Complex Multilocus Effects of Catechol-O-Methyltransferase Haplotypes Predict Pain and Pain Interference 6 Weeks After Motor Vehicle Collision

Catechol-O-methyltransferase, encoded by COMT gene, is the primary enzyme that metabolizes catecholamines. COMT haplotypes have been associated with vulnerability to persistent non-traumatic pain. In this prospective observational study, we investigated the influence of COMT on persistent pain and pain interference with life functions after motor vehicle collision (MVC) in 859 European American adults for whom overall pain (0–10 numeric rating scale) and pain interference (Brief Pain Inventory) were assessed at week 6 after MVC. Ten single nucleotide polymorphisms (SNPs) spanning the COMT gene were successfully genotyped, nine were present in three haploblocks: block 1 (rs2020917, rs737865, rs1544325), block 2 (rs4633, rs4818, rs4680, rs165774) and block 3 (rs174697, rs165599). After adjustment for multiple comparisons, haplotype TCG from block 1 predicted decreased pain interference (p =.004). The pain-protective effect of the low pain sensitivity (LPS, CGGG) haplotype from block 2 was only observed if at least one TCG haplotype was present in block 1 (haplotype × haplotype interaction p=.002 and <.0001 for pain and pain interference, respectively). Haplotype AG from block 3 was associated with pain and interference in males only (sex × haplotype interaction p=.005 and .0005, respectively). These results suggest that genetic variants in the distal promoter are important contributors to the development of persistent pain after MVC, directly and via the interaction with haplotypes in the coding region of the gene

Genetic variant rs3750625 in the 3′UTR of ADRA2A affects stress-dependent acute pain severity after trauma and alters a microRNA-34a regulatory site

α2A adrenergic receptor (α2A-AR) activation has been shown in animal models to play an important role in regulating the balance of acute pain inhibition vs. facilitation after both physical and psychological stress. To our knowledge the influence of genetic variants in the gene encoding α2A-AR, ADRA2A, on acute pain outcomes in humans experiencing traumatic stress has not been assessed. In this study, we tested whether a genetic variant in the 3′UTR of ADRA2A, rs3750625, is associated with acute musculoskeletal pain (MSP) severity following motor vehicle collision (MVC, n = 948) and sexual assault (n = 84), and whether this influence was affected by stress severity. We evaluated rs3750625 because it is located in the seed binding region of miR-34a, a microRNA (miRNA) known to regulate pain and stress responses. In both cohorts, the minor allele at rs3750625 was associated with increased MSP in distressed individuals (stress*rs3750625 p = 0.043 for MVC cohort and p = 0.007 for sexual assault cohort). We further found that (1) miR-34a binds the 3′UTR of ADRA2A, (2) the amount of repression is greater when the minor (risk) allele is present, (3) miR-34a in the IMR-32 adrenergic neuroblastoma cell line affects ADRA2A expression, (4) miR-34a and ADRA2A are expressed in tissues known to play a role in pain and stress, (5) following forced swim stress exposure, rat peripheral nerve tissue expression changes are consistent with miR-34a regulation of ADRA2A. Together these results suggest that ADRA2A rs3750625 contributes to post-stress MSP severity by modulating miR-34a regulation

Chronic widespread pain after motor vehicle collision typically occurs through immediate development and nonrecovery: results of an emergency department-based cohort study

Motor vehicle collision (MVC) can trigger chronic widespread pain (CWP) development in vulnerable individuals. Whether such CWP typically develops via the evolution of pain from regional to widespread or via the early development of widespread pain with non-recovery is currently unknown. We evaluated the trajectory of CWP development (American College of Rheumatology criteria) among 948 European-American individuals who presented to the emergency department (ED) for care in the early aftermath of MVC. Pain extent was assessed in the ED and 6 weeks, 6 months, and 1 year after MVC on 100%, 91%, 89%, and 91% of participants, respectively. Individuals who reported prior CWP at the time of ED evaluation (n = 53) were excluded. Trajectory modeling identified a two-group solution as optimal, with the Bayes Factor value (138) indicating strong model selection. Linear solution plots supported a non-recovery model. While the number of body regions with pain in the non-CWP group steadily declined, the number of body regions with pain in the CWP trajectory group (192/895, 22%) remained relatively constant over time. These data support the hypothesis that individuals who develop CWP after MVC develop widespread pain in the early aftermath of MVC which does not remit

Digital receivers for low-frequency radio telescopes UTR-2, URAN, GURT

This paper describes digital radio astronomical receivers used for decameter and meter wavelength observations. This paper describes digital radio astronomical receivers used for decameter and meter wavelength observations. Since 1998, digital receivers performing on-the-fly dynamic spectrum calculations or waveform data recording without data loss have been used at the UTR-2 radio telescope, the URAN VLBI system, and the GURT new generation radio telescope. Here we detail these receivers developed for operation in the strong interference environment that prevails in the decameter wavelength range. Data collected with these receivers allowed us to discover numerous radio astronomical objects and phenomena at low frequencies, a summary of which is also presented.Comment: 24 pages, 15 figure

Using emergency department-based inception cohorts to determine genetic characteristics associated with long term patient outcomes after motor vehicle collision: Methodology of the CRASH study

<p>Abstract</p> <p>Background</p> <p>Persistent musculoskeletal pain and psychological sequelae following minor motor vehicle collision (MVC) are common problems with a large economic cost. Prospective studies of pain following MVC have demonstrated that demographic characteristics, including female gender and low education level, and psychological characteristics, including high pre-collision anxiety, are independent predictors of persistent pain. These results have contributed to the psychological and social components of a biopsychosocial model of post-MVC pain pathogenesis, but the biological contributors to the model remain poorly defined. Recent experimental studies indicate that genetic variations in adrenergic system function influence the vulnerability to post-traumatic pain, but no studies have examined the contribution of genetic factors to existing predictive models of vulnerability to persistent pain.</p> <p>Methods/Design</p> <p>The Project CRASH study is a federally supported, multicenter, prospective study designed to determine whether variations in genes affecting synaptic catecholamine levels and alpha and beta adrenergic receptor function augment social and psychological factors in a predictive model of persistent musculoskeletal pain and posttraumatic stress disorder (PTSD) following minor MVC. The Project CRASH study will assess pain, pain interference and PTSD symptoms at 6 weeks, 6 months, and 1 year in approximately 1,000 patients enrolled from 8 Emergency Departments in four states with no-fault accident laws.</p> <p>Discussion</p> <p>The results from this study will provide insights into the pathophysiology of persistent pain and PTSD following MVC and may serve to improve the ability of clinicians and researchers to identify individuals at high risk for adverse outcomes following minor MVC.</p

Gender Differences in Acute and Chronic Pain in the Emergency Department: Results of the 2014 Academic Emergency Medicine Consensus Conference Pain Section

Pain is a leading public health problem in the United States, with an annual economic burden of more than $630 billion, and is one of the most common reasons that individuals seek emergency department (ED) care. There is a paucity of data regarding sex differences in the assessment and treatment of acute and chronic pain conditions in the ED. The Academic Emergency Medicine consensus conference convened in Dallas, Texas, in May 2014 to develop a research agenda to address this issue among others related to sex differences in the ED. Prior to the conference, experts and stakeholders from emergency medicine and the pain research field reviewed the current literature and identified eight candidate priority areas. At the conference, these eight areas were reviewed and all eight were ratified using a nominal group technique to build consensus. These priority areas were: 1) gender differences in the pharmacological and nonpharmacological interventions for pain, including differences in opioid tolerance, side effects, or misuse; 2) gender differences in pain severity perceptions, clinically meaningful differences in acute pain, and pain treatment preferences; 3) gender differences in pain outcomes of ED patients across the life span; 4) gender differences in the relationship between acute pain and acute psychological responses; 5) the influence of physician-patient gender differences and characteristics on the assessment and treatment of pain; 6) gender differences in the influence of acute stress and chronic stress on acute pain responses; 7) gender differences in biological mechanisms and molecular pathways mediating acute pain in ED populations; and 8) gender differences in biological mechanisms and molecular pathways mediating chronic pain development after trauma, stress, or acute illness exposure. These areas represent priority areas for future scientific inquiry, and gaining understanding in these will be essential to improving our understanding of sex and gender differences in the assessment and treatment of pain conditions in emergency care settings

μ-Opioid Receptor Gene A118G Polymorphism Predicts Survival in Patients With Breast Cancer

Preclinical studies suggest that opioids may promote tumor growth. Genetic polymorphisms have been shown to affect opioid receptor function and to modify the clinical effects of morphine. In this study we assessed the association between six common polymorphisms in the μ-opioid receptor gene, including the well known A118G polymorphism, and breast cancer survival

Procjena varijabli stanja sustava s gorivnim člankom i uzlaznim pretvaračem metodom brzog uzorkovanja signala

Estimation of state variables of a peak current mode (PCM) controlled DC-DC boost converter supplied by a PEM fuel cell is described in this paper. Since this system is highly nonlinear and non-minimum phase, its state variables are estimated by using fast output sampling method. Estimated state variables are the converter output voltage and its first derivative, and they are suitable for model reference adaptive control or sliding mode based control techniques. The estimator has been designed in a way that it gives a good estimate of the state variables in the continuous and in the discontinuous conduction mode of the converter, and in the presence of measurement and process noise caused by converter switching-mode operation. Experimental results of estimating the state variables on a 450 W boost converter supplied by the emulator of the PEM fuel cell BCS 64-32 show good results of the estimation, regardless of the conduction mode of the converter, i.e. the operating point determined by its output current.U ovom radu obrađena je procjena varijabli stanja sustava s istomjernim uzlaznim pretvaračem u vršnom strujnom načinu upravljanja napajanim PEM gorivnim člankom. Budući da je taj sustav izrazito nelinearan te neminimalno-fazan, za procjenu njegovih varijabli stanja upotrebljena je metoda brzog uzorkovanja izlaznog signala. Procjenjene varijable stanja su izlazni napon uzlaznog pretvarača te njegova prva derivacija, te su pogodne za adaptivno upravljanje s referentnim modelom i upravljanje temeljeno na kliznim režimima. Procjenitelj je projektiran na način da daje dobru procjenu varijabli stanja u kontinuiranom i diskontinuiranom režimu rada pretvarača, te u uvjetima mjernog i procesnog šuma uzrokovanog sklopnim načinom rada pretvarača. Eksperimentalni rezultati procjene varijabli stanja na uzlaznom pretvaraču snage 450 W napajanim emulatorom gorivnog članka BCS 64-32 pokazuju dobre rezultate procjene, neovisno o režimu rada pretvarača, odnosno radnoj točki određenoj njegovom izlaznom strujom

Modification of COMT-dependent pain sensitivity by psychological stress and sex

Catecholamine-O-methyltransferase (COMT) is a polymorphic gene whose variants affect enzymatic activity and pain sensitivity via adrenergic pathways. Although COMT represents one of the most studied genes in human pain genetics, findings regarding its association with pain phenotypes are not always replicated. Here, we investigated if interactions among functional COMT haplotypes, stress, and sex can modify the effect of COMT genetic variants on pain sensitivity. We tested these interactions in a cross-sectional study, including 2 cohorts, one of 2972 subjects tested for thermal pain sensitivity (Orofacial Pain: Prospective Evaluation and Risk Assessment) and one of 948 subjects with clinical acute pain after motor vehicle collision (post-motor vehicle collision). In both cohorts, the COMT high-pain sensitivity (HPS) haplotype showed robust interaction with stress and number of copies of the HPS haplotype was positively associated with pain sensitivity in nonstressed individuals, but not in stressed individuals. In the post-motor vehicle collision cohort, there was additional modification by sex: the HPS-stress interaction was apparent in males, but not in females. In summary, our findings indicate that stress and sex should be evaluated in association studies aiming to investigate the effect of COMT genetic variants on pain sensitivity

Older US Emergency Department Patients Are Less Likely to Receive Pain Medication Than Younger Patients: Results From a National Survey

The purpose of this study is to determine whether older adults presenting to the Emergency Department (ED) with pain are less likely to receive pain medication than younger adults