Chronic sleep restriction increases pain sensitivity over time in a periaqueductal gray and nucleus accumbens dependent manner

Sardi, Natalia Fantin; Lazzarim, Mayla K.; Guilhen, Vinicius A.; Marcílio, Renata S.; Natume, Priscila; Watanabe, Thainá C.; Lima, Marcelo M.S.; Tobaldini, Gláucia; Fischer, Luana

doi:10.1016/j.neuropharm.2018.06.022

Cited by 25 publications

(12 citation statements)

References 46 publications

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“…Genetic association between chronic pain and sleep disturbance makes it especially interesting to search for possible neural mechanisms that may mediate the association. Neuroimaging exploration of the brain mechanisms underlying a bidirectional relationship between sleep disturbance and pain has been dominated by studies mapping the effects of sleep deprivation on pain responsivity [19][20][21][22][23] . Hyperalgesia engendered by sleep loss involves increasing pain reactivity associated with heightened somatosensory cortex activity and a corresponding decrease in insula and striatum activity 22 .…”

Section: Introductionmentioning

confidence: 99%

Polygenic evidence and overlapped brain functional connectivities for the association between chronic pain and sleep disturbance

et al. 2020

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Chronic pain and sleep disturbance are highly comorbid disorders, which leads to barriers to treatment and significant healthcare costs. Understanding the underlying genetic and neural mechanisms of the interplay between sleep disturbance and chronic pain is likely to lead to better treatment. In this study, we combined 1206 participants with phenotype data, resting-state functional magnetic resonance imaging (rfMRI) data and genotype data from the Human Connectome Project and two large sample size genome-wide association studies (GWASs) summary data from published studies to identify the genetic and neural bases for the association between pain and sleep disturbance. Pittsburgh sleep quality index (PSQI) score was used for sleep disturbance, pain intensity was measured by Pain Intensity Survey. The result showed chronic pain was significantly correlated with sleep disturbance (r = 0.171, p-value < 0.001). Their genetic correlation was r g = 0.598 using linkage disequilibrium (LD) score regression analysis. Polygenic score (PGS) association analysis showed PGS of chronic pain was significantly associated with sleep and vice versa. Nine shared functional connectivity (FCs) were identified involving prefrontal cortex, temporal cortex, precentral/ postcentral cortex, anterior cingulate cortex, fusiform gyrus and hippocampus. All these FCs mediated the effect of sleep disturbance on pain and seven FCs mediated the effect of pain on sleep disturbance. The chronic pain PGS was positively associated with the FC between middle temporal gyrus and hippocampus, which further mediated the effect of chronic pain PGS on PSQI score. Mendelian randomization analysis implied a possible causal relationship from chronic pain to sleep disturbance was stronger than that of sleep disturbance to chronic pain. The results provided genetic and neural evidence for the association between pain and sleep disturbance, which may inform future treatment approaches for comorbid chronic pain states and sleep disturbance.

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Section: Introductionmentioning

confidence: 99%

Polygenic evidence and overlapped brain functional connectivities for the association between chronic pain and sleep disturbance

et al. 2020

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“…Also, FOS is closely related to a great number of small drug molecules, such as interferon beta, nadroparin calcium, alcohol, and nimodipine. Sardi et al (2018) also examined FOS expression level in SD rats and observed that chronic sleep restriction significantly increased c-FOS protein, which suggested that the FOS expression level can affect the quality of sleep.…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Gene Signatures Related to Sleep Deprivation

Ruan

Xiao

et al. 2020

Journal of Computational Biology

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This study aimed to identify possible therapeutic targets involved in sleep deprivation (SD) risks. GSE77393 data set was acquired from Gene Expression Omnibus database. Functional analysis and protein-protein interaction (PPI) analysis were used to extract the differentially expressed genes (DEGs) between two SD samples and control samples. Moreover, submodule network with the same function was further extracted and the functional enrichment analysis of corresponding genes was carried out. Afterward, the transcriptional regulation analysis and drug-gene interaction were also carried out to identify the essential genes associated with SD susceptibility. Totally, 121 DEGs, including 90 consistently upregulated DEGs and 31 downregulated DEGs, were screened and the results of functional analysis indicated that upregulated genes were related to learning or memory and response to drug, whereas downregulated DEGs were mainly responsible for response to UV and cell differentiation. Moreover, PPI network and submodule analysis revealed that many key genes (FOS and BDNF) were hub genes and the KEGG enrichment analysis found that these genes such as FOS and BDNF were considerably enriched in pathways such as MAPK signaling pathway, HTLV-I infection, and Hepatitis B. In addition, two genes (FOS and BDNF) with a higher degree were found to be key regulators and play important roles in the transcriptional regulator network and drug-gene interactions, suggesting that these two genes were associated with SD development. FOS and BDNF might be served as the potential targets for SD treatment.

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“…For example, mice subjected to sleep disturbance produce more Ly-6C high monocytes and less hypocretin (a neuropeptide that promotes wakefulness) in the lateral hypothalamus [34]. More importantly, long-term lack of sleep in rats can lead to increased neural activity in the periaqueductal grey (PAG) and the nucleus accumbens (NAc), which are closely related to perception of pain [42]. Studies of animal models of chronic pain have identified some molecular mechanisms and neurobiological activities that are associated with the transition from acute pain to chronic pain.…”

Section: Discussionmentioning

confidence: 99%

Sleep deprivation of rats increases postsurgical expression and activity of L-type calcium channel in the dorsal root ganglion and slows recovery from postsurgical pain

Zhu

et al. 2019

acta neuropathol commun

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Perioperative sleep disturbance is a risk factor for persistent pain after surgery. Clinical studies have shown that patients with insufficient sleep before and after surgery experience more intense and long-lasting postoperative pain. We hypothesize that sleep deprivation alters L-type calcium channels in the dorsal root ganglia (DRG), thus delaying the recovery from post-surgical pain. To verify this hypothesis, and to identify new predictors and therapeutic targets for persistent postoperative pain, we first established a model of postsurgical pain with perioperative sleep deprivation (SD) by administering hind paw plantar incision to sleep deprivation rats. Then we conducted behavioral tests, including tests with von Frey filaments and a laser heat test, to verify sensory pain, measured the expression of L-type calcium channels using western blotting and immunofluorescence of dorsal root ganglia (an important neural target for peripheral nociception), and examined the activity of L-type calcium channels and neuron excitability using electrophysiological measurements. We validated the findings by performing intraperitoneal injections of calcium channel blockers and microinjections of dorsal root ganglion cells with adeno-associated virus. We found that short-term sleep deprivation before and after surgery increased expression and activity of L-type calcium channels in the lumbar dorsal root ganglia, and delayed recovery from postsurgical pain. Blocking these channels reduced impact of sleep deprivation. We conclude that the increased expression and activity of L-type calcium channels is associated with the sleep deprivation-mediated prolongation of postoperative pain. L-type calcium channels are thus a potential target for management of postoperative pain.

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Chronic sleep restriction increases pain sensitivity over time in a periaqueductal gray and nucleus accumbens dependent manner

Cited by 25 publications

References 46 publications

Polygenic evidence and overlapped brain functional connectivities for the association between chronic pain and sleep disturbance

Polygenic evidence and overlapped brain functional connectivities for the association between chronic pain and sleep disturbance

Identification of Potential Gene Signatures Related to Sleep Deprivation

Sleep deprivation of rats increases postsurgical expression and activity of L-type calcium channel in the dorsal root ganglion and slows recovery from postsurgical pain

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