (−21%, P=0.006) were significantly lower, and the envelope of 2nd peep in the tail electrical shock was significantly greater (+78%, P=0.009), in REM sleep deprived rats compared to controls. However, under wet conditions the mean duration of nociceptive behaviors in the formalin test did not differ between the two groups. In conclusion, REM sleep deprivation induces a significant increase in the behavioral responses to noxious mechanical, thermal and electrical stimuli in rats.

Introduction

The interaction between sleep and pain is generating considerable interest in an endeavor to improve the management of many patients suffering from pain and poor sleep [36].

Pain has been reported to be a leading cause of insomnia in medical illness [10], [24]. Animal studies also support the evidence that pain may cause disturbed sleep. After a formalin injection in cats, an increase in sleep onset latency, a decrease in rapid eye movement (REM) sleep and deep slow wave sleep amounts were found [8]. In the same work, on days 1 and 2 after formalin injection, pain manifestations displayed a gradual decrease, while total sleep time slowly returned to normal levels. Landis et al. [26], [27] examined the diurnal sleep–wake patterns in the adjuvant arthritic rat. In contrast to controls, arthritic rats lacked a normal diurnal variation in sleep and wakefulness. Arthritic rats also had a marked increase in the fragmentation of their sleep and a decrease in the duration of episodes of deep sleep [26], [27] and REM sleep [27]. These results suggest that the amount of sleep during pain depends on the level of pain intensity.

On the other hand, non-restorative sleep has been considered to produce a decrease in pressure pain thresholds and an increase in stiffness in rheumatoid arthritis and fibromyalgia patients [11], [32]. Furthermore, recently we showed that sleep recovery consecutive to REM sleep deprivation significantly increases pressure pain threshold in rat [35].

Thus, the relationship between pain and sleep appears to be reciprocal: if pain may interrupt or disturb sleep, poor sleep can also influence pain perception. However the influence of sleep disturbances on pain sensitivity is still poorly investigated. Such disturbances are often associated with chronic pain and could participate in the maintenance of pain symptoms. The aim of this study was to assess the effect of REM sleep deprivation on the reaction of rats submitted to mechanical, thermal, electrical and chemical noxious stimuli.

Section snippets

Animals

Sixty-four Wistar male rats aged 48–51 days and weighing 276–300 g were used. In each experiment 16 rats were randomly assigned to two groups: controls (n=8) and REM sleep deprived rats (n=8). The animals were housed in individual cages (26×28×31 cm) with ad libitum access to food and water. They were kept in a quiet room with an ambient temperature of 22–24°C and maintained on a 12-h light, 12-h dark cycle (lights on at 07:00 h). Three days were allowed for adaptation to laboratory conditions

Between-group comparisons (Fig. 1)

At baseline, vocalization threshold was not different between two groups (352±12 vs. 331±11; P=0.3). Under wet conditions, vocalization threshold was significantly lower (−20%) in REM sleep deprived rats compared to control rats (251±16 vs. 314±17; P=0.005).

Intragroup comparisons (Fig. 1)

In REM sleep deprived rats, relative to baseline, a large decrease (−29%) was observed in the vocalization threshold (352±12 vs. 251±16; P<0.0001). In the control group, no statistical difference was noted between baseline and wet condition

Discussion

REM sleep deprivation induces a significant increase in the behavioral manifestations of pain to mechanical, thermal and electrical noxious stimuli in rats. However, after REM sleep deprivation, no difference was found in the reaction to noxious chemical stimulus (formalin).

Acknowledgements

This work was supported by Laboratoire L. Lafon (Maisons-Alfort, France). We are grateful to Dr Annette Gross for her helpful comments on the manuscript.

References (45)

  • D.J McGinty et al.

    Dorsal raphe neurons: depression of firing during sleep in cats

    Brain Res.

    (1976)
  • W.B Mendelson et al.

    The flower pot technique of rapid eye movement (REM) sleep deprivation

    Pharmacol. Biochem. Behav.

    (1974)
  • R Necker et al.

    Noxious thermal input from the rat tail: modulation by descending inhibitory influences

    Pain

    (1978)
  • S.H Onen et al.

    Vocalization thresholds related to noxious paw pressure are decreased by paradoxical sleep deprivation and increased after sleep recovery in rat

    Neurosci. Lett.

    (2000)
  • C Shapiro et al.

    Protein synthesis in rat brain during sleep

    Neuropharmacology

    (1981)
  • M Thakkar et al.

    Effect of REM sleep deprivation on rat brain acetylcholinesterase

    Pharmacol. Biochem. Behav.

    (1991)
  • A Tjølsen et al.

    The formalin test: an evaluation of the method

    Pain

    (1992)
  • S Tufik et al.

    Does REM sleep deprivation induce subsensitivity of presynaptic dopamine or postsynaptic acetylcholine receptors in the rat brain?

    Eur. J. Pharmacol.

    (1987)
  • O.E Ukponmwan et al.

    REM sleep deprivation decreases the antinociceptive property of enkephalinase-inhibition, morphine and cold-water-swim

    Gen. Pharmacol.

    (1984)
  • B.D Youngblood et al.

    Sleep deprivation by the ‘flower pot’ technique and spatial reference memory

    Physiol. Behav.

    (1997)
  • M Zimmermann

    Ethical guidelines for investigations of experimental pain in conscious animals (editorial)

    Pain

    (1983)
  • F.V Abott et al.

    Effects of morphine, pentobarbital and amphetamine on formalin-induced behaviours in infant rats: sedation versus specific suppression of pain

    Pain

    (1995)
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