Obstructive Sleep Apnea and Pain Intensity in Young Adults.

Rationale: Prior research studies on the association of obstructive sleep apnea (OSA) and pain intensity have examined older patients; there is a need to understand the relationship between OSA and pain intensity among younger adults.Objectives: To examine whether young adults with diagnosed OSA are more likely to report higher pain intensity compared with those without OSA.Methods: We conducted a cross-sectional analysis of a cohort study of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn veterans who had at least one visit to a Veterans Health Administration primary care clinic between 2001 and 2014. OSA was identified using one inpatient or two outpatient International Classification of Diseases, Ninth Revision codes from electronic medical records. Average pain intensity (based on the self-reported 0-10 numeric rating scale over a 12-month period) was categorized as no pain/mild (0-3; no pain) and moderate/severe (4-10; significant pain). Covariates included age, sex, education, race, mental health diagnoses, headache diagnoses, pain diagnoses, hypertension, diabetes, body mass index, and smoking status. Multivariate logistic regression models were used, and multiple imputation was performed to generate values for missing variables.Results: We identified 858,226 young adults (mean age 30 yr [SD = 7]), of whom 91,244 (10.6%) had a diagnosis of OSA and 238,587 (27.8%) reported moderate/severe pain for the 12-month average. with young adults without OSA, those with OSA were more likely to report moderate/severe pain intensity (adjusted odds ratio, 1.09; 95% confidence interval, 1.08-1.11) even after controlling for covariates.Conclusions: We found that young adults with OSA have greater odds of comorbid moderate/severe pain. Because of the high prevalence of chronic pain in younger adults, this study highlights the need to understand the impact of OSA diagnosis and treatment on pain intensity. Future work is needed to determine the role of effective OSA treatment on pain intensity over time in these young adults.

Associations between obstructive sleep apnea and prescribed opioids among veterans.

ABSTRACT: Sleep disruption caused by obstructive sleep apnea (OSA) may be associated with hyperalgesia and may contribute to poor pain control and use of prescription opioids. However, the relationship between OSA and opioid prescription is not well described. We examine this association using cross-sectional data from a national cohort of veterans from recent wars enrolled from October 1, 2001 to October 7, 2014. The primary outcome was the relative risk ratio (RRR) of receiving opioid prescriptions for acute (<90 days/year) and chronic (≥90 days/year) durations compared with no opioid prescriptions. The primary exposure was a diagnosis of OSA. We used multinomial logistic regression to control for factors that may affect diagnosis of OSA or receipt of opioid prescriptions. Of the 1,149,874 patients (mean age 38.0 ± 9.6 years) assessed, 88.1% had no opioid prescriptions, 9.4% had acute prescriptions, and 2.5% had chronic prescriptions. Ten percent had a diagnosis of OSA. Patients with OSA were more likely to be older, male, nonwhite, obese, current or former smokers, have higher pain intensity, and have medical and psychiatric comorbidities. Controlling for these differences, patients with OSA were more likely to receive acute (RRR 2.02 [95% confidence interval 1.98-2.06]) or chronic (RRR 2.15 [2.09-2.22]) opioids. Further dividing opioid categories by high vs low dosage did not yield substantially different results. Obstructive sleep apnea is associated with a two-fold likelihood of being prescribed opioids for pain. Clinicians should consider incorporating OSA treatment into multimodal pain management strategies; OSA as a target for pain management should be further studied.

RNA ligation in neurons by RtcB inhibits axon regeneration.

Activity of the RNA ligase RtcB has only two known functions: tRNA ligation after intron removal and XBP1 mRNA ligation during activation of the unfolded protein response. Here, we show that RtcB acts in neurons to inhibit axon regeneration after nerve injury. This function of RtcB is independent of its basal activities in tRNA ligation and the unfolded protein response. Furthermore, inhibition of axon regeneration is independent of the RtcB cofactor archease. Finally, RtcB is enriched at axon termini after nerve injury. Our data indicate that neurons have co-opted an ancient RNA modification mechanism to regulate specific and dynamic functions and identify neuronal RtcB activity as a critical regulator of neuronal growth potential.

EphA7 signaling guides cortical dendritic development and spine maturation.

The process by which excitatory neurons are generated and mature during the development of the cerebral cortex occurs in a stereotyped manner; coordinated neuronal birth, migration, and differentiation during embryonic and early postnatal life are prerequisites for selective synaptic connections that mediate meaningful neurotransmission in maturity. Normal cortical function depends upon the proper elaboration of neurons, including the initial extension of cellular processes that lead to the formation of axons and dendrites and the subsequent maturation of synapses. Here, we examine the role of cell-based signaling via the receptor tyrosine kinase EphA7 in guiding the extension and maturation of cortical dendrites. EphA7, localized to dendritic shafts and spines of pyramidal cells, is uniquely expressed during cortical neuronal development. On patterned substrates, EphA7 signaling restricts dendritic extent, with Src and Tsc1 serving as downstream mediators. Perturbation of EphA7 signaling in vitro and in vivo alters dendritic elaboration: Dendrites are longer and more complex when EphA7 is absent and are shorter and simpler when EphA7 is ectopically expressed. Later in neuronal maturation, EphA7 influences protrusions from dendritic shafts and the assembling of synaptic components. Indeed, synaptic function relies on EphA7; the electrophysiological maturation of pyramidal neurons is delayed in cultures lacking EphA7, indicating that EphA7 enhances synaptic function. These results provide evidence of roles for Eph signaling, first in limiting the elaboration of cortical neuronal dendrites and then in coordinating the maturation and function of synapses.