The Role Of Dream In The Regulation Of Formalin Induced Pain In Rapid Eye Movement (REM) Sleep Deprived Rats
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Date
2011-12
Authors
Siran, Rosfaiizah
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Abstract
Rapid eye movement (REM) sleep deprivation has been shown to decrease pain
threshold after various pain stimuli. Down regulatory antagonist modulator
(DREAM) is a transcriptional repressor of prodynorphin gene. This study evaluates
the effect on DREAM in relation to REM sleep deprivation, formalin induced pain or
combination of both; and its relationship to the formalin induced pain behavioural
responses. Male Sprague Dawley rats (250-300 g) were divided into four major
treatments; free moving control (n=36), REM sleep deprivation (n=36), tank control
(n=36) and sleep recovery (n=36). REM sleep deprivation was elicited for 72 hours
using the inverted flower pot technique. Each group was further divided into two
groups which consisted of rats that were either not or subjected to 2.5% formalin
subcutaneous injection. Food consumption and body weight gain were measured
before and after the treatments. The formalin induced pain behavioural responses
were recorded for one hour for rats that subjected to formalin injection. The
ventrobasal thalamic complex of brain (VB) were removed from each group for
immunohistochemistry (n=6), Western blot (n=6) and real-time PCR analysis (n=6)
separately. The ‘inverted flower’ pot technique was confirmed to induce REM sleep
deprivation in the REM sleep deprived and sleep recovered rats by the classic pattern
of hyperphagia with converse loss of body weight. There is a marked hypoalgesia
demonstrated in the second phase of formalin induced pain in the REM sleep
deprived rats. REM sleep deprivation per se did induce morphological change and
reduced the number of DREAM positive neurons (DPN) bilaterally. There was an increase in nuclear DREAM extraction bilaterally. After 72 hours sleep recovery, the
morphological changes still persisted with reduction of the DREAM mRNA
bilaterally. Formalin induced pain reduced the number of DPN bilaterally and
increased the nuclear DREAM extraction contralateral to formalin injected site.
Interestingly, REM sleep deprivation with formalin test increased the number of
DPN, cytoplasmic and nuclear DREAM extraction bilaterally which was more on the
contralateral side except for nuclear extraction. There was a significant decrease of
DREAM mRNA ipsilaterally. However the changes seem to be reversible as no
change is seen in DPN, DREAM extractions and mRNA in sleep recovery group
with formalin induced pain. . In conclusion, REM sleep deprivation and formalin
induced pain per se generated their own distinct effects on DREAM. Nevertheless,
the combination of both treatments resulted in dynamic intracellular changes which
reflected the survival ability of neuronal cells, at least by preserving its basic
functions. As DREAM is a transcriptional regulator of prodynorphin, the functional
survivability of the neuronal cells was reflected behaviourally by the significant
hypoalgesia after both REM sleep deprivation and formalin induced pain.
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Keywords
REM sleep behavior disorder