Nucleus Accumbens mediates the pronociceptive effect of sleep deprivation: the role of adenosine A2A and dopamine D2 receptors.

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Nucleus Accumbens mediates the pronociceptive effect of sleep deprivation: the role of adenosine A2A and dopamine D2 receptors.

Pain. 2017 Sep 25;:

Authors: Sardi NF, Tobaldini G, Morais RN, Fischer L

Abstract
Sleep disorders increase pain sensitivity and the risk of developing painful conditions; however the underlying mechanisms are poorly understood. It has been suggested that Nucleus Accumbens (NAc) influences sleep-wake cycle by means of a balance between adenosine activity at A2A receptors and dopamine activity at D2 receptors. Since the NAc also plays an important role in pain modulation, we hypothesized that the NAc and its A2A and D2 receptors mediate the pronociceptive effect of REM (rapid eye movement) sleep deprivation. We found that 24h of REM sleep deprivation induced an intense pronociceptive effect in Wistar rats that decreases progressively over a sleep rebound period. Although the level of fecal glucocorticoid metabolites increased with sleep deprivation within group, it did not differ between sleep deprived and control groups, indicating a stress response with similar magnitude between groups. The pronociceptive effect of REM sleep deprivation was prevented by excitotoxic lesion (NMDA, 5.5μg) of NAc and reverted by its acute blockade (Qx-314, 2%). The administration of an A2A receptor antagonist (SCH-58261, 7ng) or a D2 receptor agonist (Piribedil, 6μg) into the NAc increased home cage activity and blocked the pronociceptive effect of REM sleep deprivation. Complementarily, an A2A receptor agonist (CGS-21680, 24ng) impaired the reversal of the pronociceptive effect and decreased home cage activity, as it did a D2 receptor antagonist (Raclopride, 5μg). REM sleep deprivation did not affect the expression of c-fos protein in NAc. These data suggest that sleep deprivation increases pain by increasing NAc adenosinergic A2A activity and by decreasing NAc dopaminergic D2 activity.

PMID: 28953191 [PubMed - as supplied by publisher]

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