Samar Khoury

A Significant Increase in Breathing Amplitude Precedes Sleep Bruxism

BACKGROUND Sleep bruxism (SB) is a stereotyped movement disorder that is characterized by rhythmic masticatory muscle activity (RMMA) and tooth grinding. Evidence has suggested that SB is associated with sleep arousals and that most RMMA episodes are preceded by physiologic changes occurring in sequence, namely, a rise in autonomic sympathetic-cardiac activity followed by a rise in the frequency of EEG and suprahyoid muscle activity. In the present study, we hypothesize that an increase in respiration also characterizes the onset of SB within the arousal sequence. METHODS Polygraphic sleep recordings of 20 SB subjects without any sleep-related breathing disorders were analyzed for changes in respiration (ie, root mean square, area under the curve, peak, peak-to-peak, and length) extracted from a nasal cannula signal. Variables were analyzed and compared using analysis of variance and correlation tests. RESULTS Measurements of respiration showed significant changes over time. Four seconds before RMMA muscle activity, the amplitude of respiration is already increased (8 to 23%); the rise is higher at the onset of the suprahyoid activity (60 to 82% 1 s before RMMA); the rise is maximal during RMMA (108 to 206%) followed by a rapid return to levels preceding RMMA. A positive and significant correlation was found between the frequencies of RMMA episodes and the amplitude of breath (R(2) = 0.26; p = 0.02). The amplitude of respiratory changes was 11 times higher when arousal was associated with RMMA in comparison to arousal alone. CONCLUSIONS To our knowledge, this is the first report showing that RMMA-SB muscle activity is associated with a rise in respiration within arousal.

Rapid EEG Activity during Sleep Dominates in Mild Traumatic Brain Injury Patients with Acute Pain

Chronic pain is a highly prevalent post-concussion symptom occurring in a majority of patients with mild traumatic brain injury (mTBI). About half of patients with mTBI report sleep-wake disturbances. It is known that pain can alter sleep quality in this population, but the interaction between pain and sleep is not fully understood. This study aimed to identify how pain affects subjective sleep (Pittsburgh Sleep Quality Index [PSQI]), sleep architecture, and quantitative electroencephalographic (qEEG) brain activity after mTBI. Twenty-four mTBI patients complaining of sleep-wake disturbances, with and without pain (8 and 16, respectively), were recruited 45 (±22.7) days post-trauma on average. Data were compared with those of 18 healthy controls (no sleep or pain complaints). The PSQI, sleep architecture, and qEEG activity were analyzed. Pain was assessed using questionnaires and a 100-mm visual analogue scale. Patients with mTBI reported three times poorer sleep quality than controls on the PSQI. Sleep architecture significantly differed between patients with mTBI and controls but was within normal range. Global qEEG showed lower delta (deep sleep) and higher beta and gamma power (arousal) at certain EEG derivations in patients with mTBI compared with controls (p<0.04). Patients with mTBI with pain, however, showed greater increase in rapid EEG frequency bands, mostly during REM sleep, and beta bands in non-REM sleep compared with patients with mTBI without pain and controls (p<0.001). Pain in patients with mTBI was associated with more rapid qEEG activity, mostly during REM sleep, suggesting that pain is associated with poor sleep and is a critical factor in managing post-concussion symptoms.

Postoperative sleep disruptions: A potential catalyst of acute pain?

Despite the substantial advances in the understanding of pain mechanisms and management, postoperative pain relief remains an important health care issue. Surgical patients also frequently report postoperative sleep complaints. Major sleep alterations in the postoperative period include sleep fragmentation, reduced total sleep time, and loss of time spent in slow wave and rapid eye movement sleep. Clinical and experimental studies show that sleep disturbances may exacerbate pain, whereas pain and opioid treatments disturb sleep. Surgical stress appears to be a major contributor to both sleep disruptions and altered pain perception. However, pain and the use of opioid analgesics could worsen sleep alterations, whereas sleep disruptions may contribute to intensify pain. Nevertheless, little is known about the relationship between postoperative sleep and pain. Although the sleep-pain interaction has been addressed from both ends, this review focuses on the impact of sleep disruptions on pain perception. A better understanding of the effect of postoperative sleep disruptions on pain perception would help in selecting patients at risk for more severe pain and may facilitate the development of more effective and safer pain management programs.

Pain and sleep in post-concussion/mild traumatic brain injury

Abstract Concussion after a force to the head is called mild traumatic brain injury (mTBI). Approximately 1 in 5 patients with mTBI will develop chronic pain (headache and widespread pain, possibly of central origin) and/or sleep problems (insomnia, disordered breathing, periodic limb movements). However, the predisposing mechanisms for chronic pain in patients with mTBI are unknown. Mild traumatic brain injury is a rare model to prospectively assess the risk factors and mechanisms for pain chronification from the injury onset in the absence of pretrauma comorbidity or medication. In the acute phase, headaches and sleep disturbances seem to predict the poorest long-term cognitive and mood outcomes. Although recent studies suggest that certain brain biomarkers and mood alterations (eg, anxiety, depression) contribute, the causality of chronic pain remains unclear. In mTBI patients with pain, poor sleep quality was correlated with fast beta and gamma electroencephalographic activity in frontal, central, and occipital electroencephalographic (EEG) derivations in all sleep stages. Sleep recuperative function seems to be disturbed by persistent wake EEG activity, corroborating patient complaints such as feeling awake when asleep. Pain and sleep management in mTBI is not yet evidence-based. Treatments include cognitive behavioral and light therapies, medications, and continuous positive airway pressure (CPAP) or oral appliances for disordered sleep breathing. Customized approaches are indicated for mTBI, pain, and sleep complaints. Further studies in pediatric, sport, and transportation populations are needed to prevent TBI chronification. Improvements are emerging in biomarker sensitivity and specificity and management strategies for TBI, pain, and sleep comorbidities.

Genetic predictors of human chronic pain conditions.

Chronic pain conditions are multifactorial disorders with a high frequency in the population. Their pathophysiology is often unclear, and treatment is inefficient. During the last 20years, genetic linkage analysis and association studies have made considerable strides toward identifying key molecular contributors to the onset and maintenance of chronic pain. Here, we review the genetic variants that have been implicated in chronic pain conditions, divided into the following etiologically-grouped categories: migraine, musculoskeletal pain disorders, neuropathic pain disorders, and visceral pain disorders. In rare familial monogenic pain conditions several strong-effect mutations have been identified. In contrast, the genetic landscape of common chronic pain conditions suggests minor contributions from a large number of single nucleotide polymorphisms representing different functional pathways. A comprehensive survey of up-to-date genetic association results reveals migraine and musculoskeletal pain to be the most investigated chronic pain disorders, in which nearly half of identified genetic variability alters neurotransmission pathways.

Sleep and wake disturbances following traumatic brain injury

Traumatic brain injury (TBI) is a major health concern in industrialised countries. Sleep and wake disturbances are among the most persistent and disabling sequelae after TBI. Yet, despite the widespread complaints of post-TBI sleep and wake disturbances, studies on their etiology, pathophysiology, and treatments remain inconclusive. This narrative review aims to summarise the current state of knowledge regarding the nature of sleep and wake disturbances following TBI, both subjective and objective, spanning all levels of severity and phases post-injury. A second goal is to outline the various causes of post-TBI sleep-wake disturbances. Globally, although sleep-wake complaints are reported in all studies and across all levels of severity, consensus regarding the objective nature of these disturbances is not unanimous and varies widely across studies. In order to optimise recovery in TBI survivors, further studies are required to shed light on the complexity and heterogeneity of post-TBI sleep and wake disturbances, and to fully grasp the best timing and approach for intervention.

Are NREM sleep characteristics associated to subjective sleep complaints after mild traumatic brain injury

INTRODUCTION Sleep complaints are common after mild traumatic brain injury (mTBI). While recent findings suggest that sleep macro-architecture is preserved in mTBI, features of non-rapid eye movement (NREM) sleep micro-architecture including electroencephalography (EEG) spectral power, slow waves (SW), and sleep spindles could be affected. This study aimed to compare NREM sleep in mTBI and healthy controls, and explore whether NREM sleep characteristics correlate with sleep complaints in these groups. METHODS Thirty-four mTBI participants (mean age: 34.2 ± 11.9 yrs; post-injury delay: 10.5 ± 10.4 weeks) and 29 age-matched controls (mean age: 32.4 ± 8.2 yrs) were recruited for two consecutive nights of polysomnographic (PSG) recording. Spectral power was computed and SW and spindles were automatically detected in three derivations (F3, C3, O1) for the first three sleep cycles. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). RESULTS mTBI participants reported significant poorer sleep quality than controls on the PSQI and showed significant increases in beta power during NREM sleep at the occipital derivation only. Conversely, no group differences were found in SW and spindle characteristics. Interestingly, changes in NREM sleep characteristics were not associated with mTBI estimation of sleep quality. CONCLUSIONS Compared to controls, mTBI were found to have enhanced NREM beta power. However, these changes were not found to be associated with the subjective evaluation of sleep. While increases in beta bands during NREM sleep may be attributable to the occurrence of a brain injury, they could also be related to the presence of pain and anxiety as suggested in one prior study.

Pain with traumatic brain injury and psychological disorders

&NA; Traumatic brain injury (TBI) is the cause for long‐term disability in more than 3 million patients in the US alone, with chronic pain being the most frequently reported complain. To date, predisposing mechanisms for chronic pain in TBI patients are largely unknown. Psychological disorders, including post‐traumatic stress disorder, depression and anxiety following TBI are commonly reported comorbidities to post‐traumatic pain. Long term consequences can be debilitating and affect quality of life even when the injury is mild. In this review, we present the most commonly reported chronic pain conditions across the spectrum of severity of TBI, mainly focusing on mild TBI. We discuss chronic post‐ traumatic headaches, widespread pain as well as post‐traumatic central pain. We discuss pain in the context of injury severity and military versus civilian populations. We are only starting to understand the biological mechanisms behind post‐traumatic pain and associated psychological distress following TBI, with genetic, biochemical and imaging studies pointing to the dopaminergic, neurotrophic factors and the role of Apolipoprotein. Physiological and neurological mechanisms are proposed to partially explain this interaction between post‐traumatic pain and psychological distress. Nevertheless, the evidence for the role of structural brain damage remains incomplete and to a large extent debatable, as it is still difficult to establish clear causality between brain trauma and chronic pain. Finally, general aspects of management of chronic pain post‐TBI are addressed.

The Human Pain Genetics Database (HPGDB): a resource dedicated to human pain genetics research

Abstract The Human Pain Genetics Database (HPGDB) is a comprehensive variant-focused inventory of genetic contributors to human pain. After curation, the HPGDB currently includes 294 studies reporting associations between 434 distinct genetic variants and various pain phenotypes. Variants were then submitted to a comprehensive analysis. First, they were validated in an independent high-powered replication cohort by testing the association of each variant with 10 different pain phenotypes (n = 1320-26,973). One hundred fifty-five variants replicated successfully (false discovery rate 20%) in at least one pain phenotype, and the association P values of the HPGDB variants were significantly lower compared with those of random controls. Among the 155 replicated variants, 21 had been included in the HPGDB because of their association with analgesia-related and 13 with nociception-related phenotypes, confirming analgesia and nociception as pathways of vulnerability for pain phenotypes. Furthermore, many genetic variants were associated with multiple pain phenotypes, and the strength of their association correlated between many pairs of phenotypes. These genetic variants explained a considerable amount of the variance between different pairs of pain phenotypes, indicating a shared genetic basis among pain phenotypes. In addition, we found that HPGDB variants show many pleiotropic associations, indicating that genetic pathophysiological mechanisms are also shared among painful and nonpainful conditions. Finally, we demonstrated that the HPGDB data set is significantly enriched for functional variants that modify gene expression, are deleterious, and colocalize with open chromatin regions. As such, the HPGDB provides a validated data set that represents a valuable resource for researchers in the human pain field.

Response to the letter from Professor Helena Hachul and colleagues

Thank you for your interest regarding our recent paper entitled: “Individuals with pain need more sleep in the early stage of mild traumatic brain injury (mTBI)” published in Sleep Medicine [1]. Overall, we found that 29% of recovering mTBI individuals express an increased need for sleep (suggesting a subgroup effect) at one month post-trauma, particularly in the context of unrelieved acute pain (1). The suggested hypothesis of increased sleep needs as a compensatory mechanism for pain after TBI is a very interesting one. However, due to our study design and the lack of evidencebased data in the TBI literature, we refrained from including it in our paper. Still, we fully agree with your suggestion that an increased need for sleep and napping in early recovering TBI with pain may underlie more complex physiological processes (eg, inflammatory, immune, endocrine, chemical) related to brain recovery. Future studies on mTBI should undoubtedly try to unravel the influence or role of sleep restorative properties and their mutual influence on positive or negative TBI recovery. The following questions would be a good starting point: