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Sample records for pain model selective

  1. Beyond pain: modeling decision-making deficits in chronic pain

    Science.gov (United States)

    Hess, Leonardo Emanuel; Haimovici, Ariel; Muñoz, Miguel Angel; Montoya, Pedro

    2014-01-01

    Risky decision-making seems to be markedly disrupted in patients with chronic pain, probably due to the high cost that impose pain and negative mood on executive control functions. Patients’ behavioral performance on decision-making tasks such as the Iowa Gambling Task (IGT) is characterized by selecting cards more frequently from disadvantageous than from advantageous decks, and by switching often between competing responses in comparison with healthy controls (HCs). In the present study, we developed a simple heuristic model to simulate individuals’ choice behavior by varying the level of decision randomness and the importance given to gains and losses. The findings revealed that the model was able to differentiate the behavioral performance of patients with chronic pain and HCs at the group, as well as at the individual level. The best fit of the model in patients with chronic pain was yielded when decisions were not based on previous choices and when gains were considered more relevant than losses. By contrast, the best account of the available data in HCs was obtained when decisions were based on previous experiences and losses loomed larger than gains. In conclusion, our model seems to provide useful information to measure each individual participant extensively, and to deal with the data on a participant-by-participant basis. PMID:25136301

  2. Beyond pain: modeling decision-making deficits in chronic pain

    Directory of Open Access Journals (Sweden)

    Leonardo Emanuel Hess

    2014-08-01

    Full Text Available Risky decision-making seems to be markedly disrupted in patients with chronic pain, probably due to the high cost that impose pain and negative mood on executive control functions. Patients’ behavioral performance on decision-making tasks such as the Iowa Gambling Task (IGT is characterized by selecting cards more frequently from disadvantageous than from advantageous decks, and by switching often between competing responses in comparison with healthy controls. In the present study, we developed a simple heuristic model to simulate individuals’ choice behavior by varying the level of decision randomness and the importance given to gains and losses. The findings revealed that the model was able to differentiate the behavioral performance of patients with chronic pain and healthy controls at the group, as well as at the individual level. The best fit of the model in patients with chronic pain was yielded when decisions were not based on previous choices and when gains were considered more relevant than losses. By contrast, the best account of the available data in healthy controls was obtained when decisions were based on previous experiences and losses loomed larger than gains. In conclusion, our model seems to provide useful information to measure each individual participant extensively, and to deal with the data on a participant-by-participant basis.

  3. Beyond pain: modeling decision-making deficits in chronic pain.

    Science.gov (United States)

    Hess, Leonardo Emanuel; Haimovici, Ariel; Muñoz, Miguel Angel; Montoya, Pedro

    2014-01-01

    Risky decision-making seems to be markedly disrupted in patients with chronic pain, probably due to the high cost that impose pain and negative mood on executive control functions. Patients' behavioral performance on decision-making tasks such as the Iowa Gambling Task (IGT) is characterized by selecting cards more frequently from disadvantageous than from advantageous decks, and by switching often between competing responses in comparison with healthy controls (HCs). In the present study, we developed a simple heuristic model to simulate individuals' choice behavior by varying the level of decision randomness and the importance given to gains and losses. The findings revealed that the model was able to differentiate the behavioral performance of patients with chronic pain and HCs at the group, as well as at the individual level. The best fit of the model in patients with chronic pain was yielded when decisions were not based on previous choices and when gains were considered more relevant than losses. By contrast, the best account of the available data in HCs was obtained when decisions were based on previous experiences and losses loomed larger than gains. In conclusion, our model seems to provide useful information to measure each individual participant extensively, and to deal with the data on a participant-by-participant basis.

  4. A Comparison of the 2/3/5 Selective Positive Allosteric Modulators L-838,417 and TPA023 in Preclinical Models of Inflammatory and Neuropathic Pain

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    Sarah Nickolls

    2011-01-01

    Full Text Available GABAA receptors containing α2/3 subunits are current targets in the battle to develop new pain medications, as they are expressed in the spinal cord where increasing inhibitory drive should result in analgesia. However, this approach is prone to a range of side effects including sedation, cognitive impairment, and abuse as a consequence of the widespread influence of GABA. The ability to make subtype selective low-efficacy benzodiazepine compounds, which potentiate the action of GABA at specific α subunits, has the potential to reduce this side effect profile. In this study, we have investigated the effects of the medium-efficacy positive allosteric modulator (PAM L-838,417 and the low-efficacy PAM TPA023 in a number of preclinical inflammatory and neuropathic pain models. We conclude that either the higher level of efficacy at α2/3 or efficacy at α5 is required for compounds to have a significant analgesic effect in a range of models, and, therefore, although the side-effect profile of compounds can be reduced compared to typical benzodiazepines, it is unlikely that it can be completely eliminated.

  5. Selective Cathepsin S Inhibition with MIV-247 Attenuates Mechanical Allodynia and Enhances the Antiallodynic Effects of Gabapentin and Pregabalin in a Mouse Model of Neuropathic Pain.

    Science.gov (United States)

    Hewitt, Ellen; Pitcher, Thomas; Rizoska, Biljana; Tunblad, Karin; Henderson, Ian; Sahlberg, Britt-Louise; Grabowska, Urszula; Classon, Björn; Edenius, Charlotte; Malcangio, Marzia; Lindström, Erik

    2016-09-01

    Cathepsin S inhibitors attenuate mechanical allodynia in preclinical neuropathic pain models. The current study evaluated the effects when combining the selective cathepsin S inhibitor MIV-247 with gabapentin or pregabalin in a mouse model of neuropathic pain. Mice were rendered neuropathic by partial sciatic nerve ligation. MIV-247, gabapentin, or pregabalin were administered alone or in combination via oral gavage. Mechanical allodynia was assessed using von Frey hairs. Neurobehavioral side effects were evaluated by assessing beam walking. MIV-247, gabapentin, and pregabalin concentrations in various tissues were measured. Oral administration of MIV-247 (100-200 µmol/kg) dose-dependently attenuated mechanical allodynia by up to approximately 50% reversal when given as a single dose or when given twice daily for 5 days. No behavioral deficits were observed at any dose of MIV-247 tested. Gabapentin (58-350 µmol/kg) and pregabalin (63-377 µmol/kg) also inhibited mechanical allodynia with virtually complete reversal at the highest doses tested. The minimum effective dose of MIV-247 (100 µmol/kg) in combination with the minimum effective dose of pregabalin (75 µmol/kg) or gabapentin (146 µmol/kg) resulted in enhanced antiallodynic efficacy without augmenting side effects. A subeffective dose of MIV-247 (50 µmol/kg) in combination with a subeffective dose of pregabalin (38 µmol/kg) or gabapentin (73 µmol/kg) also resulted in substantial efficacy. Plasma levels of MIV-247, gabapentin, and pregabalin were similar when given in combination as to when given alone. Cathepsin S inhibition with MIV-247 exerts significant antiallodynic efficacy alone, and also enhances the effect of gabapentin and pregabalin without increasing side effects or inducing pharmacokinetic interactions. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  6. A Review of Select Centralized Pain Syndromes

    Directory of Open Access Journals (Sweden)

    David R. Spiegel

    2015-01-01

    Full Text Available Pain can be broadly divided into 3 classes, including nociceptive or inflammatory pain (protective, neuropathic (pathological, occurring after damage to the nervous system, or centralized (pathological, due to abnormal function but with no damage or inflammation to the nervous system. The latter has been posited to occur when descending analgesic pathways are attenuated and/or glutamatergic transmission is facilitated. Additionally, this “pain prone phenotype” can be associated with early life trauma and a suboptimal response to opiates. This article will review the relationships between centralized pain syndromes (ie, fibromyalgia, chronic low back pain, childhood sexual abuse, and opiate misuse. Finally, treatment implications, potentially effecting primary care physicians, will be discussed.

  7. The rat intervertebral disk degeneration pain model: relationships between biological and structural alterations and pain.

    Science.gov (United States)

    Kim, Jae-Sung; Kroin, Jeffrey S; Li, Xin; An, Howard S; Buvanendran, Asokumar; Yan, Dongyao; Tuman, Kenneth J; van Wijnen, Andre J; Chen, Di; Im, Hee-Jeong

    2011-01-01

    Degeneration of the interverterbral disk is as a cause of low-back pain is increasing. To gain insight into relationships between biological processes, structural alterations and behavioral pain, we created an animal model in rats. Disk degeneration was induced by removal of the nucleus pulposus (NP) from the lumbar disks (L4/L5 and L5/L6) of Sprague Dawley rats using a 0.5-mm-diameter microsurgical drill. The degree of primary hyperalgesia was assessed by using an algometer to measure pain upon external pressure on injured lumbar disks. Biochemical and histological assessments and radiographs of injured disks were used for evaluation. We investigated therapeutic modulation of chronic pain by administering pharmaceutical drugs in this animal model. After removal of the NP, pressure hyperalgesia developed over the lower back. Nine weeks after surgery we observed damaged or degenerated disks with proteoglycan loss and narrowing of disk height. These biological and structural changes in disks were closely related to the sustained pain hyperalgesia. A high dose of morphine (6.7 mg/kg) resulted in effective pain relief. However, high doses of pregabalin (20 mg/kg), a drug that has been used for treatment of chronic neuropathic pain, as well as the anti-inflammatory drugs celecoxib (50 mg/kg; a selective inhibitor of cyclooxygenase 2 (COX-2)) and ketorolac (20 mg/kg; an inhibitor of COX-1 and COX-2), did not have significant antihyperalgesic effects in our disk injury animal model. Although similarities in gene expression profiles suggest potential overlap in chronic pain pathways linked to disk injury or neuropathy, drug-testing results suggest that pain pathways linked to these two chronic pain conditions are mechanistically distinct. Our findings provide a foundation for future research on new therapeutic interventions that can lead to improvements in the treatment of patients with back pain due to disk degeneration.

  8. Biopsychosocial model of chronic recurrent pain

    Directory of Open Access Journals (Sweden)

    Zlatka Rakovec-Felser

    2009-07-01

    Full Text Available Pain is not merely a symptom of disease but a complex independent phenomenon where psychological factors are always present (Sternberg, 1973. Especially by chronic, recurrent pain it's more constructive to think of chronic pain as a syndrome that evolves over time, involving a complex interaction of physiological/organic, psychological, and behavioural processes. Study of chronic recurrent functional pain covers tension form of headache. 50 suffering persons were accidentally chosen among those who had been seeking medical help over more than year ago. We tested their pain intensity and duration, extent of subjective experience of accommodation efforts, temperament characteristics, coping strategies, personal traits, the role of pain in intra- and interpersonal communication. At the end we compared this group with control group (without any manifest physical disorders and with analyse of variance (MANOVA. The typical person who suffers and expects medical help is mostly a woman, married, has elementary or secondary education, is about 40. Pain, seems to appear in the phase of stress-induced psychophysical fatigue, by persons with lower constitutional resistance to different influences, greater irritability and number of physiologic correlates of emotional tensions. Because of their ineffective style of coping, it seems they quickly exhausted their adaptation potential too. Through their higher level of social–field dependence, reactions of other persons (doctor, spouse could be important factors of reinforcement and social learning processes. In managing of chronic pain, especially such as tension headache is, it's very important to involve bio-psychosocial model of pain and integrative model of treatment. Intra- and inter-subjective psychological functions of pain must be recognised as soon as possible.

  9. Selective attention towards painful faces among chronic pain patients: evidence from a modified version of the dot-probe.

    Science.gov (United States)

    Khatibi, Ali; Dehghani, Mohsen; Sharpe, Louise; Asmundson, Gordon J G; Pouretemad, Hamidreza

    2009-03-01

    Evidence that patients with chronic pain selectively attend to pain-related stimuli presented in modified Stroop and dot-probe paradigms is mixed. The pain-related stimuli used in these studies have been primarily verbal in nature (i.e., words depicting themes of pain). The purpose of the present study was to determine whether patients with chronic pain, relative to healthy controls, show selective attention for pictures depicting painful faces. To do so, 170 patients with chronic pain and 40 age- and education-matched healthy control participants were tested using a dot-probe task in which painful, happy, and neutral facial expressions were presented. Selective attention was denoted using the mean reaction time and the bias index. Results indicated that, while both groups shifted attention away from happy faces (and towards neutral faces), only the control group shifted attention away from painful faces. Additional analyses were conducted on chronic pain participants after dividing them into groups on the basis of fear of pain/(re)injury. The results of these analyses revealed that while chronic pain patients with high and low levels of fear both shifted attention away from happy faces, those with low fear shifted attention away from painful faces, whereas those with high fear shifted attention towards painful faces. These results suggest that patients with chronic pain selectively attend to facial expressions of pain and, importantly, that the tendency to shift attention towards such stimuli is positively influenced by high fear of pain/(re)injury. Implications of the findings and future research directions are discussed.

  10. Practical considerations and patient selection for intrathecal drug delivery in the management of chronic pain

    Directory of Open Access Journals (Sweden)

    Saulino M

    2014-11-01

    Full Text Available Michael Saulino,1,2 Philip S Kim,3,4 Erik Shaw5 1MossRehab, Elkins Park, PA, USA; 2Department of Rehabilitation Medicine, Jefferson Medical College, Philadelphia, PA, USA; 3Helen F Graham Cancer Center, Christiana Care Health System, Newark, DE, USA; 4Center for Interventional Pain Spine, LLC., Bryn Mawr, PA, USA; 5Shepherd Pain Institute, Shepherd Center, Atlanta, GA, USA Abstract: Chronic pain continues to pose substantial and growing challenges for patients, caregivers, health care professionals, and health care systems. By the time a patient with severe refractory pain sees a pain specialist for evaluation and management, that patient has likely tried and failed several nonpharmacologic and pharmacologic approaches to pain treatment. Although relegated to one of the interventions of “last resort”, intrathecal drug delivery can be useful for improving pain control, optimizing patient functionality, and minimizing the use of systemic pain medications in appropriately selected patients. Due to its clinical and logistical requirements, however, intrathecal drug delivery may fit poorly into the classic pain clinic/interventional model and may be perceived as a "critical mass" intervention that is feasible only for large practices that have specialized staff and appropriate office resources. Potentially, intrathecal drug delivery may be more readily adopted into larger practices that can commit the necessary staff and resources to support patients' needs through the trialing, initiation, monitoring, maintenance, and troubleshooting phases of this therapy. Currently, two agents – morphine and ziconotide – are approved by the United States Food and Drug Administration for long-term intrathecal delivery. The efficacy and safety profiles of morphine have been assessed in long-term, open-label, and retrospective studies of >400 patients with chronic cancer and noncancer pain types. The efficacy and safety profiles of ziconotide have been

  11. A selective review of medical cannabis in cancer pain management.

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    Blake, Alexia; Wan, Bo Angela; Malek, Leila; DeAngelis, Carlo; Diaz, Patrick; Lao, Nicholas; Chow, Edward; O'Hearn, Shannon

    2017-12-01

    Insufficient management of cancer-associated chronic and neuropathic pain adversely affects patient quality of life. Patients who do not respond well to opioid analgesics, or have severe side effects from the use of traditional analgesics are in need of alternative therapeutic op-tions. Anecdotal evidence suggests that medical cannabis has potential to effectively manage pain in this patient population. This review presents a selection of representative clinical studies, from small pilot studies conducted in 1975, to double-blind placebo-controlled trials conducted in 2014 that evaluated the efficacy of cannabinoid-based therapies containing tetrahydrocannabinol (THC) and cannabidiol (CBD) for reducing cancer-associated pain. A review of literature published on Medline between 1975 and 2017 identified five clinical studies that evaluated the effect of THC or CBD on controlling cancer pain, which have been reviewed and summarised. Five studies that evaluated THC oil capsules, THC:CBD oromucosal spray (nabiximols), or THC oromucosal sprays found some evidence of cancer pain reduction associated with these therapies. A variety of doses ranging from 2.7-43.2 mg/day THC and 0-40 mg/day CBD were administered. Higher doses of THC were correlated with increased pain relief in some studies. One study found that significant pain relief was achieved in doses as low as 2.7-10.8 mg THC in combination with 2.5-10.0 mg CBD, but there was conflicting evidence on whether higher doses provide superior pain relief. Some reported side effects include drowsiness, hypotension, mental clouding, and nausea and vomiting. There is evidence suggesting that medical cannabis reduces chronic or neu-ropathic pain in advanced cancer patients. However, the results of many studies lacked statistical power, in some cases due to limited number of study subjects. Therefore, there is a need for the conduct of further double-blind, placebo-controlled clinical trials with large sample sizes in order to

  12. Psychosocial Pain Management Moderation: The Limit, Activate, and Enhance Model.

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    Day, Melissa A; Ehde, Dawn M; Jensen, Mark P

    2015-10-01

    There is a growing emphasis in the pain literature on understanding the following second-order research questions: Why do psychosocial pain treatments work? For whom do various treatments work? This critical review summarizes research that addresses the latter question and proposes a moderation model to help guide future research. A theoretical moderation framework for matching individuals to specific psychosocial pain interventions has been lacking. However, several such frameworks have been proposed in the broad psychotherapy and implementation science literature. Drawing on these theories and adapting them specifically for psychosocial pain treatment, here we propose a Limit, Activate, and Enhance model of pain treatment moderation. This model is unique in that it includes algorithms not only for matching treatments on the basis of patient weaknesses but also for directing patients to interventions that build on their strengths. Critically, this model provides a basis for specific a priori hypothesis generation, and a selection of the possible hypotheses drawn from the model are proposed and discussed. Future research considerations are presented that could refine and expand the model based on theoretically driven empirical evidence. The Limit, Activate, and Enhance model presented here is a theoretically derived framework that provides an a priori basis for hypothesis generation regarding psychosocial pain treatment moderators. The model will advance moderation research via its unique focus on matching patients to specific treatments that (1) limit maladaptive responses, (2) activate adaptive responses, and (3) enhance treatment outcomes based on patient strengths and resources. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  13. Self-reported pain and disability outcomes from an endogenous model of muscular back pain

    Directory of Open Access Journals (Sweden)

    George Steven Z

    2011-02-01

    Full Text Available Abstract Background Our purpose was to develop an induced musculoskeletal pain model of acute low back pain and examine the relationship among pain, disability and fear in this model. Methods Delayed onset muscle soreness was induced in 52 healthy volunteers (23 women, 17 men; average age 22.4 years; average BMI 24.3 using fatiguing trunk extension exercise. Measures of pain intensity, unpleasantness, and location, and disability, were tracked for one week after exercise. Results Pain intensity ranged from 0 to 68 with 57.5% of participants reporting peak pain at 24 hours and 32.5% reporting this at 48 hours. The majority of participants reported pain in the low back with 33% also reporting pain in the legs. The ratio of unpleasantness to intensity indicated that the sensation was considered more unpleasant than intense. Statistical differences were noted in levels of reported disability between participants with and without leg pain. Pain intensity at 24 hours was correlated with pain unpleasantness, pain area and disability. Also, fear of pain was associated with pain intensity and unpleasantness. Disability was predicted by sex, presence of leg pain, and pain intensity; however, the largest amount of variance was explained by pain intensity (27% of a total 40%. The second model, predicting pain intensity only included fear of pain and explained less than 10% of the variance in pain intensity. Conclusions Our results demonstrate a significant association between pain and disability in this model in young adults. However, the model is most applicable to patients with lower levels of pain and disability. Future work should include older adults to improve the external validity of this model.

  14. Selective spider toxins reveal a role for Nav1.1 channel in mechanical pain

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    Osteen, Jeremiah D.; Herzig, Volker; Gilchrist, John; Emrick, Joshua J.; Zhang, Chuchu; Wang, Xidao; Castro, Joel; Garcia-Caraballo, Sonia; Grundy, Luke; Rychkov, Grigori Y.; Weyer, Andy D.; Dekan, Zoltan; Undheim, Eivind A. B.; Alewood, Paul; Stucky, Cheryl L.; Brierley, Stuart M.; Basbaum, Allan I.; Bosmans, Frank; King, Glenn F.; Julius, David

    2016-01-01

    Voltage-gated sodium (Nav) channels initiate action potentials in most neurons, including primary afferent nerve fibers of the pain pathway. Local anesthetics block pain through non-specific actions at all Nav channels, but the discovery of selective modulators would facilitate the analysis of individual subtypes and their contributions to chemical, mechanical, or thermal pain. Here, we identify and characterize spider toxins that selectively activate the Nav1.1 subtype, whose role in nociception and pain has not been explored. We exploit these probes to demonstrate that Nav1.1-expressing fibers are modality-specific nociceptors: their activation elicits robust pain behaviors without neurogenic inflammation and produces profound hypersensitivity to mechanical, but not thermal, stimuli. In the gut, high-threshold mechanosensitive fibers also express Nav1.1 and show enhanced toxin sensitivity in a model of irritable bowel syndrome. Altogether, these findings establish an unexpected role for Nav1.1 in regulating the excitability of sensory nerve fibers that underlie mechanical pain. PMID:27281198

  15. Pain management: a review of organisation models with integrated processes for the management of pain in adult cancer patients.

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    Brink-Huis, Anita; van Achterberg, Theo; Schoonhoven, Lisette

    2008-08-01

    This paper reports a review of the literature conducted to identify organisation models in cancer pain management that contain integrated care processes and describe their effectiveness. Pain is experienced by 30-50% of cancer patients receiving treatment and by 70-90% of those with advanced disease. Efforts to improve pain management have been made through the development and dissemination of clinical guidelines. Early improvements in pain management were focussed on just one or two single processes such as pain assessment and patient education. Little is known about organisational models with multiple integrated processes throughout the course of the disease trajectory and concerning all stages of the care process. Systematic review. The review involved a systematic search of the literature, published between 1986-2006. Subject-specific keywords used to describe patients, disease, pain management interventions and integrated care processes, relevant for this review were selected using the thesaurus of the databases. Institutional models, clinical pathways and consultation services are three alternative models for the integration of care processes in cancer pain management. A clinical pathway is a comprehensive institutionalisation model, whereas a pain consultation service is a 'stand-alone' model that can be integrated in a clinical pathway. Positive patient and process outcomes have been described for all three models, although the level of evidence is generally low. Evaluation of the quality of pain management must involve standardised measurements of both patient and process outcomes. We recommend the development of policies for referrals to a pain consultation service. These policies can be integrated within a clinical pathway. To evaluate the effectiveness of pain management models standardised outcome measures are needed.

  16. Psychological resilience, pain catastrophizing, and positive emotions: perspectives on comprehensive modeling of individual pain adaptation.

    Science.gov (United States)

    Sturgeon, John A; Zautra, Alex J

    2013-03-01

    Pain is a complex construct that contributes to profound physical and psychological dysfunction, particularly in individuals coping with chronic pain. The current paper builds upon previous research, describes a balanced conceptual model that integrates aspects of both psychological vulnerability and resilience to pain, and reviews protective and exacerbating psychosocial factors to the process of adaptation to chronic pain, including pain catastrophizing, pain acceptance, and positive psychological resources predictive of enhanced pain coping. The current paper identifies future directions for research that will further enrich the understanding of pain adaptation and espouses an approach that will enhance the ecological validity of psychological pain coping models, including introduction of advanced statistical and conceptual models that integrate behavioral, cognitive, information processing, motivational and affective theories of pain.

  17. Children's selective attention to pain and avoidance behaviour: the role of child and parental catastrophizing about pain.

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    Vervoort, Tine; Trost, Zina; Van Ryckeghem, Dimitri M L

    2013-10-01

    The present study investigated selective attention to pain in children, its implications for child avoidance behaviour, and the moderating role of dimensions comprising child and parental catastrophizing about pain (ie, rumination, magnification, and helplessness). Participants were 59 children (31 boys) aged 10-16 years and one of their parents (41 mothers). Children performed a dot-probe task in which child facial pain displays of varying pain expressiveness were presented. Child avoidance behaviour was indexed by child pain tolerance during a cold-pressor task. Children and parents completed measures of child and parent pain catastrophizing, respectively. Findings indicated that both the nature of child selective attention to pain and the impact of selective attention upon child avoidance behaviour were differentially sensitive to specific dimensions of child and parental catastrophizing. Specifically, findings showed greater tendency to shift attention away from pain faces (i.e.,, attentional avoidance) among children reporting greater pain magnification. A similar pattern was observed in terms of parental characteristics, such that children increasingly shifted attention away from pain with increasing levels of parental rumination and helplessness. Furthermore, child attentional avoidance was associated with greater avoidance behaviour (i.e., lower pain tolerance) among children reporting high levels of pain magnification and those whose parents reported greater rumination about pain. The current findings corroborate catastrophizing as a multidimensional construct that may differentially impact outcomes and attest to the importance of assessing both child and parental characteristics in relation to child pain-related attention and avoidance behaviour. Further research directions are discussed. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  18. Analyzing musculoskeletal neck pain, measured as present pain and periods of pain, with three different regression models: a cohort study

    Directory of Open Access Journals (Sweden)

    Hagberg Mats

    2009-06-01

    Full Text Available Abstract Background In the literature there are discussions on the choice of outcome and the need for more longitudinal studies of musculoskeletal disorders. The general aim of this longitudinal study was to analyze musculoskeletal neck pain, in a group of young adults. Specific aims were to determine whether psychosocial factors, computer use, high work/study demands, and lifestyle are long-term or short-term factors for musculoskeletal neck pain, and whether these factors are important for developing or ongoing musculoskeletal neck pain. Methods Three regression models were used to analyze the different outcomes. Pain at present was analyzed with a marginal logistic model, for number of years with pain a Poisson regression model was used and for developing and ongoing pain a logistic model was used. Presented results are odds ratios and proportion ratios (logistic models and rate ratios (Poisson model. The material consisted of web-based questionnaires answered by 1204 Swedish university students from a prospective cohort recruited in 2002. Results Perceived stress was a risk factor for pain at present (PR = 1.6, for developing pain (PR = 1.7 and for number of years with pain (RR = 1.3. High work/study demands was associated with pain at present (PR = 1.6; and with number of years with pain when the demands negatively affect home life (RR = 1.3. Computer use pattern (number of times/week with a computer session ≥ 4 h, without break was a risk factor for developing pain (PR = 1.7, but also associated with pain at present (PR = 1.4 and number of years with pain (RR = 1.2. Among life style factors smoking (PR = 1.8 was found to be associated to pain at present. The difference between men and women in prevalence of musculoskeletal pain was confirmed in this study. It was smallest for the outcome ongoing pain (PR = 1.4 compared to pain at present (PR = 2.4 and developing pain (PR = 2.5. Conclusion By using different regression models different

  19. Managing painful chronic wounds: the Wound Pain Management Model

    DEFF Research Database (Denmark)

    Price, Patricia; Fogh, Karsten; Glynn, Chris

    2007-01-01

    of the pain experience: location, duration, intensity, quality, onset and impact on activities of daily living. Holistic management must be based on a safe and effective mix of psychosocial approaches together with local and systemic pain management. It is no longer acceptable to ignore or inadequately...... to the wound should be handled as one of the main priorities in chronic wound management together with addressing the cause. Management of pain in chronic wounds depends on proper assessment, reporting and documenting patient experiences of pain. Assessment should be based on six critical dimensions...... document persistent wound pain and not to develop a treatment and monitoring strategy to improve the lives of persons with chronic wounds. Unless wound pain is optimally managed, patient suffering and costs to health care systems will increase. Udgivelsesdato: 2007-Apr...

  20. [Neither Descartes nor Freud? current pain models in psychosomatic medicine].

    Science.gov (United States)

    Egloff, N; Egle, U T; von Känel, R

    2008-05-14

    Models explaining chronic pain based on the mere presence or absence of peripheral somatic findings or which view pain of psychological origin when there is no somatic explanation, have their shortcomings. Current scientific knowledge calls for distinct pain concepts, which integrate neurobiological and neuropsychological aspects of pain processing.

  1. Recurrent pain is associated with decreased selective attention in a population-based sample.

    Science.gov (United States)

    Gijsen, C P; Dijkstra, J B; van Boxtel, M P J

    2011-01-01

    Studies which have examined the impact of pain on cognitive functioning in the general population are scarce. In the present study we assessed the predictive value of recurrent pain on cognitive functioning in a population-based study (N=1400). Furthermore, we investigated the effect of pain on cognitive functioning in individuals with specific pain complaints (i.e. back pain, gastric pain, muscle pain and headache). Cognitive functioning was assessed using the Stroop Color-Word Interference test (Stroop interference), the Letter-Digit-Substitution test (LDST) and the Visual Verbal learning Task (VVLT). Pain was measured with the COOP/WONCA pain scale (Dartmouth Primary Care Cooperative Information Project/World Organization of National Colleges, Academies, and Academic Associations of General Practice /Family Physicians). We controlled for the effects of age, sex, level of education and depressive symptoms. It was demonstrated that pain had a negative impact on the performance on the Stroop interference but not on the VVLT and the LDST. This indicates that subjects who reported extreme pain had more problems with selective attention and were more easily distracted. Effects were in general larger in the specific pain groups when compared to the associations found in the total group. Implications of these findings are discussed. The experience of recurrent pain has a negative influence on selective attention in a healthy population. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  2. Selective spider toxins reveal a role for Nav1.1 channel in mechanical pain

    OpenAIRE

    Osteen, Jeremiah D.; Herzig, Volker; Gilchrist, John; Emrick, Joshua J.; Zhang, Chuchu; Wang, Xidao; Castro, Joel; Garcia-Caraballo, Sonia; Grundy, Luke; Rychkov, Grigori Y.; Weyer, Andy D.; Dekan, Zoltan; Undheim, Eivind A. B.; Alewood, Paul; Stucky, Cheryl L.

    2016-01-01

    Voltage-gated sodium (Nav) channels initiate action potentials in most neurons, including primary afferent nerve fibers of the pain pathway. Local anesthetics block pain through non-specific actions at all Nav channels, but the discovery of selective modulators would facilitate the analysis of individual subtypes and their contributions to chemical, mechanical, or thermal pain. Here, we identify and characterize spider toxins that selectively activate the Nav1.1 subtype, whose role in nocicep...

  3. Recruiter Selection Model

    National Research Council Canada - National Science Library

    Halstead, John B

    2006-01-01

    .... The research uses a combination of statistical learning, feature selection methods, and multivariate statistics to determine the better prediction function approximation with features obtained...

  4. Social Modeling Influences on Pain Experience and Behaviour.

    Science.gov (United States)

    Craig, Kenneth D.

    The impact of exposure to social models displaying variably tolerant pain behaviour on observers' expressions of pain is examined. Findings indicate substantial effects on verbal reports of pain, avoidance behaviour, psychophysiological indices, power function parameters, and sensory decision theory indices. Discussion centers on how social models…

  5. Work related musculoskeletal pain among teachers in selected ...

    African Journals Online (AJOL)

    The impact of musculoskeletal pain specifically within the teaching profession has not been given sufficient attention in the literature especially in Nigeria. This study determined the prevalence of work related musculoskeletal pain among public secondary school teachers in Ife-Central Local Government Area (LGA), Osun ...

  6. Model selection in periodic autoregressions

    NARCIS (Netherlands)

    Ph.H.B.F. Franses (Philip Hans); R. Paap (Richard)

    1994-01-01

    textabstractThis paper focuses on the issue of period autoagressive time series models (PAR) selection in practice. One aspect of model selection is the choice for the appropriate PAR order. This can be of interest for the valuation of economic models. Further, the appropriate PAR order is important

  7. Interactive versus passive distraction for acute pain management in young children: the role of selective attention and development.

    Science.gov (United States)

    Wohlheiter, Karen A; Dahlquist, Lynnda M

    2013-03-01

    To examine whether age and developmental differences in selective attention influence young children's differential responses to interactive and passive distraction. 65 3- to 6-year-old children underwent three cold-pressor trials while receiving no intervention, playing a video game (interactive distraction), or watching a video game (passive distraction). In addition, children completed a test of selective attention, and parents completed ratings of attention. Consistent with neurocognitive models of pain, children benefited more from interactive distraction than from passive distraction. Although older children demonstrated superior pain tolerance overall, age and selective attention skills did not moderate children's responses to the distraction intervention. These findings suggest that younger preschoolers can benefit from interactive distraction to manage acute pain, provided that the distraction activity is developmentally appropriate. Research is needed to determine whether developmental issues are more important moderators of children's responses to distraction when faced with more challenging task demands.

  8. Modeling Natural Selection

    Science.gov (United States)

    Bogiages, Christopher A.; Lotter, Christine

    2011-01-01

    In their research, scientists generate, test, and modify scientific models. These models can be shared with others and demonstrate a scientist's understanding of how the natural world works. Similarly, students can generate and modify models to gain a better understanding of the content, process, and nature of science (Kenyon, Schwarz, and Hug…

  9. Models selection and fitting

    International Nuclear Information System (INIS)

    Martin Llorente, F.

    1990-01-01

    The models of atmospheric pollutants dispersion are based in mathematic algorithms that describe the transport, diffusion, elimination and chemical reactions of atmospheric contaminants. These models operate with data of contaminants emission and make an estimation of quality air in the area. This model can be applied to several aspects of atmospheric contamination

  10. Selected System Models

    Science.gov (United States)

    Schmidt-Eisenlohr, F.; Puñal, O.; Klagges, K.; Kirsche, M.

    Apart from the general issue of modeling the channel, the PHY and the MAC of wireless networks, there are specific modeling assumptions that are considered for different systems. In this chapter we consider three specific wireless standards and highlight modeling options for them. These are IEEE 802.11 (as example for wireless local area networks), IEEE 802.16 (as example for wireless metropolitan networks) and IEEE 802.15 (as example for body area networks). Each section on these three systems discusses also at the end a set of model implementations that are available today.

  11. Inhibition of Pain and Pain-Related Brain Activity by Heterotopic Noxious Counter-Stimulation and Selective Attention in Chronic Non-Specific Low Back Pain.

    Science.gov (United States)

    Ladouceur, Alexandra; Rustamov, Nabi; Dubois, Jean-Daniel; Tessier, Jessica; Lehmann, Alexandre; Descarreaux, Martin; Rainville, Pierre; Piché, Mathieu

    2017-10-10

    The aim of the present study was to assess inhibition of pain and somatosensory-evoked potentials (SEPs) by heterotopic noxious counter-stimulation (HNCS) and by selective attention in patients with chronic non-specific LBP. Seventeen patients and age/sex-matched controls were recruited (10 men, 7 women; mean age ± SD: 43.3 ± 10.4 and 42.7 ± 11.1, respectively). On average, patients with LBP reported pain duration of 7.6 ± 6.5 years, light to moderate disability (19.3 ± 5.7/100) and low clinical pain intensity (21.8 ± 1.5/100), while pain catastrophizing, state and trait anxiety and depressive symptoms were not significantly different between groups (all p's >0.05). HNCS and selective attention had differential inhibitory effects on pain and SEP, but no difference was observed between groups. Across both groups, HNCS decreased pain (p = 0.06) as well as the N100 and the N150 components of SEP (p's selective attention only decreased pain (p attention was directed toward the HNCS stimulus (pselective attention. Importantly, this experiment was carefully designed to control for non-specific effects associated with the repetition of the test stimulus and the effect of an innocuous counter-stimulation. It remains to be determined if these results hold for patients with severe LBP and psychological symptoms or whether symptom severity may be associated with pain inhibition deficits. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Launch vehicle selection model

    Science.gov (United States)

    Montoya, Alex J.

    1990-01-01

    Over the next 50 years, humans will be heading for the Moon and Mars to build scientific bases to gain further knowledge about the universe and to develop rewarding space activities. These large scale projects will last many years and will require large amounts of mass to be delivered to Low Earth Orbit (LEO). It will take a great deal of planning to complete these missions in an efficient manner. The planning of a future Heavy Lift Launch Vehicle (HLLV) will significantly impact the overall multi-year launching cost for the vehicle fleet depending upon when the HLLV will be ready for use. It is desirable to develop a model in which many trade studies can be performed. In one sample multi-year space program analysis, the total launch vehicle cost of implementing the program reduced from 50 percent to 25 percent. This indicates how critical it is to reduce space logistics costs. A linear programming model has been developed to answer such questions. The model is now in its second phase of development, and this paper will address the capabilities of the model and its intended uses. The main emphasis over the past year was to make the model user friendly and to incorporate additional realistic constraints that are difficult to represent mathematically. We have developed a methodology in which the user has to be knowledgeable about the mission model and the requirements of the payloads. We have found a representation that will cut down the solution space of the problem by inserting some preliminary tests to eliminate some infeasible vehicle solutions. The paper will address the handling of these additional constraints and the methodology for incorporating new costing information utilizing learning curve theory. The paper will review several test cases that will explore the preferred vehicle characteristics and the preferred period of construction, i.e., within the next decade, or in the first decade of the next century. Finally, the paper will explore the interaction

  13. The necessity of animal models in pain research.

    Science.gov (United States)

    Mogil, Jeffrey S; Davis, Karen D; Derbyshire, Stuart W

    2010-10-01

    There exists currently a fair degree of introspection in the pain research community about the value of animal research. This review represents a defense of animal research in pain. We discuss the inherent advantage of animal models over human research as well as the crucial complementary roles animal studies play vis-à-vis human imaging and genetic studies. Finally, we discuss recent developments in animal models of pain that should improve the relevance and translatability of findings using laboratory animals. We believe that pain research using animal models is a continuing necessity-to understand fundamental mechanisms, identify new analgesic targets, and inform, guide and follow up human studies-if novel analgesics are to be developed for the treatment of chronic pain. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  14. Mechanisms of Osteoarthritic Pain. Studies in Humans and Experimental Models

    Directory of Open Access Journals (Sweden)

    Annett Eitner

    2017-11-01

    Full Text Available Pain due to osteoarthritis (OA is one of the most frequent causes of chronic pain. However, the mechanisms of OA pain are poorly understood. This review addresses the mechanisms which are thought to be involved in OA pain, derived from studies on pain mechanisms in humans and in experimental models of OA. Three areas will be considered, namely local processes in the joint associated with OA pain, neuronal mechanisms involved in OA pain, and general factors which influence OA pain. Except the cartilage all structures of the joints are innervated by nociceptors. Although the hallmark of OA is the degradation of the cartilage, OA joints show multiple structural alterations of cartilage, bone and synovial tissue. In particular synovitis and bone marrow lesions have been proposed to determine OA pain whereas the contribution of the other pathologies to pain generation has been studied less. Concerning the peripheral neuronal mechanisms of OA pain, peripheral nociceptive sensitization was shown, and neuropathic mechanisms may be involved at some stages. Structural changes of joint innervation such as local loss and/or sprouting of nerve fibers were shown. In addition, central sensitization, reduction of descending inhibition, descending excitation and cortical atrophies were observed in OA. The combination of different neuronal mechanisms may define the particular pain phenotype in an OA patient. Among mediators involved in OA pain, nerve growth factor (NGF is in the focus because antibodies against NGF significantly reduce OA pain. Several studies show that neutralization of interleukin-1β and TNF may reduce OA pain. Many patients with OA exhibit comorbidities such as obesity, low grade systemic inflammation and diabetes mellitus. These comorbidities can significantly influence the course of OA, and pain research just began to study the significance of such factors in pain generation. In addition, psychologic and socioeconomic factors may aggravate

  15. Prevalence of spondylolysis and its relationship with low back pain in selected population.

    Science.gov (United States)

    Ko, Sang-Bong; Lee, Sang-Wook

    2011-03-01

    To determine the prevalence of spondylolysis in a selected population and evaluate the association of spondylolysis with low back pain (LBP). Spondylolysis is widespread in the general population but the prevalence of spondylolysis and its relationship with LBP in the Korean population is controversial. A sample of 855 participants (age, 20 to 86 years) from our medical center who underwent multidetector computed tomography (CT) imaging to assess abdominal and urological lesions were enrolled in this study. The occurrence of LBP requiring medication in the preceding 12 months was evaluated using a self-report questionnaire (a modified Nordic Low Back Pain Questionnaire). The presence of spondylolysis was characterized by CT imaging. Multiple logistic regression models were used to examine the association between spondylolysis and LBP, while adjusting for gender and age. Seventy-eight study subjects (9%) demonstrated spondylolysis on CT imaging. There was no significant difference between the age groups (p = 0.177). The p-value of gender was 0.033 but this was not significant due to the selected population bias. Three hundred eleven study subjects (36%) had back pain. There was a significant difference between gender (p = 0.001). No significant association was identified between spondylolysis and the occurrence of LBP. The prevalence of LBP was 36.37% and the prevalence of lumbar spondylolysis in a selected population, who visited hospital for abdominal or urological lesions except LBP, was 9.12% based on CT imaging. Males demonstrated a similar presence of LBP to females but a significantly higher incidence of spondylolysis (p = 0.033). The prevalence of spondylolysis was not associated with the presence of LBP and age in adulthood.

  16. A Heckman Selection- t Model

    KAUST Repository

    Marchenko, Yulia V.

    2012-03-01

    Sample selection arises often in practice as a result of the partial observability of the outcome of interest in a study. In the presence of sample selection, the observed data do not represent a random sample from the population, even after controlling for explanatory variables. That is, data are missing not at random. Thus, standard analysis using only complete cases will lead to biased results. Heckman introduced a sample selection model to analyze such data and proposed a full maximum likelihood estimation method under the assumption of normality. The method was criticized in the literature because of its sensitivity to the normality assumption. In practice, data, such as income or expenditure data, often violate the normality assumption because of heavier tails. We first establish a new link between sample selection models and recently studied families of extended skew-elliptical distributions. Then, this allows us to introduce a selection-t (SLt) model, which models the error distribution using a Student\\'s t distribution. We study its properties and investigate the finite-sample performance of the maximum likelihood estimators for this model. We compare the performance of the SLt model to the conventional Heckman selection-normal (SLN) model and apply it to analyze ambulatory expenditures. Unlike the SLNmodel, our analysis using the SLt model provides statistical evidence for the existence of sample selection bias in these data. We also investigate the performance of the test for sample selection bias based on the SLt model and compare it with the performances of several tests used with the SLN model. Our findings indicate that the latter tests can be misleading in the presence of heavy-tailed data. © 2012 American Statistical Association.

  17. Muscle activation during selected strength exercises in women with chronic neck muscle pain

    DEFF Research Database (Denmark)

    Andersen, Lars L; Kjaer, Michael; Andersen, Christoffer H

    2008-01-01

    selected strengthening exercises in women undergoing rehabilitation for chronic neck muscle pain (defined as a clinical diagnosis of trapezius myalgia). SUBJECTS: The subjects were 12 female workers (age=30-60 years) with a clinical diagnosis of trapezius myalgia and a mean baseline pain intensity of 5......BACKGROUND AND PURPOSE: Muscle-specific strength training has previously been shown to be effective in the rehabilitation of chronic neck muscle pain in women. The aim of this study was to determine the level of activation of the neck and shoulder muscles using surface electromyography (EMG) during...... muscle pain. Several of the strength exercises had high activation of neck and shoulder muscles in women with chronic neck pain. These exercises can be used equally in the attempt to achieve a beneficial treatment effect on chronic neck muscle pain....

  18. Population pharmacokinetic-pharmacodynamic modeling of ketamine-induced pain relief of chronic pain.

    Science.gov (United States)

    Dahan, Albert; Olofsen, Erik; Sigtermans, Marnix; Noppers, Ingeborg; Niesters, Marieke; Aarts, Leon; Bauer, Martin; Sarton, Elise

    2011-03-01

    Pharmacological treatment of chronic (neuropathic) pain is often disappointing. In order to enhance our insight in the complex interaction between analgesic drug and chronic pain relief, we performed a pharmacokinetic-pharmacodynamic (PK-PD) modeling study on the effect of S(+)-ketamine on pain scores in Complex Regional Pain Syndrome type 1 (CRPS-1) patients. Sixty CRPS-1 patients were randomly allocated to received a 100-h infusion of S(+)-ketamine or placebo. The drug infusion rate was slowly increased from 5 mg/h (per 70 kg) to 20 mg/h based upon the effect/side effect profile. Pain scores and drug blood samples were obtained during the treatment phase and pain scores were further obtained weekly for another 11 weeks. A population PK-PD model was developed to analyze the S(+)-ketamine-pain data. Plasma concentrations of S(+)-ketamine and its metabolite decreased rapidly upon the termination of S(+)-ketamine infusion. The chance for an analgesic effect from ketamine and placebo treatment was 67±10% and 23±9% (population value±SE), respectively. The pain data were well described by the PK-PD model with parameters C(50)=10.5±4.8 ng/ml (95% ci 4.37-21.2 ng/ml) and t½ for onset/offset=10.9±4.0 days (5.3-20.5 days). Long-term S(+)-ketamine treatment is effective in causing pain relief in CRPS-1 patients with analgesia outlasting the treatment period by 50 days. These data suggest that ketamine initiated a cascade of events, including desensitization of excitatory receptor systems in the central nervous system, which persisted but slowly abated when ketamine molecules were no longer present. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

  19. Endogenous opioid antagonism in physiological experimental pain models

    DEFF Research Database (Denmark)

    Werner, Mads U; Pereira, Manuel P; Andersen, Lars Peter H

    2015-01-01

    hyperalgesia models (6 studies), 'pain' models (25 studies), summation models (2 studies), nociceptive reflex models (3 studies) and miscellaneous models (2 studies). A consistent reversal of analgesia by a MOR-antagonist was demonstrated in 10 of the 25 ITP-studies, including stress-induced analgesia and r...... ratings, threshold assessments and somatosensory evoked potentials (SSEP), did not appear consistent in 28 out of 32 'pain' model studies. In conclusion, only in 2 experimental human pain models, i.e., stress-induced analgesia and rTMS, administration of MOR-antagonist demonstrated a consistent effect......Opioid antagonists are pharmacological tools applied as an indirect measure to detect activation of the endogenous opioid system (EOS) in experimental pain models. The objective of this systematic review was to examine the effect of mu-opioid-receptor (MOR) antagonists in placebo-controlled, double...

  20. Selected physiotherapeutic techniques and immune response in low back pain

    Directory of Open Access Journals (Sweden)

    Piotr Gawda

    2017-04-01

    Full Text Available Physiotherapy, as an element of medical rehabilitation, comprises such methods of function improvement as: massage, kinesiotherapy, physical therapy or manual therapy. In this area, medicine offers a wide range of treatment methods, practically at every stage of a patient’s recovery. Physiotherapy is used to enhance quality of life of people with disabilities, chronic diseases or after injuries, but also as a form of prevention of dysfunctions. The aim of the study  is to present the influence of physiotherapy of low back pain on factors of immune response based on literature review. Effectiveness of a given treatment is most easily noticeable in clinical practice. It is usually the patient who evaluates the efficiency of treatment, through experiencing less pain, easier performance of certain actions or overall better functioning in everyday life. Apart from registering the subjective experience of patients, the focus is on finding objective methods of evaluating effectiveness of physiotherapy and on attempts at scientific explanation of noticeable and perceptible influence of rehabilitation treatment. This also applies to the treatment of lumbar-sacral pain. The involvement of many inflammatory mediators such as nitric oxide, interleukins, matrix metalloproteinases, prostaglandin , tumor necrosis factor alpha and a group of cytokines. and a variety of cytokines have already been  identified in the dysfunction of this region.

  1. A human experimental model of episodic pain

    DEFF Research Database (Denmark)

    Petrini, Laura; Hennings, Kristian; Li, Xi

    2014-01-01

    (VRS). Physiological (blood flow and axon flare reflex), psychophysical (perception threshold and verbal pain ratings) and electrophysiological (128 channels recorded somatosensory evoked potential (SEP)) measurements were recorded. The stimulation evoked a visible axon flare reflex and caused...

  2. Suprathreshold Heat Pain Response Predicts Activity-Related Pain, but Not Rest-Related Pain, in an Exercise-Induced Injury Model

    Science.gov (United States)

    Coronado, Rogelio A.; Simon, Corey B.; Valencia, Carolina; Parr, Jeffrey J.; Borsa, Paul A.; George, Steven Z.

    2014-01-01

    Exercise-induced injury models are advantageous for studying pain since the onset of pain is controlled and both pre-injury and post-injury factors can be utilized as explanatory variables or predictors. In these studies, rest-related pain is often considered the primary dependent variable or outcome, as opposed to a measure of activity-related pain. Additionally, few studies include pain sensitivity measures as predictors. In this study, we examined the influence of pre-injury and post-injury factors, including pain sensitivity, for induced rest and activity-related pain following exercise induced muscle injury. The overall goal of this investigation was to determine if there were convergent or divergent predictors of rest and activity-related pain. One hundred forty-three participants provided demographic, psychological, and pain sensitivity information and underwent a standard fatigue trial of resistance exercise to induce injury of the dominant shoulder. Pain at rest and during active and resisted shoulder motion were measured at 48- and 96-hours post-injury. Separate hierarchical models were generated for assessing the influence of pre-injury and post-injury factors on 48- and 96-hour rest-related and activity-related pain. Overall, we did not find a universal predictor of pain across all models. However, pre-injury and post-injury suprathreshold heat pain response (SHPR), a pain sensitivity measure, was a consistent predictor of activity-related pain, even after controlling for known psychological factors. These results suggest there is differential prediction of pain. A measure of pain sensitivity such as SHPR appears more influential for activity-related pain, but not rest-related pain, and may reflect different underlying processes involved during pain appraisal. PMID:25265560

  3. A Heckman Selection- t Model

    KAUST Repository

    Marchenko, Yulia V.; Genton, Marc G.

    2012-01-01

    for sample selection bias based on the SLt model and compare it with the performances of several tests used with the SLN model. Our findings indicate that the latter tests can be misleading in the presence of heavy-tailed data. © 2012 American Statistical

  4. Cognitive load selectively influences the interruptive effect of pain on attention.

    Science.gov (United States)

    Moore, David J; Eccleston, Christopher; Keogh, Edmund

    2017-10-01

    Pain is known to interrupt attentional performance. Such interference effects seem to occur preferentially for tasks that are complex and/or difficult. However, few studies have directly manipulated memory load in the context of pain interference to test this view. Therefore, this study examines the effect of experimental manipulations of both memory load and pain on 3 tasks previously found to be sensitive to pain interference. Three experiments were conducted. A different task was examined in each experiment, each comprising of a high- and low-cognitive load versions of the task. Experiment 1 comprised an attention span (n-back) task, experiment 2 an attention switching task, and experiment 3 a divided attention task. Each task was conducted under painful and nonpainful conditions. Within the pain condition, an experimental thermal pain induction protocol was administered at the same time participants completed the task. The load manipulations were successful in all experiments. Pain-related interference occurred under the high-load condition but only for the attention span task. No effect of pain was found on either the attentional switching or divided attention task. These results suggest that while cognitive load may influence the interruptive effect of pain on attention, this effect may be selective. Because pain affected the high-load version of the n-back task but did not interrupt performance on attentional switching or dual-task paradigms, this means that our findings did not completely support our hypotheses. Future research should explore further the parameters and conditions under which pain-related interference occurs.

  5. Psychophysics, flare, and neurosecretory function in human pain models: capsaicin versus electrically evoked pain.

    Science.gov (United States)

    Geber, Christian; Fondel, Ricarda; Krämer, Heidrun H; Rolke, Roman; Treede, Rolfe-Detlef; Sommer, Claudia; Birklein, Frank

    2007-06-01

    Intradermal capsaicin injection (CAP) and electrical current stimulation (ES) are analyzed in respect to patterns and test-retest reliability of pain as well as sensory and neurosecretory changes. In 10 healthy subjects, 2x CAP (50 microg) and 2x ES (5 to 30 mA) were applied to the volar forearm. The time period between 2 identical stimulations was about 4 months. Pain ratings, areas of mechanical hyperalgesia, and allodynia were assessed. The intensity of sensory changes was quantified by using quantitative sensory testing. Neurogenic flare was assessed by using laser Doppler imaging. Calcitonin gene-related peptide (CGRP) release was quantified by dermal microdialysis in combination with an enzyme immunoassay. Time course and peak pain ratings were different between CAP and ES. Test-retest correlation was high (r > or = 0.73). Both models induced primary heat hyperalgesia and primary plus secondary pin-prick hyperalgesia. Allodynia occurred in about half of the subjects. Maximum flare sizes did not differ between CAP and ES, but flare intensities were higher for ES. Test-retest correlation was higher for flare sizes than for flare intensity. A significant CGRP release could only be measured after CAP. The different time courses of pain stimulation (CAP: rapidly decaying pain versus ES: pain plateau) led to different peripheral neurosecretory effects but induced similar central plasticity and hyperalgesia. The present study gives a detailed overview of psychophysical and neurosecretory characteristics induced by noxious stimulation with capsaicin and electrical current. We describe differences, similarities, and reproducibility of these human pain models. These data might help to interpret past and future results of human pain studies using experimental pain.

  6. Low-educated women with chronic pain were less often selected to multidisciplinary rehabilitation programs.

    Directory of Open Access Journals (Sweden)

    Anne Hammarström

    Full Text Available BACKGROUND: There is a lack of research about a potential education-related bias in assessment of patients with chronic pain. The aim of this study was to analyze whether low-educated men and women with chronic pain were less often selected to multidisciplinary rehabilitation than those with high education. METHODS: The population consisted of consecutive patients (n = 595 women, 266 men referred during a three-year period from mainly primary health care centers for a multidisciplinary team assessment at a pain rehabilitation clinic at a university hospital in Northern Sweden. Patient data were collected from the Swedish Quality Registry for Pain Rehabilitation National Pain Register. The outcome variable was being selected by the multidisciplinary team assessment to a multidisciplinary rehabilitation program. The independent variables were: sex, age, born outside Sweden, education, pain severity as well as the hospital, anxiety and depression scale (HADS. RESULTS: Low-educated women were less often selected to multidisciplinary rehabilitation programs than high-educated women (OR 0.55, CI 0.30-0.98, even after control for age, being born outside Sweden, pain intensity and HADS. No significant findings were found when comparing the results between high- and low-educated men. CONCLUSION: Our findings can be interpreted as possible discrimination against low-educated women with chronic pain in hospital referrals to pain rehabilitation. There is a need for more gender-theoretical research emphasizing the importance of taking several power dimensions into account when analyzing possible bias in health care.

  7. Efficacy of Selected Electrical Therapies on Chronic Low Back Pain: A Comparative Clinical Pilot Study.

    Science.gov (United States)

    Rajfur, Joanna; Pasternok, Małgorzata; Rajfur, Katarzyna; Walewicz, Karolina; Fras, Beata; Bolach, Bartosz; Dymarek, Robert; Rosinczuk, Joanna; Halski, Tomasz; Taradaj, Jakub

    2017-01-07

    BACKGROUND In the currently available research publications on electrical therapy of low back pain, generally no control groups or detailed randomization were used, and such studies were often conducted with relatively small groups of patients, based solely on subjective questionnaires and pain assessment scales (lacking measurement methods to objectify the therapeutic progress). The available literature also lacks a comprehensive and large-scale clinical study. The purpose of this study was to assess the effects of treating low back pain using selected electrotherapy methods. The study assesses the influence of individual electrotherapeutic treatments on reduction of pain, improvement of the range of movement in lower section of the spine, and improvement of motor functions and mobility. MATERIAL AND METHODS The 127 patients qualified for the therapy (ultimately, 123 patients completed the study) and assigned to 6 comparison groups: A - conventional TENS, B - acupuncture-like TENS, C - high-voltage electrical stimulation, D - interferential current stimulation, E - diadynamic current, and F - control group. RESULTS The research showed that using electrical stimulation with interferential current penetrating deeper into the tissues results in a significant and more efficient elimination of pain, and an improvement of functional ability of patients suffering from low back pain on the basis of an analysis of both subjective and objective parameters. The TENS currents and high voltage were helpful, but not as effective. The use of diadynamic currents appears to be useless. CONCLUSIONS Selected electrical therapies (interferential current, TENS, and high voltage) appear to be effective in treating chronic low back pain.

  8. Modeling subjective well-being in individuals with chronic pain and a physical disability: the role of pain control and pain catastrophizing.

    Science.gov (United States)

    Furrer, Angela; Michel, Gisela; Terrill, Alexandra L; Jensen, Mark P; Müller, Rachel

    2017-10-23

    To investigate the associations between subjective well-being and pain intensity, pain interference, and depression in individuals with physical disabilities. We hypothesized that (1) pain control and (2) pain catastrophizing mediate the effects of subjective well-being on pain intensity, pain interference, and depression. Analyses of cross-sectional data from 96 individuals diagnosed with spinal cord injury, multiple sclerosis, neuromuscular disease, or post-polio syndrome, with average pain intensity of ≥4 (0-10) on at least half the days in the past month. Two models tested study hypotheses using structural equation. Both models showed acceptable model fit. Pain catastrophizing significantly mediated the effect of subjective well-being on pain intensity and pain interference, but not on depression. Pain control did not significantly mediate the effect of subjective well-being on pain intensity, pain interference, or depression. Path coefficients showed significant direct effects of subjective well-being on pain control (β = 0.39), pain catastrophizing (β = -0.61), pain interference (β = -0.48; -0.42), and depression (β = -0.75; -0.78). This study supports the potential of enhancing subjective well-being and lowering pain catastrophizing for reducing pain intensity, pain interference, and depressive symptoms in individuals with chronic pain and a physical disability. The findings indicate that true experiments to test for causal associations are warranted. Implications for rehabilitation The majority of individuals with physical disabilities report having persistent moderate-to-severe pain that may negatively limit daily activities and quality of life. The present cross-sectional study indicates that individuals who reported greater subjective well-being showed significantly lower pain intensity via the mediating effect of lower pain catastrophizing. Since sample size and respective power are low, these findings should be taken as first

  9. A selective role for α3 subunit glycine receptors in inflammatory pain

    Directory of Open Access Journals (Sweden)

    Victoria L Harvey

    2009-11-01

    Full Text Available GlyR α3 has previously been found to play a critical role in pain hypersensitivity following spinal PGE2 injection, complete Freund’s adjuvant (CFA and zymosan induced peripheral inflammation. In this study, although all models displayed typical phenotypic behaviours, no significant differences were observed when comparing the pain behaviours of Glra3-/- and wild-type littermates following the injection of capsaicin, carrageenan, kaolin/ carrageenan or monosodium iodoacetate, models of rheumatoid and osteoarthritis, respectively. However, clear differences were observed following CFA injection (p < 0.01. No significant differences were observed in the pain behaviours of Glra3-/- and wild-type littermates following experimentally induced neuropathic pain (partial sciatic nerve ligation. Similarly, Glra3-/- and wild-type littermates displayed indistinguishable visceromotor responses to colorectal distension (a model of visceral pain and in vivo spinal cord dorsal horn electrophysiology revealed no differences in responses to multimodal suprathreshold stimuli, intensities which equate to higher pain scores such as those reported in the clinic. These data suggest that apart from its clear role in CFA- and zymosan-induced pain sensitisation, hypersensitivity associated with other models of inflammation, neuropathy and visceral disturbances involves mechanisms other than the EP2 receptor - GlyR α3 pathway.

  10. Rethinking the Psychogenic Model of Complex Regional Pain Syndrome: Somatoform Disorders and Complex Regional Pain Syndrome

    Science.gov (United States)

    Hill, Renee J.; Chopra, Pradeep; Richardi, Toni

    2012-01-01

    Abstract Explaining the etiology of Complex Regional Pain Syndrome (CRPS) from the psychogenic model is exceedingly unsophisticated, because neurocognitive deficits, neuroanatomical abnormalities, and distortions in cognitive mapping are features of CRPS pathology. More importantly, many people who have developed CRPS have no history of mental illness. The psychogenic model offers comfort to physicians and mental health practitioners (MHPs) who have difficulty understanding pain maintained by newly uncovered neuro inflammatory processes. With increased education about CRPS through a biopsychosocial perspective, both physicians and MHPs can better diagnose, treat, and manage CRPS symptomatology. PMID:24223338

  11. Validation and Refinement of a Pain Information Model from EHR Flowsheet Data.

    Science.gov (United States)

    Westra, Bonnie L; Johnson, Steven G; Ali, Samira; Bavuso, Karen M; Cruz, Christopher A; Collins, Sarah; Furukawa, Meg; Hook, Mary L; LaFlamme, Anne; Lytle, Kay; Pruinelli, Lisiane; Rajchel, Tari; Settergren, Theresa Tess; Westman, Kathryn F; Whittenburg, Luann

    2018-01-01

    Secondary use of electronic health record (EHR) data can reduce costs of research and quality reporting. However, EHR data must be consistent within and across organizations. Flowsheet data provide a rich source of interprofessional data and represents a high volume of documentation; however, content is not standardized. Health care organizations design and implement customized content for different care areas creating duplicative data that is noncomparable. In a prior study, 10 information models (IMs) were derived from an EHR that included 2.4 million patients. There was a need to evaluate the generalizability of the models across organizations. The pain IM was selected for evaluation and refinement because pain is a commonly occurring problem associated with high costs for pain management. The purpose of our study was to validate and further refine a pain IM from EHR flowsheet data that standardizes pain concepts, definitions, and associated value sets for assessments, goals, interventions, and outcomes. A retrospective observational study was conducted using an iterative consensus-based approach to map, analyze, and evaluate data from 10 organizations. The aggregated metadata from the EHRs of 8 large health care organizations and the design build in 2 additional organizations represented flowsheet data from 6.6 million patients, 27 million encounters, and 683 million observations. The final pain IM has 30 concepts, 4 panels (classes), and 396 value set items. Results are built on Logical Observation Identifiers Names and Codes (LOINC) pain assessment terms and extend the need for additional terms to support interoperability. The resulting pain IM is a consensus model based on actual EHR documentation in the participating health systems. The IM captures the most important concepts related to pain. Schattauer GmbH Stuttgart.

  12. Gender differences in functional connectivities between insular subdivisions and selective pain-related brain structures.

    Science.gov (United States)

    Dai, Yu-Jie; Zhang, Xin; Yang, Yang; Nan, Hai-Yan; Yu, Ying; Sun, Qian; Yan, Lin-Feng; Hu, Bo; Zhang, Jin; Qiu, Zi-Yu; Gao, Yi; Cui, Guang-Bin; Chen, Bi-Liang; Wang, Wen

    2018-03-14

    The incidence of pain disorders in women is higher than in men, making gender differences in pain a research focus. The human insular cortex is an important brain hub structure for pain processing and is divided into several subdivisions, serving different functions in pain perception. Here we aimed to examine the gender differences of the functional connectivities (FCs) between the twelve insular subdivisions and selected pain-related brain structures in healthy adults. Twenty-six healthy males and 11 age-matched healthy females were recruited in this cross-sectional study. FCs between the 12 insular subdivisions (as 12 regions of interest (ROIs)) and the whole brain (ROI-whole brain level) or 64 selected pain-related brain regions (64 ROIs, ROI-ROI level) were measured between the males and females. Significant gender differences in the FCs of the insular subdivisions were revealed: (1) The FCs between the dorsal dysgranular insula (dId) and other brain regions were significantly increased in males using two different techniques (ROI-whole brain and ROI-ROI analyses); (2) Based on the ROI-whole brain analysis, the FC increases in 4 FC-pairs were observed in males, including the left dId - the right median cingulate and paracingulate/ right posterior cingulate gyrus/ right precuneus, the left dId - the right median cingulate and paracingulate, the left dId - the left angular as well as the left dId - the left middle frontal gyrus; (3) According to the ROI-ROI analysis, increased FC between the left dId and the right rostral anterior cingulate cortex was investigated in males. In summary, the gender differences in the FCs of the insular subdivisions with pain-related brain regions were revealed in the current study, offering neuroimaging evidence for gender differences in pain processing. ClinicalTrials.gov, NCT02820974 . Registered 28 June 2016.

  13. Selective Denervation for Persistent Knee Pain After Total Knee Arthroplasty: A Report of 50 Cases.

    Science.gov (United States)

    Shi, Shao-Min; Meister, David W; Graner, Kelly C; Ninomiya, James T

    2017-03-01

    Despite the general success of total knee arthroplasty (TKA), up to 20% of patients report dissatisfaction following surgery. One potential cause of this dissatisfaction is residual pain secondary to neuroma formation in the sensory nerve branches that innervate the knee. We found, after performing a retrospective review, that up to 9.7% of patients following primary TKA and up to 21% of revision cases exhibited persistent knee pain attributable to neuroma formation. Despite the high incidence of this pathology, little is known about the effective diagnosis or treatment of neuroma formation following TKA. Between 2011 and 2014, 50 patients with persistent symptomatic neuroma pain following TKA underwent selective denervation. These patients had demonstrated the appropriate selection criteria and had failed conservative management. Patients were evaluated by the visual analog scale pain score and the Knee Society Score to determine the outcome of the described treatment. Thirty-two patients (64%) rated their outcome as excellent, 10 (20%) as good, 3 (6%) as fair, and 2 (4%) reported no change. The mean visual analog scale pain score was improved from 9.4 ± 0.8 to 1.1 ± 1.6 following surgery (P ≤ .001). The mean Knee Society Scores increased from 45.5 ± 14.3 to 94.1 ± 8.6 points (P ≤ .0001). Three patients (6%) required the second neurectomy due to recurrent pain and received excellent pain relief postoperatively. There were 2 complications of superficial skin peri-incisional hyperemia related to dressings. Average follow-up duration was 24 months (range, 16-38 months). Our study suggests that selective denervation provides an effective and long-lasting option for the management of this pathology. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Selected Tether Applications Cost Model

    Science.gov (United States)

    Keeley, Michael G.

    1988-01-01

    Diverse cost-estimating techniques and data combined into single program. Selected Tether Applications Cost Model (STACOM 1.0) is interactive accounting software tool providing means for combining several independent cost-estimating programs into fully-integrated mathematical model capable of assessing costs, analyzing benefits, providing file-handling utilities, and putting out information in text and graphical forms to screen, printer, or plotter. Program based on Lotus 1-2-3, version 2.0. Developed to provide clear, concise traceability and visibility into methodology and rationale for estimating costs and benefits of operations of Space Station tether deployer system.

  15. Traumatization and chronic pain: a further model of interaction

    Directory of Open Access Journals (Sweden)

    Egloff N

    2013-11-01

    Full Text Available Niklaus Egloff,1 Anna Hirschi,2 Roland von Känel1 1Department of General Internal Medicine, Division of Psychosomatic Medicine, Inselspital, University Hospital, Bern, Switzerland; 2Outpatient Clinic for Victims of Torture and War, Swiss Red Cross, Bern-Wabern, Switzerland Abstract: Up to 80% of patients with severe posttraumatic stress disorder are suffering from “unexplained” chronic pain. Theories about the links between traumatization and chronic pain have become the subject of increased interest over the last several years. We will give a short summary about the existing interaction models that emphasize particularly psychological and behavioral aspects of this interaction. After a synopsis of the most important psychoneurobiological mechanisms of pain in the context of traumatization, we introduce the hypermnesia–hyperarousal model, which focuses on two psychoneurobiological aspects of the physiology of learning. This hypothesis provides an answer to the hitherto open question about the origin of pain persistence and pain sensitization following a traumatic event and also provides a straightforward explanatory model for educational purposes. Keywords: posttraumatic stress disorder, chronic pain, hypermnesia, hypersensitivity, traumatization

  16. Animal models of pain and migraine in drug discovery

    DEFF Research Database (Denmark)

    Munro, Gordon; Jansen-Olesen, Inger; Olesen, Jes

    2017-01-01

    of the most commonly used models and methods employed within 'pain and migraine' drug development will be presented. Recent advances within these disciplines suggest that, with the addition of a few extra carefully chosen ancillary models and/or endpoints, the relative value in terms of resources used...

  17. Healthy volunteers can be phenotyped using cutaneous sensitization pain models

    DEFF Research Database (Denmark)

    Werner, Mads U; Petersen, Karin; Rowbotham, Michael C

    2013-01-01

    Human experimental pain models leading to development of secondary hyperalgesia are used to estimate efficacy of analgesics and antihyperalgesics. The ability to develop an area of secondary hyperalgesia varies substantially between subjects, but little is known about the agreement following repe...... repeated measurements. The aim of this study was to determine if the areas of secondary hyperalgesia were consistently robust to be useful for phenotyping subjects, based on their pattern of sensitization by the heat pain models.......Human experimental pain models leading to development of secondary hyperalgesia are used to estimate efficacy of analgesics and antihyperalgesics. The ability to develop an area of secondary hyperalgesia varies substantially between subjects, but little is known about the agreement following...

  18. Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber).

    Science.gov (United States)

    Park, Thomas J; Lu, Ying; Jüttner, René; Smith, Ewan St J; Hu, Jing; Brand, Antje; Wetzel, Christiane; Milenkovic, Nevena; Erdmann, Bettina; Heppenstall, Paul A; Laurito, Charles E; Wilson, Steven P; Lewin, Gary R

    2008-01-01

    In all mammals, tissue inflammation leads to pain and behavioral sensitization to thermal and mechanical stimuli called hyperalgesia. We studied pain mechanisms in the African naked mole-rat, an unusual rodent species that lacks pain-related neuropeptides (e.g., substance P) in cutaneous sensory fibers. Naked mole-rats show a unique and remarkable lack of pain-related behaviors to two potent algogens, acid and capsaicin. Furthermore, when exposed to inflammatory insults or known mediators, naked mole-rats do not display thermal hyperalgesia. In contrast, naked mole-rats do display nocifensive behaviors in the formalin test and show mechanical hyperalgesia after inflammation. Using electrophysiology, we showed that primary afferent nociceptors in naked mole-rats are insensitive to acid stimuli, consistent with the animal's lack of acid-induced behavior. Acid transduction by sensory neurons is observed in birds, amphibians, and fish, which suggests that this tranduction mechanism has been selectively disabled in the naked mole-rat in the course of its evolution. In contrast, nociceptors do respond vigorously to capsaicin, and we also show that sensory neurons express a transient receptor potential vanilloid channel-1 ion channel that is capsaicin sensitive. Nevertheless, the activation of capsaicin-sensitive sensory neurons in naked mole-rats does not produce pain-related behavior. We show that capsaicin-sensitive nociceptors in the naked mole-rat are functionally connected to superficial dorsal horn neurons as in mice. However, the same nociceptors are also functionally connected to deep dorsal horn neurons, a connectivity that is rare in mice. The pain biology of the naked mole-rat is unique among mammals, thus the study of pain mechanisms in this unusual species can provide major insights into what constitutes "normal" mammalian nociception.

  19. Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber.

    Directory of Open Access Journals (Sweden)

    Thomas J Park

    2008-01-01

    Full Text Available In all mammals, tissue inflammation leads to pain and behavioral sensitization to thermal and mechanical stimuli called hyperalgesia. We studied pain mechanisms in the African naked mole-rat, an unusual rodent species that lacks pain-related neuropeptides (e.g., substance P in cutaneous sensory fibers. Naked mole-rats show a unique and remarkable lack of pain-related behaviors to two potent algogens, acid and capsaicin. Furthermore, when exposed to inflammatory insults or known mediators, naked mole-rats do not display thermal hyperalgesia. In contrast, naked mole-rats do display nocifensive behaviors in the formalin test and show mechanical hyperalgesia after inflammation. Using electrophysiology, we showed that primary afferent nociceptors in naked mole-rats are insensitive to acid stimuli, consistent with the animal's lack of acid-induced behavior. Acid transduction by sensory neurons is observed in birds, amphibians, and fish, which suggests that this tranduction mechanism has been selectively disabled in the naked mole-rat in the course of its evolution. In contrast, nociceptors do respond vigorously to capsaicin, and we also show that sensory neurons express a transient receptor potential vanilloid channel-1 ion channel that is capsaicin sensitive. Nevertheless, the activation of capsaicin-sensitive sensory neurons in naked mole-rats does not produce pain-related behavior. We show that capsaicin-sensitive nociceptors in the naked mole-rat are functionally connected to superficial dorsal horn neurons as in mice. However, the same nociceptors are also functionally connected to deep dorsal horn neurons, a connectivity that is rare in mice. The pain biology of the naked mole-rat is unique among mammals, thus the study of pain mechanisms in this unusual species can provide major insights into what constitutes "normal" mammalian nociception.

  20. Modelling concentration-analgesia relationships for morphine to evaluate experimental pain models

    DEFF Research Database (Denmark)

    Sverrisdóttir, Eva; Foster, David John Richard; Upton, Richard Neil

    2015-01-01

    The aim of this study was to develop population pharmacokinetic-pharmacodynamic models for morphine in experimental pain induced by skin heat and muscle pressure, and to evaluate the experimental pain models with regard to assessment of morphine pharmacodynamics. In a randomized, double......-blind, placebo-controlled, crossover study, 39 healthy volunteers received an oral dose of 30 mg morphine hydrochloride or placebo. Non-linear mixed effects modelling was used to describe the plasma concentrations of morphine and metabolites, and the analgesic effect of morphine on experimental pain in skin...... and muscle. Baseline pain metrics varied between individuals and occasions, and were described with interindividual and interoccasion variability. Placebo-response did not change with time. For both pain metrics, morphine effect was proportional to baseline pain and was described with a linear model...

  1. Pain Relief in Nonhuman Primate Models of Arthritis.

    Science.gov (United States)

    Vierboom, Michel P M; Breedveld, Elia; Keehnen, Merei; Klomp, Rianne; Bakker, Jaco

    2017-01-01

    Animal models of rheumatoid arthritis are important in the elucidation of etiopathogenic mechanisms of the disease and for the development of promising new therapies. Species specificity of new biological compounds and their mode of action preclude safety and efficacy testing in rodent models of disease. Nonhuman primates (NHP) can fill this niche and provide the only relevant model. Over the last two decades models of collagen-induced arthritis (CIA) were developed in the rhesus monkey and the common marmoset. However, NHP are higher-order animals and complex sentient beings. So especially in models where pain is an intricate part of the disease, analgesia needs to be addressed because of ethical considerations. In our model, a morphine-based pain relief was used that does not interfere with the normal development of disease allowing us to evaluate important mechanistic aspects of the arthritis.

  2. A Model-Based Approach for Joint Analysis of Pain Intensity and Opioid Consumption in Postoperative Pain

    DEFF Research Database (Denmark)

    Juul, Rasmus V; Knøsgaard, Katrine R; Olesen, Anne E

    2016-01-01

    Joint analysis of pain intensity and opioid consumption is encouraged in trials of postoperative pain. However, previous approaches have not appropriately addressed the complexity of their interrelation in time. In this study, we applied a non-linear mixed effects model to simultaneously study pain...... intensity and opioid consumption in a 4-h postoperative period for 44 patients undergoing percutaneous kidney stone surgery. Analysis was based on 748 Numerical Rating Scale (NRS) scores of pain intensity and 51 observed morphine and oxycodone dosing events. A joint model was developed to describe...... the recurrent pattern of four key phases determining the development of pain intensity and opioid consumption in time; (A) Distribution of pain intensity scores which followed a truncated Poisson distribution with time-dependent mean score ranging from 0.93 to 2.45; (B) Probability of transition to threshold...

  3. Prevalence of Spondylolysis and Its Relationship with Low Back Pain in Selected Population

    OpenAIRE

    Ko, Sang-Bong; Lee, Sang-Wook

    2011-01-01

    Background To determine the prevalence of spondylolysis in a selected population and evaluate the association of spondylolysis with low back pain (LBP). Spondylolysis is widespread in the general population but the prevalence of spondylolysis and its relationship with LBP in the Korean population is controversial. Methods A sample of 855 participants (age, 20 to 86 years) from our medical center who underwent multidetector computed tomography (CT) imaging to assess abdominal and urological le...

  4. Translational pain research: evaluating analgesic effect in experimental visceral pain models

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Andresen, Trine; Christrup, Lona Louring

    2009-01-01

    Deep visceral pain is frequent and presents major challenges in pain management, since its pathophysiology is still poorly understood. One way to optimize treatment of visceral pain is to improve knowledge of the mechanisms behind the pain and the mode of action of analgesic substances. This can ...... studies and clinical condition in patients suffering from visceral pain, and thus constitute the missing link in translational pain research.......Deep visceral pain is frequent and presents major challenges in pain management, since its pathophysiology is still poorly understood. One way to optimize treatment of visceral pain is to improve knowledge of the mechanisms behind the pain and the mode of action of analgesic substances. This can...... facilitate minimizing the gap between knowledge gained in animal and human clinical studies. Combining experimental pain studies and pharmacokinetic studies can improve understanding of the pharmacokinetic-pharmacodynamic relationship of analgesics and, thus, provide valuable insight into optimal clinical...

  5. Healthy volunteers can be phenotyped using cutaneous sensitization pain models.

    Directory of Open Access Journals (Sweden)

    Mads U Werner

    Full Text Available BACKGROUND: Human experimental pain models leading to development of secondary hyperalgesia are used to estimate efficacy of analgesics and antihyperalgesics. The ability to develop an area of secondary hyperalgesia varies substantially between subjects, but little is known about the agreement following repeated measurements. The aim of this study was to determine if the areas of secondary hyperalgesia were consistently robust to be useful for phenotyping subjects, based on their pattern of sensitization by the heat pain models. METHODS: We performed post-hoc analyses of 10 completed healthy volunteer studies (n = 342 [409 repeated measurements]. Three different models were used to induce secondary hyperalgesia to monofilament stimulation: the heat/capsaicin sensitization (H/C, the brief thermal sensitization (BTS, and the burn injury (BI models. Three studies included both the H/C and BTS models. RESULTS: Within-subject compared to between-subject variability was low, and there was substantial strength of agreement between repeated induction-sessions in most studies. The intraclass correlation coefficient (ICC improved little with repeated testing beyond two sessions. There was good agreement in categorizing subjects into 'small area' (1(st quartile [75%] responders: 56-76% of subjects consistently fell into same 'small-area' or 'large-area' category on two consecutive study days. There was moderate to substantial agreement between the areas of secondary hyperalgesia induced on the same day using the H/C (forearm and BTS (thigh models. CONCLUSION: Secondary hyperalgesia induced by experimental heat pain models seem a consistent measure of sensitization in pharmacodynamic and physiological research. The analysis indicates that healthy volunteers can be phenotyped based on their pattern of sensitization by the heat [and heat plus capsaicin] pain models.

  6. The Animal Model of Spinal Cord Injury as an Experimental Pain Model

    OpenAIRE

    Nakae, Aya; Nakai, Kunihiro; Yano, Kenji; Hosokawa, Ko; Shibata, Masahiko; Mashimo, Takashi

    2011-01-01

    Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of patholo...

  7. Pain

    OpenAIRE

    H.W. Snyman

    1980-01-01

    The medical profession has always been under pressure to supply public explanations of the diseases with which it deals. On the other hand, it is an old characteristic of the profession to devise comprehensive and unifying theories on all sorts of medical problems. Both these statements apply to pain - one of the most important and clinically striking phenomena and expressions of man since his origin in the mists of time.

  8. Pain

    Directory of Open Access Journals (Sweden)

    H.W. Snyman

    1980-09-01

    Full Text Available The medical profession has always been under pressure to supply public explanations of the diseases with which it deals. On the other hand, it is an old characteristic of the profession to devise comprehensive and unifying theories on all sorts of medical problems. Both these statements apply to pain - one of the most important and clinically striking phenomena and expressions of man since his origin in the mists of time.

  9. Characterization of a novel model of tonic heat pain stimulation in healthy volunteers.

    Science.gov (United States)

    Naert, Arne L G; Kehlet, Henrik; Kupers, Ron

    2008-08-15

    The vast majority of the experimental pain studies have used acute, phasic heat stimuli to investigate the neurobiological mechanisms of pain. However, the validity of these models for understanding clinical forms of pain is questionable. We here describe the characteristics of a model of prolonged tonic heat pain stimulation and compared the responses on this test with other measures of pain. In 58 normal volunteers, we applied a 7-min lasting contact heat stimulation of 47 degrees C to the upper leg while participants constantly rated their pain. Average pain rating during the 7-min period was 6.2+/-0.4, females scoring higher than men (7.4+/-0.5 vs. 5.2+/-0.5; pPain ratings showed a steady increase during the first half of the stimulation period after which they stabilized. A strong interindividual variability was observed in the time profiles of the pain ratings over the course of the 7-min stimulation period. The model showed a good test-retest reproducibility. Tonic heat pain ratings only correlated moderately with the pain threshold while stronger correlations were observed with pain tolerance and ratings of suprathreshold phasic heat pain. We conclude that the tonic heat model is a suitable model that can be applied without excessive discomfort in the majority of subjects and offers a valuable addition to the armamentarium of experimental pain models. The model can be particularly suitable for brain imaging receptor binding studies which require long stimulation periods.

  10. Selective Fiber Degeneration in the Peripheral Nerve of a Patient With Severe Complex Regional Pain Syndrome

    Directory of Open Access Journals (Sweden)

    Adrien Yvon

    2018-04-01

    Full Text Available Aims: Complex regional pain syndrome (CRPS is characterized by chronic debilitating pain disproportional to the inciting event and accompanied by motor, sensory, and autonomic disturbances. The pathophysiology of CRPS remains elusive. An exceptional case of severe CRPS leading to forearm amputation provided the opportunity to examine nerve histopathological features of the peripheral nerves.Methods: A 35-year-old female developed CRPS secondary to low voltage electrical injury. The CRPS was refractory to medical therapy and led to functional loss of the forelimb, repeated cutaneous wound infections leading to hospitalization. Specifically, the patient had exhausted a targeted conservative pain management programme prior to forearm amputation. Radial, median, and ulnar nerve specimens were obtained from the amputated limb and analyzed by light and transmission electron microscopy (TEM.Results: All samples showed features of selective myelinated nerve fiber degeneration (47–58% of fibers on electron microscopy. Degenerating myelinated fibers were significantly larger than healthy fibers (p < 0.05, and corresponded to the larger Aα fibers (motor/proprioception whilst smaller Aδ (pain/temperature fibers were spared. Groups of small unmyelinated C fibers (Remak bundles also showed evidence of degeneration in all samples.Conclusions: We are the first to show large fiber degeneration in CRPS using TEM. Degeneration of Aα fibers may lead to an imbalance in nerve signaling, inappropriately triggering the smaller healthy Aδ fibers, which transmit pain and temperature. These findings suggest peripheral nerve degeneration may play a key role in CRPS. Improved knowledge of pathogenesis will help develop more targeted treatments.

  11. The contribution of spinal glial cells to chronic pain behaviour in the monosodium iodoacetate model of osteoarthritic pain

    Directory of Open Access Journals (Sweden)

    Sagar Devi

    2011-11-01

    Full Text Available Abstract Background Clinical studies of osteoarthritis (OA suggest central sensitization may contribute to the chronic pain experienced. This preclinical study used the monosodium iodoacetate (MIA model of OA joint pain to investigate the potential contribution of spinal sensitization, in particular spinal glial cell activation, to pain behaviour in this model. Experimental OA was induced in the rat by the intra-articular injection of MIA and pain behaviour (change in weight bearing and distal allodynia was assessed. Spinal cord microglia (Iba1 staining and astrocyte (GFAP immunofluorescence activation were measured at 7, 14 and 28 days post MIA-treatment. The effects of two known inhibitors of glial activation, nimesulide and minocycline, on pain behaviour and activation of microglia and astrocytes were assessed. Results Seven days following intra-articular injection of MIA, microglia in the ipsilateral spinal cord were activated (p Conclusions Here we provide evidence for a contribution of spinal glial cells to pain behaviour, in particular distal allodynia, in this model of osteoarthritic pain. Our data suggest there is a potential role of glial cells in the central sensitization associated with OA, which may provide a novel analgesic target for the treatment of OA pain.

  12. Efficacy of selected complementary and alternative medicine interventions for chronic pain.

    Science.gov (United States)

    Tan, Gabriel; Craine, Michael H; Bair, Matthew J; Garcia, M Kay; Giordano, James; Jensen, Mark P; McDonald, Shelley M; Patterson, David; Sherman, Richard A; Williams, Wright; Tsao, Jennie C I

    2007-01-01

    Complementary and alternative medicine (CAM) is a group of diverse medical and healthcare systems, therapies, and products that are not presently considered part of conventional medicine. This article provides an up-to-date review of the efficacy of selected CAM modalities in the management of chronic pain. Findings are presented according to the classification system developed by the National Institutes of Health National Center for Complementary and Alternative Medicine (formerly Office of Alternative Medicine) and are grouped into four domains: biologically based medicine, energy medicine, manipulative and body-based medicine, and mind-body medicine. Homeopathy and acupuncture are discussed separately as "whole or professionalized CAM practices." Based on the guidelines of the Clinical Psychology Division of the American Psychological Association, findings indicate that some CAM modalities have a solid track record of efficacy, whereas others are promising but require additional research. The article concludes with recommendations to pain practitioners.

  13. Effectiveness of L2 spinal nerve infiltration for selective discogenic low back pain patients

    International Nuclear Information System (INIS)

    Ohtori, Seiji; Nakamura, Shinichiro; Koshi, Takana

    2010-01-01

    It has been reported that rat L5/6 lumbar discs are innervated mainly by L2 dorsal root ganglion neurons. We previously reported that L2 spinal nerve infiltration was effective for discogenic low back pain (DLBP) patients, although the diagnosis was based only on the results of physical examination, plain films, and magnetic resonance imaging (MRI). The purpose of the current study was to evaluate L2 spinal nerve block for DLBP patients retrospectively based on MRI findings and surgical results. A total of 62 patients with only LBP and no accompanying radicular pain were investigated. Patients had only one level of disc degeneration on MRI. When pain was provoked during discography, we performed surgery at the next stage (40 patients). In all, 22 patients were excluded owing to negative discography results. Of the 40 patients, we evaluated 25 strictly selected patients suffering from DLBP. DLBP was diagnosed when the patient experienced pain relief at least 2 years after anterior lumbar interbody fusion. Fifteen patients who did not show pain relief after surgery were used for the non-DLBP group. L2 spinal nerve infiltration using 1.5 ml of lidocaine was performed in all 40 patients before surgery. The visual analogue scale (VAS) score after L2 spinal nerve infiltration was recorded, and an association of L2 spinal nerve infiltration and DLBP was explored. Low back pain scores assessed using the VAS score, the Japanese Orthopedic Association score, and the Oswestry Disability Index score in the two groups were not significantly different. L2 spinal nerve infiltration was effective for 27 patients but not effective for 13 patients; the VAS score after 15 min and 2 h improved in the DLBP group compared with that of the non-DLBP group (P<0.05). L2 spinal nerve infiltration was more effective in DLBP patients (21 patients, 84%) than in the non-DLBP group (6 patients, 40%) (P<0.05). In the current study, L2 spinal nerve infiltration was effective in 84% of selected DLBP

  14. Chronic Pain and Selective Attention to Pain Arousing Daily Activity Pictures: Evidence From an Eye Tracking Study

    Directory of Open Access Journals (Sweden)

    Masoumeh Mahmoodi-Aghdam

    2017-11-01

    Conclusion: Although these results did not provide unequivocal support for the vigilance-avoidance hypothesis, they are generally consistent with the results of studies using eye tracking technology. Furthermore, our findings put a question over characterization of attentional biases in patients with chronic pain by simply relating that to difficulty in disengaging from pain-related stimuli.

  15. Impaired behavioural pain responses in hph-1 mice with inherited deficiency in GTP cyclohydrolase 1 in models of inflammatory pain

    Science.gov (United States)

    2013-01-01

    Background GTP cyclohydrolase 1 (GTP-CH1), the rate-limiting enzyme in the synthesis of tetrahydrobiopterin (BH4), encoded by the GCH1 gene, has been implicated in the development and maintenance of inflammatory pain in rats. In humans, homozygous carriers of a “pain-protective” (PP) haplotype of the GCH1 gene have been identified exhibiting lower pain sensitivity, but only following pain sensitisation. Ex vivo, the PP GCH1 haplotype is associated with decreased induction of GCH1 after stimulation, whereas the baseline BH4 production is not affected. Contrary, loss of function mutations in the GCH1 gene results in decreased basal GCH1 expression, and is associated with DOPA-responsive dystonia (DRD). So far it is unknown if such mutations affect acute and inflammatory pain. Results In the current study, we examined the involvement of the GCH1 gene in pain models using the hyperphenylalaninemia 1 (hph-1) mouse, a genetic model for DRD, with only 10% basal GTP-CH1 activity compared to wild type mice. The study included assays for determination of acute nociception as well as models for pain after sensitisation. Pain behavioural analysis of the hph-1 mice showed reduced pain-like responses following intraplantar injection of CFA, formalin and capsaicin; whereas decreased basal level of GTP-CH1 activity had no influence in naïve hph-1 mice on acute mechanical and heat pain thresholds. Moreover, the hph-1 mice showed no signs of motor impairment or dystonia-like symptoms. Conclusions In this study, we demonstrate novel evidence that genetic mutations in the GCH1 gene modulate pain-like hypersensitivity. Together, the present data suggest that BH4 is not important for basal heat and mechanical pain, but they support the hypothesis that BH4 plays a role in inflammation-induced hypersensitivity. Our studies suggest that the BH4 pathway could be a therapeutic target for the treatment of inflammatory pain conditions. Moreover, the hph-1 mice provide a valid model to

  16. A novel and selective poly (ADP-ribose polymerase inhibitor ameliorates chemotherapy-induced painful neuropathy.

    Directory of Open Access Journals (Sweden)

    Lauren E Ta

    Full Text Available Chemotherapy-induced neuropathy is the principle dose limiting factor requiring discontinuation of many chemotherapeutic agents, including cisplatin and oxaliplatin. About 30 to 40% of patients receiving chemotherapy develop pain and sensory changes. Given that poly (ADP-ribose polymerase (PARP inhibition has been shown to provide neuroprotection, the current study was developed to test whether the novel PARP inhibitor compound 4a (analog of ABT-888 would attenuate pain in cisplatin and oxaliplatin-induced neuropathy in mice.An established chemotherapy-induced painful neuropathy model of two weekly cycles of 10 intraperitoneal (i.p. injections separated by 5 days rest was used to examine the therapeutic potential of the PARP inhibitor compound 4a. Behavioral testing using von Frey, paw radiant heat, cold plate, and exploratory behaviors were taken at baseline, and followed by testing at 3, 6, and 8 weeks from the beginning of drug treatment.Cisplatin-treated mice developed heat hyperalgesia and mechanical allodynia while oxaliplatin-treated mice exhibited cold hyperalgesia and mechanical allodynia. Co-administration of 50 mg/kg or 25 mg/kg compound 4a with platinum regimen, attenuated cisplatin-induced heat hyperalgesia and mechanical allodynia in a dose dependent manner. Similarly, co-administration of 50 mg/kg compound 4a attenuated oxaliplatin-induced cold hyperalgesia and mechanical allodynia. These data indicate that administration of a novel PARP inhibitor may have important applications as a therapeutic agent for human chemotherapy-induced painful neuropathy.

  17. A novel and selective poly (ADP-ribose) polymerase inhibitor ameliorates chemotherapy-induced painful neuropathy.

    Science.gov (United States)

    Ta, Lauren E; Schmelzer, James D; Bieber, Allan J; Loprinzi, Charles L; Sieck, Gary C; Brederson, Jill D; Low, Philip A; Windebank, Anthony J

    2013-01-01

    Chemotherapy-induced neuropathy is the principle dose limiting factor requiring discontinuation of many chemotherapeutic agents, including cisplatin and oxaliplatin. About 30 to 40% of patients receiving chemotherapy develop pain and sensory changes. Given that poly (ADP-ribose) polymerase (PARP) inhibition has been shown to provide neuroprotection, the current study was developed to test whether the novel PARP inhibitor compound 4a (analog of ABT-888) would attenuate pain in cisplatin and oxaliplatin-induced neuropathy in mice. An established chemotherapy-induced painful neuropathy model of two weekly cycles of 10 intraperitoneal (i.p.) injections separated by 5 days rest was used to examine the therapeutic potential of the PARP inhibitor compound 4a. Behavioral testing using von Frey, paw radiant heat, cold plate, and exploratory behaviors were taken at baseline, and followed by testing at 3, 6, and 8 weeks from the beginning of drug treatment. Cisplatin-treated mice developed heat hyperalgesia and mechanical allodynia while oxaliplatin-treated mice exhibited cold hyperalgesia and mechanical allodynia. Co-administration of 50 mg/kg or 25 mg/kg compound 4a with platinum regimen, attenuated cisplatin-induced heat hyperalgesia and mechanical allodynia in a dose dependent manner. Similarly, co-administration of 50 mg/kg compound 4a attenuated oxaliplatin-induced cold hyperalgesia and mechanical allodynia. These data indicate that administration of a novel PARP inhibitor may have important applications as a therapeutic agent for human chemotherapy-induced painful neuropathy.

  18. Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritis

    Directory of Open Access Journals (Sweden)

    Izumi Masashi

    2012-08-01

    Full Text Available Abstract Background Recent data have suggested a relationship between acute arthritic pain and acid sensing ion channel 3 (ASIC3 on primary afferent fibers innervating joints. The purpose of this study was to clarify the role of ASIC3 in a rat model of osteoarthritis (OA which is considered a degenerative rather than an inflammatory disease. Methods We induced OA via intra-articular mono-iodoacetate (MIA injection, and evaluated pain-related behaviors including weight bearing measured with an incapacitance tester and paw withdrawal threshold in a von Frey hair test, histology of affected knee joint, and immunohistochemistry of knee joint afferents. We also assessed the effect of ASIC3 selective peptide blocker (APETx2 on pain behavior, disease progression, and ASIC3 expression in knee joint afferents. Results OA rats showed not only weight-bearing pain but also mechanical hyperalgesia outside the knee joint (secondary hyperalgesia. ASIC3 expression in knee joint afferents was significantly upregulated approximately twofold at Day 14. Continuous intra-articular injections of APETx2 inhibited weight distribution asymmetry and secondary hyperalgesia by attenuating ASIC3 upregulation in knee joint afferents. Histology of ipsilateral knee joint showed APETx2 worked chondroprotectively if administered in the early, but not late phase. Conclusions Local ASIC3 immunoreactive nerve is strongly associated with weight-bearing pain and secondary hyperalgesia in MIA-induced OA model. APETx2 inhibited ASIC3 upregulation in knee joint afferents regardless of the time-point of administration. Furthermore, early administration of APETx2 prevented cartilage damage. APETx2 is a novel, promising drug for OA by relieving pain and inhibiting disease progression.

  19. Selected sports talent development models

    Directory of Open Access Journals (Sweden)

    Michal Vičar

    2017-06-01

    Full Text Available Background: Sports talent in the Czech Republic is generally viewed as a static, stable phenomena. It stands in contrast with widespread praxis carried out in Anglo-Saxon countries that emphasise its fluctuant nature. This is reflected in the current models describing its development. Objectives: The aim is to introduce current models of talent development in sport. Methods: Comparison and analysing of the following models: Balyi - Long term athlete development model, Côté - Developmental model of sport participation, Csikszentmihalyi - The flow model of optimal expertise, Bailey and Morley - Model of talent development. Conclusion: Current models of sport talent development approach talent as dynamic phenomenon, varying in time. They are based in particular on the work of Simonton and his Emergenic and epigenic model and of Gagné and his Differentiated model of giftedness and talent. Balyi's model is characterised by its applicability and impications for practice. Côté's model highlights the role of family and deliberate play. Both models describe periodization of talent development. Csikszentmihalyi's flow model explains how the athlete acquires experience and develops during puberty based on the structure of attention and flow experience. Bailey and Morley's model accents the situational approach to talent and development of skills facilitating its growth.

  20. Intervertebral Foramen Injection of Ozone Relieves Mechanical Allodynia and Enhances Analgesic Effect of Gabapentin in Animal Model of Neuropathic Pain.

    Science.gov (United States)

    Luo, Wen-Jun; Yang, Fan; Yang, Fei; Sun, Wei; Zheng, Wei; Wang, Xiao-Liang; Wu, Fang-Fang; Wang, Jiang-Lin; Wang, Jia-Shuang; Guan, Su-Min; Chen, Jun

    2017-07-01

    In a 5-year follow-up study in a hospital in southern China, it was shown that intervertebral foramen (IVF) injection of ozone at the involved segmental levels could significantly alleviate paroxysmal spontaneous pain and mechanical allodynia in patients with chronic, intractable postherpetic neuralgia (PHN) and improve the quality of life. However, so far no proof-of-concept studies in animals have been available. This study was designed to investigate whether IVF ozone has an analgesic effect on animal models of neuropathic and inflammatory pain. Experimental trial in rats. Institute for Biomedical Sciences of Pain. By IVF injection, a volume of 50 µl containing 30 µg/mL ozone-oxygen mixture or 50 µl air was carried out on male Sprague-Dawley rats of naïve, inflammatory pain states produced by injections of either bee venom or complete Freud's adjuvant, and neuropathic pain state produced by spared nerve injury, respectively. The effects of IVF ozone on pain-related behaviors were evaluated for 2 weeks or one month. Then combined use of gabapentin (100 mg/1 kg body weight) with IVF ozone was evaluated in rats with neuropathic pain by intraperitoneal administration 5 days after the ozone treatment. Finally, the analgesic effects of another 4 drugs, AMD3100 (a CXCR4 antagonist), A-803467 (a selective Nav1.8 blocker), rapamycin (the mTOR inhibitor), and MGCD0103 (a selective histone deacetylase inhibitor) were evaluated for long term through IVF injection, respectively. (1) IVF injection of ozone at L4-5 was only effective in suppression of mechanical allodynia in rats with neuropathic pain but not with inflammatory pain; (2) the analgesic effects of IVF ozone lasted much longer (> 14 days) than other selective molecular target drugs (bee venom, complete Freud's adjuvant.

  1. Selected sports talent development models

    OpenAIRE

    Michal Vičar

    2017-01-01

    Background: Sports talent in the Czech Republic is generally viewed as a static, stable phenomena. It stands in contrast with widespread praxis carried out in Anglo-Saxon countries that emphasise its fluctuant nature. This is reflected in the current models describing its development. Objectives: The aim is to introduce current models of talent development in sport. Methods: Comparison and analysing of the following models: Balyi - Long term athlete development model, Côté - Developmen...

  2. Investigating Circadian Rhythmicity in Pain Sensitivity Using a Neural Circuit Model for Spinal Cord Processing of Pain

    DEFF Research Database (Denmark)

    Crodelle, Jennifer; Piltz, Sofia Helena; Booth, Victoria

    2017-01-01

    Primary processing of painful stimulation occurs in the dorsal horn of the spinal cord. In this article, we introduce mathematical models of the neural circuitry in the dorsal horn responsible for processing nerve fiber inputs from noxious stimulation of peripheral tissues and generating the resu......Primary processing of painful stimulation occurs in the dorsal horn of the spinal cord. In this article, we introduce mathematical models of the neural circuitry in the dorsal horn responsible for processing nerve fiber inputs from noxious stimulation of peripheral tissues and generating...... the resultant pain signal. The differential equation models describe the average firing rates of excitatory and inhibitory interneuron populations, as well as the wide dynamic range (WDR) neurons whose output correlates with the pain signal. The temporal profile of inputs on the different afferent nerve fibers...

  3. Characterization of a novel model of tonic heat pain stimulation in healthy volunteers

    DEFF Research Database (Denmark)

    Naert, A.L.; Kehlet, H.; Kupers, R.

    2008-01-01

    .2+/-0.4, females scoring higher than men (7.4+/-0.5 vs. 5.2+/-0.5; pstimulation period after which they stabilized. A strong interindividual variability was observed in the time profiles of the pain ratings over the course of the 7-min...... tonic heat pain stimulation and compared the responses on this test with other measures of pain. In 58 normal volunteers, we applied a 7-min lasting contact heat stimulation of 47 degrees C to the upper leg while participants constantly rated their pain. Average pain rating during the 7-min period was 6...... stimulation period. The model showed a good test-retest reproducibility. Tonic heat pain ratings only correlated moderately with the pain threshold while stronger correlations were observed with pain tolerance and ratings of suprathreshold phasic heat pain. We conclude that the tonic heat model is a suitable...

  4. Toward the development of a motivational model of pain self-management.

    Science.gov (United States)

    Jensen, Mark P; Nielson, Warren R; Kerns, Robert D

    2003-11-01

    Adaptive management of chronic pain depends to a large degree on how patients choose to cope with pain and its impact. Consequently, patient motivation is an important factor in determining how well patients learn to manage pain. However, the role of patient motivation in altering coping behavior and maintaining those changes is seldom discussed, and theoretically based research on motivation for pain treatment is lacking. This article reviews theories that have a direct application to understanding motivational issues in pain coping and presents a preliminary motivational model of pain self-management. The implications of this model for enhancing engagement in and adherence to chronic pain treatment programs are then discussed. The article ends with a call for research to better understand motivation as it applies to chronic pain self-management. In particular, there is a need to determine whether (and which) motivation enhancement interventions increase active participation in self-management treatment programs for chronic pain.

  5. A data science approach to candidate gene selection of pain regarded as a process of learning and neural plasticity.

    Science.gov (United States)

    Ultsch, Alfred; Kringel, Dario; Kalso, Eija; Mogil, Jeffrey S; Lötsch, Jörn

    2016-12-01

    The increasing availability of "big data" enables novel research approaches to chronic pain while also requiring novel techniques for data mining and knowledge discovery. We used machine learning to combine the knowledge about n = 535 genes identified empirically as relevant to pain with the knowledge about the functions of thousands of genes. Starting from an accepted description of chronic pain as displaying systemic features described by the terms "learning" and "neuronal plasticity," a functional genomics analysis proposed that among the functions of the 535 "pain genes," the biological processes "learning or memory" (P = 8.6 × 10) and "nervous system development" (P = 2.4 × 10) are statistically significantly overrepresented as compared with the annotations to these processes expected by chance. After establishing that the hypothesized biological processes were among important functional genomics features of pain, a subset of n = 34 pain genes were found to be annotated with both Gene Ontology terms. Published empirical evidence supporting their involvement in chronic pain was identified for almost all these genes, including 1 gene identified in March 2016 as being involved in pain. By contrast, such evidence was virtually absent in a randomly selected set of 34 other human genes. Hence, the present computational functional genomics-based method can be used for candidate gene selection, providing an alternative to established methods.

  6. MODEL SELECTION FOR SPECTROPOLARIMETRIC INVERSIONS

    International Nuclear Information System (INIS)

    Asensio Ramos, A.; Manso Sainz, R.; Martínez González, M. J.; Socas-Navarro, H.; Viticchié, B.; Orozco Suárez, D.

    2012-01-01

    Inferring magnetic and thermodynamic information from spectropolarimetric observations relies on the assumption of a parameterized model atmosphere whose parameters are tuned by comparison with observations. Often, the choice of the underlying atmospheric model is based on subjective reasons. In other cases, complex models are chosen based on objective reasons (for instance, the necessity to explain asymmetries in the Stokes profiles) but it is not clear what degree of complexity is needed. The lack of an objective way of comparing models has, sometimes, led to opposing views of the solar magnetism because the inferred physical scenarios are essentially different. We present the first quantitative model comparison based on the computation of the Bayesian evidence ratios for spectropolarimetric observations. Our results show that there is not a single model appropriate for all profiles simultaneously. Data with moderate signal-to-noise ratios (S/Ns) favor models without gradients along the line of sight. If the observations show clear circular and linear polarization signals above the noise level, models with gradients along the line are preferred. As a general rule, observations with large S/Ns favor more complex models. We demonstrate that the evidence ratios correlate well with simple proxies. Therefore, we propose to calculate these proxies when carrying out standard least-squares inversions to allow for model comparison in the future.

  7. Clinical diagnostic model for sciatica developed in primary care patients with low back-related leg pain

    Science.gov (United States)

    Konstantinou, Kika; Ogollah, Reuben; Hay, Elaine M.; Dunn, Kate M.

    2018-01-01

    Background Identification of sciatica may assist timely management but can be challenging in clinical practice. Diagnostic models to identify sciatica have mainly been developed in secondary care settings with conflicting reference standard selection. This study explores the challenges of reference standard selection and aims to ascertain which combination of clinical assessment items best identify sciatica in people seeking primary healthcare. Methods Data on 394 low back-related leg pain consulters were analysed. Potential sciatica indicators were seven clinical assessment items. Two reference standards were used: (i) high confidence sciatica clinical diagnosis; (ii) high confidence sciatica clinical diagnosis with confirmatory magnetic resonance imaging findings. Multivariable logistic regression models were produced for both reference standards. A tool predicting sciatica diagnosis in low back-related leg pain was derived. Latent class modelling explored the validity of the reference standard. Results Model (i) retained five items; model (ii) retained six items. Four items remained in both models: below knee pain, leg pain worse than back pain, positive neural tension tests and neurological deficit. Model (i) was well calibrated (p = 0.18), discrimination was area under the receiver operating characteristic curve (AUC) 0.95 (95% CI 0.93, 0.98). Model (ii) showed good discrimination (AUC 0.82; 0.78, 0.86) but poor calibration (p = 0.004). Bootstrapping revealed minimal overfitting in both models. Agreement between the two latent classes and clinical diagnosis groups defined by model (i) was substantial, and fair for model (ii). Conclusion Four clinical assessment items were common in both reference standard definitions of sciatica. A simple scoring tool for identifying sciatica was developed. These criteria could be used clinically and in research to improve accuracy of identification of this subgroup of back pain patients. PMID:29621243

  8. Comparison of burrowing and stimuli-evoked pain behaviors as end-points in rat models of inflammatory pain and peripheral neuropathic pain

    Directory of Open Access Journals (Sweden)

    Arjun eMuralidharan

    2016-05-01

    Full Text Available Establishment and validation of ethologically-relevant, non-evoked behavioral end-points as surrogate measures of spontaneous pain in rodent pain models has been proposed as a means to improve preclinical to clinical research translation in the pain field. Here, we compared the utility of burrowing behavior with hypersensitivity to applied mechanical stimuli for pain assessment in rat models of chronic inflammatory and peripheral neuropathic pain. Briefly, groups of male Sprague-Dawley rats were habituated to the burrowing environment and trained over a 5-day period. Rats that burrowed ≤450g of gravel on any two days of the individual training phase were excluded from the study. The remaining rats received either a unilateral intraplantar injection of Freund’s complete adjuvant (FCA or saline, or underwent unilateral chronic constriction injury (CCI of the sciatic nerve- or sham-surgery. Baseline burrowing behavior and evoked pain behaviors were assessed prior to model induction, and twice-weekly until study completion on day 14. For FCA- and CCI-rats, but not the corresponding groups of sham-rats, evoked mechanical hypersensitivity developed in a temporal manner in the ipsilateral hindpaws. Although burrowing behavior also decreased in a temporal manner for both FCA- and CCI-rats, there was considerable inter-animal variability. By contrast, mechanical hyperalgesia and mechanical allodynia in the ipsilateral hindpaws of FCA- and CCI-rats respectively, exhibited minimal inter-animal variability. Our data collectively show that burrowing behavior is altered in rodent models of chronic inflammatory pain and peripheral neuropathic pain. However, large group sizes are needed to ensure studies are adequately powered due to considerable inter-animal variability.

  9. Chronic Low Back Pain: Toward an Integrated Psychosocial Assessment Model.

    Science.gov (United States)

    Strong, Jenny; And Others

    1994-01-01

    Integrated six dimensions of chronic low back pain (pain intensity, functional disability, attitudes toward pain, pain coping strategies, depression, illness behavior) to provide multidimensional patient profile. Data from 100 patients revealed presence of three distinct patient groups: patients who were in control, patients who were depressed and…

  10. Pregabalin reduces acute inflammatory and persistent pain associated with nerve injury and cancer in rat models of orofacial pain.

    Science.gov (United States)

    Hummig, Wagner; Kopruszinski, Caroline Machado; Chichorro, Juliana Geremias

    2014-01-01

    To assess the analgesic effect of pregabalin in orofacial models of acute inflammatory pain and of persistent pain associated with nerve injury and cancer, and so determine its effectiveness in controlling orofacial pains having different underlying mechanisms. Orofacial capsaicin and formalin tests were employed in male Wistar rats to assess the influence of pregabalin (or vehicle) pretreatment in acute pain models, and the results from these experiments were analyzed by one-way analysis of variance (ANOVA) followed by Newman Keuls post-hoc test. Pregabalin (or vehicle) treatment was also tested on the facial heat hyperalgesia that was evaluated in rats receiving injection of the inflammatory irritant carrageenan into the upper lip, as well as after constriction of the infraorbital nerve (a model of trigeminal neuropathic pain), or after inoculation of tumor cells into the facial vibrissal pad; two-way repeated measures ANOVA followed by Newman-Keuls post-hoc test was used to analyze data from these experiments. Facial grooming induced by capsaicin was abolished by pretreatment with pregabalin at 10 and 30 mg/kg. However, pregabalin failed to modify the first phase of the formalin response, but reduced the second phase at both doses (10 and 30 mg/kg). In addition, treatment of rats with pregabalin reduced the heat hyperalgesia induced by carrageenan, as well as by nerve injury and facial cancer. Pregabalin produced a marked antinociceptive effect in rat models of facial inflammatory pain as well as in facial neuropathic and cancer pain models, suggesting that it may represent an important agent for the clinical control of orofacial pain.

  11. A Computational Model of Selection by Consequences

    Science.gov (United States)

    McDowell, J. J.

    2004-01-01

    Darwinian selection by consequences was instantiated in a computational model that consisted of a repertoire of behaviors undergoing selection, reproduction, and mutation over many generations. The model in effect created a digital organism that emitted behavior continuously. The behavior of this digital organism was studied in three series of…

  12. Risk prediction model for knee pain in the Nottingham community: a Bayesian modelling approach.

    Science.gov (United States)

    Fernandes, G S; Bhattacharya, A; McWilliams, D F; Ingham, S L; Doherty, M; Zhang, W

    2017-03-20

    Twenty-five percent of the British population over the age of 50 years experiences knee pain. Knee pain can limit physical ability and cause distress and bears significant socioeconomic costs. The objectives of this study were to develop and validate the first risk prediction model for incident knee pain in the Nottingham community and validate this internally within the Nottingham cohort and externally within the Osteoarthritis Initiative (OAI) cohort. A total of 1822 participants from the Nottingham community who were at risk for knee pain were followed for 12 years. Of this cohort, two-thirds (n = 1203) were used to develop the risk prediction model, and one-third (n = 619) were used to validate the model. Incident knee pain was defined as pain on most days for at least 1 month in the past 12 months. Predictors were age, sex, body mass index, pain elsewhere, prior knee injury and knee alignment. A Bayesian logistic regression model was used to determine the probability of an OR >1. The Hosmer-Lemeshow χ 2 statistic (HLS) was used for calibration, and ROC curve analysis was used for discrimination. The OAI cohort from the United States was also used to examine the performance of the model. A risk prediction model for knee pain incidence was developed using a Bayesian approach. The model had good calibration, with an HLS of 7.17 (p = 0.52) and moderate discriminative ability (ROC 0.70) in the community. Individual scenarios are given using the model. However, the model had poor calibration (HLS 5866.28, p prediction model for knee pain, regardless of underlying structural changes of knee osteoarthritis, in the community using a Bayesian modelling approach. The model appears to work well in a community-based population but not in individuals with a higher risk for knee osteoarthritis, and it may provide a convenient tool for use in primary care to predict the risk of knee pain in the general population.

  13. Mind-body dualism and the biopsychosocial model of pain: what did Descartes really say?

    Science.gov (United States)

    Duncan, G

    2000-08-01

    In the last two decades there have been many critics of western biomedicine's poor integration of social and psychological factors in questions of human health. Such critiques frequently begin with a rejection of Descartes' mind-body dualism, viewing this as the decisive philosophical moment, radically separating the two realms in both theory and practice. It is argued here, however, that many such readings of Descartes have been selective and misleading. Contrary to the assumptions of many recent authors, Descartes' dualism does attempt to explain the union of psyche and soma - with more depth than is often appreciated. Pain plays a key role in Cartesian as well as contemporary thinking about the problem of dualism. Theories of the psychological origins of pain symptoms persisted throughout the history of modern medicine and were not necessarily discouraged by Cartesian mental philosophy. Moreover, the recently developed biopsychosocial model of pain may have more in common with Cartesian dualism than it purports to have. This article presents a rereading of Descartes' mental philosophy and his views on pain. The intention is not to defend his theories, but to re-evaluate them and to ask in what respect contemporary theories represent any significant advance in philosophical terms.

  14. Promoting culturally competent chronic pain management using the clinically relevant continuum model.

    Science.gov (United States)

    Monsivais, Diane B

    2011-06-01

    This article reviews the culture of biomedicine and current practices in pain management education, which often merge to create a hostile environment for effective chronic pain care. Areas of cultural tensions in chronic pain frequently involve the struggle to achieve credibility regarding one's complaints of pain (or being believed that the pain is real) and complying with pain medication protocols. The clinically relevant continuum model is presented as a framework allowing providers to approach care from an evidence-based, culturally appropriate (patient centered) perspective that takes into account the highest level of evidence available, provider expertise, and patient preferences and values. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Human experimental pain models: A review of standardized methods in drug development

    Directory of Open Access Journals (Sweden)

    K. Sunil kumar Reddy

    2012-01-01

    Full Text Available Human experimental pain models are essential in understanding the pain mechanisms and appear to be ideally suited to test analgesic compounds. The challenge that confronts both the clinician and the scientist is to match specific treatments to different pain-generating mechanisms and hence reach a pain treatment tailored to each individual patient. Experimental pain models offer the possibility to explore the pain system under controlled settings. Standardized stimuli of different modalities (i.e., mechanical, thermal, electrical, or chemical can be applied to the skin, muscles, and viscera for a differentiated and comprehensive assessment of various pain pathways and mechanisms. Using a multimodel-multistructure testing, the nociception arising from different body structures can be explored and modulation of specific biomarkers by new and existing analgesic drugs can be profiled. The value of human experimental pain models is to link animal and clinical pain studies, providing new possibilities for designing successful clinical trials. Spontaneous pain, the main compliant of the neuropathic patients, but currently there is no human model available that would mimic chronic pain. Therefore, current human pain models cannot replace patient studies for studying efficacy of analgesic compounds, although being helpful for proof-of-concept studies and dose finding.

  16. Experimental human pain models in gastro-esophageal reflux disease and unexplained chest pain

    Institute of Scientific and Technical Information of China (English)

    Asbj(φ)rn Mohr Drewes; Lars Arendt-Nielsen; Peter Funch-Jensen; Hans Gregersen

    2006-01-01

    Methods related to experimental human pain research aim at activating different nociceptors, evoke pain from different organs and activate specific pathways and mechanisms. The different possibilities for using mechanical, electrical, thermal and chemical methods in visceral pain research are discussed with emphasis of combinations (e.g., the multimodal approach). The methods have been used widely in assessment of pain mechanisms in the esophagus and have contributed to our understanding of the symptoms reported in these patients. Hence abnormal activation and plastic changes of central pain pathways seem to play a major role in the symptoms in some patients with gastro-esophageal reflux disease and in patients with functional chest pain of esophageal origin. These findings may lead to an alternative approach for treatment in patients that does not respond to conventional medical or surgical therapy.

  17. Experimental human pain models in gastro-esophageal reflux disease and unexplained chest pain

    Science.gov (United States)

    Drewes, Asbjørn Mohr; Arendt-Nielsen, Lars; Funch-Jensen, Peter; Gregersen, Hans

    2006-01-01

    Methods related to experimental human pain research aim at activating different nociceptors, evoke pain from different organs and activate specific pathways and mechanisms. The different possibilities for using mechanical, electrical, thermal and chemical methods in visceral pain research are discussed with emphasis of combinations (e.g., the multimodal approach). The methods have been used widely in assessment of pain mechanisms in the esophagus and have contributed to our understanding of the symptoms reported in these patients. Hence abnormal activation and plastic changes of central pain pathways seem to play a major role in the symptoms in some patients with gastro-esophageal reflux disease and in patients with functional chest pain of esophageal origin. These findings may lead to an alternative approach for treatment in patients that does not respond to conventional medical or surgical therapy. PMID:16718803

  18. A computational model of selection by consequences.

    OpenAIRE

    McDowell, J J

    2004-01-01

    Darwinian selection by consequences was instantiated in a computational model that consisted of a repertoire of behaviors undergoing selection, reproduction, and mutation over many generations. The model in effect created a digital organism that emitted behavior continuously. The behavior of this digital organism was studied in three series of computational experiments that arranged reinforcement according to random-interval (RI) schedules. The quantitative features of the model were varied o...

  19. Central Sensitization and Neuropathic Features of Ongoing Pain in a Rat Model of Advanced Osteoarthritis.

    Science.gov (United States)

    Havelin, Joshua; Imbert, Ian; Cormier, Jennifer; Allen, Joshua; Porreca, Frank; King, Tamara

    2016-03-01

    Osteoarthritis (OA) pain is most commonly characterized by movement-triggered joint pain. However, in advanced disease, OA pain becomes persistent, ongoing and resistant to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). The mechanisms underlying ongoing pain in advanced OA are poorly understood. We recently showed that intra-articular (i.a.) injection of monosodium iodoacetate (MIA) into the rat knee joint produces concentration-dependent outcomes. Thus, a low dose of i.a. MIA produces NSAID-sensitive weight asymmetry without evidence of ongoing pain and a high i.a. MIA dose produces weight asymmetry and NSAID-resistant ongoing pain. In the present study, palpation of the ipsilateral hind limb of rats treated 14 days previously with high, but not low, doses of i.a. MIA produced expression of the early oncogene, FOS, in the spinal dorsal horn. Inactivation of descending pain facilitatory pathways using a microinjection of lidocaine within the rostral ventromedial medulla induced conditioned place preference selectively in rats treated with the high dose of MIA. Conditioned place preference to intra-articular lidocaine was blocked by pretreatment with duloxetine (30 mg/kg, intraperitoneally at -30 minutes). These observations are consistent with the likelihood of a neuropathic component of OA that elicits ongoing, NSAID-resistant pain and central sensitization that is mediated, in part, by descending modulatory mechanisms. This model provides a basis for exploration of underlying mechanisms promoting neuropathic components of OA pain and for the identification of mechanisms that might guide drug discovery for treatment of advanced OA pain without the need for joint replacement. Difficulty in managing advanced OA pain often results in joint replacement therapy in these patients. Improved understanding of mechanisms driving NSAID-resistant ongoing OA pain might facilitate development of alternatives to joint replacement therapy. Our findings suggest

  20. Antinociception induced by atorvastatin in different pain models.

    Science.gov (United States)

    Garcia, G G; Miranda, H F; Noriega, V; Sierralta, F; Olavarría, L; Zepeda, R J; Prieto, J C

    2011-11-01

    Atorvastatin is a statin that inhibits the 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase. Several landmark clinical trials have demonstrated the beneficial effects of statin therapy for primary and secondary prevention of cardiovascular disease. It is assumed that the beneficial effects of statin therapy are entirely due to cholesterol reduction. Statins have an additional activity (pleiotropic effect) that has been associated to their anti-inflammatory effects. The aim of the present study was to assess the antinociceptive activity of atorvastatin in five animal pain models. The daily administration of 3-100mg/kg of atorvastatin by oral gavage induced a significant dose-dependent antinociception in the writhing, tail-flick, orofacial formalin and formalin hind paw tests. However, this antinociceptive activity of atorvastatin was detectable only at high concentrations in the hot plate assay. The data obtained in the present study demonstrates the effect of atorvastatin to reduce nociception and inflammation in different animal pain models. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Bayesian Model Selection under Time Constraints

    Science.gov (United States)

    Hoege, M.; Nowak, W.; Illman, W. A.

    2017-12-01

    Bayesian model selection (BMS) provides a consistent framework for rating and comparing models in multi-model inference. In cases where models of vastly different complexity compete with each other, we also face vastly different computational runtimes of such models. For instance, time series of a quantity of interest can be simulated by an autoregressive process model that takes even less than a second for one run, or by a partial differential equations-based model with runtimes up to several hours or even days. The classical BMS is based on a quantity called Bayesian model evidence (BME). It determines the model weights in the selection process and resembles a trade-off between bias of a model and its complexity. However, in practice, the runtime of models is another weight relevant factor for model selection. Hence, we believe that it should be included, leading to an overall trade-off problem between bias, variance and computing effort. We approach this triple trade-off from the viewpoint of our ability to generate realizations of the models under a given computational budget. One way to obtain BME values is through sampling-based integration techniques. We argue with the fact that more expensive models can be sampled much less under time constraints than faster models (in straight proportion to their runtime). The computed evidence in favor of a more expensive model is statistically less significant than the evidence computed in favor of a faster model, since sampling-based strategies are always subject to statistical sampling error. We present a straightforward way to include this misbalance into the model weights that are the basis for model selection. Our approach follows directly from the idea of insufficient significance. It is based on a computationally cheap bootstrapping error estimate of model evidence and is easy to implement. The approach is illustrated in a small synthetic modeling study.

  2. Involvement of TRPM2 in a wide range of inflammatory and neuropathic pain mouse models

    Directory of Open Access Journals (Sweden)

    Kanako So

    2015-03-01

    Full Text Available Recent evidence suggests a role of transient receptor potential melastatin 2 (TRPM2 in immune and inflammatory responses. We previously reported that TRPM2 deficiency attenuated inflammatory and neuropathic pain in some pain mouse models, including formalin- or carrageenan-induced inflammatory pain, and peripheral nerve injury-induced neuropathic pain models, while it had no effect on the basal mechanical and thermal nociceptive sensitivities. In this study, we further explored the involvement of TRPM2 in various pain models using TRPM2-knockout mice. There were no differences in the chemonociceptive behaviors evoked by intraplantar injection of capsaicin or hydrogen peroxide between wildtype and TRPM2-knockout mice, while acetic acid-induced writhing behavior was significantly attenuated in TRPM2-knockout mice. In the postoperative incisional pain model, no difference in mechanical allodynia was observed between the two genotypes. By contrast, mechanical allodynia in the monosodium iodoacetate-induced osteoarthritis pain model and the experimental autoimmune encephalomyelitis model were significantly attenuated in TRPM2-knockout mice. Furthermore, mechanical allodynia in paclitaxel-induced peripheral neuropathy and streptozotocin-induced painful diabetic neuropathy models were significantly attenuated in TRPM2-knockout mice. Taken together, these results suggest that TRPM2 plays roles in a wide range of pathological pain models based on peripheral and central neuroinflammation, rather than physiological nociceptive pain.

  3. A Dynamic Model for Limb Selection

    NARCIS (Netherlands)

    Cox, R.F.A; Smitsman, A.W.

    2008-01-01

    Two experiments and a model on limb selection are reported. In Experiment 1 left-handed and right-handed participants (N = 36) repeatedly used one hand for grasping a small cube. After a clear switch in the cube’s location, perseverative limb selection was revealed in both handedness groups. In

  4. A Gambler's Model of Natural Selection.

    Science.gov (United States)

    Nolan, Michael J.; Ostrovsky, David S.

    1996-01-01

    Presents an activity that highlights the mechanism and power of natural selection. Allows students to think in terms of modeling a biological process and instills an appreciation for a mathematical approach to biological problems. (JRH)

  5. The Animal Model of Spinal Cord Injury as an Experimental Pain Model

    Directory of Open Access Journals (Sweden)

    Aya Nakae

    2011-01-01

    Full Text Available Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results can be easily misunderstood and falsely interpreted. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models.

  6. The Animal Model of Spinal Cord Injury as an Experimental Pain Model

    Science.gov (United States)

    Nakae, Aya; Nakai, Kunihiro; Yano, Kenji; Hosokawa, Ko; Shibata, Masahiko; Mashimo, Takashi

    2011-01-01

    Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results can be easily misunderstood and falsely interpreted. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models. PMID:21436995

  7. Review and selection of unsaturated flow models

    Energy Technology Data Exchange (ETDEWEB)

    Reeves, M.; Baker, N.A.; Duguid, J.O. [INTERA, Inc., Las Vegas, NV (United States)

    1994-04-04

    Since the 1960`s, ground-water flow models have been used for analysis of water resources problems. In the 1970`s, emphasis began to shift to analysis of waste management problems. This shift in emphasis was largely brought about by site selection activities for geologic repositories for disposal of high-level radioactive wastes. Model development during the 1970`s and well into the 1980`s focused primarily on saturated ground-water flow because geologic repositories in salt, basalt, granite, shale, and tuff were envisioned to be below the water table. Selection of the unsaturated zone at Yucca Mountain, Nevada, for potential disposal of waste began to shift model development toward unsaturated flow models. Under the US Department of Energy (DOE), the Civilian Radioactive Waste Management System Management and Operating Contractor (CRWMS M&O) has the responsibility to review, evaluate, and document existing computer models; to conduct performance assessments; and to develop performance assessment models, where necessary. This document describes the CRWMS M&O approach to model review and evaluation (Chapter 2), and the requirements for unsaturated flow models which are the bases for selection from among the current models (Chapter 3). Chapter 4 identifies existing models, and their characteristics. Through a detailed examination of characteristics, Chapter 5 presents the selection of models for testing. Chapter 6 discusses the testing and verification of selected models. Chapters 7 and 8 give conclusions and make recommendations, respectively. Chapter 9 records the major references for each of the models reviewed. Appendix A, a collection of technical reviews for each model, contains a more complete list of references. Finally, Appendix B characterizes the problems used for model testing.

  8. Review and selection of unsaturated flow models

    International Nuclear Information System (INIS)

    Reeves, M.; Baker, N.A.; Duguid, J.O.

    1994-01-01

    Since the 1960's, ground-water flow models have been used for analysis of water resources problems. In the 1970's, emphasis began to shift to analysis of waste management problems. This shift in emphasis was largely brought about by site selection activities for geologic repositories for disposal of high-level radioactive wastes. Model development during the 1970's and well into the 1980's focused primarily on saturated ground-water flow because geologic repositories in salt, basalt, granite, shale, and tuff were envisioned to be below the water table. Selection of the unsaturated zone at Yucca Mountain, Nevada, for potential disposal of waste began to shift model development toward unsaturated flow models. Under the US Department of Energy (DOE), the Civilian Radioactive Waste Management System Management and Operating Contractor (CRWMS M ampersand O) has the responsibility to review, evaluate, and document existing computer models; to conduct performance assessments; and to develop performance assessment models, where necessary. This document describes the CRWMS M ampersand O approach to model review and evaluation (Chapter 2), and the requirements for unsaturated flow models which are the bases for selection from among the current models (Chapter 3). Chapter 4 identifies existing models, and their characteristics. Through a detailed examination of characteristics, Chapter 5 presents the selection of models for testing. Chapter 6 discusses the testing and verification of selected models. Chapters 7 and 8 give conclusions and make recommendations, respectively. Chapter 9 records the major references for each of the models reviewed. Appendix A, a collection of technical reviews for each model, contains a more complete list of references. Finally, Appendix B characterizes the problems used for model testing

  9. Evaluation of the effects of patient-selected music therapy on the sleep quality and pain intensity of burn patients

    Directory of Open Access Journals (Sweden)

    Fatemeh Muhaddith Ardabili

    2016-02-01

    Full Text Available Background: Sleep disturbances and pain are some of the most common problems among burn patients, which have adverse effects on recovery process and patient comfort. Given the use of music as a non-pharmacological approach to alleviate pain and provide comfort, this study aimed to evaluate the effect of patient-selected music on sleep quality and pain intensity in burn patients. Methods: This clinical trial was conducted on burn patients hospitalized in one of the hospitals of Tehran, Iran in 2015. In total, 50 patients were selected using randomized convenience sampling and divided into two intervention (n=25 and control (n=25 groups. Intervention was carried out for the intervention group through playing instrumental music, selected by the patients, in three consecutive 45-minute sessions before sleep. Severity of pain in the participants was evaluated for three nights (before and five minutes after the intervention using visual analog scale (VAS. In addition, sleep quality of the samples was assessed three days before the intervention using Pittsburgh sleep quality index (PSQI and during the post-intervention days through interviews. The mentioned scales were applied for the control group as well. Data analysis was performed in SPSS version 18 using Chi-square, as well as paired and independent t-tests. Results: In this study, a significant improvement was observed in sleep quality (P<0.001 and pain intensity (P=0.012 in the participants of intervention group after listening to music. Moreover, a significant difference was observed between the study groups after the intervention in terms of mean sleep quality score (P<0.001 and pain intensity (P=0.046. Conclusion: According to the results of this study, application of patient-selected music therapy could be associated with a significant improve in sleep quality and decrease in pain intensity in burn patients. Therefore, it is recommended that this intervention approach be applied by

  10. Evaluation of the effect of patient-selected music on sleep quality and pain intensity in burn patients

    Directory of Open Access Journals (Sweden)

    Mohaddes Ardabili Fatemeh

    2016-08-01

    Full Text Available Background and Objective: Sleep disturbances and pain are some of the most common problems among burn patients, which have adverse effects on recovery process and patient comfort. Given the use of music as a non-pharmacological approach to alleviate pain and provide comfort, this study aimed to evaluate the effect of patient-selected music on sleep quality and pain intensity in burn patients. Materials and Method: This clinical trial was conducted on burn patients hospitalized in one of the hospitals of Tehran, Iran in 2015. In total, 50 patients were selected using randomized convenience sampling and divided into two intervention (n=25 and control (n=25 groups. Intervention was carried out for the intervention group through playing instrumental music, selected by the patients, in three consecutive 45-minute sessions before sleep. Severity of pain in the participants was evaluated for three nights (before and five minutes after the intervention using visual analog scale (VAS. In addition, sleep quality of the samples was assessed three days before the intervention using Pittsburgh sleep quality index (PSQI and during the post-intervention days through interviews. The mentioned scales were applied for the control group as well. Data analysis was performed in SPSS version 18 using Chi-square, as well as paired and independent t-tests. Results: In this study, a significant improvement was observed in sleep quality (P<0.001  and pain intensity (P=0.012 in the participants of intervention group after listening to music. Moreover, a significant difference was observed between the study groups after the intervention in terms of mean sleep quality score (P<0.001 and pain intensity (P=0.046. Conclusion: According to the results of this study, application of patient-selected music therapy could be associated with a significant improve in sleep quality and decrease in pain intensity in burn patients. Therefore, it is recommended that this intervention

  11. A review of the evidence linking adult attachment theory and chronic pain: presenting a conceptual model.

    Science.gov (United States)

    Meredith, Pamela; Ownsworth, Tamara; Strong, Jenny

    2008-03-01

    It is now well established that pain is a multidimensional phenomenon, affected by a gamut of psychosocial and biological variables. According to diathesis-stress models of chronic pain, some individuals are more vulnerable to developing disability following acute pain because they possess particular psychosocial vulnerabilities which interact with physical pathology to impact negatively upon outcome. Attachment theory, a theory of social and personality development, has been proposed as a comprehensive developmental model of pain, implicating individual adult attachment pattern in the ontogenesis and maintenance of chronic pain. The present paper reviews and critically appraises studies which link adult attachment theory with chronic pain. Together, these papers offer support for the role of insecure attachment as a diathesis (or vulnerability) for problematic adjustment to pain. The Attachment-Diathesis Model of Chronic Pain developed from this body of literature, combines adult attachment theory with the diathesis-stress approach to chronic pain. The evidence presented in this review, and the associated model, advances our understanding of the developmental origins of chronic pain conditions, with potential application in guiding early pain intervention and prevention efforts, as well as tailoring interventions to suit specific patient needs.

  12. Selective peripheral nerve resection for treatment of persistent pain around the knee joint after total knee arthroplasty.

    Science.gov (United States)

    Zhong, Guangjun; Liang, Zhu; Kan, Jiang; Muheremu, Aikeremujiang

    2018-01-01

    Objective This study was performed to determine the efficacy of selective peripheral nerve resection for treatment of persistent neuropathic pain after total knee arthroplasty (TKA). Methods Patients who underwent TKA in our department from January 2013 to July 2016 and experienced persistent pain around the knee joint after TKA were retrospectively included in the current study. Sixty patients were divided into experimental and control groups according the treatment they received. The treatment effect was evaluated by the Hospital for Special Surgery (HSS) knee score and visual analog scale (VAS) pain score preoperatively and at 1, 2, 3, 6, and 12 months postoperatively. Results The HSS knee scores were higher in both groups after than before the treatment, and HSS knee scores were significantly higher in the experimental group than in the control group. The VAS pain scores were lower in both groups after than before the treatment, and VAS pain scores were significantly lower in the experimental group than in the control group. Conclusions Selective peripheral nerve resection is an effective treatment method for persistent neuropathic pain after TKA.

  13. Model Selection with the Linear Mixed Model for Longitudinal Data

    Science.gov (United States)

    Ryoo, Ji Hoon

    2011-01-01

    Model building or model selection with linear mixed models (LMMs) is complicated by the presence of both fixed effects and random effects. The fixed effects structure and random effects structure are codependent, so selection of one influences the other. Most presentations of LMM in psychology and education are based on a multilevel or…

  14. An evolutionary algorithm for model selection

    Energy Technology Data Exchange (ETDEWEB)

    Bicker, Karl [CERN, Geneva (Switzerland); Chung, Suh-Urk; Friedrich, Jan; Grube, Boris; Haas, Florian; Ketzer, Bernhard; Neubert, Sebastian; Paul, Stephan; Ryabchikov, Dimitry [Technische Univ. Muenchen (Germany)

    2013-07-01

    When performing partial-wave analyses of multi-body final states, the choice of the fit model, i.e. the set of waves to be used in the fit, can significantly alter the results of the partial wave fit. Traditionally, the models were chosen based on physical arguments and by observing the changes in log-likelihood of the fits. To reduce possible bias in the model selection process, an evolutionary algorithm was developed based on a Bayesian goodness-of-fit criterion which takes into account the model complexity. Starting from systematically constructed pools of waves which contain significantly more waves than the typical fit model, the algorithm yields a model with an optimal log-likelihood and with a number of partial waves which is appropriate for the number of events in the data. Partial waves with small contributions to the total intensity are penalized and likely to be dropped during the selection process, as are models were excessive correlations between single waves occur. Due to the automated nature of the model selection, a much larger part of the model space can be explored than would be possible in a manual selection. In addition the method allows to assess the dependence of the fit result on the fit model which is an important contribution to the systematic uncertainty.

  15. Genetic search feature selection for affective modeling

    DEFF Research Database (Denmark)

    Martínez, Héctor P.; Yannakakis, Georgios N.

    2010-01-01

    Automatic feature selection is a critical step towards the generation of successful computational models of affect. This paper presents a genetic search-based feature selection method which is developed as a global-search algorithm for improving the accuracy of the affective models built....... The method is tested and compared against sequential forward feature selection and random search in a dataset derived from a game survey experiment which contains bimodal input features (physiological and gameplay) and expressed pairwise preferences of affect. Results suggest that the proposed method...

  16. Can multivariate models based on MOAKS predict OA knee pain? Data from the Osteoarthritis Initiative

    Science.gov (United States)

    Luna-Gómez, Carlos D.; Zanella-Calzada, Laura A.; Galván-Tejada, Jorge I.; Galván-Tejada, Carlos E.; Celaya-Padilla, José M.

    2017-03-01

    Osteoarthritis is the most common rheumatic disease in the world. Knee pain is the most disabling symptom in the disease, the prediction of pain is one of the targets in preventive medicine, this can be applied to new therapies or treatments. Using the magnetic resonance imaging and the grading scales, a multivariate model based on genetic algorithms is presented. Using a predictive model can be useful to associate minor structure changes in the joint with the future knee pain. Results suggest that multivariate models can be predictive with future knee chronic pain. All models; T0, T1 and T2, were statistically significant, all p values were 0.60.

  17. Stress-Induced Visceral Pain: Toward Animal Models of Irritable-Bowel Syndrome and Associated Comorbidities

    Science.gov (United States)

    Moloney, Rachel D.; O’Mahony, Siobhain M.; Dinan, Timothy G.; Cryan, John F.

    2015-01-01

    Visceral pain is a global term used to describe pain originating from the internal organs, which is distinct from somatic pain. It is a hallmark of functional gastrointestinal disorders such as irritable-bowel syndrome (IBS). Currently, the treatment strategies targeting visceral pain are unsatisfactory, with development of novel therapeutics hindered by a lack of detailed knowledge of the underlying mechanisms. Stress has long been implicated in the pathophysiology of visceral pain in both preclinical and clinical studies. Here, we discuss the complex etiology of visceral pain reviewing our current understanding in the context of the role of stress, gender, gut microbiota alterations, and immune functioning. Furthermore, we review the role of glutamate, GABA, and epigenetic mechanisms as possible therapeutic strategies for the treatment of visceral pain for which there is an unmet medical need. Moreover, we discuss the most widely described rodent models used to model visceral pain in the preclinical setting. The theory behind, and application of, animal models is key for both the understanding of underlying mechanisms and design of future therapeutic interventions. Taken together, it is apparent that stress-induced visceral pain and its psychiatric comorbidities, as typified by IBS, has a multifaceted etiology. Moreover, treatment strategies still lag far behind when compared to other pain modalities. The development of novel, effective, and specific therapeutics for the treatment of visceral pain has never been more pertinent. PMID:25762939

  18. The effect of self-selected soothing music on fistula puncture-related pain in hemodialysis patients.

    Science.gov (United States)

    Shabandokht-Zarmi, Hosniyeh; Bagheri-Nesami, Masoumeh; Shorofi, Seyed Afshin; Mousavinasab, Seyed Nouraddin

    2017-11-01

    This study was intended to examine the effect of selective soothing music on fistula puncture-related pain in hemodialysis patients. This is a randomized clinical trial in which 114 participants were selected from two hemodialysis units by means of a non-random, convenience sampling method. The participants were then allocated in three groups of music (N = 38), headphone (N = 38), and control (N = 38). The fistula puncture-related pain was measured 1 min after venipuncture procedure in all three groups. The music group listened to their self-selected and preferred music 6 min before needle insertion into a fistula until the end of procedure. The headphone group wore a headphone alone without listening to music 6 min before needle insertion into a fistula until the end of procedure. The control group did not receive any intervention from the research team during needle insertion into a fistula. The pain intensity was measured immediately after the intervention in all three groups. This study showed a significant difference between the music and control groups, and the music and headphone groups in terms of the mean pain score after the intervention. However, the analysis did not indicate any significant difference between the headphone and control groups with regard to the mean pain score after the intervention. It is concluded that music can be used effectively for pain related to needle insertion into a fistula in hemodialysis patients. Future research should investigate the comparative effects of pharmacological and non-pharmacological interventions on fistula puncture-related pain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. The Effect of Parental Modeling on Child Pain Responses: The Role of Parent and Child Sex.

    Science.gov (United States)

    Boerner, Katelynn E; Chambers, Christine T; McGrath, Patrick J; LoLordo, Vincent; Uher, Rudolf

    2017-06-01

    Social modeling is a process by which pain behaviors are learned, and research has found parents act as models for their children's behavior. Despite social learning theory predicting that same-sex models have greater effect, no experimental investigation to date has examined the role of sex of the model or observer in social learning of pediatric pain. The present study recruited 168 parent-child dyads (equal father-son, father-daughter, mother-son, and mother-daughter dyads) in which children were generally healthy and 6 to 8 years old. Unbeknownst to their child, parents were randomly assigned to exaggerate their expression of pain, minimize their expression of pain, or act naturally during the cold pressor task (CPT). Parents completed the CPT while their child observed, then children completed the CPT themselves. Children whose parents were in the exaggerate condition reported higher anxiety than children of parents in the minimize condition. Additionally, girls in the exaggerate condition rated their overall pain intensity during the CPT significantly higher than boys in the same condition. No child sex differences were observed in pain intensity for the control or minimize conditions. Parent expressions of pain affects children's anxiety, and sex-specific effects of parental exaggerated pain expression on children's own subsequent pain experience are present. This article describes how parental expressions of pain influence children's pain and anxiety, specifically examining the relevance of parent and child sex in this process. These findings have implications for children of parents with chronic pain, or situations in which parents experience pain in the presence of their child (eg, vaccinations). Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

  20. Melody Track Selection Using Discriminative Language Model

    Science.gov (United States)

    Wu, Xiao; Li, Ming; Suo, Hongbin; Yan, Yonghong

    In this letter we focus on the task of selecting the melody track from a polyphonic MIDI file. Based on the intuition that music and language are similar in many aspects, we solve the selection problem by introducing an n-gram language model to learn the melody co-occurrence patterns in a statistical manner and determine the melodic degree of a given MIDI track. Furthermore, we propose the idea of using background model and posterior probability criteria to make modeling more discriminative. In the evaluation, the achieved 81.6% correct rate indicates the feasibility of our approach.

  1. Model selection for Gaussian kernel PCA denoising

    DEFF Research Database (Denmark)

    Jørgensen, Kasper Winther; Hansen, Lars Kai

    2012-01-01

    We propose kernel Parallel Analysis (kPA) for automatic kernel scale and model order selection in Gaussian kernel PCA. Parallel Analysis [1] is based on a permutation test for covariance and has previously been applied for model order selection in linear PCA, we here augment the procedure to also...... tune the Gaussian kernel scale of radial basis function based kernel PCA.We evaluate kPA for denoising of simulated data and the US Postal data set of handwritten digits. We find that kPA outperforms other heuristics to choose the model order and kernel scale in terms of signal-to-noise ratio (SNR...

  2. Spinal NF-κB and chemokine ligand 5 expression during spinal glial cell activation in a neuropathic pain model.

    Directory of Open Access Journals (Sweden)

    Qin Yin

    Full Text Available BACKGROUND: The NF-κB pathway and chemokine (C-C motif ligand 5 (CCL5 are involved in pain modulation; however, the precise mechanisms of their interactions in chronic neuropathic pain have yet to be established. METHODS: The present study examined the roles of spinal NF-κB and CCL5 in a neuropathic pain model after chronic constriction injury (CCI surgery. CCI-induced pain facilitation was evaluated using the Plantar and von Frey tests. The changes in NF-κB and CCL5 expression were analyzed by immunohistochemistry and Western blot analyses. RESULTS: Spinal NF-κB and CCL5 expression increased after CCI surgery. Repeated intrathecal infusions of pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor decreased CCL5 expression, inhibited the activation of microglia and astrocytes, and attenuated CCI-induced allodynia and hyperalgesia. Intrathecal injection of a CCL5-neutralizing antibody attenuated CCI-induced pain facilitation and also suppressed spinal glial cell activation after CCI surgery. However, the CCL5-neutralizing antibody did not affect NF-κB expression. Furthermore, selective glial inhibitors, minocycline and fluorocitrate, attenuated the hyperalgesia induced by intrathecal CCL5. CONCLUSIONS: The inhibition of spinal CCL5 expression may provide a new method to prevent and treat nerve injury-induced neuropathic pain.

  3. Evaluation of Pain Assessment Techniques and Analgesia Efficacy in a Female Guinea Pig (Cavia porcellus) Model of Surgical Pain

    Science.gov (United States)

    Oliver, Vanessa L; Athavale, Stephanie; Simon, Katherine E; Kendall, Lon V; Nemzek, Jean A; Lofgren, Jennifer L

    2017-01-01

    Guinea pigs (Cavia porcellus) are a frequently used species in research, often involving potentially painful procedures. Therefore, evidence-based recommendations regarding analgesia are critically needed to optimize their wellbeing. Our laboratory examined the efficacy of carprofen and extended-release (ER) buprenorphine, alone and as a multimodal combination, for relieving postsurgical pain in guinea pigs. Animals were assessed by using evoked (mechanical hypersensitivity), nonevoked (video ethogram, cageside ethogram, time-to-consumption test), and clinical (weight loss) measurements for 96 h during baseline, anesthesia–analgesia, and hysterectomy conditions. In addition, ER buprenorphine was evaluated pharmacologically. Guinea pigs treated with a single analgesic showed increased mechanical sensitivity for at least 96 h and indices of pain according to the video ethogram for as long as 8 h, compared with levels recorded during anesthesia–analgesia. In contrast, animals given both analgesics demonstrated increased mechanical sensitivity and behavioral evidence of pain for only 2 h after surgery compared with anesthesia–analgesia. The cageside ethogram and time-to-consumption tests failed to identify differences between conditions or treatment groups, highlighting the difficulty of identifying pain in guinea pigs without remote observation. Guinea pigs treated with multimodal analgesia or ER buprenorphine lost at least 10% of their baseline weights, whereas weight loss in carprofen animals was significantly lower (3%). Plasma levels for ER buprenorphine exceeded 0.9 ng/mL from 8 to 96 h after injection. Of the 3 analgesia regimens evaluated, multimodal analgesia provided the most effective pain control in guinea pigs. However the weight loss in the ER buprenorphine–treated animals may need to be considered during analgesia selection. PMID:28724492

  4. Pattern and Pain Assessment of Musculoskeletal Disorders Attending to Physiotherapy Services in Selected Physiotherapy Centres of Dhaka City

    Directory of Open Access Journals (Sweden)

    Md Ruhul Amin

    2015-07-01

    Full Text Available Background: Musculoskeletal disorders are the most common causes of severe long-term pain and physical disability, affecting hundreds of millions of people around the world. Among different modalities of treatment and management for musculoskeletal pain, physiotherapy might be cost-effective. Objective: The aim of the study was to determine the pattern and pain assessment of musculoskeletal disorders attending to physiotherapy services in selected physiotherapy centers of Dhaka city. Materials and method: It was a cross sectional study. Sample size was 400 and a pre-tested, modified, semi-structured questionnaire was used to collect the data. Data were analyzed using SPSS software version 16.0. Results: Majority of the respondents (69.2% belonged to 46-65 year age group with least in extreme age groups. Mean±SD of age was 33.58±12.33 years. Most of the respondents were male (69.2%. Study revealed that neck pain (75.2% was the major complaint followed by back pain (48.00%. Regarding pattern of pain, intermittent (73.2% type was predominant. Muscle spasm (29.2% was the main cause for musculoskeletal pain followed by degenerative diseases (27.5%. Of the respondents 55.00% received traction, 91.25% exercise, 21.25% manipulation, 97.95% short wave diathermy, 85.00% ultrasound therapy, 33.75% infra red ray, and 12.75% electrical stimulation as physiotherapy treatment. There were statistically significant difference between sex and severity of pain (p=0.019, educational status and pain persisting time in years (p=0.000. There was also statistically highly significant difference between severity of pain responses before and after physiotherapy treatment (p=0.000. Conclusion: Study concluded that common areas of musculoskeletal pain were neck followed by back and shoulder and pain characteristics were intermittent, radiating, numbness, burning in nature. Respondents had taken medication and different type of physiotherapy services, including traction

  5. Selective blockade of TRPA1 channel attenuates pathological pain without altering noxious cold sensation or body temperature regulation.

    Science.gov (United States)

    Chen, Jun; Joshi, Shailen K; DiDomenico, Stanley; Perner, Richard J; Mikusa, Joe P; Gauvin, Donna M; Segreti, Jason A; Han, Ping; Zhang, Xu-Feng; Niforatos, Wende; Bianchi, Bruce R; Baker, Scott J; Zhong, Chengmin; Simler, Gricelda H; McDonald, Heath A; Schmidt, Robert G; McGaraughty, Steve P; Chu, Katharine L; Faltynek, Connie R; Kort, Michael E; Reilly, Regina M; Kym, Philip R

    2011-05-01

    Despite the increasing interest in TRPA1 channel as a pain target, its role in cold sensation and body temperature regulation is not clear; the efficacy and particularly side effects resulting from channel blockade remain poorly understood. Here we use a potent, selective, and bioavailable antagonist to address these issues. A-967079 potently blocks human (IC(50): 51 nmol/L, electrophysiology, 67 nmol/L, Ca(2+) assay) and rat TRPA1 (IC(50): 101 nmol/L, electrophysiology, 289 nmol/L, Ca(2+) assay). It is >1000-fold selective over other TRP channels, and is >150-fold selective over 75 other ion channels, enzymes, and G-protein-coupled receptors. Oral dosing of A-967079 produces robust drug exposure in rodents, and exhibits analgesic efficacy in allyl isothiocyanate-induced nocifensive response and osteoarthritic pain in rats (ED(50): 23.2 mg/kg, p.o.). A-967079 attenuates cold allodynia produced by nerve injury but does not alter noxious cold sensation in naive animals, suggesting distinct roles of TRPA1 in physiological and pathological states. Unlike TRPV1 antagonists, A-967079 does not alter body temperature. It also does not produce locomotor or cardiovascular side effects. Collectively, these data provide novel insights into TRPA1 function and suggest that the selective TRPA1 blockade may present a viable strategy for alleviating pain without untoward side effects. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  6. Spinal fusion for chronic low back pain: systematic review on the accuracy of tests for patient selection

    NARCIS (Netherlands)

    Willems, P.C.P.H.; Staal, J.B.; Walenkamp, G.H.; Bie, R.A. de

    2013-01-01

    BACKGROUND CONTEXT: Spinal fusion is a common but controversial treatment for chronic low back pain (LBP) with outcomes similar to those of programmed conservative care. To improve the results of fusion, tests for patient selection are used in clinical practice. PURPOSE: To determine the prognostic

  7. Expert System Model for Educational Personnel Selection

    Directory of Open Access Journals (Sweden)

    Héctor A. Tabares-Ospina

    2013-06-01

    Full Text Available The staff selection is a difficult task due to the subjectivity that the evaluation means. This process can be complemented using a system to support decision. This paper presents the implementation of an expert system to systematize the selection process of professors. The management of software development is divided into 4 parts: requirements, design, implementation and commissioning. The proposed system models a specific knowledge through relationships between variables evidence and objective.

  8. Towards a new model of attentional biases in the development, maintenance, and management of pain.

    Science.gov (United States)

    Todd, Jemma; Sharpe, Louise; Johnson, Ameika; Nicholson Perry, Kathryn; Colagiuri, Ben; Dear, Blake F

    2015-09-01

    Individuals with chronic pain demonstrate attentional biases (ABs) towards pain-related stimuli. However, the clinical importance of these biases is yet to be determined and a sound theoretical model for explaining the role of ABs in the development and maintenance of pain is lacking. Within this article, we (1) systematically review prospective and experimental research exploring ABs and pain outcomes in light of current theoretical models and (2) propose a theoretical framework for understanding AB in pain. Across prospective research, an attentional pattern of vigilance-avoidance was observed. Interventions targeting ABs were less consistent; however, there were promising findings among studies that found attentional training effects, particularly for laboratory research. The proposed Threat Interpretation Model suggests a relationship between threat, interpretation, and stimuli in determining attentional processes, which while tentative generates important testable predictions regarding the role of attention in pain and builds on previous theoretical and empirical work in this area.

  9. The role of pain behaviour and family caregiver responses in the link between pain catastrophising and pain intensity : A moderated mediation model

    NARCIS (Netherlands)

    Mohammadi, Somayyeh; Dehghani, Mohsen; Sanderman, Robbert; Hagedoorn, Mariët

    2017-01-01

    Objectives: This study investigated the mediating role of pain behaviours in the association between pain catastrophising and pain intensity and explored the moderating role of family caregivers’ responses to pain in the link between pain behaviours and pain intensity. Methods: The sample consisted

  10. The role of pain behaviour and family caregiver responses in the link between pain catastrophising and pain intensity : A moderated mediation model

    NARCIS (Netherlands)

    Mohammadi, Somayyeh; Dehghani, Mohsen; Sanderman, Robbert; Hagedoorn, Mariet

    2017-01-01

    Objectives: This study investigated the mediating role of pain behaviours in the association between pain catastrophising and pain intensity and explored the moderating role of family caregivers' responses to pain in the link between pain behaviours and pain intensity. Methods: The sample consisted

  11. The β-lactam clavulanic acid mediates glutamate transport-sensitive pain relief in a rat model of neuropathic pain

    DEFF Research Database (Denmark)

    Kristensen, P J; Gegelashvili, G; Munro, G

    2017-01-01

    -regulates glutamate transporters both in vitro and in vivo. Crucially, a similar up-regulation of glutamate transporters in human spinal astrocytes by clavulanic acid supports the development of novel β-lactam-based analgesics, devoid of antibacterial activity, for the clinical treatment of chronic pain.......BACKGROUND: Following nerve injury, down-regulation of astroglial glutamate transporters (GluTs) with subsequent extracellular glutamate accumulation is a key factor contributing to hyperexcitability within the spinal dorsal horn. Some β-lactam antibiotics can up-regulate GluTs, one of which......, ceftriaxone, displays analgesic effects in rodent chronic pain models. METHODS: Here, the antinociceptive actions of another β-lactam clavulanic acid, which possesses negligible antibiotic activity, were compared with ceftriaxone in rats with chronic constriction injury (CCI)-induced neuropathic pain...

  12. Automated sample plan selection for OPC modeling

    Science.gov (United States)

    Casati, Nathalie; Gabrani, Maria; Viswanathan, Ramya; Bayraktar, Zikri; Jaiswal, Om; DeMaris, David; Abdo, Amr Y.; Oberschmidt, James; Krause, Andreas

    2014-03-01

    It is desired to reduce the time required to produce metrology data for calibration of Optical Proximity Correction (OPC) models and also maintain or improve the quality of the data collected with regard to how well that data represents the types of patterns that occur in real circuit designs. Previous work based on clustering in geometry and/or image parameter space has shown some benefit over strictly manual or intuitive selection, but leads to arbitrary pattern exclusion or selection which may not be the best representation of the product. Forming the pattern selection as an optimization problem, which co-optimizes a number of objective functions reflecting modelers' insight and expertise, has shown to produce models with equivalent quality to the traditional plan of record (POR) set but in a less time.

  13. Pediatric Fear-Avoidance Model of Chronic Pain: Foundation, Application and Future Directions

    Directory of Open Access Journals (Sweden)

    Gordon JG Asmundson

    2012-01-01

    Full Text Available The fear-avoidance model of chronic musculoskeletal pain has become an increasingly popular conceptualization of the processes and mechanisms through which acute pain can become chronic. Despite rapidly growing interest and research regarding the influence of fear-avoidance constructs on pain-related disability in children and adolescents, there have been no amendments to the model to account for unique aspects of pediatric chronic pain. A comprehensive understanding of the role of fear-avoidance in pediatric chronic pain necessitates understanding of both child/adolescent and parent factors implicated in its development and maintenance. The primary purpose of the present article is to propose an empirically-based pediatric fear-avoidance model of chronic pain that accounts for both child/adolescent and parent factors as well as their potential interactive effects. To accomplish this goal, the present article will define important fear-avoidance constructs, provide a summary of the general fear-avoidance model and review the growing empirical literature regarding the role of fear-avoidance constructs in pediatric chronic pain. Assessment and treatment options for children with chronic pain will also be described in the context of the proposed pediatric fear-avoidance model of chronic pain. Finally, avenues for future investigation will be proposed.

  14. Variable selection and model choice in geoadditive regression models.

    Science.gov (United States)

    Kneib, Thomas; Hothorn, Torsten; Tutz, Gerhard

    2009-06-01

    Model choice and variable selection are issues of major concern in practical regression analyses, arising in many biometric applications such as habitat suitability analyses, where the aim is to identify the influence of potentially many environmental conditions on certain species. We describe regression models for breeding bird communities that facilitate both model choice and variable selection, by a boosting algorithm that works within a class of geoadditive regression models comprising spatial effects, nonparametric effects of continuous covariates, interaction surfaces, and varying coefficients. The major modeling components are penalized splines and their bivariate tensor product extensions. All smooth model terms are represented as the sum of a parametric component and a smooth component with one degree of freedom to obtain a fair comparison between the model terms. A generic representation of the geoadditive model allows us to devise a general boosting algorithm that automatically performs model choice and variable selection.

  15. Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain

    DEFF Research Database (Denmark)

    Hald, Andreas; Ding, Ming; Egerod, Kristoffer Lihme

    2008-01-01

    Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment with can......Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment...... with cannabinoid agonists. However, the use of cannabinoid agonists in humans may be hampered by CNS related side effects and development of tolerance. In the present study, we investigated the effect of repeated low dose administration of the synthetic cannabinoid agonist WIN 55,212-2 on bone cancer pain...... and neuropathic pain in mice. In addition, we investigated the development of CNS related side effects and tolerance. We found that 0.5 mg/kg/day for 18 days reduced pain related behavior and expression of spinal glial fibrillary acidic protein in the bone cancer pain model but not in the neuropathic pain model...

  16. A potent and selective calcitonin gene-related peptide (CGRP) receptor antagonist, MK-8825, inhibits responses to nociceptive trigeminal activation: Role of CGRP in orofacial pain.

    Science.gov (United States)

    Romero-Reyes, Marcela; Pardi, Vanessa; Akerman, Simon

    2015-09-01

    Temporomandibular disorders (TMDs) are orofacial pains within the trigeminal distribution, which involve the masticatory musculature, the temporomandibular joint or both. Their pathophysiology remains unclear, as inflammatory mediators are thought to be involved, and clinically TMD presents pain and sometimes limitation of function, but often appears without gross indications of local inflammation, such as visible edema, redness and increase in temperature. Calcitonin gene-related peptide (CGRP) has been implicated in other pain disorders with trigeminal distribution, such as migraine, of which TMD shares a significant co-morbidity. CGRP causes activation and sensitization of trigeminal primary afferent neurons, independent of any inflammatory mechanisms, and thus may also be involved in TMD. Here we used a small molecule, selective CGRP receptor antagonist, MK-8825, to dissect the role of CGRP in inducing spontaneous nociceptive facial grooming behaviors, neuronal activation in the trigeminal nucleus, and systemic release of pro-inflammatory cytokines, in a mouse model of acute orofacial masseteric muscle pain that we have developed, as a surrogate of acute TMD. We show that CFA masseteric injection causes significant spontaneous orofacial pain behaviors, neuronal activation in the trigeminal nucleus, and release of interleukin-6 (IL-6). In mice pre-treated with MK-8825 there is a significant reduction in these spontaneous orofacial pain behaviors. Also, at 2 and 24h after CFA injection the level of Fos immunoreactivity in the trigeminal nucleus, used as a marker of neuronal activation, was much lower on both ipsilateral and contralateral sides after pre-treatment with MK-8825. There was no effect of MK-8825 on the release of IL-6. These data suggest that CGRP may be involved in TMD pathophysiology, but not via inflammatory mechanisms, at least in the acute stage. Furthermore, CGRP receptor antagonists may have therapeutic efficacy in the treatment of TMD, as they

  17. Longitudinal Structural and Functional Brain Network Alterations in a Mouse Model of Neuropathic Pain.

    Science.gov (United States)

    Bilbao, Ainhoa; Falfán-Melgoza, Claudia; Leixner, Sarah; Becker, Robert; Singaravelu, Sathish Kumar; Sack, Markus; Sartorius, Alexander; Spanagel, Rainer; Weber-Fahr, Wolfgang

    2018-04-22

    Neuropathic pain affects multiple brain functions, including motivational processing. However, little is known about the structural and functional brain changes involved in the transition from an acute to a chronic pain state. Here we combined behavioral phenotyping of pain thresholds with multimodal neuroimaging to longitudinally monitor changes in brain metabolism, structure and connectivity using the spared nerve injury (SNI) mouse model of chronic neuropathic pain. We investigated stimulus-evoked pain responses prior to SNI surgery, and one and twelve weeks following surgery. A progressive development and potentiation of stimulus-evoked pain responses (cold and mechanical allodynia) were detected during the course of pain chronification. Voxel-based morphometry demonstrated striking decreases in volume following pain induction in all brain sites assessed - an effect that reversed over time. Similarly, all global and local network changes that occurred following pain induction disappeared over time, with two notable exceptions: the nucleus accumbens, which played a more dominant role in the global network in a chronic pain state and the prefrontal cortex and hippocampus, which showed lower connectivity. These changes in connectivity were accompanied by enhanced glutamate levels in the hippocampus, but not in the prefrontal cortex. We suggest that hippocampal hyperexcitability may contribute to alterations in synaptic plasticity within the nucleus accumbens, and to pain chronification. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Developing a model for measuring fear of pain in Norwegian samples: The Fear of Pain Questionnaire Norway

    DEFF Research Database (Denmark)

    Vambheim, Sara M; Lyby, Peter Solvoll; Aslaksen, Per M

    2017-01-01

    Fear of pain is highly correlated with pain report and physiological measures of arousal when pain is inflicted. The Fear of Pain Questionnaire III (FPQ-III) and The Fear of Pain Questionnaire Short Form (FPQ-SF) are self-report inventories developed for assessment of fear of pain (FOP). A previous...

  19. Model Selection in Data Analysis Competitions

    DEFF Research Database (Denmark)

    Wind, David Kofoed; Winther, Ole

    2014-01-01

    The use of data analysis competitions for selecting the most appropriate model for a problem is a recent innovation in the field of predictive machine learning. Two of the most well-known examples of this trend was the Netflix Competition and recently the competitions hosted on the online platform...... performers from Kaggle and use previous personal experiences from competing in Kaggle competitions. The stated hypotheses about feature engineering, ensembling, overfitting, model complexity and evaluation metrics give indications and guidelines on how to select a proper model for performing well...... Kaggle. In this paper, we will state and try to verify a set of qualitative hypotheses about predictive modelling, both in general and in the scope of data analysis competitions. To verify our hypotheses we will look at previous competitions and their outcomes, use qualitative interviews with top...

  20. Adverse selection model regarding tobacco consumption

    Directory of Open Access Journals (Sweden)

    Dumitru MARIN

    2006-01-01

    Full Text Available The impact of introducing a tax on tobacco consumption can be studied trough an adverse selection model. The objective of the model presented in the following is to characterize the optimal contractual relationship between the governmental authorities and the two type employees: smokers and non-smokers, taking into account that the consumers’ decision to smoke or not represents an element of risk and uncertainty. Two scenarios are run using the General Algebraic Modeling Systems software: one without taxes set on tobacco consumption and another one with taxes set on tobacco consumption, based on an adverse selection model described previously. The results of the two scenarios are compared in the end of the paper: the wage earnings levels and the social welfare in case of a smoking agent and in case of a non-smoking agent.

  1. A selective inhibition of c-Fos/activator protein-1 as a potential therapeutic target for intervertebral disc degeneration and associated pain.

    Science.gov (United States)

    Makino, Hiroto; Seki, Shoji; Yahara, Yasuhito; Shiozawa, Shunichi; Aikawa, Yukihiko; Motomura, Hiraku; Nogami, Makiko; Watanabe, Kenta; Sainoh, Takeshi; Ito, Hisakatsu; Tsumaki, Noriyuki; Kawaguchi, Yoshiharu; Yamazaki, Mitsuaki; Kimura, Tomoatsu

    2017-12-05

    Intervertebral disc (IVD) degeneration is a major cause of low back pain. The transcription factor c-Fos/Activator Protein-1 (AP-1) controls the expression of inflammatory cytokines and matrix metalloproteinases (MMPs) that contribute to the pathogenesis IVD degeneration. We investigated the effects of inhibition of c-Fos/AP-1 on IVD degeneration and associated pain. A selective inhibitor, T-5224, significantly suppressed the interleukin-1β-induced up-regulation of Mmp-3, Mmp-13 and Adamts-5 transcription in human nucleus pulposus cells and in a mouse explant culture model of IVD degeneration. We used a tail disc percutaneous needle puncture method to further assess the effects of oral administration of T-5224 on IVD degeneration. Analysis of disc height, T2-magnetic resonance imaging (MRI) findings, and histology revealed that IVD degeneration was significantly mitigated by T-5224. Further, oral administration of T-5224 ameliorated pain as indicated by the extended tail-flick latency in response to heat stimulation of rats with needle-puncture-induced IVD degeneration. These findings suggest that the inhibition of c-Fos/AP-1 prevents disc degeneration and its associated pain and that T-5224 may serve as a drug for the prevention of IVD degeneration.

  2. Abnormal muscle afferent function in a model of Taxol chemotherapy-induced painful neuropathy

    OpenAIRE

    Chen, Xiaojie; Green, Paul G.; Levine, Jon D.

    2011-01-01

    Despite muscle pain being a well-described symptom in patients with diverse forms of peripheral neuropathy, the role of neuropathic mechanisms in muscle pain have received remarkably little attention. We have recently demonstrated in a well-established model of chemotherapy-induced painful neuropathy (CIPN) that the anti-tumor drug paclitaxel (Taxol) produces mechanical hyperalgesia in skeletal muscle, of similar time course to and with shared mechanism with cutaneous symptoms. In the present...

  3. Behavioral, medical imaging and histopathological features of a new rat model of bone cancer pain.

    Directory of Open Access Journals (Sweden)

    Louis Doré-Savard

    2010-10-01

    Full Text Available Pre-clinical bone cancer pain models mimicking the human condition are required to respond to clinical realities. Breast or prostate cancer patients coping with bone metastases experience intractable pain, which affects their quality of life. Advanced monitoring is thus required to clarify bone cancer pain mechanisms and refine treatments. In our model of rat femoral mammary carcinoma MRMT-1 cell implantation, pain onset and tumor growth were monitored for 21 days. The surgical procedure performed without arthrotomy allowed recording of incidental pain in free-moving rats. Along with the gradual development of mechanical allodynia and hyperalgesia, behavioral signs of ambulatory pain were detected at day 14 by using a dynamic weight-bearing apparatus. Osteopenia was revealed from day 14 concomitantly with disorganization of the trabecular architecture (µCT. Bone metastases were visualized as early as day 8 by MRI (T(1-Gd-DTPA before pain detection. PET (Na(18F co-registration revealed intra-osseous activity, as determined by anatomical superimposition over MRI in accordance with osteoclastic hyperactivity (TRAP staining. Pain and bone destruction were aggravated with time. Bone remodeling was accompanied by c-Fos (spinal and ATF3 (DRG neuronal activation, sustained by astrocyte (GFAP and microglia (Iba1 reactivity in lumbar spinal cord. Our animal model demonstrates the importance of simultaneously recording pain and tumor progression and will allow us to better characterize therapeutic strategies in the future.

  4. Association between composites of selected motion palpation and pain provocation tests for sacroiliac joint disorders.

    Science.gov (United States)

    Soleimanifar, Manijeh; Karimi, Noureddin; Arab, Amir Massoud

    2017-04-01

    The sacroiliac joint (SIJ) has been implicated as a potential source of low back and buttock pain. Several types of motion palpation and pain provocation tests are used to evaluate SIJ dysfunction. The purpose of this study was to investigate the relationship between motion palpation and pain provocation tests in assessment of SIJ problems. This study is Descriptive Correlation. 50 patients between the ages of 20 and 65 participated. Four motion palpation tests (Sitting flexion, Standing flexion, Prone knee flexion, Gillet test) and three pain provocation tests (FABER, Posterior shear, Resisted abduction test) were examined. Chi-square analysis was used to assess the relationship between results of the individuals and composites of these two groups of tests. No significant relationship was found between these two groups of tests. It seems that motion palpation tests assess SIJ dysfunction and provocative tests assessed SIJ pain which do not appear to be related. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Quantifying and Characterizing Tonic Thermal Pain Across Subjects From EEG Data Using Random Forest Models.

    Science.gov (United States)

    Vijayakumar, Vishal; Case, Michelle; Shirinpour, Sina; He, Bin

    2017-12-01

    Effective pain assessment and management strategies are needed to better manage pain. In addition to self-report, an objective pain assessment system can provide a more complete picture of the neurophysiological basis for pain. In this study, a robust and accurate machine learning approach is developed to quantify tonic thermal pain across healthy subjects into a maximum of ten distinct classes. A random forest model was trained to predict pain scores using time-frequency wavelet representations of independent components obtained from electroencephalography (EEG) data, and the relative importance of each frequency band to pain quantification is assessed. The mean classification accuracy for predicting pain on an independent test subject for a range of 1-10 is 89.45%, highest among existing state of the art quantification algorithms for EEG. The gamma band is the most important to both intersubject and intrasubject classification accuracy. The robustness and generalizability of the classifier are demonstrated. Our results demonstrate the potential of this tool to be used clinically to help us to improve chronic pain treatment and establish spectral biomarkers for future pain-related studies using EEG.

  6. Morphine- and buprenorphine-induced analgesia and antihyperalgesia in a human inflammatory pain model

    DEFF Research Database (Denmark)

    Ravn, Pernille; Secher, EL; Skram, U

    2013-01-01

    Opioid therapy is associated with the development of tolerance and paradoxically increased sensitivity to pain. It has been suggested that buprenorphine is associated with a higher antihyperalgesia/analgesia ratio than μ-opioid receptor agonists. The primary outcome of this study was therefore...... to investigate relative differences in antihyperalgesia and analgesia effects between morphine and buprenorphine in an inflammatory pain model in volunteers. The secondary outcome was to examine the relationship between pain sensitivity and opioid-induced effects on analgesia, antihyperalgesia, and descending...... pain modulation....

  7. Review and selection of unsaturated flow models

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-09-10

    Under the US Department of Energy (DOE), the Civilian Radioactive Waste Management System Management and Operating Contractor (CRWMS M&O) has the responsibility to review, evaluate, and document existing computer ground-water flow models; to conduct performance assessments; and to develop performance assessment models, where necessary. In the area of scientific modeling, the M&O CRWMS has the following responsibilities: To provide overall management and integration of modeling activities. To provide a framework for focusing modeling and model development. To identify areas that require increased or decreased emphasis. To ensure that the tools necessary to conduct performance assessment are available. These responsibilities are being initiated through a three-step process. It consists of a thorough review of existing models, testing of models which best fit the established requirements, and making recommendations for future development that should be conducted. Future model enhancement will then focus on the models selected during this activity. Furthermore, in order to manage future model development, particularly in those areas requiring substantial enhancement, the three-step process will be updated and reported periodically in the future.

  8. Addicted to Pain: A Preliminary Model of Sexual Masochism as Addiction.

    Science.gov (United States)

    Kurt, Holly; Ronel, Natti

    2017-11-01

    An exploratory, qualitative, phenomenological study focused on the experience of pain while participating in sexual masochistic acts. Semi-structured interviews were conducted with nine individuals (four female, five male) who regularly participate in sexually masochistic acts and point to pain as central to their experience. Qualitative analysis of the data revealed several key characteristics of the participant's experience: the first time, intoxication, craving and withdrawal, tolerance, pain as control, and the pain inducing partner. The findings indicate that the way pain is experienced while mitigated through masochistic behavior creates an addictive process that coincides with a chronic behavioral spin contextualization. This article presents a preliminary model of addiction to physical pain in light of the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) definition of substance-related and addictive disorders and the behavioral spin theory.

  9. Expatriates Selection: An Essay of Model Analysis

    Directory of Open Access Journals (Sweden)

    Rui Bártolo-Ribeiro

    2015-03-01

    Full Text Available The business expansion to other geographical areas with different cultures from which organizations were created and developed leads to the expatriation of employees to these destinations. Recruitment and selection procedures of expatriates do not always have the intended success leading to an early return of these professionals with the consequent organizational disorders. In this study, several articles published in the last five years were analyzed in order to identify the most frequently mentioned dimensions in the selection of expatriates in terms of success and failure. The characteristics in the selection process that may increase prediction of adaptation of expatriates to new cultural contexts of the some organization were studied according to the KSAOs model. Few references were found concerning Knowledge, Skills and Abilities dimensions in the analyzed papers. There was a strong predominance on the evaluation of Other Characteristics, and was given more importance to dispositional factors than situational factors for promoting the integration of the expatriates.

  10. Post-model selection inference and model averaging

    Directory of Open Access Journals (Sweden)

    Georges Nguefack-Tsague

    2011-07-01

    Full Text Available Although model selection is routinely used in practice nowadays, little is known about its precise effects on any subsequent inference that is carried out. The same goes for the effects induced by the closely related technique of model averaging. This paper is concerned with the use of the same data first to select a model and then to carry out inference, in particular point estimation and point prediction. The properties of the resulting estimator, called a post-model-selection estimator (PMSE, are hard to derive. Using selection criteria such as hypothesis testing, AIC, BIC, HQ and Cp, we illustrate that, in terms of risk function, no single PMSE dominates the others. The same conclusion holds more generally for any penalised likelihood information criterion. We also compare various model averaging schemes and show that no single one dominates the others in terms of risk function. Since PMSEs can be regarded as a special case of model averaging, with 0-1 random-weights, we propose a connection between the two theories, in the frequentist approach, by taking account of the selection procedure when performing model averaging. We illustrate the point by simulating a simple linear regression model.

  11. Effects of fluoxetine on changes of pain sensitivity in chronic stress model rats.

    Science.gov (United States)

    Lian, Yan-Na; Chang, Jin-Long; Lu, Qi; Wang, Yi; Zhang, Ying; Zhang, Feng-Min

    2017-06-09

    Exposure to stress could facilitate or inhibit pain responses (stress-induced hyperalgesia or hypoalgesia, respectively). Fluoxetine is a selective serotonin (5-HT) reuptake inhibitor antidepressant. There have been contradictory reports on whether fluoxetine produces antinociceptive effects. The purpose of this study was to elucidate changes in pain sensitivity after chronic stress exposure, and the effects of fluoxetine on these changes. We measured thermal, mechanical, and formalin-induced acute and inflammatory pain by using the tail-flick, von Frey, and formalin tests respectively. The results showed that rats exposed to chronic stress exhibited thermal and formalin-induced acute and inflammatory hypoalgesia and transient mechanical hyperalgesia. Furthermore, fluoxetine promoted hypoalgesia in thermal and inflammatory pain and induced mechanical hyperalgesia. Our results indicate that the 5-HT system could be involved in hypoalgesia of thermal and inflammatory pain and induce transient mechanical hyperalgesia after stress exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Skewed factor models using selection mechanisms

    KAUST Repository

    Kim, Hyoung-Moon

    2015-12-21

    Traditional factor models explicitly or implicitly assume that the factors follow a multivariate normal distribution; that is, only moments up to order two are involved. However, it may happen in real data problems that the first two moments cannot explain the factors. Based on this motivation, here we devise three new skewed factor models, the skew-normal, the skew-tt, and the generalized skew-normal factor models depending on a selection mechanism on the factors. The ECME algorithms are adopted to estimate related parameters for statistical inference. Monte Carlo simulations validate our new models and we demonstrate the need for skewed factor models using the classic open/closed book exam scores dataset.

  13. Skewed factor models using selection mechanisms

    KAUST Repository

    Kim, Hyoung-Moon; Maadooliat, Mehdi; Arellano-Valle, Reinaldo B.; Genton, Marc G.

    2015-01-01

    Traditional factor models explicitly or implicitly assume that the factors follow a multivariate normal distribution; that is, only moments up to order two are involved. However, it may happen in real data problems that the first two moments cannot explain the factors. Based on this motivation, here we devise three new skewed factor models, the skew-normal, the skew-tt, and the generalized skew-normal factor models depending on a selection mechanism on the factors. The ECME algorithms are adopted to estimate related parameters for statistical inference. Monte Carlo simulations validate our new models and we demonstrate the need for skewed factor models using the classic open/closed book exam scores dataset.

  14. Model structure selection in convolutive mixtures

    DEFF Research Database (Denmark)

    Dyrholm, Mads; Makeig, S.; Hansen, Lars Kai

    2006-01-01

    The CICAAR algorithm (convolutive independent component analysis with an auto-regressive inverse model) allows separation of white (i.i.d) source signals from convolutive mixtures. We introduce a source color model as a simple extension to the CICAAR which allows for a more parsimonious represent......The CICAAR algorithm (convolutive independent component analysis with an auto-regressive inverse model) allows separation of white (i.i.d) source signals from convolutive mixtures. We introduce a source color model as a simple extension to the CICAAR which allows for a more parsimonious...... representation in many practical mixtures. The new filter-CICAAR allows Bayesian model selection and can help answer questions like: ’Are we actually dealing with a convolutive mixture?’. We try to answer this question for EEG data....

  15. PAIN IN A PARKINSON`S DISEASE RODENT ANIMAL MODEL INDUCED WITH 6-HYDROXYDOPAMINE

    Directory of Open Access Journals (Sweden)

    Antioch, I

    2017-06-01

    Full Text Available Pain phenomenon, the unpleasant sensory and emotional event, appears to evidently intrude in Parkinson disease (PD, a disease formally considered to be restricted only to motor deficits. Although over a half of persons with PD suffer from pain manifestations, there are very few reports targeting this issue. Considering the cases when motor symptoms of PD are eclipsed by severe pain disclosure, there is an obvious need of clarifying the intricate implications of pain in PD context. Because there are few studies researching the link between pain and PD in clinical context, but as well in animal models we chose to explore the effects of pain stimuli on a rodent model of PD. Materials and methods: We experimentally induced a PD model in Wistar rats (n=12 by injecting in the substantia nigra, a brain area known to be involved in PD occurrence, one dose of a 6-hydroxidopamine (6-OHDA solution (8µm 6-OHDA base and 4µm physiological saline, utilizing neurosurgery, while their control peers received same dose of saline solution. Two weeks after the intervention the animals were subjected to the hot-plate test, a behavioral task for acquiring pain sensitivity. Results: There was noticed a statistical significant (F(1,10 = 5.67, p=0.038 sensibility of the 6-OHDA rats to thermal pain stimuli (8.2 s ± 0.8 s in 6-OHDA group as compared to their peers (13.8 s ± 1.6 s in controls. Conclusions: The involvement of pain in PD animal models is demonstrated raising questions of how it influences PD evolution. Moreover, this result increases awareness of deficient diagnostic methods of pain in PD and as a consequence, poor treatment of pain manifestations.

  16. Improving pain care through implementation of the Stepped Care Model at a multisite community health center

    Directory of Open Access Journals (Sweden)

    Anderson DR

    2016-11-01

    Full Text Available Daren R Anderson,1 Ianita Zlateva,1 Emil N Coman,2 Khushbu Khatri,1 Terrence Tian,1 Robert D Kerns3 1Weitzman Institute, Community Health Center, Inc., Middletown, 2UCONN Health Disparities Institute, University of Connecticut, Farmington, 3VA Connecticut Healthcare System, West Haven, CT, USA Purpose: Treating pain in primary care is challenging. Primary care providers (PCPs receive limited training in pain care and express low confidence in their knowledge and ability to manage pain effectively. Models to improve pain outcomes have been developed, but not formally implemented in safety net practices where pain is particularly common. This study evaluated the impact of implementing the Stepped Care Model for Pain Management (SCM-PM at a large, multisite Federally Qualified Health Center. Methods: The Promoting Action on Research Implementation in Health Services framework guided the implementation of the SCM-PM. The multicomponent intervention included: education on pain care, new protocols for pain assessment and management, implementation of an opioid management dashboard, telehealth consultations, and enhanced onsite specialty resources. Participants included 25 PCPs and their patients with chronic pain (3,357 preintervention and 4,385 postintervention cared for at Community Health Center, Inc. Data were collected from the electronic health record and supplemented by chart reviews. Surveys were administered to PCPs to assess knowledge, attitudes, and confidence. Results: Providers’ pain knowledge scores increased to an average of 11% from baseline; self-rated confidence in ability to manage pain also increased. Use of opioid treatment agreements and urine drug screens increased significantly by 27.3% and 22.6%, respectively. Significant improvements were also noted in documentation of pain, pain treatment, and pain follow-up. Referrals to behavioral health providers for patients with pain increased by 5.96% (P=0.009. There was no

  17. Application of the BPCQ questionnaire to assess pain management in selected types of cancer

    Directory of Open Access Journals (Sweden)

    Aleksandra Czerw

    2016-09-01

    With regards to the source of pain management, only the internal control of pain is diversified by the primary site. The external factors were regarded as having the strongest influence by respondents diagnosed with colorectal or breast cancer. The major socio-economic variables differentiating the way in which pain control is perceived are education and net income-per-household-member. The results of analyses of individual groups of patients revealled strong correlations between the beliefs in the doctors' influence, and the beliefs in chance events and socio-economic factors.

  18. Patient-Clinician Communication About Pain: A Conceptual Model and Narrative Review.

    Science.gov (United States)

    Henry, Stephen G; Matthias, Marianne S

    2018-02-01

    Productive patient-clinician communication is an important component of effective pain management, but we know little about how patients and clinicians actually talk about pain in clinical settings and how it might be improved to produce better patient outcomes. The objective of this review was to create a conceptual model of patient-clinician communication about noncancer pain, review and synthesize empirical research in this area, and identify priorities for future research. A conceptual model was developed that drew on existing pain and health communication research. CINAHL, EMBASE, and PubMed were searched to find studies reporting empirical data on patient-clinician communication about noncancer pain; results were supplemented with manual searches. Studies were categorized and analyzed to identify crosscutting themes and inform model development. The conceptual model comprised the following components: contextual factors, clinical interaction, attitudes and beliefs, and outcomes. Thirty-nine studies met inclusion criteria and were analyzed based on model components. Studies varied widely in quality, methodology, and sample size. Two provisional conclusions were identified: contrary to what is often reported in the literature, discussions about analgesics are most frequently characterized by patient-clinician agreement, and self-presentation during patient-clinician interactions plays an important role in communication about pain and opioids. Published studies on patient-clinician communication about noncancer pain are few and diverse. The conceptual model presented here can help to identify knowledge gaps and guide future research on communication about pain. Investigating the links between communication and pain-related outcomes is an important priority for future research. © 2018 American Academy of Pain Medicine. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  19. The role of fear of movement and injury in selective attentional processing in patients with chronic low back pain: a dot-probe evaluation.

    Science.gov (United States)

    Roelofs, Jeffrey; Peters, Madelon L; Fassaert, Thijs; Vlaeyen, Johan W S

    2005-05-01

    The present study sought to investigate to what extent patients with chronic low back pain and pain-free control subjects selectively attend to pain-related stimuli as measured with 2 dot-probe tasks with word stimuli and pictorial stimuli. Selective attentional processing was measured by means of 3 indices: the bias index, a congruency effect, and an incongruency effect. Pain-related fear as a trait measure (Tampa Scale for Kinesiophobia [TSK]) was expected to be positively associated with all indices of selective attentional processing of pain stimuli. Results were analyzed with repeated-measures analysis of variance. An incongruency effect was found for patients and to a significantly less degree for pain-free control subjects on the dot-probe task with pictorial stimuli, indicating that pain patients have difficulty disengaging from threat pictures. Pain-related fear as a trait measure (TSK) was not associated with selective attentional processing of word and pictorial stimuli in either pain patients or control subjects. Results from the present study are discussed, and directions for future research are provided. Demonstrating difficulty to disengage from threat might be clinically relevant because patients might pay less attention to fear-disconfirming information and remain engaged in avoidance, which might eventually lead to prolonged anxiety states.

  20. Behavioral optimization models for multicriteria portfolio selection

    Directory of Open Access Journals (Sweden)

    Mehlawat Mukesh Kumar

    2013-01-01

    Full Text Available In this paper, behavioral construct of suitability is used to develop a multicriteria decision making framework for portfolio selection. To achieve this purpose, we rely on multiple methodologies. Analytical hierarchy process technique is used to model the suitability considerations with a view to obtaining the suitability performance score in respect of each asset. A fuzzy multiple criteria decision making method is used to obtain the financial quality score of each asset based upon investor's rating on the financial criteria. Two optimization models are developed for optimal asset allocation considering simultaneously financial and suitability criteria. An empirical study is conducted on randomly selected assets from National Stock Exchange, Mumbai, India to demonstrate the effectiveness of the proposed methodology.

  1. Robust inference in sample selection models

    KAUST Repository

    Zhelonkin, Mikhail; Genton, Marc G.; Ronchetti, Elvezio

    2015-01-01

    The problem of non-random sample selectivity often occurs in practice in many fields. The classical estimators introduced by Heckman are the backbone of the standard statistical analysis of these models. However, these estimators are very sensitive to small deviations from the distributional assumptions which are often not satisfied in practice. We develop a general framework to study the robustness properties of estimators and tests in sample selection models. We derive the influence function and the change-of-variance function of Heckman's two-stage estimator, and we demonstrate the non-robustness of this estimator and its estimated variance to small deviations from the model assumed. We propose a procedure for robustifying the estimator, prove its asymptotic normality and give its asymptotic variance. Both cases with and without an exclusion restriction are covered. This allows us to construct a simple robust alternative to the sample selection bias test. We illustrate the use of our new methodology in an analysis of ambulatory expenditures and we compare the performance of the classical and robust methods in a Monte Carlo simulation study.

  2. Robust inference in sample selection models

    KAUST Repository

    Zhelonkin, Mikhail

    2015-11-20

    The problem of non-random sample selectivity often occurs in practice in many fields. The classical estimators introduced by Heckman are the backbone of the standard statistical analysis of these models. However, these estimators are very sensitive to small deviations from the distributional assumptions which are often not satisfied in practice. We develop a general framework to study the robustness properties of estimators and tests in sample selection models. We derive the influence function and the change-of-variance function of Heckman\\'s two-stage estimator, and we demonstrate the non-robustness of this estimator and its estimated variance to small deviations from the model assumed. We propose a procedure for robustifying the estimator, prove its asymptotic normality and give its asymptotic variance. Both cases with and without an exclusion restriction are covered. This allows us to construct a simple robust alternative to the sample selection bias test. We illustrate the use of our new methodology in an analysis of ambulatory expenditures and we compare the performance of the classical and robust methods in a Monte Carlo simulation study.

  3. Efficiently adapting graphical models for selectivity estimation

    DEFF Research Database (Denmark)

    Tzoumas, Kostas; Deshpande, Amol; Jensen, Christian S.

    2013-01-01

    cardinality estimation without making the independence assumption. By carefully using concepts from the field of graphical models, we are able to factor the joint probability distribution over all the attributes in the database into small, usually two-dimensional distributions, without a significant loss...... in estimation accuracy. We show how to efficiently construct such a graphical model from the database using only two-way join queries, and we show how to perform selectivity estimation in a highly efficient manner. We integrate our algorithms into the PostgreSQL DBMS. Experimental results indicate...

  4. Efficacy of Selected Electrical Therapies on Chronic Low Back Pain: A Comparative Clinical Pilot Study

    OpenAIRE

    Rajfur, Joanna; Pasternok, Ma?gorzata; Rajfur, Katarzyna; Walewicz, Karolina; Fras, Beata; Bolach, Bartosz; Dymarek, Robert; Rosinczuk, Joanna; Halski, Tomasz; Taradaj, Jakub

    2017-01-01

    Background In the currently available research publications on electrical therapy of low back pain, generally no control groups or detailed randomization were used, and such studies were often conducted with relatively small groups of patients, based solely on subjective questionnaires and pain assessment scales (lacking measurement methods to objectify the therapeutic progress). The available literature also lacks a comprehensive and large-scale clinical study. The purpose of this study was ...

  5. Motivational and behavioural models of change: A longitudinal analysis of change among men with chronic haemophilia-related joint pain.

    Science.gov (United States)

    Elander, J; Richardson, C; Morris, J; Robinson, G; Schofield, M B

    2017-09-01

    Motivational and behavioural models of adjustment to chronic pain make different predictions about change processes, which can be tested in longitudinal analyses. We examined changes in motivation, coping and acceptance among 78 men with chronic haemophilia-related joint pain. Using cross-lagged regression analyses of changes from baseline to 6 months as predictors of changes from 6 to 12 months, with supplementary structural equation modelling, we tested two models in which motivational changes influence behavioural changes, and one in which behavioural changes influence motivational changes. Changes in motivation to self-manage pain influenced later changes in pain coping, consistent with the motivational model of pain self-management, and also influenced later changes in activity engagement, the behavioural component of pain acceptance. Changes in activity engagement influenced later changes in pain willingness, consistent with the behavioural model of pain acceptance. Based on the findings, a combined model of changes in pain self-management and acceptance is proposed, which could guide combined interventions based on theories of motivation, coping and acceptance in chronic pain. This study adds longitudinal evidence about sequential change processes; a test of the motivational model of pain self-management; and tests of behavioural versus motivational models of pain acceptance. © 2017 European Pain Federation - EFIC®.

  6. Analgesic efficacy of CR4056, a novel imidazoline-2 receptor ligand, in rat models of inflammatory and neuropathic pain

    Directory of Open Access Journals (Sweden)

    Ferrari F

    2011-04-01

    Full Text Available Flora Ferrari1, Simonetta Fiorentino1, Laura Mennuni1, Paolo Garofalo1, Ornella Letari1, Stefano Mandelli2, Antonio Giordani3, Marco Lanza1, Gianfranco Caselli11Department of Pharmacology and Toxicology; 2Department of Medicinal Chemistry; 3R&D Chemistry Drug Development and OS, Rottapharm S.p.A., Monza (MB, ItalyAbstract: Two decades of investigations have failed to unequivocally clarify the functions and the molecular nature of imidazoline-2 receptors (I2R. However, there is robust pharmacological evidence for the functional modulation of monoamino oxidase (MAO and other important enzyme activities by I2 site ligands. Some compounds of this class proved to be active experimental tools in preventing both experimental pain and opioid tolerance and dependence. Unfortunately, even though these compounds bind with high potency to central I2 sites, they fail to represent a valid clinical opportunity due to their pharmacokinetic, selectivity or side-effects profile. This paper presents the preclinical profile of a novel I2 ligand (2-phenyl-6-(1H-imidazol-1ylquinazoline; [CR4056] that selectively inhibits the activity of human recombinant MAO-A in a concentration-dependent manner. A sub-chronic four day oral treatment of CR4056 increased norepinephrine (NE tissue levels both in the rat cerebral cortex (63.1% ± 4.2%; P<0.05 and lumbar spinal cord (51.3% ± 6.7%; P < 0.05. In the complete Freund's adjuvant (CFA rat model of inflammatory pain, CR4056 was found to be orally active (ED50 = 5.8 mg/kg, by mouth [p.o.]. In the acute capsaicin model, CR4056 completely blocked mechanical hyperalgesia in the injured hind paw (ED50 = 4.1 mg/kg, p.o.; ED100 = 17.9 mg/kg, p.o.. This effect was dose-dependently antagonized by the non-selective imidazoline I2/α2 antagonist idazoxan. In rat models of neuropathic pain, oral administration of CR4056 significantly attenuated mechanical hyperalgesia and allodynia. In summary, the present study suggests a novel

  7. The structural model of pain, cognitive strategies, and negative emotions in functional gastrointestinal disorders

    Directory of Open Access Journals (Sweden)

    Mina Mazaheri

    2016-01-01

    Full Text Available Background: Patients with functional gastrointestinal disorders (FGIDs may use specific coping strategies. We intend to provide a mediating role of the relationship between pain (intensity and acceptance, cognitive emotion regulation strategies, and negative emotions in patients with FGIDs. Materials and Methods: Participants were 176 inpatients, all experiencing significant FGIDs symptomatology as confirmed by gastroenterologists. Patients completed data on cognitive emotion regulation questionnaire, short form of depression, anxiety, stress scale, chronic pain acceptance questionnaire-revised, and pain intensity scale. Data were analyzed using structural equation modeling method. Results: The pain intensity had significantly direct effect on cognitive emotion regulation strategies and indirect effect on negative emotions. Besides, the mediating role of negative emotions in the relationship between the strategies and pain acceptance were supported, whereas indirect relationships between pain intensity and acceptance through cognitive strategies were not confirmed. Conclusion: The results of the study emphasize the role of pain intensity in the development of negative emotions through cognitive strategies and the role of the strategies in pain acceptance through negative emotions. In fact, cognitive strategies to be related to pain and emotions.

  8. Low Back Pain Preventive Behaviors Among Nurses Based on the Health Belief Model Constructs

    Directory of Open Access Journals (Sweden)

    Naser Sharafkhani

    2014-12-01

    Full Text Available The nursing profession is physically demanding as it is ranked second from the viewpoint of physical activity, following industrial occupations. Nursing is considered a profession with high musculoskeletal disorders, specifically low back pain. This article evaluated the nurses’ educational needs based on the Health Belief Model (HBM with focus on the low back pain and adoption of preventive behaviors. This analytical cross-sectional study was conducted on 133 nurses who were selected randomly from three public educational hospitals affiliated with Arak University of Medical Sciences. Data collection was performed with a questionnaire, which included demographic characteristics, questions on HBM constructs, and a checklist for explaining the performances. The collected data were analyzed using descriptive and analytical tests and Pearson’s correlation coefficient. In this study, among the HBM constructs, the cues to action and the perceived barriers were the main predictors of optimal performance among the sample subjects (B = 0.09, p < .01. Moreover, there was a significant relationship between the nurses’ performance on adopting the preventive behaviors and the scores of perceived barriers, self-efficacy, and cues to action (p < .05. However, no significant relationship was observed between the nurses’ performance and perceived susceptibility, severity, and benefits. In this study, as for behavior barriers, the nurses complained about unfamiliarity with the workplace ergonomics and inappropriate conditions based on ergonomic principles, which requires educational planning with the aim of overcoming perceived barriers, improving managerial activities, and enhancing the working place conditions.

  9. Multivariate prognostic modeling of persistent pain following lumbar discectomy.

    LENUS (Irish Health Repository)

    Hegarty, Dominic

    2013-03-04

    Persistent postsurgical pain (PPSP) affects between 10% and 50% of surgical patients, the development of which is a complex and poorly understood process. To date, most studies on PPSP have focused on specific surgical procedures where individuals do not suffer from chronic pain before the surgical intervention. Individuals who have a chronic nerve injury are likely to have established peripheral and central sensitization which may increase the risk of developing PPSP. Concurrent analyses of the possible factors contributing to the development of PPSP following lumbar discectomy have not been examined.

  10. The short- and medium-term effectiveness of CT-guided selective cervical nerve root injection for pain and disability

    Energy Technology Data Exchange (ETDEWEB)

    Desai, Amidevi; Saha, Shouvik; Sharma, Naveen; Huckerby, Lauren; Houghton, Russell [Guy' s and St. Thomas' Hospitals, Department of Radiology, London (United Kingdom)

    2014-07-15

    CT-guided cervical nerve root injection with corticosteroid and/or local anesthetic is a recognized technique in the evaluation and treatment of cervical radiculopathy. There are few prospective studies on the efficacy of the various techniques employed in cervical nerve root injection. We present our results from a 1-year prospective series using a CT-guided anterolateral transforaminal approach for cervical nerve root injection of bupivacaine and dexamethasone. Pain using a numeric rating scale was assessed at pre-injection, 15 min post-injection, 1 month, and 3 months. Disability was assessed using the Oswestry Neck Disability Index (NDI) questionnaire at pre-injection, 1 month post-injection, and 3 months. In total, 50 patients were followed for 3 months. The mean reductions in pain were: 15 min (77 %), 1 month (39 %), and 3 months (33 %). The mean reductions in NDI were: 1 month (26 %) and 3 months (also 26 %). Results were statistically significant. CT-guided selective cervical nerve root injection in the treatment of cervical radicular pain and related disability produces statistically significant reductions in pain and disability to at least 3 months post-procedure. (orig.)

  11. The short- and medium-term effectiveness of CT-guided selective cervical nerve root injection for pain and disability

    International Nuclear Information System (INIS)

    Desai, Amidevi; Saha, Shouvik; Sharma, Naveen; Huckerby, Lauren; Houghton, Russell

    2014-01-01

    CT-guided cervical nerve root injection with corticosteroid and/or local anesthetic is a recognized technique in the evaluation and treatment of cervical radiculopathy. There are few prospective studies on the efficacy of the various techniques employed in cervical nerve root injection. We present our results from a 1-year prospective series using a CT-guided anterolateral transforaminal approach for cervical nerve root injection of bupivacaine and dexamethasone. Pain using a numeric rating scale was assessed at pre-injection, 15 min post-injection, 1 month, and 3 months. Disability was assessed using the Oswestry Neck Disability Index (NDI) questionnaire at pre-injection, 1 month post-injection, and 3 months. In total, 50 patients were followed for 3 months. The mean reductions in pain were: 15 min (77 %), 1 month (39 %), and 3 months (33 %). The mean reductions in NDI were: 1 month (26 %) and 3 months (also 26 %). Results were statistically significant. CT-guided selective cervical nerve root injection in the treatment of cervical radicular pain and related disability produces statistically significant reductions in pain and disability to at least 3 months post-procedure. (orig.)

  12. Tanezumab: a selective humanized mAb for chronic lower back pain

    Directory of Open Access Journals (Sweden)

    Webb MP

    2018-02-01

    Full Text Available Michael P Webb,1 Erik M Helander,2 Bethany L Menard,2 Richard D Urman,3 Alan D Kaye2 1Department of Anesthesiology, North Shore Hospital, Auckland, New Zealand; 2Department of Anesthesiology, LSU School of Medicine, New Orleans, LA, USA; 3Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Abstract: Chronic lower back pain is a significant disease that affects nearly 20% of the worldwide population. Along with hindering patients’ quality of life, chronic lower back pain is considered to be the second most common cause of disability among Americans. Treating chronic lower back pain is often a challenge for providers, especially in light of our current opioid epidemic. With this epidemic and an increased aging population, there is an imminent need for development of new pharmacologic therapeutic options, which are not only effective but also pose minimal adverse effects to the patient. With these considerations, a novel therapeutic agent called tanezumab has been developed and studied. Tanezumab is a humanized monoclonal immunoglobulin G2 antibody that works by inhibiting the binding of NGF to its receptors. NGF is involved in the function of sensory neurons and fibers involved in nociceptive transduction. It is commonly seen in excess in inflammatory joint conditions and in chronic pain patients. Nociceptors are dependent on NGF for growth and ongoing function. The inhibition of NGF binding to its receptors is a mechanism by which pain pathways can be interrupted. In this article, a number of recent randomized controlled trials are examined relating to the efficacy and safety of tanezumab in the treatment of chronic lower back pain. Although tanezumab was shown to be an effective pain modulator in major trials, several adverse effects were seen among different doses of the medication, one of which led to a clinical hold placed by the US Food and Drug

  13. Effect of sex in the MRMT-1 model of cancer-induced bone pain

    DEFF Research Database (Denmark)

    Falk, Sarah; Al-Dihaissy, Tamara; Mezzanotte, Laura

    2015-01-01

    An overwhelming amount of evidence demonstrates sex-induced variation in pain processing, and has thus increased the focus on sex as an essential parameter for optimization of in vivo models in pain research. Mammary cancer cells are often used to model metastatic bone pain in vivo......, and are commonly used in both males and females. Here we demonstrate that compared to male rats, female rats have an increased capacity for recovery following inoculation of MRMT-1 mammary cells, thus potentially causing a sex-dependent bias in interpretation of the data....

  14. Item selection via Bayesian IRT models.

    Science.gov (United States)

    Arima, Serena

    2015-02-10

    With reference to a questionnaire that aimed to assess the quality of life for dysarthric speakers, we investigate the usefulness of a model-based procedure for reducing the number of items. We propose a mixed cumulative logit model, which is known in the psychometrics literature as the graded response model: responses to different items are modelled as a function of individual latent traits and as a function of item characteristics, such as their difficulty and their discrimination power. We jointly model the discrimination and the difficulty parameters by using a k-component mixture of normal distributions. Mixture components correspond to disjoint groups of items. Items that belong to the same groups can be considered equivalent in terms of both difficulty and discrimination power. According to decision criteria, we select a subset of items such that the reduced questionnaire is able to provide the same information that the complete questionnaire provides. The model is estimated by using a Bayesian approach, and the choice of the number of mixture components is justified according to information criteria. We illustrate the proposed approach on the basis of data that are collected for 104 dysarthric patients by local health authorities in Lecce and in Milan. Copyright © 2014 John Wiley & Sons, Ltd.

  15. A surgical ankle sprain pain model in the rat: Effects of morphine and indomethacin

    OpenAIRE

    Young Kim, Hee; Wang, Jigong; Chung, Kyungsoon; Mo Chung, Jin

    2008-01-01

    Ankle sprain is a frequent injury in humans that results in pain, swelling and difficulty in walking on the affected ankle. Currently a suitable animal model resembling human ankle sprain is lacking. Here, we describe an animal ankle sprain model induced by ankle ligament injury (ALI) in rats. Cutting combinations of the lateral ankle ligament complex produced pain, edema and difficulty of weight bearing, thereby mimicking severe (grade III) ankle sprain in humans. Analgesic compounds, morphi...

  16. Computational Modeling and Analysis of Mechanically Painful Stimulations

    DEFF Research Database (Denmark)

    Manafi Khanian, Bahram

    Cuff algometry is used for quantitative assessment of deep-tissue sensitivity. The main purpose of this PhD dissertation is to provide a novel insight into the intrinsic and extrinsic factors which are involved in mechanically induced pain during cuff pressure algometry. A computational 3D finite...

  17. The Src family kinase inhibitor dasatinib delays pain-related behaviour and conserves bone in a rat model of cancer-induced bone pain

    DEFF Research Database (Denmark)

    Appel, Camilla Kristine; Gallego-Pedersen, Simone; Andersen, Line

    2017-01-01

    Pain is a severe and debilitating complication of metastatic bone cancer. Current analgesics do not provide sufficient pain relief for all patients, creating a great need for new treatment options. The Src kinase, a non-receptor protein tyrosine kinase, is implicated in processes involved in cancer......-induced bone pain, including cancer growth, osteoclastic bone degradation and nociceptive signalling. Here we investigate the role of dasatinib, an oral Src kinase family and Bcr-Abl tyrosine kinase inhibitor, in an animal model of cancer-induced bone pain. Daily administration of dasatinib (15 mg/kg, p...

  18. Face-to-face comparison of the predictive validity of two models of neuropathic pain in the rat: analgesic activity of pregabalin, tramadol and duloxetine.

    Science.gov (United States)

    Le Cudennec, Camille; Castagné, Vincent

    2014-07-15

    We compared the preclinical analgesic activity of three marketed drugs with different pharmacological properties, pregabalin, tramadol and duloxetine, described as effective against neuropathic pain in the clinic. These drugs were tested against evoked pain in two different neuropathic models in the rat, the Bennett (CCI) and the Chung (SNL) models. The selected endpoints were tactile allodynia, tactile hyperalgesia, heat hyperalgesia and cold allodynia. Although all three drugs displayed analgesic activity, the effects observed varied according to the behavioral evaluation. Pregabalin showed clear analgesic effects against cold allodynia and tactile hyperalgesia in both the CCI and Chung models. Tramadol was active against all four endpoints in the Chung model with similar effects in the CCI model, apart from tactile allodynia. Duloxetine inhibited tactile allodynia and heat hyperalgesia in both neuropathic pain models. It also displayed efficacy against tactile hyperalgesia in the CCI model and against cold allodynia in the Chung model. These data confirm that the CCI and the Chung models of neuropathic pain do not detect the activity of analgesics with the same sensitivity. Furthermore, the mode of stimulation (tactile or thermal) and the type of endpoint (allodynia or hyperalgesia) can further influence the observed efficacy of gold standards as well as novel compounds developed for treating neuropathic pain symptoms. Copyright © 2014. Published by Elsevier B.V.

  19. Perceiving pain in others: validation of a dual processing model.

    Science.gov (United States)

    McCrystal, Kalie N; Craig, Kenneth D; Versloot, Judith; Fashler, Samantha R; Jones, Daniel N

    2011-05-01

    Accurate perception of another person's painful distress would appear to be accomplished through sensitivity to both automatic (unintentional, reflexive) and controlled (intentional, purposive) behavioural expression. We examined whether observers would construe diverse behavioural cues as falling within these domains, consistent with cognitive neuroscience findings describing activation of both automatic and controlled neuroregulatory processes. Using online survey methodology, 308 research participants rated behavioural cues as "goal directed vs. non-goal directed," "conscious vs. unconscious," "uncontrolled vs. controlled," "fast vs. slow," "intentional (deliberate) vs. unintentional," "stimulus driven (obligatory) vs. self driven," and "requiring contemplation vs. not requiring contemplation." The behavioural cues were the 39 items provided by the PROMIS pain behaviour bank, constructed to be representative of the diverse possibilities for pain expression. Inter-item correlations among rating scales provided evidence of sufficient internal consistency justifying a single score on an automatic/controlled dimension (excluding the inconsistent fast vs. slow scale). An initial exploratory factor analysis on 151 participant data sets yielded factors consistent with "controlled" and "automatic" actions, as well as behaviours characterized as "ambiguous." A confirmatory factor analysis using the remaining 151 data sets replicated EFA findings, supporting theoretical predictions that observers would distinguish immediate, reflexive, and spontaneous reactions (primarily facial expression and paralinguistic features of speech) from purposeful and controlled expression (verbal behaviour, instrumental behaviour requiring ongoing, integrated responses). There are implicit dispositions to organize cues signaling pain in others into the well-defined categories predicted by dual process theory. Copyright © 2011 International Association for the Study of Pain. Published by

  20. The Src family kinase inhibitor dasatinib delays pain-related behaviour and conserves bone in a rat model of cancer-induced bone pain

    DEFF Research Database (Denmark)

    Appel, Camilla Kristine; Gallego-Pedersen, Simone; Andersen, Line

    2017-01-01

    -induced bone pain, including cancer growth, osteoclastic bone degradation and nociceptive signalling. Here we investigate the role of dasatinib, an oral Src kinase family and Bcr-Abl tyrosine kinase inhibitor, in an animal model of cancer-induced bone pain. Daily administration of dasatinib (15 mg/kg, p...

  1. Factors influencing creep model equation selection

    International Nuclear Information System (INIS)

    Holdsworth, S.R.; Askins, M.; Baker, A.; Gariboldi, E.; Holmstroem, S.; Klenk, A.; Ringel, M.; Merckling, G.; Sandstrom, R.; Schwienheer, M.; Spigarelli, S.

    2008-01-01

    During the course of the EU-funded Advanced-Creep Thematic Network, ECCC-WG1 reviewed the applicability and effectiveness of a range of model equations to represent the accumulation of creep strain in various engineering alloys. In addition to considering the experience of network members, the ability of several models to describe the deformation characteristics of large single and multi-cast collations of ε(t,T,σ) creep curves have been evaluated in an intensive assessment inter-comparison activity involving three steels, 21/4 CrMo (P22), 9CrMoVNb (Steel-91) and 18Cr13NiMo (Type-316). The choice of the most appropriate creep model equation for a given application depends not only on the high-temperature deformation characteristics of the material under consideration, but also on the characteristics of the dataset, the number of casts for which creep curves are available and on the strain regime for which an analytical representation is required. The paper focuses on the factors which can influence creep model selection and model-fitting approach for multi-source, multi-cast datasets

  2. Radiation-induced relief of pain in an animal model with bone invasion from cancer

    International Nuclear Information System (INIS)

    Seong, J.; Kim, J.; Kim, K.H.; Kim, U.J.; Lee, B.W.

    2003-01-01

    In clinic, local radiation is effective for relief of pain from cancer invasion into the bones. This effect is usually observed before the regression of tumor occurs, which implies radiation-induced pain relief by mechanisms other than tumor irradication. In this study, possible mechanisms were explored in animal model system. To establish an animal model, syngeneic hepatocarcinoma, HCa-I was transplanted on femoral periosteum of C3H/HeJ male mice and bone-invasive tumor growth was identified through the histological analysis. Development of tumor-induced pain was assessed by von Frey filament test, acetone test, and radiant heat test. Animals were also irradiated for their tumors. Any change in pain was analyzed by above tests for the quantitative change and by immunohistochemical stain for the expression of molecules such as c-fos, substance P, and calcitonin gene-related peptide (CGRP) in lumbar spinal cord. Cancer invasion into the bone was started from 7th day after transplantation and became evident at day 14. Objective increase of pain in the ipsilateral thigh was observed at day 14 on von Frey filament test and acetone test, while there was no remarkable regression of the tumors. In this model system, local radiation of tumor resulted in decrease in objective pain on von Frey filament test and acetone test. In the immunohistochemical stain for lumbar spinal cord, the expression of substance P and CGRP but not c-fos increased in tumor-bearing animal compared to the control. The expression of these molecules decreased in animals given local radiation. In summary, an animal model system was established for objective pain from cancer invasion into the bones. Local radiation of tumor induced objective pain relief and this effect seems to be mediated not by tumor regression but through altered production of pain-related molecules

  3. Radiation-induced relief of pain in an animal model with bone invasion from cancer

    Energy Technology Data Exchange (ETDEWEB)

    Seong, J; Kim, J; Kim, K H; Kim, U J; Lee, B W [Yonsei University Medical College, (Korea, Republic of)

    2003-07-01

    In clinic, local radiation is effective for relief of pain from cancer invasion into the bones. This effect is usually observed before the regression of tumor occurs, which implies radiation-induced pain relief by mechanisms other than tumor irradication. In this study, possible mechanisms were explored in animal model system. To establish an animal model, syngeneic hepatocarcinoma, HCa-I was transplanted on femoral periosteum of C3H/HeJ male mice and bone-invasive tumor growth was identified through the histological analysis. Development of tumor-induced pain was assessed by von Frey filament test, acetone test, and radiant heat test. Animals were also irradiated for their tumors. Any change in pain was analyzed by above tests for the quantitative change and by immunohistochemical stain for the expression of molecules such as c-fos, substance P, and calcitonin gene-related peptide (CGRP) in lumbar spinal cord. Cancer invasion into the bone was started from 7th day after transplantation and became evident at day 14. Objective increase of pain in the ipsilateral thigh was observed at day 14 on von Frey filament test and acetone test, while there was no remarkable regression of the tumors. In this model system, local radiation of tumor resulted in decrease in objective pain on von Frey filament test and acetone test. In the immunohistochemical stain for lumbar spinal cord, the expression of substance P and CGRP but not c-fos increased in tumor-bearing animal compared to the control. The expression of these molecules decreased in animals given local radiation. In summary, an animal model system was established for objective pain from cancer invasion into the bones. Local radiation of tumor induced objective pain relief and this effect seems to be mediated not by tumor regression but through altered production of pain-related molecules.

  4. Evaluation of intradural stimulation efficiency and selectivity in a computational model of spinal cord stimulation.

    Directory of Open Access Journals (Sweden)

    Bryan Howell

    Full Text Available Spinal cord stimulation (SCS is an alternative or adjunct therapy to treat chronic pain, a prevalent and clinically challenging condition. Although SCS has substantial clinical success, the therapy is still prone to failures, including lead breakage, lead migration, and poor pain relief. The goal of this study was to develop a computational model of SCS and use the model to compare activation of neural elements during intradural and extradural electrode placement. We constructed five patient-specific models of SCS. Stimulation thresholds predicted by the model were compared to stimulation thresholds measured intraoperatively, and we used these models to quantify the efficiency and selectivity of intradural and extradural SCS. Intradural placement dramatically increased stimulation efficiency and reduced the power required to stimulate the dorsal columns by more than 90%. Intradural placement also increased selectivity, allowing activation of a greater proportion of dorsal column fibers before spread of activation to dorsal root fibers, as well as more selective activation of individual dermatomes at different lateral deviations from the midline. Further, the results suggest that current electrode designs used for extradural SCS are not optimal for intradural SCS, and a novel azimuthal tripolar design increased stimulation selectivity, even beyond that achieved with an intradural paddle array. Increased stimulation efficiency is expected to increase the battery life of implantable pulse generators, increase the recharge interval of rechargeable implantable pulse generators, and potentially reduce stimulator volume. The greater selectivity of intradural stimulation may improve the success rate of SCS by mitigating the sensitivity of pain relief to malpositioning of the electrode. The outcome of this effort is a better quantitative understanding of how intradural electrode placement can potentially increase the selectivity and efficiency of SCS

  5. Uncovering the influence of social skills and psychosociological factors on pain sensitivity using structural equation modeling.

    Science.gov (United States)

    Tanaka, Yoichi; Nishi, Yuki; Nishi, Yuki; Osumi, Michihiro; Morioka, Shu

    2017-01-01

    Pain is a subjective emotional experience that is influenced by psychosociological factors such as social skills, which are defined as problem-solving abilities in social interactions. This study aimed to reveal the relationships among pain, social skills, and other psychosociological factors by using structural equation modeling. A total of 101 healthy volunteers (41 men and 60 women; mean age: 36.6±12.7 years) participated in this study. To evoke participants' sense of inner pain, we showed them images of painful scenes on a PC screen and asked them to evaluate the pain intensity by using the visual analog scale (VAS). We examined the correlation between social skills and VAS, constructed a hypothetical model based on results from previous studies and the current correlational analysis results, and verified the model's fit using structural equation modeling. We found significant positive correlations between VAS and total social skills values, as well as between VAS and the "start of relationships" subscales. Structural equation modeling revealed that the values for "start of relationships" had a direct effect on VAS values (path coefficient =0.32, p social support. The results indicated that extroverted people are more sensitive to inner pain and tend to get more social support and maintain a better psychological condition.

  6. Bridging the gap between mind and body: a biobehavioral model of the effects of guided imagery on pain, pain disability, and depression.

    Science.gov (United States)

    Lewandowski, Wendy; Jacobson, Ann

    2013-12-01

    Chronic noncancer pain (CNCP) is a common and complex disorder associated with declines in physical health and functional status, emotional well-being, and quality of life. To best address the complexity of this condition, research and clinical practice for CNCP should be guided by a framework incorporating both biologic and psychologic factors. This article presents a biobehavioral model of chronic pain that hypothesizes mechanisms related to the effectiveness of a complementary therapy, guided imagery (GI), for this population. Using the research-to-model/theory strategy, we mapped findings from published reports of interdisciplinary research into physiologic and psychologic aspects of the nature and mechanisms of pain, as well as the use of GI for pain, to build the model of GI's effects on pain, pain disability, and depression. In the model, these outcomes of GI for persons experiencing CNCP are mediated by psychologic (pain self-efficacy and pain beliefs) and physiologic (immune-mediated analgesia and sickness response) variables. A biobehavioral approach to nursing phenomena will advance understanding of health and health-related issues and has the potential to improve outcomes through delineation of mechanisms underlying relationships between psychologic and biologic factors. Increased consumer use of complementary therapies to treat pain, the current cost-driven health care system, and the mandate for evidence-based practice support the need to validate the efficacy of such therapies. This empirically derived model provides a framework for practice and research for nurses and other health care providers to promote health, function, and well-being in persons with CNCP. Copyright © 2013 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  7. Prevalence and risk factors for low back pain among shopkeepers/salesman at model town link road, lahore, pakistan

    International Nuclear Information System (INIS)

    Hussain, T.; Taufiq, F.; Hassan, T.U.

    2017-01-01

    Objective: To find the prevalence and intensity of low back pain (LBP) among shopkeepers and their associated risk factors and to determine working postures and activities of shopkeepers which make them vulnerable to low back pain. Methodology: This cross sectional study was conducted at Model Town Link Road, Lahore, Pakistan for a period of five months. 96 shopkeepers were selected by non-probability convenience sampling. Prevalence was measured by modified Nordic questionnaire and intensity of pain by Visual Analog Scale. Results: Prevalence of LBP was 56.25%. Of these, 81(84.38%) were male and 15(15.63%) were female. LBP was most common in age group 18-24 years. 58.8% of them had difficulty at job due to LBP. More working hours and prolonged standing or sitting in poor postures were associated with LBP. Conclusion: About half of the shopkeepers (56.25%) suffered from LBP. Working hours and poor posture were risk factors. Therefore, ergonomic advice is needed to prevent from low back pain. (author)

  8. Posttraumatic stress symptoms and the diathesis-stress model of chronic pain and disability in patients undergoing major surgery.

    Science.gov (United States)

    Martin, Andrea L; Halket, Eileen; Asmundson, Gordon J G; Flora, David B; Katz, Joel

    2010-01-01

    To (1) use structural equation modeling (SEM) to examine relationships proposed in Turk's diathesis-stress model of chronic pain and disability as well as (2) investigate what role, if any, posttraumatic stress symptoms (PTSS) play in predicting pain disability, relative to some of the other factors in the model. The study sample consisted of 208 patients scheduled for general surgery, 21 to 60 years of age (mean age=47.18 y, SD=9.72 y), who reported experiencing persistent pain for an average of 5.56 years (SD=7.90 y). At their preadmission hospital visit, patients completed the Anxiety Sensitivity Index, Pain Catastrophizing Scale, Pain Anxiety Symptoms Scale-20, Pain Disability Index, posttraumatic stress disorder Checklist, and rated the average intensity of their pain (0 to 10 numeric rating scale). SEM was used to test a model of chronic pain disability and to explore potential relationships between PTSS and factors in the diathesis-stress model. SEM results provided support for a model in which anxiety sensitivity predicted fear of pain and catastrophizing, fear of pain predicted escape/avoidance, and escape/avoidance predicted pain disability. Results also provided support for a feedback loop between disability and fear of pain. SEM analyses provided preliminary support for the inclusion of PTSS in the diathesis-stress model, with PTSS accounting for a significant proportion of the variance in pain disability. Results provide empirical support for aspects of Turk's diathesis-stress model in a sample of patients with persistent pain. Findings also offer preliminary support for the role of PTSS in fear-avoidance models of chronic pain.

  9. Do number of days with low back pain and patterns of episodes of pain have similar outcomes in a biopsychosocial prediction model?

    DEFF Research Database (Denmark)

    Lemeunier, N; Leboeuf-Yde, C; Gagey, O

    2016-01-01

    are similar, regardless which of the two classifications is used. METHOD: During 1 year, 49- or 50-year-old people from the Danish general population were sent fortnightly automated text messages (SMS-Track) asking them if they had any LBP in the past fortnight. Responses for the whole year were......PURPOSES: We used two different methods to classify low back pain (LBP) in the general population (1) to assess the overlapping of individuals within the different subgroups in those two classifications, (2) to explore if the associations between LBP and some selected bio-psychosocial factors...... with a questionnaire at baseline 9 years earlier, were entered into regression models to investigate their associations with the subgroups of the two classifications of LBP and the results compared. RESULTS: The percentage of agreement between categories of the two classification systems was above 68 % (Kappa 0...

  10. Stress and visceral pain: from animal models to clinical therapies

    Science.gov (United States)

    Larauche, Muriel; Mulak, Agata; Taché, Yvette

    2011-01-01

    Epidemiological studies have implicated stress (psychosocial and physical) as a trigger of first onset or exacerbation of irritable bowel syndrome (IBS) symptoms of which visceral pain is an integrant landmark. A number of experimental acute or chronic exteroceptive or interoceptive stressors induce visceral hyperalgesia in rodents although recent evidence also points to stress-related visceral analgesia as established in the somatic pain field. Underlying mechanisms of stress-related visceral hypersensitivity may involve a combination of sensitization of primary afferents, central sensitization in response to input from the viscera and dysregulation of descending pathways that modulate spinal nociceptive transmission or analgesic response. Biochemical coding of stress involves the recruitment of corticotropin releasing factor (CRF) signaling pathways. Experimental studies established that activation of brain and peripheral CRF receptor subtype 1 plays a primary role in the development of stress-related delayed visceral hyperalgesia while subtype 2 activation induces analgesic response. In line with stress pathways playing a role in IBS, non-pharmacologic and pharmacologic treatment modalities aimed at reducing stress perception using a broad range of evidence-based mind-body interventions and centrally-targeted medications to reduce anxiety impact on brain patterns activated by visceral stimuli and dampen visceral pain. PMID:21575632

  11. USING THE SELECTIVE FUNCTIONAL MOVEMENT ASSESSMENT AND REGIONAL INTERDEPENDENCE THEORY TO GUIDE TREATMENT OF AN ATHLETE WITH BACK PAIN: A CASE REPORT.

    Science.gov (United States)

    Goshtigian, Gabriella R; Swanson, Brian T

    2016-08-01

    Despite the multidirectional quality of human movement, common measurement procedures used in physical therapy examination are often uni-planar and lack the ability to assess functional complexities involved in daily activities. Currently, there is no widely accepted, validated standard to assess movement quality. The Selective Functional Movement Assessment (SFMA) is one possible system to objectively assess complex functional movements. The purpose of this case report is to illustrate the application of the SFMA as a guide to the examination, evaluation, and management of a patient with non-specific low back pain (LBP). An adolescent male athlete with LBP was evaluated using the SFMA. It was determined that the patient had mobility limitations remote to the site of pain (thoracic spine and hips) which therapists hypothesized were leading to compensatory hypermobility at the lumbar spine. Guided by the SFMA, initial interventions focused on local (lumbar) symptom management, progressing to remote mobility deficits, and then addressing the local stability deficit. All movement patterns became functional/non-painful except the right upper extremity medial rotation-extension pattern. At discharge, the patient demonstrated increased soft tissue extensibility of hip musculature and joint mobility of the thoracic spine along with normalization of lumbopelvic motor control. Improvements in pain exceeded minimal clinically important differences, from 2-7/10 on a verbal analog scale at initial exam to 0-2/10 at discharge. Developing and progressing a plan of care for an otherwise healthy and active adolescent with non-specific LBP can be challenging. Human movement is a collaborative effort of muscle groups that are interdependent; the use of a movement-based assessment model can help identify weak links affecting overall function. The SFMA helped guide therapists to dysfunctional movements not seen with more conventional examination procedures. Level 4.

  12. High-dimensional model estimation and model selection

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    I will review concepts and algorithms from high-dimensional statistics for linear model estimation and model selection. I will particularly focus on the so-called p>>n setting where the number of variables p is much larger than the number of samples n. I will focus mostly on regularized statistical estimators that produce sparse models. Important examples include the LASSO and its matrix extension, the Graphical LASSO, and more recent non-convex methods such as the TREX. I will show the applicability of these estimators in a diverse range of scientific applications, such as sparse interaction graph recovery and high-dimensional classification and regression problems in genomics.

  13. Halo models of HI selected galaxies

    Science.gov (United States)

    Paul, Niladri; Choudhury, Tirthankar Roy; Paranjape, Aseem

    2018-06-01

    Modelling the distribution of neutral hydrogen (HI) in dark matter halos is important for studying galaxy evolution in the cosmological context. We use a novel approach to infer the HI-dark matter connection at the massive end (m_H{I} > 10^{9.8} M_{⊙}) from radio HI emission surveys, using optical properties of low-redshift galaxies as an intermediary. In particular, we use a previously calibrated optical HOD describing the luminosity- and colour-dependent clustering of SDSS galaxies and describe the HI content using a statistical scaling relation between the optical properties and HI mass. This allows us to compute the abundance and clustering properties of HI-selected galaxies and compare with data from the ALFALFA survey. We apply an MCMC-based statistical analysis to constrain the free parameters related to the scaling relation. The resulting best-fit scaling relation identifies massive HI galaxies primarily with optically faint blue centrals, consistent with expectations from galaxy formation models. We compare the Hi-stellar mass relation predicted by our model with independent observations from matched Hi-optical galaxy samples, finding reasonable agreement. As a further application, we make some preliminary forecasts for future observations of HI and optical galaxies in the expected overlap volume of SKA and Euclid/LSST.

  14. Bisphosphonates Inhibit Pain, Bone Loss, and Inflammation in a Rat Tibia Fracture Model of Complex Regional Pain Syndrome.

    Science.gov (United States)

    Wang, Liping; Guo, Tian-Zhi; Hou, Saiyun; Wei, Tzuping; Li, Wen-Wu; Shi, Xiaoyou; Clark, J David; Kingery, Wade S

    2016-10-01

    Bisphosphonates are used to prevent the bone loss and fractures associated with osteoporosis, bone metastases, multiple myeloma, and osteogenesis deformans. Distal limb fractures cause regional bone loss with cutaneous inflammation and pain in the injured limb that can develop into complex regional pain syndrome (CRPS). Clinical trials have reported that antiresorptive bisphosphonates can prevent fracture-induced bone loss, inhibit serum inflammatory cytokine levels, and alleviate CRPS pain. Previously, we observed that the inhibition of inflammatory cytokines or adaptive immune responses attenuated the development of pain behavior in a rat fracture model of CRPS, and we hypothesized that bisphosphonates could prevent pain behavior, trabecular bone loss, postfracture cutaneous cytokine upregulation, and adaptive immune responses in this CRPS model. Rats underwent tibia fracture and cast immobilization for 4 weeks and were chronically administered either subcutaneously perfused alendronate or oral zoledronate. Behavioral measurements included hindpaw von Frey allodynia, unweighting, warmth, and edema. Bone microarchitecture was measured by microcomputed tomography, and bone cellular activity was evaluated by static and dynamic histomorphometry. Spinal cord Fos immunostaining was performed, and skin cytokine (tumor necrosis factor, interleukin [IL]-1, IL-6) and nerve growth factor (NGF) levels were determined by enzyme immunoassay. Skin and sciatic nerve immunoglobulin levels were determined by enzyme immunoassay. Rats with tibia fractures developed hindpaw allodynia, unweighting, warmth, and edema, increased spinal Fos expression and trabecular bone loss in the lumbar vertebra and bilateral distal femurs as measured by microcomputed tomography, increased trabecular bone resorption and osteoclast surface with decreased bone formation rates, increased cutaneous inflammatory cytokine and NGF expression, and elevated immunocomplex deposition in skin and nerve

  15. Predictive models of pain following root canal treatment: a prospective clinical study.

    Science.gov (United States)

    Arias, A; de la Macorra, J C; Hidalgo, J J; Azabal, M

    2013-08-01

    To determine the probability of the incidence, intensity, duration and triggering of post-endodontic pain, considering factors related to the patient (age, gender, medical evaluation) and to the affected tooth (group, location, number of canals, pulp vitality, preoperative pain, periapical radiolucencies, previous emergency access, presence of occlusal contacts with antagonist). A total of 500 one-visit root canal treatments (RCTs) were performed on patients referred to an endodontist. Shaping of root canals was performed manually with Gates-Glidden drills and K-Flexofiles, and apical patency was maintained with a size 10 file. A 5% NaOCl solution was used for irrigation, and canals were filled with lateral compaction and AH-Plus sealer. Independent factors were recorded during the treatment, and characteristics of post-endodontic pain (incidence, intensity, type and duration) were later surveyed through questionnaires. Of the 500 questionnaires, 374 were properly returned and split in two groups for two different statistical purposes: 316 cases were used to adjust the logistic regression models to predict each characteristic of post-endodontic pain using predictive factors, and the remaining 58 cases were used to test the validity of each model. The predictive models showed that the incidence of post-endodontic pain was significantly lower when the treated tooth was not a molar (P = 0.003), demonstrated periapical radiolucencies (P = 0.003), had no history of previous pain (P = 0.006) or emergency endodontic treatment (P = 0.045) and had no occlusal contact (P endodontic pain were generated and validated taking account of the interrelation of multiple concomitant clinical factors. A predictive model for triggering post-endodontic pain could not be established. © 2013 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  16. Selecting a model of supersymmetry breaking mediation

    International Nuclear Information System (INIS)

    AbdusSalam, S. S.; Allanach, B. C.; Dolan, M. J.; Feroz, F.; Hobson, M. P.

    2009-01-01

    We study the problem of selecting between different mechanisms of supersymmetry breaking in the minimal supersymmetric standard model using current data. We evaluate the Bayesian evidence of four supersymmetry breaking scenarios: mSUGRA, mGMSB, mAMSB, and moduli mediation. The results show a strong dependence on the dark matter assumption. Using the inferred cosmological relic density as an upper bound, minimal anomaly mediation is at least moderately favored over the CMSSM. Our fits also indicate that evidence for a positive sign of the μ parameter is moderate at best. We present constraints on the anomaly and gauge mediated parameter spaces and some previously unexplored aspects of the dark matter phenomenology of the moduli mediation scenario. We use sparticle searches, indirect observables and dark matter observables in the global fit and quantify robustness with respect to prior choice. We quantify how much information is contained within each constraint.

  17. Selective Oxidation of Lignin Model Compounds.

    Science.gov (United States)

    Gao, Ruili; Li, Yanding; Kim, Hoon; Mobley, Justin K; Ralph, John

    2018-05-02

    Lignin, the planet's most abundant renewable source of aromatic compounds, is difficult to degrade efficiently to welldefined aromatics. We developed a microwave-assisted catalytic Swern oxidation system using an easily prepared catalyst, MoO 2 Cl 2 (DMSO) 2 , and DMSO as the solvent and oxidant. It demonstrated high efficiency in transforming lignin model compounds containing the units and functional groups found in native lignins. The aromatic ring substituents strongly influenced the selectivity of β-ether phenolic dimer cleavage to generate sinapaldehyde and coniferaldehyde, monomers not usually produced by oxidative methods. Time-course studies on two key intermediates provided insight into the reaction pathway. Owing to the broad scope of this oxidation system and the insight gleaned with regard to its mechanism, this strategy could be adapted and applied in a general sense to the production of useful aromatic chemicals from phenolics and lignin. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Intradural approach to selective stimulation in the spinal cord for treatment of intractable pain: design principles and wireless protocol

    Science.gov (United States)

    Howard, M. A.; Utz, M.; Brennan, T. J.; Dalm, B. D.; Viljoen, S.; Jeffery, N. D.; Gillies, G. T.

    2011-08-01

    We introduce an intradural approach to spinal cord stimulation for the relief of intractable pain, and describe the biophysical rationale that underlies its design and performance requirements. The proposed device relies on wireless, inductive coupling between a pial surface implant and its epidural controller, and we present the results of benchtop experiments that demonstrate the ability to transmit and receive a frequency-modulated 1.6 MHz carrier signal between micro-coil antennae scaled to the ≈ 1 cm dimensions of the implant, at power levels of about 5 mW. Plans for materials selection, microfabrication, and other aspects of future development are presented and discussed.

  19. Manipulation and selective exercises decrease pelvic anteversion and low-back pain: a pilot study.

    Science.gov (United States)

    Barbosa, Alexandre Carvalho; Martins, Fábio Luiz Mendonça; Barbosa, Michelle Cristina Sales Almeida; Dos Santos, Rúbia Tenile

    2013-01-01

    To study the effect of a protocol involving joint manipulation and specific exercises for pelvic stability to influence proprioceptive input to the spinal tissues and to observe the effects on sensorimotor function. Seven patients with pelvic anteversion and low back pain participated in an eight-week protocol (three sessions per week/nonconsecutive days). At each session, a high-velocity, low-amplitude manipulative thrust was applied to the sacroiliac joint, followed by quadriceps eccentric and hamstring concentric contractions. The perceived pain symptoms, pelvic anteversion as determined by photogrammetry analysis, and the electromyographic activity of the rectus femoris and lateral and medial hamstrings during flexion and extension exercises were assessed before and after treatment. Non-parametric tests were used to compare the groups before and after treatment with α=0.05. Perceived pain symptoms decreased after treatment (p=0.0007). The differences in the pelvis angles (p=0.0130) suggested significant differences between the assessments, and the electromyographic activities of all the muscles during isometric voluntary contraction increased. The eight-week manipulation/exercise protocol was effective for these subjects' needs. Further research should include a greater sample size to confirm the results and to determine the lead factors of pelvic stability.

  20. Clinical Prediction Model and Tool for Assessing Risk of Persistent Pain After Breast Cancer Surgery

    DEFF Research Database (Denmark)

    Meretoja, Tuomo J; Andersen, Kenneth Geving; Bruce, Julie

    2017-01-01

    are missing. The aim was to develop a clinically applicable risk prediction tool. Methods The prediction models were developed and tested using three prospective data sets from Finland (n = 860), Denmark (n = 453), and Scotland (n = 231). Prediction models for persistent pain of moderate to severe intensity......), high body mass index ( P = .039), axillary lymph node dissection ( P = .008), and more severe acute postoperative pain intensity at the seventh postoperative day ( P = .003) predicted persistent pain in the final prediction model, which performed well in the Danish (ROC-AUC, 0.739) and Scottish (ROC......-AUC, 0.740) cohorts. At the 20% risk level, the model had 32.8% and 47.4% sensitivity and 94.4% and 82.4% specificity in the Danish and Scottish cohorts, respectively. Conclusion Our validated prediction models and an online risk calculator provide clinicians and researchers with a simple tool to screen...

  1. Estimation of a multivariate mean under model selection uncertainty

    Directory of Open Access Journals (Sweden)

    Georges Nguefack-Tsague

    2014-05-01

    Full Text Available Model selection uncertainty would occur if we selected a model based on one data set and subsequently applied it for statistical inferences, because the "correct" model would not be selected with certainty.  When the selection and inference are based on the same dataset, some additional problems arise due to the correlation of the two stages (selection and inference. In this paper model selection uncertainty is considered and model averaging is proposed. The proposal is related to the theory of James and Stein of estimating more than three parameters from independent normal observations. We suggest that a model averaging scheme taking into account the selection procedure could be more appropriate than model selection alone. Some properties of this model averaging estimator are investigated; in particular we show using Stein's results that it is a minimax estimator and can outperform Stein-type estimators.

  2. Anti-allodynic Effect of Nefopam and Morphine in a Rat Model of Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Taraneh Moini Zanjani

    2013-05-01

    Full Text Available Please cite this article as: Moini Zanjani T, Saghaei E, Ameli H, Sabetkasaei M. Anti-allodynic Effect of Nefopam and Morphine in a Rat Model of Neuropathic Pain. Novel Biomed 2013;1:16-22.Background: Neuropathic pain is a chronic pain due to a disorder in the peripheral or central nervous system with different pathophysiological mechanisms. Current treatments are not effective. Here we compared the analgesic effect of nefopam, and morphine in chronic constriction injury (CCI model of neuropathic pain.Methods: Male wistar rat (150-200g, n=8 were divided into 3 different groups: 1- Saline-treated CCI group, 2- Saline-treated sham group, and 3- Drug-treated CCI groups. In CCI model of neuropathic pain, the left sciatic nerve was exposed and 4 loose chromic gut ligatures were placed around the nerve proximal to the trifurcation. Ketamine 60mg/kg and xylazine 10 mg/kg were used for anesthesia. Nefopam (10, 20, 30mg/kg, and morphine (1, 3, 5mg/kg were injected 30 minutes before surgery and continued daily to day 14 post-ligation. Von Frey filaments for mechanical allodynia and acetone test for cold allodynia were respectively used as pain behavioral tests. Experiments were performed on day 0 (before surgery and days 1, 3, 5,7,10 and 14 post injury. Behavioral studies were performed in a quiet room between 9:00 to 11:00 AM. All experiments followed the IASP guidelines on ethical standards for investigation of experimental pain in animals.Results: Nefopam (20 and 30mg/kg blocked mechanical and cold allodynia during the experimental period, but the analgesic effects of morphine (5mg/kg lasted for 7 days.Conclusions: It seems that nefopam could effectively reduce pain behavior compared to morphine with reduced adverse effects.

  3. The empathy impulse: A multinomial model of intentional and unintentional empathy for pain.

    Science.gov (United States)

    Cameron, C Daryl; Spring, Victoria L; Todd, Andrew R

    2017-04-01

    Empathy for pain is often described as automatic. Here, we used implicit measurement and multinomial modeling to formally quantify unintentional empathy for pain: empathy that occurs despite intentions to the contrary. We developed the pain identification task (PIT), a sequential priming task wherein participants judge the painfulness of target experiences while trying to avoid the influence of prime experiences. Using multinomial modeling, we distinguished 3 component processes underlying PIT performance: empathy toward target stimuli (Intentional Empathy), empathy toward prime stimuli (Unintentional Empathy), and bias to judge target stimuli as painful (Response Bias). In Experiment 1, imposing a fast (vs. slow) response deadline uniquely reduced Intentional Empathy. In Experiment 2, inducing imagine-self (vs. imagine-other) perspective-taking uniquely increased Unintentional Empathy. In Experiment 3, Intentional and Unintentional Empathy were stronger toward targets with typical (vs. atypical) pain outcomes, suggesting that outcome information matters and that effects on the PIT are not reducible to affective priming. Typicality of pain outcomes more weakly affected task performance when target stimuli were merely categorized rather than judged for painfulness, suggesting that effects on the latter are not reducible to semantic priming. In Experiment 4, Unintentional Empathy was stronger for participants who engaged in costly donation to cancer charities, but this parameter was also high for those who donated to an objectively worse but socially more popular charity, suggesting that overly high empathy may facilitate maladaptive altruism. Theoretical and practical applications of our modeling approach for understanding variation in empathy are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  4. Hidden Markov Model for Stock Selection

    Directory of Open Access Journals (Sweden)

    Nguyet Nguyen

    2015-10-01

    Full Text Available The hidden Markov model (HMM is typically used to predict the hidden regimes of observation data. Therefore, this model finds applications in many different areas, such as speech recognition systems, computational molecular biology and financial market predictions. In this paper, we use HMM for stock selection. We first use HMM to make monthly regime predictions for the four macroeconomic variables: inflation (consumer price index (CPI, industrial production index (INDPRO, stock market index (S&P 500 and market volatility (VIX. At the end of each month, we calibrate HMM’s parameters for each of these economic variables and predict its regimes for the next month. We then look back into historical data to find the time periods for which the four variables had similar regimes with the forecasted regimes. Within those similar periods, we analyze all of the S&P 500 stocks to identify which stock characteristics have been well rewarded during the time periods and assign scores and corresponding weights for each of the stock characteristics. A composite score of each stock is calculated based on the scores and weights of its features. Based on this algorithm, we choose the 50 top ranking stocks to buy. We compare the performances of the portfolio with the benchmark index, S&P 500. With an initial investment of $100 in December 1999, over 15 years, in December 2014, our portfolio had an average gain per annum of 14.9% versus 2.3% for the S&P 500.

  5. Psyche Mission: Scientific Models and Instrument Selection

    Science.gov (United States)

    Polanskey, C. A.; Elkins-Tanton, L. T.; Bell, J. F., III; Lawrence, D. J.; Marchi, S.; Park, R. S.; Russell, C. T.; Weiss, B. P.

    2017-12-01

    NASA has chosen to explore (16) Psyche with their 14th Discovery-class mission. Psyche is a 226-km diameter metallic asteroid hypothesized to be the exposed core of a planetesimal that was stripped of its rocky mantle by multiple hit and run collisions in the early solar system. The spacecraft launch is planned for 2022 with arrival at the asteroid in 2026 for 21 months of operations. The Psyche investigation has five primary scientific objectives: A. Determine whether Psyche is a core, or if it is unmelted material. B. Determine the relative ages of regions of Psyche's surface. C. Determine whether small metal bodies incorporate the same light elements as are expected in the Earth's high-pressure core. D. Determine whether Psyche was formed under conditions more oxidizing or more reducing than Earth's core. E. Characterize Psyche's topography. The mission's task was to select the appropriate instruments to meet these objectives. However, exploring a metal world, rather than one made of ice, rock, or gas, requires development of new scientific models for Psyche to support the selection of the appropriate instruments for the payload. If Psyche is indeed a planetary core, we expect that it should have a detectable magnetic field. However, the strength of the magnetic field can vary by orders of magnitude depending on the formational history of Psyche. The implications of both the extreme low-end and the high-end predictions impact the magnetometer and mission design. For the imaging experiment, what can the team expect for the morphology of a heavily impacted metal body? Efforts are underway to further investigate the differences in crater morphology between high velocity impacts into metal and rock to be prepared to interpret the images of Psyche when they are returned. Finally, elemental composition measurements at Psyche using nuclear spectroscopy encompass a new and unexplored phase space of gamma-ray and neutron measurements. We will present some end

  6. Analgesic effects of lappaconitine in leukemia bone pain in a mouse model

    Directory of Open Access Journals (Sweden)

    Xiao-Cui Zhu

    2015-05-01

    Full Text Available Bone pain is a common and severe symptom in cancer patients. The present study employed a mouse model of leukemia bone pain by injection K562 cells into tibia of mouse to evaluate the analgesic effects of lappacontine. Our results showed that the lappaconitine treatment at day 15, 17 and 19 could effectively reduce the spontaneous pain scoring values, restore reduced degree in the inclined-plate test induced by injection of K562 cells, as well as restore paw mechanical withdrawal threshold and paw withdrawal thermal latency induced by injection of K562 cells to the normal levels. Additionally, the molecular mechanisms of lappaconitine’s analgesic effects may be related to affect the expression levels of endogenous opioid system genes (POMC, PENK and MOR, as well as apoptosis-related genes (Xiap, Smac, Bim, NF-κB and p53. Our present results indicated that lappaconitine may become a new analgesic agent for leukemia bone pain management.

  7. Downregulation of selective microRNAs in trigeminal ganglion neurons following inflammatory muscle pain

    Directory of Open Access Journals (Sweden)

    Wei Dong

    2007-06-01

    Full Text Available Abstract Active regulation of gene expression in the nervous system plays an important role in the development and/or maintenance of inflammatory pain. MicroRNA (miRNA negatively regulates gene expression via posttranscriptional or transcriptional inhibition of specific genes. To explore the possible involvement of miRNA in gene regulation during inflammatory pain, we injected complete Freund's adjuvant (CFA unilaterally into the rat masseter muscle and quantified changes in neuron-specific mature miRNAs in the trigeminal ganglion (TG. Real-time reverse-transcription polymerase chain reaction revealed significant, but differential, downregulation of mature miR-10a, -29a, -98, -99a, -124a, -134, and -183 in the ipsilateral mandibular division (V3 of the TG within 4 hr after CFA. In contrast, levels of tested miRNAs did not change significantly in the contralateral V3 or the ipsilateral ophthalmic and maxillary divisions of the TG from inflamed rats, nor in the ipsilateral V3 of saline-injected animals. The downregulated miRNAs recovered differentially to a level equal to or higher than that in naive animals. Full recovery time varied with miRNA species but was at least 4 days. Expression and downregulation of some miRNAs were further confirmed by in situ hybridization of TG neurons that innervate the inflamed muscle. Although neurons of all sizes expressed these miRNAs, their signals varied between neurons. Our results indicate that miRNA species specific to neurons are quickly regulated following inflammatory muscle pain.

  8. Tramadol can selectively manage moderate pain in children following European advice limiting codeine use.

    Science.gov (United States)

    Marzuillo, Pierluigi; Calligaris, Lorenzo; Barbi, Egidio

    2014-11-01

    The European Medicine Agency recommendations limiting codeine use in children have created a void in managing moderate pain. We review the evidence on the pharmacokinetic, pharmacodynamic and safety profile of tramadol, a possible substitute for codeine. Tramadol appears to be safe in both paediatric inpatients and outpatients. It may be appropriate to limit the current use of tramadol to monitored settings in children with risk factors for respiratory depression, subject to further safety evidence. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  9. Analgesic effect of GT-0198, a structurally novel glycine transporter 2 inhibitor, in a mouse model of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Yu Omori

    2015-03-01

    Full Text Available This study was conducted to identify the characteristic pharmacological features of GT-0198 that is phenoxymethylbenzamide derivatives. GT-0198 inhibited the function of glycine transporter 2 (GlyT2 in human GlyT2-expressing HEK293 cells and did not bind various major transporters or receptors of neurotransmitters in a competitive manner. Thus, GT-0198 is considered to be a comparatively selective GlyT2 inhibitor. Intravenous, oral, and intrathecal injections of GT-0198 decreased the pain-related response in a model of neuropathic pain with partial sciatic nerve ligation. This result suggests that GT-0198 has an analgesic effect. The analgesic effect of GT-0198 was abolished by the intrathecal injection of strychnine, a glycine receptor antagonist. Therefore, GT-0198 is considered to exhibit its analgesic effect via the activation of a glycine receptor by glycine following presynaptic GlyT2 inhibition in the spinal cord. In summary, GT-0198 is a structurally novel GlyT2 inhibitor bearing a phenoxymethylbenzamide moiety with in vivo efficacy in behavioral models of neuropathic pain.

  10. Localized Sympathectomy Reduces Mechanical Hypersensitivity by Restoring Normal Immune Homeostasis in Rat Models of Inflammatory Pain.

    Science.gov (United States)

    Xie, Wenrui; Chen, Sisi; Strong, Judith A; Li, Ai-Ling; Lewkowich, Ian P; Zhang, Jun-Ming

    2016-08-17

    Some forms of chronic pain are maintained or enhanced by activity in the sympathetic nervous system (SNS), but attempts to model this have yielded conflicting findings. The SNS has both pro- and anti-inflammatory effects on immunity, confounding the interpretation of experiments using global sympathectomy methods. We performed a "microsympathectomy" by cutting the ipsilateral gray rami where they entered the spinal nerves near the L4 and L5 DRG. This led to profound sustained reductions in pain behaviors induced by local DRG inflammation (a rat model of low back pain) and by a peripheral paw inflammation model. Effects of microsympathectomy were evident within one day, making it unlikely that blocking sympathetic sprouting in the local DRGs or hindpaw was the sole mechanism. Prior microsympathectomy greatly reduced hyperexcitability of sensory neurons induced by local DRG inflammation observed 4 d later. Microsympathectomy reduced local inflammation and macrophage density in the affected tissues (as indicated by paw swelling and histochemical staining). Cytokine profiling in locally inflamed DRG showed increases in pro-inflammatory Type 1 cytokines and decreases in the Type 2 cytokines present at baseline, changes that were mitigated by microsympathectomy. Microsympathectomy was also effective in reducing established pain behaviors in the local DRG inflammation model. We conclude that the effect of sympathetic fibers in the L4/L5 gray rami in these models is pro-inflammatory. This raises the possibility that therapeutic interventions targeting gray rami might be useful in some chronic inflammatory pain conditions. Sympathetic blockade is used for many pain conditions, but preclinical studies show both pro- and anti-nociceptive effects. The sympathetic nervous system also has both pro- and anti-inflammatory effects on immune tissues and cells. We examined effects of a very localized sympathectomy. By cutting the gray rami to the spinal nerves near the lumbar sensory

  11. Spontaneous behavioral responses in the orofacial region: A model of trigeminal pain in mouse

    Science.gov (United States)

    Romero-Reyes, Marcela; Akerman, Simon; Nguyen, Elaine; Vijjeswarapu, Alice; Hom, Betty; Dong, Hong-Wei; Charles, Andrew C.

    2012-01-01

    OBJECTIVES To develop a translational mouse model for the study and measurement of non-evoked pain in the orofacial region by establishing markers of nociceptive-specific grooming behaviors in the mouse. BACKGROUND Some of the most prevalent and debilitating conditions involve pain in the trigeminal distribution. Although there are current therapies for these pain conditions, for many patients they are far from optimal. Understanding the pathophysiology of pain disorders arising from structures innervated by the trigeminal nerve is still limited and most animal behavioral models focus on the measurement of evoked pain. In patients, spontaneous (non-evoked) pain responses provide a more accurate representation of the pain experience than do responses that are evoked by an artificial stimulus. Therefore, the development of animal models that measure spontaneous nociceptive behaviors may provide a significant translational tool for a better understanding of pain neurobiology. METHODS C57BL/6 mice received either an injection of 0.9% Saline solution or complete Freund’s adjuvant (CFA) into the right masseter muscle. Animals were video recorded and then analyzed by an observer blind to the experiment group. The duration of different facial grooming patterns performed in the area of injection were measured. After 2 hrs, mice were euthanized, perfused and the brainstem was removed. Fos protein expression in the trigeminal nucleus caudalis was quantified using immunohistochemistry to investigate nociceptive-specific neuronal activation. A separate group of animals was treated with morphine sulfate, to determine the nociceptive-specific nature of their behaviors. RESULTS We characterized and quantified 3 distinct patterns of acute grooming behaviors: fore-paw rubbing, lower lip skin/cheek rubbing against enclosure floor and hind paw scratching. These behaviors occurred with a reproducible frequency and time course, and were inhibited by the analgesic morphine. CFA

  12. Behavioral cues to expand a pain model of the cognitively impaired elderly in long-term care

    Directory of Open Access Journals (Sweden)

    Burfield AH

    2012-07-01

    Full Text Available Allison H Burfield,1 Thomas TH Wan,2 Mary Lou Sole,3 James W Cooper41School of Nursing, College of Health and Human Services, University of North Carolina-Charlotte, Charlotte, NC, 2Administration, and Medical Education, Doctoral Program in Public Affairs, College of Health and Public Affairs, 3College of Nursing, University of Central Florida, Orlando, FL, 4College of Pharmacy, University of Georgia, Athens, GA, USABackground: The purpose of this study was to determine the relationship between hypothesized pain behaviors in the elderly and a measurement model of pain derived from the Minimum Data Set-Resident Assessment Instrument (MDS-RAI 2.0 items.Methods: This work included a longitudinal cohort recruited from Medicare-certified long-term care facilities across the United States. MDS data were collected from 52,996 residents (mean age 83.7 years. Structural equation modeling was used to build a measurement model of pain to test correlations between indicators and the fit of the model by cognitive status. The model evaluates the theoretical constructs of pain to improve how pain is assessed and detected within cognitive levels.Results: Using pain frequency and intensity as the only indicators of pain, the overall prevalence of pain was 31.2%; however, analysis by cognitive status showed that 47.7% of the intact group was in pain, while only 18.2% of the severely, 29.4% of the moderately, and 39.6% of the mildly cognitively impaired groups were experiencing pain. This finding supports previous research indicating that pain is potentially under-reported in severely cognitively impaired elderly nursing home residents. With adjustments to the measurement model, a revised format containing affective, behavioral, and inferred pain indicates a better fit of the data to include these domains, as a more complete measure of the pain construct.Conclusion: Pain has a significant effect on quality of life and long-term health outcomes in nursing home

  13. Pain Intensity Moderates the Relationship Between Age and Pain Interference in Chronic Orofacial Pain Patients.

    Science.gov (United States)

    Boggero, Ian A; Geiger, Paul J; Segerstrom, Suzanne C; Carlson, Charles R

    2015-01-01

    BACKGROUND/STUDY CONTEXT: Chronic pain is associated with increased interference in daily functioning that becomes more pronounced as pain intensity increases. Based on previous research showing that older adults maintain well-being in the face of pain as well as or better than their younger counterparts, the current study examined the interaction of age and pain intensity on interference in a sample of chronic orofacial pain patients. Data were obtained from the records of 508 chronic orofacial pain patients being seen for an initial evaluation from 2008 to 2012. Collected data included age (range: 18-78) and self-reported measures of pain intensity and pain interference. Bivariate correlations and regression models were used to assess for statistical interactions. Regression analyses revealed that pain intensity positively predicted pain interference (R(2) = .35, B = 10.40, SE = 0.62, t(507) = 16.70, p theories, including socioemotional selectivity theory, which posits that as people age, they become more motivated to maximize positive emotions and minimize negative ones. The results highlight the importance of studying the mechanisms older adults use to successfully cope with pain.

  14. Pharmacodynamic Modelling of Placebo and Buprenorphine Effects on Event-Related Potentials in Experimental Pain

    DEFF Research Database (Denmark)

    Juul, Rasmus V; Foster, David J R; Upton, Richard N

    2014-01-01

    The purpose of the study was to investigate placebo and buprenorphine effects on event-related potentials (ERPs) in experimental pain and the potential benefit of population pharmacodynamic modelling in data analysis. Nineteen healthy volunteers received transdermal placebo and buprenorphine...... in a cross-over study. Drug plasma concentrations and ERPs after electrical stimulation at the median nerve with intensity adjusted to pain detection threshold were recorded until 144 hrs after administration. Placebo and concentration-effect models were fitted to data using non-linear mixed......, pharmacodynamic modelling was successfully implemented to allow for placebo and variability correction in ERP of experimental pain. Improved outcome of ERP studies can be expected if variation between subjects and study occasions can be identified and described....

  15. Systemic synergism between codeine and morphine in three pain models in mice.

    Science.gov (United States)

    Miranda, Hugo F; Noriega, Viviana; Zepeda, Ramiro J; Sierralta, Fernando; Prieto, Juan C

    2013-01-01

    The combination of two analgesic agents offers advantages in pain treatment. Codeine and morphine analgesia is due to activation of opioid receptor subtypes. This study, performed in mice using isobolographic analysis, evaluated the type of interaction in intraperitoneal (ip) or intrathecal (it) coadministration of codeine and morphine, in three nociceptive behavioral models. Intrathecal morphine resulted to be 7.5 times more potent than ip morphine in the writhing test, 55.6 times in the tail flick test and 1.7 times in phase II of the orofacial formalin test; however, in phase I of the same test ip was 1.2 times more potent than it morphine. Intrathecal codeine resulted being 3.4 times more potent than ip codeine in the writhing test, 1.6 times in the tail flick test, 2.5 times in phase I and 6.7 times in phase II of the orofacial formalin test. Opioid coadministration had a synergistic effect in the acute tonic pain (acetic acid writhing test), acute phasic pain (tail flick test) and inflammatory pain (orofacial formalin test). The interaction index ranged between 0.284 (writhing ip) and 0.440 (orofacial formalin phase II ip). This synergy may relate to the different pathways of pain transmission and to the different intracellular signal transduction. The present findings also raise the possibility of potential clinical advantages in combining opioids in pain management.

  16. Nerve Regenerative Effects of GABA-B Ligands in a Model of Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Valerio Magnaghi

    2014-01-01

    Full Text Available Neuropathic pain arises as a direct consequence of a lesion or disease affecting the peripheral somatosensory system. It may be associated with allodynia and increased pain sensitivity. Few studies correlated neuropathic pain with nerve morphology and myelin proteins expression. Our aim was to test if neuropathic pain is related to nerve degeneration, speculating whether the modulation of peripheral GABA-B receptors may promote nerve regeneration and decrease neuropathic pain. We used the partial sciatic ligation- (PSL- induced neuropathic model. The biochemical, morphological, and behavioural outcomes of sciatic nerve were analysed following GABA-B ligands treatments. Simultaneous 7-days coadministration of baclofen (10 mg/kg and CGP56433 (3 mg/kg alters tactile hypersensitivity. Concomitantly, specific changes of peripheral nerve morphology, nerve structure, and myelin proteins (P0 and PMP22 expression were observed. Nerve macrophage recruitment decreased and step coordination was improved. The PSL-induced changes in nociception correlate with altered nerve morphology and myelin protein expression. Peripheral synergic effects, via GABA-B receptor activation, promote nerve regeneration and likely ameliorate neuropathic pain.

  17. Maternal Smoking During Pregnancy Is Associated With Offspring's Musculoskeletal Pain in Adolescence: Structural Equation Modeling.

    Science.gov (United States)

    Määttä, Anni-Julia; Paananen, Markus; Marttila, Riikka; Auvinen, Juha; Miettunen, Jouko; Karppinen, Jaro

    2017-07-01

    Smoking and behavioral problems are related to musculoskeletal (MS) pain in adolescence. Maternal smoking during pregnancy (MSDP) is associated with offspring's behavioral problems but its relation to MS pain in adolescence is unknown. Our purpose was to investigate whether there is an association between MSDP, the number of pain sites in adolescence, and the factors that potentially mediate this relationship. We evaluated the association of MSDP with offspring's MS pain at 16 years among participants of the Northern Finland Birth Cohort 1986 (n = 6436, 3360 girls, 68% of all births) using Chi-square test and independent samples t test. We used structural equation modeling to assess the mediating factors stratified by gender. MSDP was frequent (22%) associating with paternal smoking (p adolescents whose mothers had smoked during pregnancy than among those whose mothers were nonsmokers (p = .002 boys, p = .012 girls). The association between MSDP and MS pain at 16 years was mediated by externalizing problems at 8 years (p adolescence, and the association was mediated by offspring's externalizing problems during childhood and early adolescence. This study indicates that MSDP increases the risk of MS pain in adolescence and the effect is mediated by externalizing problems. Our results add to the evidence on harmfulness of MSDP for offspring, and can be used as additional information in interventions aiming to influence MSDP. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Modeling the onset and offset of dental pain relief by ibuprofen.

    Science.gov (United States)

    Li, Hanbin; Mandema, Jaap; Wada, Russell; Jayawardena, Shyamalie; Desjardins, Paul; Doyle, Geraldine; Kellstein, David

    2012-01-01

    Onset and offset of dental pain relief by ibuprofen following third molar extraction were modeled in a randomized, double-blind, placebo-controlled, parallel-group, 8-hour study of patients receiving either a novel effervescent ibuprofen tablet (400 mg; N = 30), standard ibuprofen tablets (Nurofen(®) 2 × 200 mg; N = 22), or placebo (N = 37). An Emax model was fit to pain relief scores. Linear hazard models were used to analyze the time to first perceptible relief (TFPR), the time to meaningful pain relief (TMPR), and time to remedication (REMD). Nomograms were created to correlate TFPR, TMPR, and REMD with different ibuprofen pharmacokinetic profiles. Effervescent ibuprofen was absorbed rapidly with 95% completion within 15 minutes. Maximum pain relief score by ibuprofen was 1.8 units greater than placebo, with an EC50 (effect-site) for ibuprofen concentration of 10.2 µg·mL(-1). The likelihood to achieve TFPR and TMPR was doubled for every 10 µg·mL(-1) increase in ibuprofen plasma concentration. REMD risk decreased 40-fold as the categorical pain relief score increased from 0 to 3. Rapid absorption of ibuprofen effervescent resulted in an earlier TFPR and TMPR, and a lower REMD rate than standard ibuprofen. The nomograms may be useful in predicting the onset and offset of new faster acting ibuprofen formulations, based on pharmacokinetic profiles.

  19. A new Russell model for selecting suppliers

    NARCIS (Netherlands)

    Azadi, Majid; Shabani, Amir; Farzipoor Saen, Reza

    2014-01-01

    Recently, supply chain management (SCM) has been considered by many researchers. Supplier evaluation and selection plays a significant role in establishing an effective SCM. One of the techniques that can be used for selecting suppliers is data envelopment analysis (DEA). In some situations, to

  20. The Ultrasonographic Findings of Trigger Points of Myofascial Pain Syndrome in a Rabbit Model

    International Nuclear Information System (INIS)

    Moon, Kyung Mi; Park, Seog Hee; Lee, Sang Heon; Kim, Joo Hyun; Kim, Han Kyum

    2005-01-01

    Myofascial pain syndrome (MPS) is a common cause of musculoskeletal pain. Myofascial trigger points (MTrPs) have been repeatedly described by numerous authors. However, there have been few studies in which their existence and behavior was supported and their location confirmed. The purpose of this study was to determine whether diagnostic ultrasonography is an objective diagnostic tool which is able to significantly identify or detect the soft tissue changes in the region of clinically identified active MTrPs by using a rabbit experimental model. Ten MPS model rabbits were used in this study. We made an MPS animal model by causing the rabbits to overuse one leg for 3 weeks by cutting the contralateral L4 spinal nerve root. We compared the ultrasonographic findings of the taut band at pre-OP with those at post-OP during the consecutive three week period. To find the taut bands of the muscle, after skin exposure, the muscles were gently rubbed or pinched with the thumb and index finger on the two opposing surfaces of the muscle across the direction of the fibers. Then, the muscle was held in the same way, but with a 5-8 MHz stick probe being used in place of the thumb. After the palpation of various muscles, we selected the hardest and largest myofascial trigger nodule, in order to observe the ultrasonographic and power Doppler findings of the MPS. The size, shape, echogenecity and vascularity of the MTrPs were observed. The analysis of the results of the ultrasonography revealed that all MTrPs have a hyperechoic area. The mean thickness of the hyperechoic lesion in the biceps was 0.96±0.14 cm in the MPS site (at pre-OP?), and 0.49±0.12 cm at post-OP 3weeks (p < 0.01). The hyperechoic lesions in all of the studied biceps femoris of the rabbits were observed by high resolution ultrasonography. No definitively decreased vascularity was observed within the hyperechoic area by power Doppler imaging. Until now, there has been no objective method for the diagnosis of MPS

  1. The Development of a Technology-Based Hierarchy to Assess Chronic Low Back Pain and Pain-Related Anxiety From a Fear-Avoidance Model.

    Science.gov (United States)

    Springer, Kristen S; George, Steven Z; Robinson, Michael E

    2016-08-01

    Previous studies have not examined the assessment of chronic low back pain (CLBP) and pain-related anxiety from a fear avoidance model through the use of motion-capture software and virtual human technologies. The aim of this study was to develop and assess the psychometric properties of an interactive, technologically based hierarchy that can be used to assess patients with pain and pain-related anxiety. We enrolled 30 licensed physical therapists and 30 participants with CLBP. Participants rated 21 video clips of a 3-D animated character (avatar) engaging in activities that are typically feared by patients with CLBP. The results of the study indicate that physical therapists found the virtual hierarchy clips acceptable and depicted realistic patient experiences. Most participants with CLBP reported at least 1 video clip as being sufficiently anxiety-provoking for use clinically. Therefore, this study suggests a hierarchy of fears can be created out of 21 virtual patient video clips paving the way for future clinical use in patients with CLBP. This report describes the development of a computer-based virtual patient system for the assessment of back pain-related fear and anxiety. Results show that people with back pain as well as physical therapists found the avatar to be realistic, and the depictions of behavior anxiety- and fear-provoking. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  2. Nursing patients with acute chest pain: practice guided by the Prince Edward Island conceptual model for nursing.

    Science.gov (United States)

    Blanchard, Janelle F; Murnaghan, Donna A

    2010-01-01

    Current research suggests that pain is a relatively common phenomenon with 60-90% of patients presenting to emergency departments reporting pain (e.g., chest pain, trauma, extremity fractures and migraine headache) that require treatment [Hogan, S.L., 2005. Patient satisfaction with pain management in the emergency department. Advanced Emergency Nursing Journal 27(4), 284-294]. This article explores the use of conceptual theoretical empirical (C-T-E) framework to guide a senior nursing student in a case study of patient with chest pain. The Middle Range Theory of Pain described by Good [Good, M., 1998. A middle-range theory of acute pain management: use in research. Nursing Outlook 46(3), 120-124] and Melzack's [Melzack, R., 1987. The short-form McGill pain questionnaire. Pain, 30, 191-197] short form McGill pain questionnaire were applied along with the Prince Edward Island conceptual model (PEICM) for nursing. Results indicate that the nursing student increased her ability to work in partnership, assess relevant and specific information, and identify a number of strategies to help the patient achieve pain control by using a complement of pharmacological and non-pharmacological interventions. Moreover, the C-T-E approach provided an organized and systematic theoretical approach for the nursing student to assist a patient in pain control.

  3. An integrated model for supplier selection process

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    In today's highly competitive manufacturing environment, the supplier selection process becomes one of crucial activities in supply chain management. In order to select the best supplier(s) it is not only necessary to continuously tracking and benchmarking performance of suppliers but also to make a tradeoff between tangible and intangible factors some of which may conflict. In this paper an integration of case-based reasoning (CBR), analytical network process (ANP) and linear programming (LP) is proposed to solve the supplier selection problem.

  4. Comparison of Repeated Measurement Design and Mixed Models in Evaluation of the Entonox Effect on Labor Pain

    Directory of Open Access Journals (Sweden)

    Nasim Karimi

    2017-01-01

    Full Text Available Background & objectives: In many medical studies, the response variable is measured repeatedly over time to evaluate the treatment effect that is known as longitudinal study. The analysis method for this type of data is repeated measures ANOVA that uses only one correlation structure and the results are not valid with inappropriate correlation structure. To avoid this problem, a convenient alternative is mixed models. So, the aim of this study was to compare of mixed and repeated measurement models for examination of the Entonox effect on the labor pain. Methods: This experimental study was designed to compare the effect of Entonox and oxygen inhalation on pain relief between two groups. Data were analyzed using repeated measurement and mixed models with different correlation structures. Selection and comparison of proper correlation structures performed using Akaike information criterion, Bayesian information criterion and restricted log-likelihood. Data were analyzed using SPSS-22. Results: Results of our study showed that all variables containing analgesia methods, labor duration of the first and second stages, and time were significant in these tests. In mixed model, heterogeneous first-order autoregressive, first-order autoregressive, heterogeneous Toeplitz and unstructured correlation structures were recognized as the best structures. Also, all variables were significant in these structures. Unstructured variance covariance matrix was recognized as the worst structure and labor duration of the first and second stages was not significant in this structure. Conclusions: This study showed that the Entonox inhalation has a significant effect on pain relief in primiparous and it is confirmed by all of the models.

  5. Electroacupuncture Alleviates Pain Responses and Inflammation in a Rat Model of Acute Gout Arthritis

    Directory of Open Access Journals (Sweden)

    Wenxin Chai

    2018-01-01

    Full Text Available Acute gout arthritis is one of the most painful inflammatory conditions. Treatments for gout pain are limited to colchicine, nonsteroidal anti-inflammatory drugs, and corticosteroids, which oftentimes result in severe adverse effects. Electroacupuncture (EA has been proved to be effective in relieving many inflammatory pain conditions with few side effects. Here, we aim to investigate the therapeutic potentials of EA on pain and inflammation of a rat model of acute gout arthritis and underlying mechanisms. We found that 2/100 Hz EA produced the most robust analgesic effect on mechanical hyperalgesia of acute gout arthritis rat model compared with 2 and 100 Hz. EA produced similar analgesic effect compared with indomethacin. 2/100 Hz EA also significantly alleviates the ongoing pain behavior, thermal hyperalgesia, and ankle edema. Locally applied μ and κ-opioid receptor antagonists but not adenosine A1 receptor antagonist significantly abolished the analgesic effect of EA. Locally applied μ and κ-opioid receptor agonists produced significant antiallodynia on acute gout arthritis rats, mimicking EA. Furthermore, 2/100 Hz EA upregulated β-endorphin expression in inflamed ankle skin tissue. Our results demonstrated, for the first time, that EA can be used for relieving acute gout arthritis with effect dependent on peripheral opioid system and comparable with the one obtained with indomethacin.

  6. Bone hyperalgesia after mechanical impact stimulation: a human experimental pain model.

    Science.gov (United States)

    Finocchietti, Sara; Graven-Nielsen, Thomas; Arendt-Nielsen, Lars

    2014-12-01

    Hyperalgesia in different musculoskeletal structures including bones is a major clinical problem. An experimental bone hyperalgesia model was developed in the present study. Hyperalgesia was induced by three different weights impacted on the shinbone in 16 healthy male and female subjects. The mechanical impact pain threshold (IPT) was measured as the height from which three weights (165, 330, and 660 g) should be dropped to elicit pain at the shinbone. Temporal summation of pain to repeated impact stimuli was assessed. All these stimuli caused bone hyperalgesia. The pressure pain threshold (PPT) was assessed by a computerized pressure algometer using two different probes (1.0 and 0.5 cm(2)). All parameters were recorded before (0), 24, 72, and 96 h after the initial stimulations. The IPTs were lowest 24 h after hyperalgesia induction for all three weights and the effect lasted up to 72 h (p pain and hyperalgesia model may provide the basis for studying this fundamental mechanism of bone-related hyperalgesia and be used for profiling compounds developed for this target.

  7. Orofacial neuropathic pain mouse model induced by Trigeminal Inflammatory Compression (TIC of the infraorbital nerve

    Directory of Open Access Journals (Sweden)

    Ma Fei

    2012-12-01

    Full Text Available Abstract Background Trigeminal neuropathic pain attacks can be excruciating for patients, even after being lightly touched. Although there are rodent trigeminal nerve research models to study orofacial pain, few models have been applied to studies in mice. A mouse trigeminal inflammatory compression (TIC model is introduced here which successfully and reliably promotes vibrissal whisker pad hypersensitivity. Results The chronic orofacial neuropathic pain model is induced after surgical placement of chromic gut suture in the infraorbital nerve fissure in the maxillary bone. Slight compression and chemical effects of the chromic gut suture on the portion of the infraorbital nerve contacted cause mild nerve trauma. Nerve edema is observed in the contacting infraorbital nerve bundle as well as macrophage infiltration in the trigeminal ganglia. Centrally in the spinal trigeminal nucleus, increased immunoreactivity for an activated microglial marker is evident (OX42, postoperative day 70. Mechanical thresholds of the affected whisker pad are significantly decreased on day 3 after chromic gut suture placement, persisting at least 10 weeks. The mechanical allodynia is reversed by suppression of microglial activation. Cold allodynia was detected at 4 weeks. Conclusions A simple, effective, and reproducible chronic mouse model mimicking clinical orofacial neuropathic pain (Type 2 is induced by placing chromic gut suture between the infraorbital nerve and the maxillary bone. The method produces mild inflammatory compression with significant continuous mechanical allodynia persisting at least 10 weeks and cold allodynia measureable at 4 weeks.

  8. Dealing with selection bias in educational transition models

    DEFF Research Database (Denmark)

    Holm, Anders; Jæger, Mads Meier

    2011-01-01

    This paper proposes the bivariate probit selection model (BPSM) as an alternative to the traditional Mare model for analyzing educational transitions. The BPSM accounts for selection on unobserved variables by allowing for unobserved variables which affect the probability of making educational tr...... account for selection on unobserved variables and high-quality data are both required in order to estimate credible educational transition models.......This paper proposes the bivariate probit selection model (BPSM) as an alternative to the traditional Mare model for analyzing educational transitions. The BPSM accounts for selection on unobserved variables by allowing for unobserved variables which affect the probability of making educational...... transitions to be correlated across transitions. We use simulated and real data to illustrate how the BPSM improves on the traditional Mare model in terms of correcting for selection bias and providing credible estimates of the effect of family background on educational success. We conclude that models which...

  9. A Bayesian random effects discrete-choice model for resource selection: Population-level selection inference

    Science.gov (United States)

    Thomas, D.L.; Johnson, D.; Griffith, B.

    2006-01-01

    Modeling the probability of use of land units characterized by discrete and continuous measures, we present a Bayesian random-effects model to assess resource selection. This model provides simultaneous estimation of both individual- and population-level selection. Deviance information criterion (DIC), a Bayesian alternative to AIC that is sample-size specific, is used for model selection. Aerial radiolocation data from 76 adult female caribou (Rangifer tarandus) and calf pairs during 1 year on an Arctic coastal plain calving ground were used to illustrate models and assess population-level selection of landscape attributes, as well as individual heterogeneity of selection. Landscape attributes included elevation, NDVI (a measure of forage greenness), and land cover-type classification. Results from the first of a 2-stage model-selection procedure indicated that there is substantial heterogeneity among cow-calf pairs with respect to selection of the landscape attributes. In the second stage, selection of models with heterogeneity included indicated that at the population-level, NDVI and land cover class were significant attributes for selection of different landscapes by pairs on the calving ground. Population-level selection coefficients indicate that the pairs generally select landscapes with higher levels of NDVI, but the relationship is quadratic. The highest rate of selection occurs at values of NDVI less than the maximum observed. Results for land cover-class selections coefficients indicate that wet sedge, moist sedge, herbaceous tussock tundra, and shrub tussock tundra are selected at approximately the same rate, while alpine and sparsely vegetated landscapes are selected at a lower rate. Furthermore, the variability in selection by individual caribou for moist sedge and sparsely vegetated landscapes is large relative to the variability in selection of other land cover types. The example analysis illustrates that, while sometimes computationally intense, a

  10. Antinociceptive effects of topical mepivacaine in a rat model of HIV-associated peripheral neuropathic pain

    Directory of Open Access Journals (Sweden)

    Sagen J

    2016-06-01

    Full Text Available Jacqueline Sagen, Daniel A Castellanos,† Aldric T Hama The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA †Daniel A Castellanos passed away on April 14, 2010 Background: A consequence of HIV infection is sensory neuropathy, a debilitating condition that degrades the quality of life of HIV patients. Furthermore, life-extending antiretroviral treatment may exacerbate HIV sensory neuropathy. Analgesics that relieve other neuropathic pains show little or no efficacy in ameliorating HIV sensory neuropathy. Thus, there is a need for analgesics for people with this particular pain. While lidocaine is used in the management of painful peripheral neuropathies, another local anesthetic mepivacaine, with a potentially improved bioavailability, could be utilized for the management of HIV neuropathic pain.Methods: The efficacy of topical anesthetics was evaluated in a preclinical rodent model of painful peripheral neuropathy induced by epineural administration of the HIV envelope protein gp120 delivered using saturated oxidized cellulose implanted around the sciatic nerve. Beginning at 2 weeks following gp120 administration, the effects of local anesthetics topically applied via gauze pads were tested on heat and mechanical hyperalgesia in the hind paw. Rats were tested using several concentrations of mepivacaine or lidocaine during the following 2 weeks.Results: By 2 weeks following epineural gp120 implantation, the ipsilateral hind paw developed significant hypersensitivity to noxious pressure and heat hyperalgesia. A short-lasting, concentration-dependent amelioration of pressure and heat hyperalgesia was observed following topical application of mepivacaine to the ipsilateral plantar hind paw. By contrast, topical lidocaine ameliorated heat hyperalgesia in a concentration-dependent manner but not pressure hyperalgesia. Equipotent concentrations of mepivacaine and lidocaine applied topically to the

  11. Frutalin reduces acute and neuropathic nociceptive behaviours in rodent models of orofacial pain.

    Science.gov (United States)

    Damasceno, Marina B M V; de Melo Júnior, José de Maria A; Santos, Sacha Aubrey A R; Melo, Luana T M; Leite, Laura Hévila I; Vieira-Neto, Antonio E; Moreira, Renato de A; Monteiro-Moreira, Ana Cristina de O; Campos, Adriana R

    2016-08-25

    Orofacial pain is a highly prevalent clinical condition, yet difficult to control effectively with available drugs. Much attention is currently focused on the anti-inflammatory and antinociceptive properties of lectins. The purpose of this study was to evaluate the antinociceptive effect of frutalin (FTL) using rodent models of inflammatory and neuropathic orofacial pain. Acute pain was induced by formalin, glutamate or capsaicin (orofacial model) and hypertonic saline (corneal model). In one experiment, animals were pretreated with l-NAME and naloxone to investigate the mechanism of antinociception. The involvement of the lectin domain in the antinociceptive effect of FTL was verified by allowing the lectin to bind to its specific ligand. In another experiment, animals pretreated with FTL or saline were submitted to the temporomandibular joint formalin test. In yet another, animals were submitted to infraorbital nerve transection to induce chronic pain, followed by induction of thermal hypersensitivity using acetone. Motor activity was evaluated with the rotarod test. A molecular docking was performed using the TRPV1 channel. Pretreatment with FTL significantly reduced nociceptive behaviour associated with acute and neuropathic pain, especially at 0.5 mg/kg. Antinociception was effectively inhibited by l-NAME and d-galactose. In line with in vivo experiments, docking studies indicated that FTL may interact with TRPV1. Our results confirm the potential pharmacological relevance of FTL as an inhibitor of orofacial nociception in acute and chronic pain mediated by TRPA1, TRPV1 and TRPM8 receptor. Copyright © 2016. Published by Elsevier Ireland Ltd.

  12. Analgesic effect of the neuropeptide cortistatin in murine models of arthritic inflammatory pain.

    Science.gov (United States)

    Morell, Maria; Souza-Moreira, Luciana; Caro, Marta; O'Valle, Francisco; Forte-Lago, Irene; de Lecea, Luis; Gonzalez-Rey, Elena; Delgado, Mario

    2013-05-01

    To investigate the role of the antiinflammatory neuropeptide cortistatin in chronic pain evoked by joint inflammation. Thermal and mechanical hyperalgesia was evoked in mouse knee joints by intraplantar injection of tumor necrosis factor α and intraarticular infusion of Freund's complete adjuvant, and the analgesic effects of cortistatin, administered centrally, peripherally, and systemically, were assessed. In addition, the effects of cortistatin on the production of nociceptive peptides and the activation of pain signaling were assayed in dorsal root ganglion cultures and in inflammatory pain models. The role of endogenous cortistatin in pain sensitization and perpetuation of chronic inflammatory states was evaluated in cortistatin-deficient mice. Finally, the effect of noxious/inflammatory stimuli in the production of cortistatin by the peripheral nociceptive system was assayed in vitro and in vivo. Expression of cortistatin was observed in peptidergic nociceptors of the peripheral nociceptive system, and endogenous cortistatin was found to participate in the tuning of pain sensitization, especially in pathologic inflammatory conditions. Results showed that cortistatin acted both peripherally and centrally to reduce the tactile allodynia and heat hyperalgesia evoked by arthritis and peripheral tissue inflammation in mice, via mechanisms that were independent of its antiinflammatory action. These mechanisms involved direct action on nociceptive neurons and regulation of central sensitization. The analgesic effects of cortistatin in murine arthritic pain were linked to binding of the neuropeptide to somatostatin and ghrelin receptors, activation of the G protein subunit Gαi , impairment of ERK signaling, and decreased production of calcitonin gene-related peptide in primary nociceptors. These findings indicate that cortistatin is an antiinflammatory factor with potent analgesic effects that may offer a new approach to pain therapy in pathologic inflammatory

  13. Modelling the PKPD of oxycodone in experimental pain - impact of opioid receptor polymorphisms

    DEFF Research Database (Denmark)

    Olsen, Rasmus; Foster, David J R; Upton, Richard N

    2016-01-01

    BACKGROUND: Polymorphisms in the opioid receptor genes may affect the pharmacodynamics (PD) of oxycodone and be part of the reason behind the diversity in clinical response. The aim of the analysis was to model the exposure-response profile of oxycodone for three different pain variables and search...... for genetic covariates. Model simulations were used to predict how population and effect-size impact the power to detect clinical significant SNPs. METHOD: The population pharmacokinetic-pharmacodynamic (PKPD) model of oral single-dosed oxycodone was based on pooled data from three published studies...... in healthy volunteers. Pain tolerance data from muscle pressure (n=36), visceral pressure (n=54) and skin pinch (n=34) were included. Genetic associations with 18 opioid-receptor SNPs were explored using a stepwise covariate approach. Model simulations were performed using the estimated model parameters...

  14. Social redistribution of pain and money.

    Science.gov (United States)

    Story, Giles W; Vlaev, Ivo; Metcalfe, Robert D; Crockett, Molly J; Kurth-Nelson, Zeb; Darzi, Ara; Dolan, Raymond J

    2015-10-30

    People show empathic responses to others' pain, yet how they choose to apportion pain between themselves and others is not well understood. To address this question, we observed choices to reapportion social allocations of painful stimuli and, for comparison, also elicited equivalent choices with money. On average people sought to equalize allocations of both pain and money, in a manner which indicated that inequality carried an increasing marginal cost. Preferences for pain were more altruistic than for money, with several participants assigning more than half the pain to themselves. Our data indicate that, given concern for others, the fundamental principle of diminishing marginal utility motivates spreading costs across individuals. A model incorporating this assumption outperformed existing models of social utility in explaining the data. By implementing selected allocations for real, we also found that while inequality per se did not influence pain perception, altruistic behavior had an intrinsic analgesic effect for the recipient.

  15. Impaired behavioural pain responses in hph-1 mice with inherited deficiency in GTP cyclohydrolase 1 in models of inflammatory pain

    DEFF Research Database (Denmark)

    Nasser, A.; Bjerrum, Ole Jannik; Heegaard, A.-M.

    2013-01-01

    following intraplantar injection of CFA, formalin and capsaicin; whereas decreased basal level of GTP-CH1 activity had no influence in naïve hph-1 mice on acute mechanical and heat pain thresholds. Moreover, the hph-1 mice showed no signs of motor impairment or dystonia-like symptoms......Background: GTP cyclohydrolase 1 (GTP-CH1), the rate-limiting enzyme in the synthesis of tetrahydrobiopterin (BH4), encoded by the GCH1 gene, has been implicated in the development and maintenance of inflammatory pain in rats. In humans, homozygous carriers of a " pain-protective" (PP) haplotype...... of the GCH1 gene have been identified exhibiting lower pain sensitivity, but only following pain sensitisation. Ex vivo, the PP GCH1 haplotype is associated with decreased induction of GCH1 after stimulation, whereas the baseline BH4 production is not affected. Contrary, loss of function mutations in the GCH...

  16. Uncertainty associated with selected environmental transport models

    International Nuclear Information System (INIS)

    Little, C.A.; Miller, C.W.

    1979-11-01

    A description is given of the capabilities of several models to predict accurately either pollutant concentrations in environmental media or radiological dose to human organs. The models are discussed in three sections: aquatic or surface water transport models, atmospheric transport models, and terrestrial and aquatic food chain models. Using data published primarily by model users, model predictions are compared to observations. This procedure is infeasible for food chain models and, therefore, the uncertainty embodied in the models input parameters, rather than the model output, is estimated. Aquatic transport models are divided into one-dimensional, longitudinal-vertical, and longitudinal-horizontal models. Several conclusions were made about the ability of the Gaussian plume atmospheric dispersion model to predict accurately downwind air concentrations from releases under several sets of conditions. It is concluded that no validation study has been conducted to test the predictions of either aquatic or terrestrial food chain models. Using the aquatic pathway from water to fish to an adult for 137 Cs as an example, a 95% one-tailed confidence limit interval for the predicted exposure is calculated by examining the distributions of the input parameters. Such an interval is found to be 16 times the value of the median exposure. A similar one-tailed limit for the air-grass-cow-milk-thyroid for 131 I and infants was 5.6 times the median dose. Of the three model types discussed in this report,the aquatic transport models appear to do the best job of predicting observed concentrations. However, this conclusion is based on many fewer aquatic validation data than were availaable for atmospheric model validation

  17. Effect of tramadol on pain-related behaviors and bladder overactivity in rodent cystitis models.

    Science.gov (United States)

    Oyama, Tatsuya; Homan, Takashi; Kyotani, Junko; Oka, Michiko

    2012-02-15

    Tramadol is a widely used analgesic that stimulates the μ opioid receptor and inhibits serotonin and noradrenalin reuptake. There have been studies on the analgesic effects of tramadol based on the tail-flick test, the formalin test, and the induction of allodynia by sciatic-nerve ligation. However, the effects of tramadol on behaviors related to bladder pain and bladder overactivity induced by cystitis have not been reported. To investigate the usefulness of tramadol for patients with cystitis, we investigated these effects of tramadol in rodent cystitis models. Intraperitoneal injection of cyclophosphamide caused bladder-specific inflammation and increases in pain-related behaviors, the number of voids and bladder weight in mice. Tramadol suppressed the cyclophosphamide-induced pain-related behaviors but did not affect the number of voids or the bladder weight. During continuous-infusion cystometrograms in anesthetized rats, cyclophosphamide shortened the intercontraction interval, indicating bladder overactivity. Tramadol significantly prolonged the intercontraction interval, and the effect was partially blocked by the opioid antagonist naloxone. This finding indicates that μ opioid receptors may be involved in the action of tramadol. In conclusion, tramadol ameliorated cyclophosphamide-induced bladder-pain-related behaviors and bladder overactivity in rodents. These findings suggest that tramadol might be a treatment option for cystitis-induced bladder pain and bladder overactivity. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Comparative Analysis of Pain Behaviours in Humanized Mouse Models of Sickle Cell Anemia.

    Directory of Open Access Journals (Sweden)

    Jianxun Lei

    Full Text Available Pain is a hallmark feature of sickle cell anemia (SCA but management of chronic as well as acute pain remains a major challenge. Mouse models of SCA are essential to examine the mechanisms of pain and develop novel therapeutics. To facilitate this effort, we compared humanized homozygous BERK and Townes sickle mice for the effect of gender and age on pain behaviors. Similar to previously characterized BERK sickle mice, Townes sickle mice show more mechanical, thermal, and deep tissue hyperalgesia with increasing age. Female Townes sickle mice demonstrate more hyperalgesia compared to males similar to that reported for BERK mice and patients with SCA. Mechanical, thermal and deep tissue hyperalgesia increased further after hypoxia/reoxygenation (H/R treatment in Townes sickle mice. Together, these data show BERK sickle mice exhibit a significantly greater degree of hyperalgesia for all behavioral measures as compared to gender- and age-matched Townes sickle mice. However, the genetically distinct "knock-in" strategy of human α and β transgene insertion in Townes mice as compared to BERK mice, may provide relative advantage for further genetic manipulations to examine specific mechanisms of pain.

  19. Antinociceptive effect of intrathecal microencapsulated human pheochromocytoma cell in a rat model of bone cancer pain.

    Science.gov (United States)

    Li, Xiao; Li, Guoqi; Wu, Shaoling; Zhang, Baiyu; Wan, Qing; Yu, Ding; Zhou, Ruijun; Ma, Chao

    2014-07-08

    Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l) lysine-alginate (APA) microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat model of bone cancer pain, and this effect was blocked by opioid antagonist naloxone and alpha 2-adrenergic antagonist rauwolscine. Neurochemical changes of cerebrospinal fluid are in accordance with the analgesic responses. Taken together, these data support that human pheochromocytoma cell implant-induced antinociception was mediated by met-enkephalin and norepinephrine secreted from the cell implants and acting at spinal receptors. Spinal implantation of microencapsulated human pheochromocytoma cells may provide an alternative approach for the therapy of chronic intractable pain.

  20. Antinociceptive Effect of Intrathecal Microencapsulated Human Pheochromocytoma Cell in a Rat Model of Bone Cancer Pain

    Directory of Open Access Journals (Sweden)

    Xiao Li

    2014-07-01

    Full Text Available Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l lysine-alginate (APA microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat model of bone cancer pain, and this effect was blocked by opioid antagonist naloxone and alpha 2-adrenergic antagonist rauwolscine. Neurochemical changes of cerebrospinal fluid are in accordance with the analgesic responses. Taken together, these data support that human pheochromocytoma cell implant-induced antinociception was mediated by met-enkephalin and norepinephrine secreted from the cell implants and acting at spinal receptors. Spinal implantation of microencapsulated human pheochromocytoma cells may provide an alternative approach for the therapy of chronic intractable pain.

  1. Using zero-inflated models to explain chronic illness, pain, and complementary and alternative medicine use.

    Science.gov (United States)

    Ayers, Stephanie L; Kronenfeld, Jennie J

    2011-07-01

    To extend knowledge of complementary and alternative medicine (CAM) use by understanding how poor health influences both trying CAM and number of CAM types used. Using the 2002 National Health Interview Survey's Supplemental Section, zero-inflated models were employed to examine CAM use across 5 domains. Results indicate that level of pain is the only consistent predictor of both the likelihood of trying CAM and how many types of CAM are used. Pain increased the odds ratio and number of CAM types used across all domains. Findings, however, were mixed for health status and chronic conditions. Only prayer was associated with higher odds ratio (OR=1.705, PCAM types used for chronic illnesses (OR=1.024, PCAM use behaviors. Pain is the only consistent predictor of both trying CAM and the number of CAM types used. Chronic illness is only consistently influential for prayer.

  2. Quality Quandaries- Time Series Model Selection and Parsimony

    DEFF Research Database (Denmark)

    Bisgaard, Søren; Kulahci, Murat

    2009-01-01

    Some of the issues involved in selecting adequate models for time series data are discussed using an example concerning the number of users of an Internet server. The process of selecting an appropriate model is subjective and requires experience and judgment. The authors believe an important...... consideration in model selection should be parameter parsimony. They favor the use of parsimonious mixed ARMA models, noting that research has shown that a model building strategy that considers only autoregressive representations will lead to non-parsimonious models and to loss of forecasting accuracy....

  3. Attentional Avoidance is Associated with Increased Pain Sensitivity in Patients with Chronic Posttraumatic Pain and Comorbid Posttraumatic Stress

    DEFF Research Database (Denmark)

    Harvold, Mathea; MacLeod, Colin; Vaegter, Henrik Bjarke

    2018-01-01

    posttraumatic pain patients is unknown. This study investigated AB for linguistic pain- and trauma-related stimuli, and clinical and thermal sensitivity in patients with chronic posttraumatic pain with and without PTSD. METHODS: Thirty-four patients with chronic posttraumatic cervical pain performed the visual......OBJECTIVES: Posttraumatic stress disorder (PTSD) is common in chronic posttraumatic pain. Theoretical models suggest that attentional biases (AB) contribute to the development and maintenance of chronic pain and PTSD, however, the influence of AB on clinical and heat pain sensitivity in chronic...... attentional probe task assessing patterns of selective attentional responding to trauma cues and to pain cues. The task used short (500 ms) and long (1250 ms) stimulus exposure durations to ensure sensitivity to both the orienting and maintenance of attention. Heat pain threshold (HPT) was assessed at the non-painful...

  4. Long-term follow-up after mesh removal and selective neurectomy for persistent inguinal postherniorrhaphy pain

    DEFF Research Database (Denmark)

    Bischoff, J M; Enghuus, Casper Nørskov; Werner, M U

    2013-01-01

    PURPOSE: Persistent inguinal pain, influencing daily activities, is seen in about 5 % of patients following inguinal herniorrhaphy. Surgical treatment of patients with persistent postherniorrhaphy pain has been associated with pain relief and improvement in functional status. However, the detailed...... and functional ability when comparing preoperative and postoperative assessments. RESULTS: Pain intensities (average, maximum, and during activity) were significantly lower at all time points during follow-up compared to preoperative values (p ...

  5. Stage-dependent analgesia of electro-acupuncture in a mouse model of cutaneous cancer pain.

    Science.gov (United States)

    Mao-Ying, Qi-Liang; Cui, Ke-Mi; Liu, Qiong; Dong, Zhi-Qiang; Wang, Wei; Wang, Jun; Sha, Hong; Wu, Gen-Cheng; Wang, Yan-Qing

    2006-11-01

    Acupuncture is one of the most effective alternative medical treatments in pain management with the advantages of simple application, low cost and minimal side effects. However its scientific evidence and laws of action are not very clear in cancer pain relieving. The aim of this study was to examine the immediate and therapeutic anti-hyperalgesic effect of electro-acupuncture (EA) on a mouse model of cutaneous cancer pain. B16-BL6 melanoma cells were inoculated into the plantar region of unilateral hind paw and the thermal hyperalgesia was measured by using radiant heat test and hot plate test. C57BL/6 mice showed moderate and marked hyperalgesia during days 8-12 and from day 14 after the orthotopic inoculation of B16-BL6 melanoma cells into the hind paw. Single EA on day 8 after inoculation showed significant analgesic effect immediately after the treatment, the analgesic effect reached its maximum within 15-30min and declined to its minimum at 50min after EA treatment. Single EA treatment on day 20 showed no significant analgesic effect; Repeated EA treatments (started from day 8, once every other day) showed therapeutic analgesic effect, while it showed no therapeutic effect when started from day 16, a relatively late stage of this cancer pain model. The results demonstrated that EA had anti-hyperalgesic effect on early stage of cutaneous cancer pain but not on late stage. These results indicated a tight correlation of EA anti-hyperalgesic effects with the time window of cancer pain.

  6. Preventive Treatment with Ketamine Attenuates the Ischaemia-Reperfusion Response in a Chronic Postischaemia Pain Model

    Directory of Open Access Journals (Sweden)

    Suryamin Liman

    2015-01-01

    Full Text Available Ischemia and inflammation may be pathophysiological mechanisms of complex regional pain syndrome (CRPS. Ketamine has proposed anti-inflammatory effects and has been used for treating CRPS. This study aimed to evaluate anti-inflammatory and analgesic effects of ketamine after ischaemia-reperfusion injury in a chronic postischaemia pain (CPIP model of CRPS-I. Using this model, ischemia was induced in the hindlimbs of male Sprague-Dawley rats. Ketamine, methylprednisolone, or saline was administered immediately after reperfusion. Physical effects, (oedema, temperature, and mechanical and cold allodynia in the bilateral hindpaws, were assessed from 48 hours after reperfusion. Fewer (56% rats in the ketamine group developed CPIP at the 48th hour after reperfusion (nonsignificant. Ketamine treated rats showed a significantly lower temperature in the ischaemic hindpaw compared to saline (P<0.01 and methylprednisolone (P<0.05 groups. Mechanical and cold allodynia were significantly lower in the ischaemic side in the ketamine group (P<0.05. Proinflammatory cytokines TNF-α and IL-2 were significantly lower at the 48th hour after reperfusion in ketamine and methylprednisolone groups, compared to saline (all P<0.05. In conclusion, immediate administration of ketamine after an ischaemia-reperfusion injury can alleviate pain and inflammation in the CPIP model and has potential to treat postischaemic pain.

  7. A mouse model for chronic pain-induced increase in ethanol consumption.

    Science.gov (United States)

    Butler, Ryan K; Knapp, Darin J; Ulici, Veronica; Longobardi, Lara; Loeser, Richard F; Breese, George R

    2017-03-01

    Chronic pain conditions are often comorbid with alcohol abuse. "Self-medication" with alcohol introduces a host of problems associated with the abuse of alcohol which over time has the potential of exacerbating the painful condition. Despite the prevalence of chronic pain being associated with alcohol abuse, rodent models which mimic the comorbid conditions are lacking. In this study, we model osteoarthritis (OA) in C57BL/6J mice by surgically destabilizing the medial meniscus (DMM). Sham-operated mice served as controls. Thirteen weeks after surgery, DMM but not sham-operated mice exhibited pronounced incapacitance of the surgically manipulated hind limb compared with the nonsurgically manipulated hind limb. At this time, the mice were exposed to the 2-bottle ethanol choice, beginning with 2.5% with a gradual increasing to 20%. Compared with sham controls, DMM mice consumed more EtOH and preferred EtOH over water at the 20% EtOH concentration. Histological analysis verified that the DMM mice exhibited significant damage to the articular cartilage and osteophyte growth compared with sham controls and these measures of the severity of OA correlated with the amount of ethanol intake. Thus, the combination of the DMM model of OA with the enhanced two-bottle ethanol choice is a potential preclinical approach in mice by which the basis of the comorbid association of alcohol abuse and chronic pain conditions can be explored.

  8. Dynamic changes to the endocannabinoid system in models of chronic pain

    Science.gov (United States)

    Rani Sagar, Devi; Burston, James J.; Woodhams, Stephen G.; Chapman, Victoria

    2012-01-01

    The analgesic effects of cannabinoid ligands, mediated by CB1 receptors are well established. However, the side-effect profile of CB1 receptor ligands has necessitated the search for alternative cannabinoid-based approaches to analgesia. Herein, we review the current literature describing the impact of chronic pain states on the key components of the endocannabinoid receptor system, in terms of regionally restricted changes in receptor expression and levels of key metabolic enzymes that influence the local levels of the endocannabinoids. The evidence that spinal CB2 receptors have a novel role in the modulation of nociceptive processing in models of neuropathic pain, as well as in models of cancer pain and arthritis is discussed. Recent advances in our understanding of the spinal location of the key enzymes that regulate the levels of the endocannabinoid 2-AG are discussed alongside the outcomes of recent studies of the effects of inhibiting the catabolism of 2-AG in models of pain. The complexities of the enzymes capable of metabolizing both anandamide (AEA) and 2-AG have become increasingly apparent. More recently, it has come to light that some of the metabolites of AEA and 2-AG generated by cyclooxygenase-2, lipoxygenases and cytochrome P450 are biologically active and can either exacerbate or inhibit nociceptive signalling. PMID:23108548

  9. Cost-effectiveness modeling for neuropathic pain treatments: investigating the relative importance of parameters using an open-source model.

    Science.gov (United States)

    Hirst, Matthew; Bending, Matthew W; Baio, Gianluca; Yesufu-Udechuku, Amina; Dunlop, William C N

    2018-06-08

    The study objective was to develop an open-source replicate of a cost-effectiveness model developed by National Institute for Health and Care (NICE) in order to explore uncertainties in health economic modeling of novel pharmacological neuropathic pain treatments. The NICE model, consisting of a decision tree with branches for discrete levels of pain relief and adverse event (AE) severities, was replicated using R and used to compare a hypothetical neuropathic pain drug to pregabalin. Model parameters were sourced from NICE's clinical guidelines and associated with probability distributions to account for underlying uncertainty. A simulation-based scenario analysis was conducted to assess how uncertainty in efficacy and AEs affected the net monetary benefit (NMB) for the hypothetical treatment at a cost-effectiveness threshold of £20,000 per QALY. Relative to pregabalin, an increase in efficacy was associated with greater NMB than an improvement in tolerability. A greater NMB was observed when efficacy was marginally higher than that of pregabalin while maintaining the same level of AEs than when efficacy was equivalent to pregabalin but with a more substantial reduction in AEs. In the latter scenario, the NMB was only positive at a low cost-effectiveness threshold. The replicate model shares the limitations described in the NICE guidelines. There is a lack of support in scientific literature for the assumption that increased efficacy is associated with a greater reduction in tolerability. The replicate model also included a single comparator, unlike the NICE model. Pain relief is a stronger driver of NMB than tolerability at a cost-effectiveness threshold of £20,000 per QALY. Health technology assessment decisions which are influenced by NICE's model may reward efficacy gains even if they are associated with more severe AEs. This contrasts with recommendations from clinical guidelines for neuropathic pain which place more equal weighting on improvements in

  10. Cognitive bias in back pain patients attending osteopathy: testing the enmeshment model in reference to future thinking.

    Science.gov (United States)

    Read, Jessica; Pincus, Tamar

    2004-12-01

    Depressive symptoms are common in chronic pain. Previous research has found differences in information-processing biases in depressed pain patients and depressed people without pain. The schema enmeshment model of pain (SEMP) has been proposed to explain chronic pain patients' information-processing biases. Negative future thinking is common in depression but has not been explored in relation to chronic pain and information-processing models. The study aimed to test the SEMP with reference to future thinking. An information-processing paradigm compared endorsement and recall bias between depressed and non-depressed chronic low back pain patients and control participants. Twenty-five depressed and 35 non-depressed chronic low back pain patients and 25 control participants (student osteopaths) were recruited from an osteopathy practice. Participants were asked to endorse positive and negative ill-health, depression-related, and neutral (control) adjectives, encoded in reference to either current or future time-frame. Incidental recall of the adjectives was then tested. While the expected hypothesis of a recall bias by depressed pain patients towards ill-health stimuli in the current condition was confirmed, the recall bias was not present in the future condition. Additionally, patterns of endorsement and recall bias differed. Results extend understanding of future thinking in chronic pain within the context of the SEMP.

  11. Pain genes.

    Directory of Open Access Journals (Sweden)

    Tom Foulkes

    2008-07-01

    Full Text Available Pain, which afflicts up to 20% of the population at any time, provides both a massive therapeutic challenge and a route to understanding mechanisms in the nervous system. Specialised sensory neurons (nociceptors signal the existence of tissue damage to the central nervous system (CNS, where pain is represented in a complex matrix involving many CNS structures. Genetic approaches to investigating pain pathways using model organisms have identified the molecular nature of the transducers, regulatory mechanisms involved in changing neuronal activity, as well as the critical role of immune system cells in driving pain pathways. In man, mapping of human pain mutants as well as twin studies and association studies of altered pain behaviour have identified important regulators of the pain system. In turn, new drug targets for chronic pain treatment have been validated in transgenic mouse studies. Thus, genetic studies of pain pathways have complemented the traditional neuroscience approaches of electrophysiology and pharmacology to give us fresh insights into the molecular basis of pain perception.

  12. Antinociceptive activity of Buddleja globosa (matico) in several models of pain.

    Science.gov (United States)

    Backhouse, Nadine; Delporte, Carla; Apablaza, Cecia; Farías, Mariela; Goïty, León; Arrau, Sylvia; Negrete, Rosa; Castro, Consuelo; Miranda, Hugo

    2008-09-02

    Leaf extracts of Buddleja globosa (Buddlejaceae) are used in Chilean folk medicine for wound healing. The anti-inflammatory (topic and per os), analgesic (per os) effects and the antioxidant activity of Buddleja globosa were for the first time reported by us. Assess the antinociceptive activity of the methanol sequential and global extracts using complementary chemical and thermal models of pain, characterize pharmacologically the antinociception induced, evaluate seasonal influence to support Buddleja globosa medicinal use. Global methanol, sequential methanol and ethanol (leaves collected in autumn and summer) extracts were evaluated for oral and topic analgesia in tail flick, formalin and writhing models, verbascoside and 7-O-luteolin glucoside were assayed in tail flick and writhing. Ibuprofen was used as reference. For characterization of induced antinociception, naltrexone, naltrindole, tropisetron, nor-binaltorphimine, prazosin, yohimbine, atropine, and N-nitro-l-arginine methyl ester were used as antagonists and inhibitors drugs. Seasonal influence was observed since autumn extract resulted less active. Extracts showed a dose-dependent antinociceptive activity in all assays, the highest effects were obtained for the formalin and writhing test. Verbascoside was more active than ibuprofen in the writhing test (67.6% and 50.0% at equimolar doses) and showed similar effects in the tail flick (topic and oral) near 25% at equivalent doses - ED25 or EC25 - to ibuprofen. Luteolin 7-O-glucoside was slightly more active in the tail flick test and nearly half active than verbascoside in the writhing assay. Effectiveness was higher for the sequential than for global alcoholic extracts, and can be increased by selective blocking of opioid receptors. Global methanol extract seems modulated only by naltrexone. Analgesic effect of Buddleja globosa is here demonstrated validating its use in traditional medicine. Season influence is important to be considered.

  13. Topical combinations aimed at treating microvascular dysfunction reduce allodynia in rat models of CRPS-I and neuropathic pain.

    Science.gov (United States)

    Ragavendran, J Vaigunda; Laferrière, André; Xiao, Wen Hua; Bennett, Gary J; Padi, Satyanarayana S V; Zhang, Ji; Coderre, Terence J

    2013-01-01

    Growing evidence indicates that various chronic pain syndromes exhibit tissue abnormalities caused by microvasculature dysfunction in the blood vessels of skin, muscle, or nerve. We tested whether topical combinations aimed at improving microvascular function would relieve allodynia in animal models of complex regional pain syndrome type I (CRPS-I) and neuropathic pain. We hypothesized that topical administration of either α(2)-adrenergic (α(2)A) receptor agonists or nitric oxide (NO) donors combined with either phosphodiesterase (PDE) or phosphatidic acid (PA) inhibitors would effectively reduce allodynia in these animal models of chronic pain. Single topical agents produced significant dose-dependent antiallodynic effects in rats with chronic postischemia pain, and the antiallodynic dose-response curves of PDE and PA inhibitors were shifted 2.5- to 10-fold leftward when combined with nonanalgesic doses of α(2)A receptor agonists or NO donors. Topical combinations also produced significant antiallodynic effects in rats with sciatic nerve injury, painful diabetic neuropathy, and chemotherapy-induced painful neuropathy. These effects were shown to be produced by a local action, lasted up to 6 hours after acute treatment, and did not produce tolerance over 15 days of chronic daily dosing. The present results support the hypothesis that allodynia in animal models of CRPS-I and neuropathic pain is effectively relieved by topical combinations of α(2)A or NO donors with PDE or PA inhibitors. This suggests that topical treatments aimed at improving microvascular function may reduce allodynia in patients with CRPS-I and neuropathic pain. This article presents the synergistic antiallodynic effects of combinations of α(2)A or NO donors with PDE or PA inhibitors in animal models of CRPS-I and neuropathic pain. The data suggest that effective clinical treatment of chronic neuropathic pain may be achieved by therapies that alleviate microvascular dysfunction in affected

  14. Synthesis and Analgesic Effects of μ-TRTX-Hhn1b on Models of Inflammatory and Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Yu Liu

    2014-08-01

    Full Text Available μ-TRTX-Hhn1b (HNTX-IV is a 35-amino acid peptide isolated from the venom of the spider, Ornithoctonus hainana. It inhibits voltage-gated sodium channel Nav1.7, which has been considered as a therapeutic target for pain. The goal of the present study is to elucidate the analgesic effects of synthetic μ-TRTX-Hhn1b on animal models of pain. The peptide was first synthesized and then successfully refolded/oxidized. The synthetic peptide had the same inhibitory effect on human Nav1.7 current transiently expressed in HEK 293 cells as the native toxin. Furthermore, the analgesic potentials of the synthetic peptide were examined on models of inflammatory pain and neuropathic pain. μ-TRTX-Hhn1b produced an efficient reversal of acute nociceptive pain in the abdominal constriction model, and significantly reduced the pain scores over the 40-min period in the formalin model. The efficiency of μ-TRTX-Hhn1b on both models was equivalent to that of morphine. In the spinal nerve model, the reversal effect of μ-TRTX-Hhn1b on allodynia was longer and higher than mexiletine. These results demonstrated that μ-TRTX-Hhn1b efficiently alleviated acute inflammatory pain and chronic neuropathic pain in animals and provided an attractive template for further clinical analgesic drug design.

  15. The Locus Coeruleus–Norepinephrine System Mediates Empathy for Pain through Selective Up-Regulation of P2X3 Receptor in Dorsal Root Ganglia in Rats

    Directory of Open Access Journals (Sweden)

    Yun-Fei Lü

    2017-09-01

    Full Text Available Empathy for pain (vicariously felt pain, an ability to feel, recognize, understand and share the painful emotions of others, has been gradually accepted to be a common identity in both humans and rodents, however, the underlying neural and molecular mechanisms are largely unknown. Recently, we have developed a rat model of empathy for pain in which pain can be transferred from a cagemate demonstrator (CD in pain to a naïve cagemate observer (CO after 30 min dyadic priming social interaction. The naïve CO rats display both mechanical pain hypersensitivity (hyperalgesia and enhanced spinal nociception. Chemical lesions of bilateral medial prefrontal cortex (mPFC abolish the empathic pain response completely, suggesting existence of a top-down facilitation system in production of empathy for pain. However, the social transfer of pain was not observed in non-cagemate observer (NCO after dyadic social interaction with a non-cagemate demonstrator (NCD in pain. Here we showed that dyadic social interaction with a painful CD resulted in elevation of circulating norepinephrine (NE and increased neuronal activity in the locus coeruleus (LC in the CO rats. Meanwhile, CO rats also had over-expression of P2X3, but not TRPV1, in the dorsal root ganglia (DRG. Chemical lesion of the LC-NE neurons by systemic DSP-4 and pharmacological inhibition of central synaptic release of NE by clonidine completely abolished increase in circulating NE and P2X3 receptor expression, as well as the sympathetically-maintained development of empathic mechanical hyperalgesia. However, in the NCO rats, neither the LC-NE neuronal activity nor the P2X3 receptor expression was altered after dyadic social interaction with a painful NCD although the circulating corticosterone and NE were elevated. Finally, in the periphery, both P2X3 receptor and α1 adrenergic receptor were found to be involved in the development of empathic mechanical hyperalgesia. Taken together with our previous

  16. Selection of Hydrological Model for Waterborne Release

    International Nuclear Information System (INIS)

    Blanchard, A.

    1999-01-01

    This evaluation will aid in determining the potential impacts of liquid releases to downstream populations on the Savannah River. The purpose of this report is to evaluate the two available models and determine the appropriate model for use in following waterborne release analyses. Additionally, this report will document the Design Basis and Beyond Design Basis accidents to be used in the future study

  17. Development Of A Multivariate Prognostic Model For Pain And Activity Limitation In People With Low Back Disorders Receiving Physiotherapy.

    Science.gov (United States)

    Ford, Jon J; Richards BPhysio, Matt C; Surkitt BPhysio, Luke D; Chan BPhysio, Alexander Yp; Slater, Sarah L; Taylor, Nicholas F; Hahne, Andrew J

    2018-05-28

    To identify predictors for back pain, leg pain and activity limitation in patients with early persistent low back disorders. Prospective inception cohort study; Setting: primary care private physiotherapy clinics in Melbourne, Australia. 300 adults aged 18-65 years with low back and/or referred leg pain of ≥6-weeks and ≤6-months duration. Not applicable. Numerical rating scales for back pain and leg pain as well as the Oswestry Disability Scale. Prognostic factors included sociodemographics, treatment related factors, subjective/physical examination, subgrouping factors and standardized questionnaires. Univariate analysis followed by generalized estimating equations were used to develop a multivariate prognostic model for back pain, leg pain and activity limitation. Fifty-eight prognostic factors progressed to the multivariate stage where 15 showed significant (pduration, high multifidus tone, clinically determined inflammation, higher back and leg pain severity, lower lifting capacity, lower work capacity and higher pain drawing percentage coverage). The preliminary model identifying predictors of low back disorders explained up to 37% of the variance in outcome. This study evaluated a comprehensive range of prognostic factors reflective of both the biomedical and psychosocial domains of low back disorders. The preliminary multivariate model requires further validation before being considered for clinical use. Copyright © 2018. Published by Elsevier Inc.

  18. Attenuation of TRPV1 and TRPV4 Expression and Function in Mouse Inflammatory Pain Models Using Electroacupuncture

    Directory of Open Access Journals (Sweden)

    Wei-Hsin Chen

    2012-01-01

    Full Text Available Although pain is a major human affliction, our understanding of pain mechanisms is limited. TRPV1 (transient receptor potential vanilloid subtype 1 and TRPV4 are two crucial receptors involved in inflammatory pain, but their roles in EA- (electroacupuncture- mediated analgesia are unknown. We injected mice with carrageenan (carra or a complete Freund’s adjuvant (CFA to model inflammatory pain and investigated the analgesic effect of EA using animal behavior tests, immunostaining, Western blotting, and a whole-cell recording technique. The inflammatory pain model mice developed both mechanical and thermal hyperalgesia. Notably, EA at the ST36 acupoint reversed these phenomena, indicating its curative effect in inflammatory pain. The protein levels of TRPV1 and TRPV4 in DRG (dorsal root ganglion neurons were both increased at day 4 after the initiation of inflammatory pain and were attenuated by EA, as demonstrated by immunostaining and Western blot analysis. We verified DRG electrophysiological properties to confirm that EA ameliorated peripheral nerve hyperexcitation. Our results indicated that the AP (action potential threshold, rise time, and fall time, and the percentage and amplitude of TRPV1 and TRPV4 were altered by EA, indicating that EA has an antinociceptive role in inflammatory pain. Our results demonstrate a novel role for EA in regulating TRPV1 and TRPV4 protein expression and nerve excitation in mouse inflammatory pain models.

  19. Application of Bayesian Model Selection for Metal Yield Models using ALEGRA and Dakota.

    Energy Technology Data Exchange (ETDEWEB)

    Portone, Teresa; Niederhaus, John Henry; Sanchez, Jason James; Swiler, Laura Painton

    2018-02-01

    This report introduces the concepts of Bayesian model selection, which provides a systematic means of calibrating and selecting an optimal model to represent a phenomenon. This has many potential applications, including for comparing constitutive models. The ideas described herein are applied to a model selection problem between different yield models for hardened steel under extreme loading conditions.

  20. Melatonin Alters the Mechanical and Thermal Hyperalgesia Induced by Orofacial Pain Model in Rats.

    Science.gov (United States)

    Scarabelot, Vanessa Leal; Medeiros, Liciane Fernandes; de Oliveira, Carla; Adachi, Lauren Naomi Spezia; de Macedo, Isabel Cristina; Cioato, Stefania Giotti; de Freitas, Joice S; de Souza, Andressa; Quevedo, Alexandre; Caumo, Wolnei; Torres, Iraci Lucena da Silva

    2016-10-01

    Melatonin is a neuroendocrine hormone that presents a wide range of physiological functions including regulating circadian rhythms and sleep, enhancing immune function, sleep improvement, and antioxidant effects. In addition, melatonin has received special attention in pain treatment since it is effective and presents few adverse effects. In this study, we evaluated the effect of acute dose of melatonin upon hyperalgesia induced by complete Freund's adjuvant in a chronic orofacial pain model in Sprague-Dawley rats. Nociceptive behavior was assessed by facial Von Frey and the hot plate tests at baseline and thereafter 30, 60, and 120 min, 24 h, and 7 days after melatonin treatment. We demonstrated that acute melatonin administration alters mechanical and thermal hyperalgesia induced by an orofacial pain model (TMD), highlighting that the melatonin effect upon mechanical hyperalgesia remained until 7 days after its administration. Besides, we observed specific tissue profiles of neuroimmunomodulators linked to pain conditions and/or melatonin effect (brain-derived neurotrophic factor, nerve growth factor, and interleukins 6 and 10) in the brainstem levels, and its effects were state-dependent of the baseline of these animals.

  1. Effect of pain chronification and chronic pain on an endogenous pain modulation circuit in rats.

    Science.gov (United States)

    Miranda, J; Lamana, S M S; Dias, E V; Athie, M; Parada, C A; Tambeli, C H

    2015-02-12

    We tested the hypothesis that chronic pain development (pain chronification) and ongoing chronic pain (chronic pain) reduce the activity and induce plastic changes in an endogenous analgesia circuit, the ascending nociceptive control. An important mechanism mediating this form of endogenous analgesia, referred to as capsaicin-induced analgesia, is its dependence on nucleus accumbens μ-opioid receptor mechanisms. Therefore, we also investigated whether pain chronification and chronic pain alter the requirement for nucleus accumbens μ-opioid receptor mechanisms in capsaicin-induced analgesia. We used an animal model of pain chronification in which daily subcutaneous prostaglandin E2 (PGE2) injections into the rat's hind paw for 14 days, referred to as the induction period of persistent hyperalgesia, induce a long-lasting state of nociceptor sensitization referred to as the maintenance period of persistent hyperalgesia, that lasts for at least 30 days following the cessation of the PGE2 treatment. The nociceptor hypersensitivity was measured by the shortening of the time interval for the animal to respond to a mechanical stimulation of the hind paw. We found a significant reduction in the duration of capsaicin-induced analgesia during the induction and maintenance period of persistent mechanical hyperalgesia. Intra-accumbens injection of the μ-opioid receptor selective antagonist Cys(2),Tyr(3),Orn(5),Pen(7)amide (CTOP) 10 min before the subcutaneous injection of capsaicin into the rat's fore paw blocked capsaicin-induced analgesia. Taken together, these findings indicate that pain chronification and chronic pain reduce the duration of capsaicin-induced analgesia, without affecting its dependence on nucleus accumbens μ-opioid receptor mechanisms. The attenuation of endogenous analgesia during pain chronification and chronic pain suggests that endogenous pain circuits play an important role in the development and maintenance of chronic pain. Copyright © 2014 IBRO

  2. Astrophysical Model Selection in Gravitational Wave Astronomy

    Science.gov (United States)

    Adams, Matthew R.; Cornish, Neil J.; Littenberg, Tyson B.

    2012-01-01

    Theoretical studies in gravitational wave astronomy have mostly focused on the information that can be extracted from individual detections, such as the mass of a binary system and its location in space. Here we consider how the information from multiple detections can be used to constrain astrophysical population models. This seemingly simple problem is made challenging by the high dimensionality and high degree of correlation in the parameter spaces that describe the signals, and by the complexity of the astrophysical models, which can also depend on a large number of parameters, some of which might not be directly constrained by the observations. We present a method for constraining population models using a hierarchical Bayesian modeling approach which simultaneously infers the source parameters and population model and provides the joint probability distributions for both. We illustrate this approach by considering the constraints that can be placed on population models for galactic white dwarf binaries using a future space-based gravitational wave detector. We find that a mission that is able to resolve approximately 5000 of the shortest period binaries will be able to constrain the population model parameters, including the chirp mass distribution and a characteristic galaxy disk radius to within a few percent. This compares favorably to existing bounds, where electromagnetic observations of stars in the galaxy constrain disk radii to within 20%.

  3. Diagnostic utility of selective nerve root blocks in the diagnosis of lumbosacral radicular pain: systematic review and update of current evidence.

    Science.gov (United States)

    Datta, Sukdeb; Manchikanti, Laxmaiah; Falco, Frank J E; Calodney, Aaron K; Atluri, Sairam; Benyamin, Ramsin M; Buenaventura, Ricardo M; Cohen, Steven P

    2013-04-01

      Lumbosacral selective nerve root blocks and/ or transforaminal epidural injections are used for diagnosis and treatment of different disorders causing low back and lower extremity pain. A clear consensus on the use of selective nerve root injections as a diagnostic tool does not currently exist. Additionally, the validity of this procedure as a diagnostic tool is not clear. To evaluate and update the accuracy of selective nerve root injections in diagnosing lumbar spinal disorders. A systematic review of selective nerve root blocks for the diagnosis of low back and lower extremity pain. Methodological quality assessment of included studies was performed using the Quality Appraisal of Reliability Studies (QAREL) checklist. Only diagnostic accuracy studies meeting at least 50% of the designated inclusion criteria were utilized for analysis. Studies scoring less than 50% are presented descriptively and analyzed critically. The level of evidence was classified as good, fair, or limited or poor based on the quality of evidence grading scale developed by the United States Preventive Services Task Force (USPSTF). Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to September 2012, and manual searches of the bibliographies of known primary and review articles. In this review, we evaluated studies in which controlled local anesthetic blocks were performed using at least 50% pain relief as the reference standard. There is limited evidence for the accuracy of selective nerve root injections as a diagnostic tool for lumbosacral disorders. There is limited evidence for their use in the preoperative evaluation of patients with negative or inconclusive imaging studies. The limitations of this systematic review include a paucity of literature, variations in technique, and variable criterion standards for the diagnosis of lumbar radicular pain. There is limited evidence for selective nerve root injections as a diagnostic tool in

  4. A model for selecting leadership styles.

    Science.gov (United States)

    Perkins, V J

    1992-01-01

    Occupational therapists lead a variety of groups during their professional activities. Such groups include therapy groups, treatment teams and management meetings. Therefore it is important for each therapist to understand theories of leadership and be able to select the most effective style for him or herself in specific situations. This paper presents a review of leadership theory and research as well as therapeutic groups. It then integrates these areas to assist students and new therapists in identifying a style that is effective for a particular group.

  5. Blocking spinal CCR2 with AZ889 reversed hyperalgesia in a model of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Vaillancourt François

    2010-12-01

    Full Text Available Abstract Background The CCR2/CCL2 system has been identified as a regulator in the pathogenesis of neuropathy-induced pain. However, CCR2 target validation in analgesia and the mechanism underlying antinociception produced by CCR2 antagonists remains poorly understood. In this study, in vitro and in vivo pharmacological approaches using a novel CCR2 antagonist, AZ889, strengthened the hypothesis of a CCR2 contribution to neuropathic pain and provided confidence over the possibilities to treat neuropathic pain with CCR2 antagonists. Results We provided evidence that dorsal root ganglia (DRG cells harvested from CCI animals responded to stimulation by CCL2 with a concentration-dependent calcium rise involving PLC-dependent internal stores. This response was associated with an increase in evoked neuronal action potentials suggesting these cells were sensitive to CCR2 signalling. Importantly, treatment with AZ889 abolished CCL2-evoked excitation confirming that this activity is CCR2-mediated. Neuronal and non-neuronal cells in the spinal cord were also excited by CCL2 applications indicating an important role of spinal CCR2 in neuropathic pain. We next showed that in vivo spinal intrathecal injection of AZ889 produced dose-dependent analgesia in CCI rats. Additionally, application of AZ889 to the exposed spinal cord inhibited evoked neuronal activity and confirmed that CCR2-mediated analgesia involved predominantly the spinal cord. Furthermore, AZ889 abolished NMDA-dependent wind-up of spinal withdrawal reflex pathway in neuropathic animals giving insight into the spinal mechanism underlying the analgesic properties of AZ889. Conclusions Overall, this study strengthens the important role of CCR2 in neuropathic pain and highlights feasibility that interfering on this mechanism at the spinal level with a selective antagonist can provide new analgesia opportunities.

  6. On Optimal Input Design and Model Selection for Communication Channels

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yanyan [ORNL; Djouadi, Seddik M [ORNL; Olama, Mohammed M [ORNL

    2013-01-01

    In this paper, the optimal model (structure) selection and input design which minimize the worst case identification error for communication systems are provided. The problem is formulated using metric complexity theory in a Hilbert space setting. It is pointed out that model selection and input design can be handled independently. Kolmogorov n-width is used to characterize the representation error introduced by model selection, while Gel fand and Time n-widths are used to represent the inherent error introduced by input design. After the model is selected, an optimal input which minimizes the worst case identification error is shown to exist. In particular, it is proven that the optimal model for reducing the representation error is a Finite Impulse Response (FIR) model, and the optimal input is an impulse at the start of the observation interval. FIR models are widely popular in communication systems, such as, in Orthogonal Frequency Division Multiplexing (OFDM) systems.

  7. "The empathy impulse: A multinomial model of intentional and unintentional empathy for pain": Correction.

    Science.gov (United States)

    2018-04-01

    Reports an error in "The empathy impulse: A multinomial model of intentional and unintentional empathy for pain" by C. Daryl Cameron, Victoria L. Spring and Andrew R. Todd ( Emotion , 2017[Apr], Vol 17[3], 395-411). In this article, there was an error in the calculation of some of the effect sizes. The w effect size was manually computed incorrectly. The incorrect number of total observations was used, which affected the final effect size estimates. This computing error does not change any of the results or interpretations about model fit based on the G² statistic, or about significant differences across conditions in process parameters. Therefore, it does not change any of the hypothesis tests or conclusions. The w statistics for overall model fit should be .02 instead of .04 in Study 1, .01 instead of .02 in Study 2, .01 instead of .03 for the OIT in Study 3 (model fit for the PIT remains the same: .00), and .02 instead of .03 in Study 4. The corrected tables can be seen here: http://osf.io/qebku at the Open Science Framework site for the article. (The following abstract of the original article appeared in record 2017-01641-001.) Empathy for pain is often described as automatic. Here, we used implicit measurement and multinomial modeling to formally quantify unintentional empathy for pain: empathy that occurs despite intentions to the contrary. We developed the pain identification task (PIT), a sequential priming task wherein participants judge the painfulness of target experiences while trying to avoid the influence of prime experiences. Using multinomial modeling, we distinguished 3 component processes underlying PIT performance: empathy toward target stimuli (Intentional Empathy), empathy toward prime stimuli (Unintentional Empathy), and bias to judge target stimuli as painful (Response Bias). In Experiment 1, imposing a fast (vs. slow) response deadline uniquely reduced Intentional Empathy. In Experiment 2, inducing imagine-self (vs. imagine

  8. Anti-allodynic effects of N-demethylsinomenine, an active metabolite of sinomenine, in a mouse model of postoperative pain.

    Science.gov (United States)

    Ou, Yuntao; Su, Man; Ling, Yong; Wei, Qianqian; Pan, Fei; Li, Jiejia; Li, Jun-Xu; Zhu, Qing

    2018-03-15

    Sinomenine, a major bioactive ingredient isolated from traditional Chinese medicine Sinomenium acutum, has been reported to have analgesic effects in various pain animal models. N-demethylsinomenine, the N-demethylated product of sinomenine, has been identified to be the major metabolite of sinomenine and is also a natural component extracted from Sinomenium acutum. This study examined the anti-allodynic effects of N-demethylsinomenine in a mouse model of postoperative pain. A significant and sustained mechanical allodynia that lasted for 4 days was induced by making a surgical incision on the right hind paw in mice. Acute treatment with N-demethylsinomenine (10-40 mg/kg, s.c.) relieved the mechanical allodynia in a dose-dependent manner. Although there was no difference in maximal analgesic effect between N-demethylsinomenine (40 mg/kg, s.c.) and sinomenine (40 mg/kg, s.c.), the onset of action of N-demethylsinomenine was quicker than sinomenine. Repeated treatment with N-demethylsinomenine (10-40 mg/kg/day, s.c.) also dose-dependently exerted sustained antinociception against postoperative allodynia and did not produce analgesic tolerance and carry-over effect. The anti-allodynia induced by N-demethylsinomenine (40 mg/kg, s.c.) was attenuated by bicuculline, a selective γ-aminobutyric acid type A (GABA A ) receptor antagonist. In addition, the doses of N-demethylsinomenine used here did not alter the locomotor activity in mice. Our findings demonstrated that N-demethylsinomenine exerts behaviorally-specific anti-allodynia against postoperative allodynia mediated through the GABA A receptors, suggesting it may be a useful novel pharmacotherapy for the control of postoperative pain. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. The effect of exercise frequency on neuropathic pain and pain-related cellular reactions in the spinal cord and midbrain in a rat sciatic nerve injury model

    Directory of Open Access Journals (Sweden)

    Sumizono M

    2018-02-01

    Full Text Available Megumi Sumizono,1,2 Harutoshi Sakakima,1 Shotaro Otsuka,1 Takuto Terashi,1 Kazuki Nakanishi,1,2 Koki Ueda,1,2 Seiya Takada,1,2 Kiyoshi Kikuchi3 1Course of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima, Japan; 2Kirishima Orthopedics, Kirishima, Japan; 3Division of Brain Science, Department of Physiology, Kurume University School of Medicine, Kurume, Japan Background: Exercise regimens are established methods that can relieve neuropathic pain. However, the relationship between frequency and intensity of exercise and multiple cellular responses of exercise-induced alleviation of neuropathic pain is still unclear. We examined the influence of exercise frequency on neuropathic pain and the intracellular responses in a sciatic nerve chronic constriction injury (CCI model. Materials and methods: Rats were assigned to four groups as follows: CCI and high-frequency exercise (HFE group, CCI and low-frequency exercise (LFE group, CCI and no exercise (No-Ex group, and naive animals (control group. Rats ran on a treadmill, at a speed of 20 m/min, for 30 min, for 5 (HFE or 3 (LFE days a week, for a total of 5 weeks. The 50% withdrawal threshold was evaluated for mechanical sensitivity. The activation of glial cells (microglia and astrocytes, expression of brain-derived neurotrophic factor (BDNF and μ-opioid receptor in the spinal dorsal horn and endogenous opioid in the midbrain were examined using immunohistochemistry. Opioid receptor antagonists (naloxone were administered using intraperitoneal injection. Results: The development of neuropathic pain was related to the activation of glial cells, increased BDNF expression, and downregulation of the μ-opioid receptor in the ipsilateral spinal dorsal horn. In the No-Ex group, neuropathic pain showed the highest level of mechanical hypersensitivity at 2 weeks, which improved slightly until 5 weeks after CCI. In both exercise groups, the alleviation of

  10. Performance on selected visual and auditory subtests of the Wechsler Memory Scale-Fourth Edition during laboratory-induced pain.

    Science.gov (United States)

    Etherton, Joseph L; Tapscott, Brian E

    2015-01-01

    Although chronic pain patients commonly report problems with concentration and memory, recent research indicates that induced pain alone causes little or no impairment on several Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) subtests, suggesting that cognitive complaints in chronic pain may be attributable to factors other than pain. The current studies examined potential effects of induced pain on Wechsler Memory Scale-Fourth Edition (WMS-IV) visual working memory index (VWM) subtests (Experiment 1, n = 32) and on the immediate portions of WMS-IV auditory memory (IAM) subtests (Experiment 2, n = 55). In both studies, participants were administered one of two subtests (Symbol Span or Spatial Addition for Experiment 1; Logical Memory or Verbal Paired Associates for Experiment 2) normally and were then administered the alternate subtest while experiencing either cold pressor pain induction or a nonpainful control condition. Results indicate that induced pain in nonclinical volunteers did not impair performance on either VWM or IAM performance, suggesting that pain alone does not account for complaints or deficits in these domains in chronic pain patients. Nonpainful variables such as sleep deprivation or emotional disturbance may be responsible for reported cognitive complaints in chronic pain patients.

  11. Model selection in kernel ridge regression

    DEFF Research Database (Denmark)

    Exterkate, Peter

    2013-01-01

    Kernel ridge regression is a technique to perform ridge regression with a potentially infinite number of nonlinear transformations of the independent variables as regressors. This method is gaining popularity as a data-rich nonlinear forecasting tool, which is applicable in many different contexts....... The influence of the choice of kernel and the setting of tuning parameters on forecast accuracy is investigated. Several popular kernels are reviewed, including polynomial kernels, the Gaussian kernel, and the Sinc kernel. The latter two kernels are interpreted in terms of their smoothing properties......, and the tuning parameters associated to all these kernels are related to smoothness measures of the prediction function and to the signal-to-noise ratio. Based on these interpretations, guidelines are provided for selecting the tuning parameters from small grids using cross-validation. A Monte Carlo study...

  12. Model Selection in Kernel Ridge Regression

    DEFF Research Database (Denmark)

    Exterkate, Peter

    Kernel ridge regression is gaining popularity as a data-rich nonlinear forecasting tool, which is applicable in many different contexts. This paper investigates the influence of the choice of kernel and the setting of tuning parameters on forecast accuracy. We review several popular kernels......, including polynomial kernels, the Gaussian kernel, and the Sinc kernel. We interpret the latter two kernels in terms of their smoothing properties, and we relate the tuning parameters associated to all these kernels to smoothness measures of the prediction function and to the signal-to-noise ratio. Based...... on these interpretations, we provide guidelines for selecting the tuning parameters from small grids using cross-validation. A Monte Carlo study confirms the practical usefulness of these rules of thumb. Finally, the flexible and smooth functional forms provided by the Gaussian and Sinc kernels makes them widely...

  13. Methods for model selection in applied science and engineering.

    Energy Technology Data Exchange (ETDEWEB)

    Field, Richard V., Jr.

    2004-10-01

    Mathematical models are developed and used to study the properties of complex systems and/or modify these systems to satisfy some performance requirements in just about every area of applied science and engineering. A particular reason for developing a model, e.g., performance assessment or design, is referred to as the model use. Our objective is the development of a methodology for selecting a model that is sufficiently accurate for an intended use. Information on the system being modeled is, in general, incomplete, so that there may be two or more models consistent with the available information. The collection of these models is called the class of candidate models. Methods are developed for selecting the optimal member from a class of candidate models for the system. The optimal model depends on the available information, the selected class of candidate models, and the model use. Classical methods for model selection, including the method of maximum likelihood and Bayesian methods, as well as a method employing a decision-theoretic approach, are formulated to select the optimal model for numerous applications. There is no requirement that the candidate models be random. Classical methods for model selection ignore model use and require data to be available. Examples are used to show that these methods can be unreliable when data is limited. The decision-theoretic approach to model selection does not have these limitations, and model use is included through an appropriate utility function. This is especially important when modeling high risk systems, where the consequences of using an inappropriate model for the system can be disastrous. The decision-theoretic method for model selection is developed and applied for a series of complex and diverse applications. These include the selection of the: (1) optimal order of the polynomial chaos approximation for non-Gaussian random variables and stationary stochastic processes, (2) optimal pressure load model to be

  14. Selection of Hydrological Model for Waterborne Release

    International Nuclear Information System (INIS)

    Blanchard, A.

    1999-01-01

    Following a request from the States of South Carolina and Georgia, downstream radiological consequences from postulated accidental aqueous releases at the three Savannah River Site nonreactor nuclear facilities will be examined. This evaluation will aid in determining the potential impacts of liquid releases to downstream populations on the Savannah River. The purpose of this report is to evaluate the two available models and determine the appropriate model for use in following waterborne release analyses. Additionally, this report will document the accidents to be used in the future study

  15. Analgesic effect of Minocycline in rat model of inflammation-induced visceral pain

    Science.gov (United States)

    Kannampalli, Pradeep; Pochiraju, Soumya; Bruckert, Mitchell; Shaker, Reza; Banerjee, Banani; Sengupta, Jyoti N.

    2014-01-01

    The present study investigates the analgesic effect of minocycline, a semi-synthetic tetracycline antibiotic, in a rat model of inflammation-induced visceral pain. Inflammation was induced in male rats by intracolonic administration of tri-nitrobenzenesulphonic acid (TNBS). Visceral hyperalgesia was assessed by comparing the viscero-motor response (VMR) to graded colorectal distension (CRD) prior and post 7 days after TNBS treatment. Electrophysiology recordings from CRD-sensitive pelvic nerve afferents (PNA) and lumbo-sacral (LS) spinal neurons were performed in naïve and inflamed rats. Colonic inflammation produced visceral hyperalgesia characterized by increase in the VMRs to CRD accompanied with simultaneous activation of microglia in the spinal cord and satellite glial cells (SGCs) in the dorsal root ganglions (DRGs). Selectively inhibiting the glial activation following inflammation by araC (Arabinofuranosyl Cytidine) prevented the development of visceral hyperalgesia. Intrathecal minocycline significantly attenuated the VMR to CRD in inflamed rats, whereas systemic minocycline produced a delayed effect. In electrophysiology experiments, minocycline significantly attenuated the mechanotransduction of CRD-sensitive PNAs and the responses of CRD-sensitive LS spinal neurons in TNBS-treated rats. While the spinal effect of minocycline was observed within 5 min of administration, systemic injection of the drug produced a delayed effect (60 min) in inflamed rats. Interestingly, minocycline did not exhibit analgesic effect in naïve, non-inflamed rats. The results demonstrate that intrathecal injection of minocycline can effectively attenuate inflammation-induced visceral hyperalgesia. Minocycline might as well act on neuronal targets in the spinal cord of inflamed rats, in addition to the widely reported glial inhibitory action to produce analgesia. PMID:24485889

  16. Selective Radiofrequency Stimulation of the Dorsal Root Ganglion (DRG) as a Method for Predicting Targets for Neuromodulation in Patients With Post Amputation Pain: A Case Series.

    Science.gov (United States)

    Hunter, Corey W; Yang, Ajax; Davis, Tim

    2017-10-01

    While spinal cord stimulation (SCS) has established itself as an accepted and validated treatment for neuropathic pain, there are a number of conditions where it has experienced less, long-term success: post amputee pain (PAP) being one of them. Dorsal root ganglion (DRG) stimulation has shown great promise, particularly in conditions where traditional SCS has fallen short. One major difference between DRG stimulation and traditional SCS is the ability to provide focal stimulation over targeted areas. While this may be a contributing factor to its superiority, it can also be a limitation insofar stimulating the wrong DRG(s) can lead to failure. This is particularly relevant in conditions like PAP where neuroplastic maladaptation occurs causing the pain to deviate from expected patterns, thus creating uncertainty and variability in predicting targets for stimulation. We propose selective radiofrequency (RF) stimulation of the DRG as a method for preoperatively predicting targets for neuromodulation in patients with PAP. We present four patients with PAP of the lower extremities. RF stimulation was used to selectively stimulate individual DRG's, creating areas of paresthesias to see which most closely correlated/overlapped with the painful area(s). RF stimulation to the DRG's that resulted in the desirable paresthesia coverage in the residual or the missing limb(s) was recorded as "positive." Trial DRG leads were placed based on the positive RF stimulation findings. In each patient, stimulating one or more DRG(s) produced paresthesias patterns that were contradictory to know dermatomal patterns. Upon completion of a one-week trial all four patients reported 60-90% pain relief, with coverage over the painful areas, and opted for permanent implant. Mapping the DRG via RF stimulation appears to provide improved accuracy for determining lead placement in the setting of PAP where pain patterns are known to deviate from conventional dermatomal mapping. © 2017

  17. Spinal cord stimulation of dorsal columns in a rat model of neuropathic pain: evidence for a segmental spinal mechanism of pain relief.

    Science.gov (United States)

    Smits, H; van Kleef, M; Joosten, E A

    2012-01-01

    Although spinal cord stimulation (SCS) of the dorsal columns is an established method for treating chronic neuropathic pain, patients still suffer from a substantial level of pain. From a clinical perspective it is known that the location of the SCS is of pivotal importance, thereby suggesting a segmental spinal mode of action. However, experimental studies suggest that SCS acts also through the modulation of supraspinal mechanisms, which might suggest that the location is unimportant. Here we investigated the effect of the rostrocaudal location of SCS stimulation and the effectiveness of pain relief in a rat model of chronic neuropathic pain. Adult male rats (n=45) were submitted to a partial ligation of the sciatic nerve. The majority of animals developed tactile hypersensitivity in the nerve lesioned paw. All allodynic rats were submitted to SCS (n=33) for 30 minutes (f=50 Hz; pulse width 0.2 ms). In one group (n=16) the electrodes were located at the level where the injured sciatic nerve afferents enter the spinal cord (T13), and in a second group (n=17) the electrodes were positioned at more rostral levels (T11) as verified by X-ray. A repositioning experiment of electrodes from T12 to T13 was performed in 2 animals. Our data demonstrate that SCS of the dorsal columns at the level where the injured fibers enter the spinal cord dorsal horn result in a much better pain-relieving effect than SCS at more rostral levels. From this we conclude that SCS in treatment of neuropathic pain acts through a segmental spinal site of action. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  18. The analgesic effect of tramadol in animal models of neuropathic pain and fibromyalgia.

    Science.gov (United States)

    Kaneko, Kumi; Umehara, Masato; Homan, Takashi; Okamoto, Ken; Oka, Michiko; Oyama, Tatsuya

    2014-03-06

    (±)-Tramadol hydrochloride (tramadol) is a widely used analgesic for the treatment of cancer pain and chronic pain. Although many animal studies have shown antinociceptive effects of tramadol in both acute and chronic pain, little is known about the effect of tramadol in putative animal models of fibromyalgia. In this study, we compared the antiallodynic effects of oral administration of tramadol in two kinds of rat chronic pain models, neuropathic pain induced by partial sciatic nerve ligation (PSL) and reserpine-induced myalgia (RIM). In PSL rats, the threshold for responses induced by tactile stimulation with von Frey filaments was significantly decreased seven days after the operation, suggesting that the operation induced tactile allodynia. Orally administered tramadol showed a potent and dose-dependent antiallodynic effect on PSL-induced allodynia. In RIM rats, the threshold was significantly decreased five days after reserpine treatment. Orally administered tramadol also attenuated reserpine-induced tactile allodynia. To explore the mechanism of the antiallodynic effect of tramadol in RIM rats, we investigated the effect of the opioid antagonist naloxone on the tramadol-induced analgesic effect in these rats. The effect of tramadol was partially antagonized by naloxone, suggesting that the opioid receptor is involved at least in part in the antiallodynic effect of tramadol in RIM rats. These data indicate that orally administered tramadol produced improvement in both PSL rats and RIM rats at similar doses and provide evidence that the opioid system is partly involved in the analgesic effect of tramadol in RIM rats. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Pharmacological kynurenine 3-monooxygenase enzyme inhibition significantly reduces neuropathic pain in a rat model.

    Science.gov (United States)

    Rojewska, Ewelina; Piotrowska, Anna; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna

    2016-03-01

    Recent studies have highlighted the involvement of the kynurenine pathway in the pathology of neurodegenerative diseases, but the role of this system in neuropathic pain requires further extensive research. Therefore, the aim of our study was to examine the role of kynurenine 3-monooxygenase (Kmo), an enzyme that is important in this pathway, in a rat model of neuropathy after chronic constriction injury (CCI) to the sciatic nerve. For the first time, we demonstrated that the injury-induced increase in the Kmo mRNA levels in the spinal cord and the dorsal root ganglia (DRG) was reduced by chronic administration of the microglial inhibitor minocycline and that this effect paralleled a decrease in the intensity of neuropathy. Further, minocycline administration alleviated the lipopolysaccharide (LPS)-induced upregulation of Kmo mRNA expression in microglial cell cultures. Moreover, we demonstrated that not only indirect inhibition of Kmo using minocycline but also direct inhibition using Kmo inhibitors (Ro61-6048 and JM6) decreased neuropathic pain intensity on the third and the seventh days after CCI. Chronic Ro61-6048 administration diminished the protein levels of IBA-1, IL-6, IL-1beta and NOS2 in the spinal cord and/or the DRG. Both Kmo inhibitors potentiated the analgesic properties of morphine. In summary, our data suggest that in neuropathic pain model, inhibiting Kmo function significantly reduces pain symptoms and enhances the effectiveness of morphine. The results of our studies show that the kynurenine pathway is an important mediator of neuropathic pain pathology and indicate that Kmo represents a novel pharmacological target for the treatment of neuropathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Development of a mouse model of neuropathic pain following photochemically induced ischemia in the sciatic nerve.

    Science.gov (United States)

    Hao, J X; Blakeman, K H; Yu, W; Hultenby, K; Xu, X J; Wiesenfeld-Hallin, Z

    2000-05-01

    A mouse model of neuropathic pain was developed by a photochemically induced ischemic nerve injury in normal male C57/BL6 mice. The ischemia was induced by unilateral irradiation of the sciatic nerve with an argon ion laser after intravenous administration of a photosensitizing dye, erythrosin B. The nerve injury resulted in a significant decrease in withdrawal threshold of the hindpaws to mechanical stimulation with von Frey hairs, as well as increased responsiveness to cold and heat stimulation. The mice, however, did not exhibit overt spontaneous pain-like behaviors. The evoked pain-related behaviors were observed bilaterally, although the ipsilateral changes were greater than on the contralateral side. The extent and time course of the behavioral changes were related to the duration of laser irradiation, with 1-min exposure producing the most consistent effect. Morphological examination at the light microscopic level revealed partial demyelination and axonal degeneration of the large myelinated fibers at the epicenter of the lesion 1 week postirradiation. The extent of the damage was correlated with the duration of irradiation. Injury and loss of unmyelinated fibers were also observed at the electronmicroscopic level. We conclude that an intravascular photochemical reaction leading to ischemia results in graded damage to the sciatic nerve in mice. Moreover, the nerve injury is associated with the development of abnormal pain-related behaviors. Both the behavioral and the morphological changes are correlated with the duration of irradiation. These results establish a mouse model of partial nerve injury with neuropathic pain-like behaviors which may be useful in studies using genetically modified mice. Copyright 2000 Academic Press.

  1. Random effect selection in generalised linear models

    DEFF Research Database (Denmark)

    Denwood, Matt; Houe, Hans; Forkman, Björn

    We analysed abattoir recordings of meat inspection codes with possible relevance to onfarm animal welfare in cattle. Random effects logistic regression models were used to describe individual-level data obtained from 461,406 cattle slaughtered in Denmark. Our results demonstrate that the largest...

  2. Adapting AIC to conditional model selection

    NARCIS (Netherlands)

    T. van Ommen (Thijs)

    2012-01-01

    textabstractIn statistical settings such as regression and time series, we can condition on observed information when predicting the data of interest. For example, a regression model explains the dependent variables $y_1, \\ldots, y_n$ in terms of the independent variables $x_1, \\ldots, x_n$.

  3. The effect of FAAH, MAGL, and Dual FAAH/MAGL inhibition on inflammatory and colorectal distension-induced visceral pain models in Rodents.

    Science.gov (United States)

    Sakin, Y S; Dogrul, A; Ilkaya, F; Seyrek, M; Ulas, U H; Gulsen, M; Bagci, S

    2015-07-01

    Recent studies showed that the pharmacological inhibition of endocannabinoid degrading enzymes such as fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) elicit promising analgesic effects in a variety of nociceptive models without serious side effects. However, the full spectrum of activities is not observed upon inhibition of either FAAH or MAGL enzymes alone and thus dual FAAH and MAGL inhibitors have been described. Visceral pain is strongly associated with inflammation and distension of the gut. Thus, we explored the comparable effects of FAAH, MAGL, and dual FAAH/MAGL inhibitors on inflammatory and mechanically evoked visceral pain models. Visceral inflammatory and distension-induced pain were assessed with the 0.6% acetic acid writhing test in mice and colorectal distension (CRD) test in rats, respectively. The selective FAAH inhibitor PF 3845, MAGL inhibitor JZL 184, dual inhibitor JZL 195, and the cannabis analog CP 55,940 were given systemically 30 min prior to nociceptive testing. PF 3845 (5, 10, and 20 mg/kg), JZL 184 (5, 10, and 20 mg/kg), and JZL 195 (5, 10, and 20 mg/kg) elicit dose-dependent antinociceptive in the acetic acid writhing test. In the CRD model, while JZL 195 (5, 10, or 20 mg/kg) and PF3845 (10, 20, and 40 mg/kg) produced dose-dependent antinociceptive effects comparable to those of CP 55,940 (0.1, 0.3, or 1 mg/kg), JZL 184 (10, 20, and 40 mg/kg) alone did not alter the visceromotor response (VMR). The selective FAAH inhibitor and dual FAAH/MAGL inhibitors were effective in both inflammatory and mechanically evoked visceral pain, while the MAGL inhibitor elicited an analgesic effect in inflammatory, but not in distension-induced, visceral pain. © 2015 John Wiley & Sons Ltd.

  4. A Permutation Approach for Selecting the Penalty Parameter in Penalized Model Selection

    Science.gov (United States)

    Sabourin, Jeremy A; Valdar, William; Nobel, Andrew B

    2015-01-01

    Summary We describe a simple, computationally effcient, permutation-based procedure for selecting the penalty parameter in LASSO penalized regression. The procedure, permutation selection, is intended for applications where variable selection is the primary focus, and can be applied in a variety of structural settings, including that of generalized linear models. We briefly discuss connections between permutation selection and existing theory for the LASSO. In addition, we present a simulation study and an analysis of real biomedical data sets in which permutation selection is compared with selection based on the following: cross-validation (CV), the Bayesian information criterion (BIC), Scaled Sparse Linear Regression, and a selection method based on recently developed testing procedures for the LASSO. PMID:26243050

  5. Proteomic identification of altered cerebral proteins in the complex regional pain syndrome animal model.

    Science.gov (United States)

    Nahm, Francis Sahngun; Park, Zee-Yong; Nahm, Sang-Soep; Kim, Yong Chul; Lee, Pyung Bok

    2014-01-01

    Complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder. Although the exact pathophysiology of CRPS is not fully understood, central and peripheral mechanisms might be involved in the development of this disorder. To reveal the central mechanism of CRPS, we conducted a proteomic analysis of rat cerebrum using the chronic postischemia pain (CPIP) model, a novel experimental model of CRPS. After generating the CPIP animal model, we performed a proteomic analysis of the rat cerebrum using a multidimensional protein identification technology, and screened the proteins differentially expressed between the CPIP and control groups. Results. A total of 155 proteins were differentially expressed between the CPIP and control groups: 125 increased and 30 decreased; expressions of proteins related to cell signaling, synaptic plasticity, regulation of cell proliferation, and cytoskeletal formation were increased in the CPIP group. However, proenkephalin A, cereblon, and neuroserpin were decreased in CPIP group. Altered expression of cerebral proteins in the CPIP model indicates cerebral involvement in the pathogenesis of CRPS. Further study is required to elucidate the roles of these proteins in the development and maintenance of CRPS.

  6. Proteomic Identification of Altered Cerebral Proteins in the Complex Regional Pain Syndrome Animal Model

    Directory of Open Access Journals (Sweden)

    Francis Sahngun Nahm

    2014-01-01

    Full Text Available Background. Complex regional pain syndrome (CRPS is a rare but debilitating pain disorder. Although the exact pathophysiology of CRPS is not fully understood, central and peripheral mechanisms might be involved in the development of this disorder. To reveal the central mechanism of CRPS, we conducted a proteomic analysis of rat cerebrum using the chronic postischemia pain (CPIP model, a novel experimental model of CRPS. Materials and Methods. After generating the CPIP animal model, we performed a proteomic analysis of the rat cerebrum using a multidimensional protein identification technology, and screened the proteins differentially expressed between the CPIP and control groups. Results. A total of 155 proteins were differentially expressed between the CPIP and control groups: 125 increased and 30 decreased; expressions of proteins related to cell signaling, synaptic plasticity, regulation of cell proliferation, and cytoskeletal formation were increased in the CPIP group. However, proenkephalin A, cereblon, and neuroserpin were decreased in CPIP group. Conclusion. Altered expression of cerebral proteins in the CPIP model indicates cerebral involvement in the pathogenesis of CRPS. Further study is required to elucidate the roles of these proteins in the development and maintenance of CRPS.

  7. Duloxetine and 8-OH-DPAT, but not fluoxetine, reduce depression-like behaviour in an animal model of chronic neuropathic pain.

    Science.gov (United States)

    Hu, Bing; Doods, Henri; Treede, Rolf-Detlef; Ceci, Angelo

    2016-04-21

    The current study assessed whether antidepressant and/or antinociceptive drugs, duloxetine, fluoxetine as well as (±)-8-hydroxy-2-[di-n-propylamino] tetralin (8-OH-DPAT), are able to reverse depression-like behaviour in animals with chronic neuropathic pain. Chronic constriction injury (CCI) of the sciatic nerve in rats was selected as neuropathic pain model. Mechanical hypersensitivity and depression-like behaviour were evaluated 4 weeks after surgery by "electronic algometer" and forced swimming test (FST), which measured the time of immobility, and active behaviours climbing and swimming. The selective noradrenergic and serotonergic uptake blocker duloxetine (20mg/kg) and the selective 5-HT1A agonist 8-OH-DPAT (0.5mg/kg) significantly reversed both mechanical hypersensitivity and depression-like behaviour in CCI animals. Duloxetine significantly reversed depression-like behaviour in CCI rats by increasing the time of climbing and swimming, while 8-OH-DPAT attenuated depression-like behaviour mainly by increasing the time of swimming. However, the selective serotonergic uptake blocker fluoxetine (20mg/kg) failed to attenuate mechanical hypersensitivity and depression-like behaviour, possibly due to confounding pro-nociceptive actions at 5-HT3 receptors. These data suggest to target noradrenergic and 5-HT1A receptors for treatment of chronic pain and its comorbidity depression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Hyperalgesia in a human model of acute inflammatory pain: a methodological study

    DEFF Research Database (Denmark)

    Pedersen, J L; Kehlet, H

    1998-01-01

    as significant for all variables with fewer than 12 subjects in a cross-over design (2alpha = 5% and power = 80%). Between-day comparisons demanded up to 25 subjects to detect changes of the same magnitude. The burns caused mild to moderate pain (VAS: mean 29, SD 14) and the subjects (all right-handed) were more......The aim of the study was to examine reproducibility of primary and secondary hyperalgesia in a psychophysical model of human inflammatory pain. Mild burns were produced on the crura of 12 volunteers with a 50 x 25 mm thermode (47 degrees C, 7 min). Assessments of (i) cold and warm detection...... thresholds, (ii) mechanical and heat pain thresholds, (iii) pain to heat (43 degrees C and 45 degrees C, 5 s), (iv) secondary hyperalgesia, and (v) skin erythema were made 1.75 and 0.5 h before, and 0, 1, 2, 4, and 6 h after a burn injury. Sensory thresholds and hyperalgesia to heat and mechanical stimuli...

  9. A novel model of inflammatory pain in human skin involving topical application of sodium lauryl sulfate.

    Science.gov (United States)

    Petersen, L J; Lyngholm, A M; Arendt-Nielsen, L

    2010-09-01

    Sodium lauryl sulfate (SLS) is a known irritant. It releases pro-inflammatory mediators considered pivotal in inflammatory pain. The sensory effects of SLS in the skin remain largely unexplored. In this study, SLS was evaluated for its effect on skin sensory functions. Eight healthy subjects were recruited for this study. Skin sites were randomized to topical SLS 0.25, 0.5, 1, 2% and vehicle for 24 h. Topical capsaicin 1% was applied for 30 min at 24 h after SLS application. Assessments included laser Doppler imaging of local vasodilation and flare reactions, rating of spontaneous pain, assessment of primary thermal and tactile hyperalgesia, and determination of secondary dynamic and static hyperalgesia. SLS induced significant and dose-dependent local inflammation and primary hyperalgesia to tactile and thermal stimulation at 24 h after application, with SLS 2% treatment eliciting results comparable to those observed following treatment with capsaicin 1%. SLS induced no spontaneous pain, small areas of flare, and minimal secondary hyperalgesia. The primary hyperalgesia vanished within 2-3 days, whereas the skin inflammation persisted and was only partly normalized by Day 6. SLS induces profound perturbations of skin sensory functions lasting 2-3 days. SLS-induced inflammation may be a useful model for studying the mechanisms of inflammatory pain.

  10. Impact of Psychological Stress on Pain Perception in an Animal Model of Endometriosis.

    Science.gov (United States)

    Hernandez, Siomara; Cruz, Myrella L; Seguinot, Inevy I; Torres-Reveron, Annelyn; Appleyard, Caroline B

    2017-10-01

    Pain in patients with endometriosis is considered a significant source of stress but does not always correlate with severity of the condition. We have demonstrated that stress can worsen endometriosis in an animal model. Here, we tested the impact of a psychological stress protocol on pain thresholds and pain receptors. Endometriosis was induced in female rats by suturing uterine horn tissue next to the intestinal mesentery. Sham rats had sutures only. Rats were exposed to water avoidance stress for 7 consecutive days or handled for 5 minutes (no stress). Fecal pellets and serum corticosterone (CORT) levels were measured as an index of anxiety. Pain perception was assessed using hot plate and Von Frey tests. Substance P, enkephalin, endomorphin-2, Mu opioid receptor (MOR), and neurokinin-1 receptor expression in the spinal cord were measured by immunohistochemistry. Fecal pellets and CORT were significantly higher in the endo-stress (ES) group than endo-no stress (ENS; P stress groups (SNS; P stress reversed the allodynic effect caused by endo ( P stress develop more severe symptoms but interestingly stress seems to have beneficial effects on abdominal allodynia, which could be a consequence of the stress-induced analgesia phenomenon.

  11. Prior stress exposure increases pain behaviors in a rat model of full thickness thermal injury.

    Science.gov (United States)

    Nyland, Jennifer E; McLean, Samuel A; Averitt, Dayna L

    2015-12-01

    Thermal burns among individuals working in highly stressful environments, such as firefighters and military Service Members, are common. Evidence suggests that pre-injury stress may exaggerate pain following thermal injury; however current animal models of burn have not evaluated the potential influence of pre-burn stress. This sham-controlled study evaluated the influence of prior stress exposure on post-burn thermal and mechanical sensitivity in male Sprague-Dawley rats. Rats were exposed to 20 min of inescapable swim stress or sham stress once per day for three days. Exposure to inescapable swim stress (1) increased the intensity and duration of thermal hyperalgesia after subsequent burn and (2) accelerated the onset of thermal hyperalgesia and mechanical allodynia after subsequent burn. This stress-induced exacerbation of pain sensitivity was reversed by pretreatment and concurrent treatment with the serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine. These data suggest a better understanding of mechanisms by which prior stress augments pain after thermal burn may lead to improved pain treatments for burn survivors. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

  12. The genealogy of samples in models with selection.

    Science.gov (United States)

    Neuhauser, C; Krone, S M

    1997-02-01

    We introduce the genealogy of a random sample of genes taken from a large haploid population that evolves according to random reproduction with selection and mutation. Without selection, the genealogy is described by Kingman's well-known coalescent process. In the selective case, the genealogy of the sample is embedded in a graph with a coalescing and branching structure. We describe this graph, called the ancestral selection graph, and point out differences and similarities with Kingman's coalescent. We present simulations for a two-allele model with symmetric mutation in which one of the alleles has a selective advantage over the other. We find that when the allele frequencies in the population are already in equilibrium, then the genealogy does not differ much from the neutral case. This is supported by rigorous results. Furthermore, we describe the ancestral selection graph for other selective models with finitely many selection classes, such as the K-allele models, infinitely-many-alleles models. DNA sequence models, and infinitely-many-sites models, and briefly discuss the diploid case.

  13. Behavioral testing in rodent models of orofacial neuropathic and inflammatory pain

    Science.gov (United States)

    Krzyzanowska, Agnieszka; Avendaño, Carlos

    2012-01-01

    Orofacial pain conditions are often very debilitating to the patient and difficult to treat. While clinical interest is high, the proportion of studies performed in the orofacial region in laboratory animals is relatively low, compared with other body regions. This is partly due to difficulties in testing freely moving animals and therefore lack of reliable testing methods. Here we present a comprehensive review of the currently used rodent models of inflammatory and neuropathic pain adapted to the orofacial areas, taking into account the difficulties and drawbacks of the existing approaches. We examine the available testing methods and procedures used for assessing the behavioral responses in the face in both mice and rats and provide a summary of some pharmacological agents used in these paradigms to date. The use of these agents in animal models is also compared with outcomes observed in the clinic. PMID:23139912

  14. Modeling shape selection of buckled dielectric elastomers

    Science.gov (United States)

    Langham, Jacob; Bense, Hadrien; Barkley, Dwight

    2018-02-01

    A dielectric elastomer whose edges are held fixed will buckle, given a sufficiently applied voltage, resulting in a nontrivial out-of-plane deformation. We study this situation numerically using a nonlinear elastic model which decouples two of the principal electrostatic stresses acting on an elastomer: normal pressure due to the mutual attraction of oppositely charged electrodes and tangential shear ("fringing") due to repulsion of like charges at the electrode edges. These enter via physically simplified boundary conditions that are applied in a fixed reference domain using a nondimensional approach. The method is valid for small to moderate strains and is straightforward to implement in a generic nonlinear elasticity code. We validate the model by directly comparing the simulated equilibrium shapes with the experiment. For circular electrodes which buckle axisymetrically, the shape of the deflection profile is captured. Annular electrodes of different widths produce azimuthal ripples with wavelengths that match our simulations. In this case, it is essential to compute multiple equilibria because the first model solution obtained by the nonlinear solver (Newton's method) is often not the energetically favored state. We address this using a numerical technique known as "deflation." Finally, we observe the large number of different solutions that may be obtained for the case of a long rectangular strip.

  15. Effects of an intervention based on the Transtheoretical Model on back muscle endurance, physical function and pain in rice farmers with chronic low back pain.

    Science.gov (United States)

    Thanawat, Thanakorn; Nualnetr, Nomjit

    2017-01-01

    Chronic low back pain (LBP) can be managed by exercises which should be tailored to an individual's readiness to behavioral change. To evaluate the effects of an intervention program based on the Transtheoretical Model of behavioral change (TTM) on back muscle endurance, physical function and pain in rice farmers with chronic LBP. In a 32-week study, 126 rice farmers were allocated to the TTM (n= 62) and non-TTM (n= 64) groups. Modified Biering-Sorensen test, Oswestry Disability Questionnaire and visual analogue scale were used for evaluating back muscle endurance, physical function and severity of pain, respectively. The evaluations were performed at baseline and at weeks 8, 20 and 32 of the study. Data were analyzed using repeated measure ANOVA. The back muscle endurance was significantly greater in the TTM group than in the non-TTM group at week 32 (p= 0.025). Physical function and severity of pain were significantly improved in the TTM group when compared with the non-TTM group at weeks 20 and 32 (pback muscle endurance and physical function, and reduce the pain in rice farmers with LBP. Further studies should be considered to explore the long-term effects of this intervention.

  16. Synergistic interactions between paracetamol and oxcarbazepine in somatic and visceral pain models in rodents.

    Science.gov (United States)

    Tomić, Maja A; Vucković, Sonja M; Stepanović-Petrović, Radica M; Ugresić, Nenad D; Prostran, Milica S; Bosković, Bogdan

    2010-04-01

    Combination therapy is a valid approach in pain treatment, in which a reduction of doses could reduce side effects and still achieve optimal analgesia. We examined the effects of coadministered paracetamol, a widely used non-opioid analgesic, and oxcarbazepine, a relatively novel anticonvulsant with analgesic properties, in a rat model of paw inflammatory hyperalgesia and in a mice model of visceral pain and determined the type of interaction between components. The effects of paracetamol, oxcarbazepine, and their combinations were examined in carrageenan-induced (0.1 mL, 1%) paw inflammatory hyperalgesia in rats and in an acetic acid-induced (10 mg/kg, 0.75%) writhing test in mice. In both models, drugs were coadministered in fixed-dose fractions of the 50% effective dose (ED(50)), and type of interaction was determined by isobolographic analysis. Paracetamol (50-200 mg/kg peroral), oxcarbazepine (40-160 mg/kg peroral), and their combination (1/8, 1/4, 1/3, and 1/2 of a single drug ED(50)) produced a significant, dose-dependent antihyperalgesia in carrageenan-injected rats. In the writhing test in mice, paracetamol (60-180 mg/kg peroral), oxcarbazepine (20-80 mg/kg peroral), and their combination (1/16, 1/8, 1/4, and 1/2 of a single drug ED(50)) significantly and dose dependently reduced the number of writhes. In both models, isobolographic analysis revealed a significant synergistic interaction between paracetamol and oxcarbazepine, with a >4-fold reduction of doses of both drugs in combination, compared with single drugs ED(50). The synergistic interaction between paracetamol and oxcarbazepine provides new information about combination pain treatment and should be explored further in patients, especially with somatic and/or visceral pain.

  17. Analgesic Microneedle Patch for Neuropathic Pain Therapy.

    Science.gov (United States)

    Xie, Xi; Pascual, Conrado; Lieu, Christopher; Oh, Seajin; Wang, Ji; Zou, Bende; Xie, Julian; Li, Zhaohui; Xie, James; Yeomans, David C; Wu, Mei X; Xie, Xinmin Simon

    2017-01-24

    Neuropathic pain caused by nerve injury is debilitating and difficult to treat. Current systemic pharmacological therapeutics for neuropathic pain produce limited pain relief and have undesirable side effects, while current local anesthetics tend to nonspecifically block both sensory and motor functions. Calcitonin gene related peptide (CGRP), a neuropeptide released from sensory nerve endings, appears to play a significant role in chronic neuropathic pain. In this study, an analgesic microneedle (AMN) patch was developed using dissolvable microneedles to transdermally deliver selective CGRP antagonist peptide in a painless manner for the treatment of localized neuropathic pain. Local analgesic effects were evaluated in rats by testing behavioral pain sensitivity in response to thermal and mechanical stimuli using neuropathic pain models such as spared-nerve injury and diabetic neuropathy pain, as well as neurogenic inflammatory pain model induced by ultraviolet B (UVB) radiation. Unlike several conventional therapies, the AMN patches produced effective analgesia on neuropathic pain without disturbing the normal nociception and motor function of the rat, resulting from the high specificity of the delivered peptide against CGRP receptors. The AMN patches did not cause skin irritation or systemic side effects. These results demonstrate that dissolvable microneedle patches delivering CGRP antagonist peptide provide an effective, safe, and simple approach to mitigate neuropathic pain with significant advantages over current treatments.

  18. Modeling HIV-1 drug resistance as episodic directional selection.

    Science.gov (United States)

    Murrell, Ben; de Oliveira, Tulio; Seebregts, Chris; Kosakovsky Pond, Sergei L; Scheffler, Konrad

    2012-01-01

    The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS) which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance.

  19. Modeling HIV-1 drug resistance as episodic directional selection.

    Directory of Open Access Journals (Sweden)

    Ben Murrell

    Full Text Available The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance.

  20. A comparative behavioural study of mechanical hypersensitivity in 2 pain models in rats and humans.

    Science.gov (United States)

    Reitz, Marie-Céline; Hrncic, Dragan; Treede, Rolf-Detlef; Caspani, Ombretta

    2016-06-01

    The assessment of pain sensitivity in humans has been standardized using quantitative sensory testing, whereas in animals mostly paw withdrawal thresholds to diverse stimuli are measured. This study directly compares tests used in quantitative sensory testing (pinpricks, pressure algometer) with tests used in animal studies (electronic von Frey test: evF), which we applied to the dorsal hind limbs of humans after high frequency stimulation and rats after tibial nerve transection. Both experimental models induce profound mechanical hypersensitivity. At baseline, humans and rats showed a similar sensitivity to evF with 0.2 mm diameter tips, but significant differences for other test stimuli (all P pain models (P pain sensitivity, but probe size and shape should be standardized. Hypersensitivity to blunt pressure-the leading positive sensory sign after peripheral nerve injury in humans-is a novel finding in the tibial nerve transection model. By testing outside the primary zone of nerve damage (rat) or activation (humans), our methods likely involve effects of central sensitization in both species.

  1. Synergism between COX-3 inhibitors in two animal models of pain.

    Science.gov (United States)

    Muñoz, J; Navarro, C; Noriega, V; Pinardi, G; Sierralta, F; Prieto, J C; Miranda, H F

    2010-04-01

    The antinociception induced by the intraperitoneal coadministration in mice of combinations of metamizol and paracetamol was evaluated in the tail flick test and orofacial formalin test. The antinociception of each drugs alone and the interaction of the combinations was evaluated by isobolographic analysis in the tail-flick and in the formalin orofacial assay of mice. Mice pretreated with the drugs demonstrated that the antinociception of metamizol and paracetamol is dose-dependent. The potency range on the antinocifensive responses for metamizol or paracetamol was as follows: orofacial (Phase II) > orofacial (Phase I) > tail flick. In addition, the coadministration of metamizol with paracetamol induced a strong synergistic antinociception in the algesiometer assays. Both drugs showed effectiveness in inflammatory pain. These actions can be related to the differential selectivity of the drugs for inhibition of COX isoforms and also to the several additional antinociception mechanisms and pathways initiated by the analgesic drugs on pain transmission. Since the efficacy of the combination of metamizol with paracetamol has been demonstrated in the present study, this association could have a potential beneficial effect on the pharmacological treatment of clinical pain.

  2. Variable selection for mixture and promotion time cure rate models.

    Science.gov (United States)

    Masud, Abdullah; Tu, Wanzhu; Yu, Zhangsheng

    2016-11-16

    Failure-time data with cured patients are common in clinical studies. Data from these studies are typically analyzed with cure rate models. Variable selection methods have not been well developed for cure rate models. In this research, we propose two least absolute shrinkage and selection operators based methods, for variable selection in mixture and promotion time cure models with parametric or nonparametric baseline hazards. We conduct an extensive simulation study to assess the operating characteristics of the proposed methods. We illustrate the use of the methods using data from a study of childhood wheezing. © The Author(s) 2016.

  3. A multilevel structural equation modeling analysis of vulnerabilities and resilience resources influencing affective adaptation to chronic pain.

    Science.gov (United States)

    Sturgeon, John A; Zautra, Alex J; Arewasikporn, Anne

    2014-02-01

    The processes of individual adaptation to chronic pain are complex and occur across multiple domains. We examined the social, cognitive, and affective context of daily pain adaptation in individuals with fibromyalgia and osteoarthritis. By using a sample of 260 women with fibromyalgia or osteoarthritis, we examined the contributions of pain catastrophizing, negative interpersonal events, and positive interpersonal events to daily negative and positive affect across 30days of daily diary data. Individual differences and daily fluctuations in predictor variables were estimated simultaneously by utilizing multilevel structural equation modeling techniques. The relationships between pain and negative and positive affect were mediated by stable and day-to-day levels of pain catastrophizing as well as day-to-day positive interpersonal events, but not negative interpersonal events. There were significant and independent contributions of pain catastrophizing and positive interpersonal events to adaptation to pain and pain-related affective dysregulation. These effects occur both between persons and within a person's everyday life. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  4. Two-step variable selection in quantile regression models

    Directory of Open Access Journals (Sweden)

    FAN Yali

    2015-06-01

    Full Text Available We propose a two-step variable selection procedure for high dimensional quantile regressions, in which the dimension of the covariates, pn is much larger than the sample size n. In the first step, we perform ℓ1 penalty, and we demonstrate that the first step penalized estimator with the LASSO penalty can reduce the model from an ultra-high dimensional to a model whose size has the same order as that of the true model, and the selected model can cover the true model. The second step excludes the remained irrelevant covariates by applying the adaptive LASSO penalty to the reduced model obtained from the first step. Under some regularity conditions, we show that our procedure enjoys the model selection consistency. We conduct a simulation study and a real data analysis to evaluate the finite sample performance of the proposed approach.

  5. Partner Selection Optimization Model of Agricultural Enterprises in Supply Chain

    OpenAIRE

    Feipeng Guo; Qibei Lu

    2013-01-01

    With more and more importance of correctly selecting partners in supply chain of agricultural enterprises, a large number of partner evaluation techniques are widely used in the field of agricultural science research. This study established a partner selection model to optimize the issue of agricultural supply chain partner selection. Firstly, it constructed a comprehensive evaluation index system after analyzing the real characteristics of agricultural supply chain. Secondly, a heuristic met...

  6. Buddleja thyrsoides Lam. crude extract presents antinociceptive effect on an arthritic pain model in mice.

    Science.gov (United States)

    Fialho, Maria Fernanda Pessano; Brusco, Indiara; da Silva Brum, Evelyne; Piana, Mariana; Boligon, Aline Augusti; Trevisan, Gabriela; Oliveira, Sara Marchesan

    2017-08-17

    Arthritis is a chronic inflammatory disease which reduces the life quality of affected individuals. Therapeutic tools used for treating inflammatory pain are associated with several undesirable effects. Buddleja thyrsoides Lam., known as 'Barbasco' or 'Cambara', is mostly used in several disorders and possesses antirheumatic, anti-inflammatory, and analgesic properties. Here, we investigated the antinociceptive and anti-inflammatory effects of the B. thyrsoides crude extract applied orally and topically in acute pain models and an arthritic pain model induced by complete Freund's adjuvant (CFA) paw injection in male mice (25-30 g). The high-performance liquid chromatography (HPLC) of the B. thyrsoides extract crude revealed the presence of the lupeol, stigmasterol, and β-sitosterol. The stability study of the B. thyrsoides gel did not show relevant changes at low temperatures. The oral treatment with the B. thrysoides extract prevented the capsaicin-induced spontaneous nociception and the acetic acid-induced abdominal writhing, but did not alter the thermal threshold in the tail immersion test. The B. thyrsoides antinociceptive effect was not reversed by naloxone in the capsaicin test. The B. thyrsoides oral or topical treatment reversed the CFA-induced mechanical allodynia and thermal hyperalgesia with maximum inhibition ( I max ) of 69 ± 6 and 68 ± 5% as well as 78 ± 15 and 87 ± 12%, respectively. Moreover, the topical but not oral treatment inhibited the CFA-induced cell infiltration, but did not reduce the paw edema significantly. The oral treatment with B. thyrsoides did not cause adverse effects. These findings suggest that the oral or topical treatment with B. thyrsoides presents antinociceptive actions in an arthritic pain model without causing adverse effects. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  7. Effect of Model Selection on Computed Water Balance Components

    NARCIS (Netherlands)

    Jhorar, R.K.; Smit, A.A.M.F.R.; Roest, C.W.J.

    2009-01-01

    Soil water flow modelling approaches as used in four selected on-farm water management models, namely CROPWAT. FAIDS, CERES and SWAP, are compared through numerical experiments. The soil water simulation approaches used in the first three models are reformulated to incorporate ail evapotranspiration

  8. Laminoplasty Does not Lead to Worsening Axial Neck Pain in the Properly Selected Patient With Cervical Myelopathy: A Comparison With Laminectomy and Fusion.

    Science.gov (United States)

    Stephens, Byron F; Rhee, John M; Neustein, Thomas M; Arceo, Rafael

    2017-12-15

    Retrospective cohort study of prospectively collected data. To determine if laminoplasty (LP) is associated with worsening axial neck pain in patients with multilevel cervical myelopathy, and to compare neck pain, clinical outcomes, and radiographic measures in a group undergoing laminectomy and fusion (LF). Postoperative new or worsening axial neck pain is commonly cited as a major disadvantage of laminoplasty. However, there remains a paucity of corroborative data from large series. Following institutional review board approval, we reviewed the medical records, radiographs, and prospective clinical outcomes database of 85 patients undergoing LP and 52 patients undergoing LF for cervical myelopathy with minimum 1-year radiographic follow-up and average clinical follow-up of 18.5 months. LP was performed in those with neutral to lordotic C2-7 alignment and who did not complain of diffuse axial pain. Otherwise, LF was performed. Clinical outcomes included visual analogue score (VAS)-neck pain, VAS-total pain, neck disability index (NDI), short form 36, modified Japanese Orthopaedic Association (mJOA), and several radiographic parameters. VAS-neck did not worsen in LP (-0.2, P = 0.54) and did improve in LF (-2.0, P = 0.0013). VAS-total improved significantly in both groups (LF -1.04 ± 0.52, P = 0.05; LP -1.4 ± 0.51, P = 0.008). NDI improved in both groups, but was significant in only LP (LP decreased 6.79 ± 2.25, P = 0.0032; LF decreased 4.01 ± 3.05, P = 0.19). mJOA scores improved significantly in both groups (LP improved 2.89 ± 0.27, P cervical lordosis in both groups that was significant in LP (LP 2.92° loss, P = 0.0181; LF 1.25° loss, P = 0.53). In a carefully selected group of myelopathic patients without significant diffuse axial pain preoperatively and appropriate sagittal alignment, laminoplasty did not lead to worsening axial neck pain, and it was associated with significant improvements in other

  9. Ensembling Variable Selectors by Stability Selection for the Cox Model

    Directory of Open Access Journals (Sweden)

    Qing-Yan Yin

    2017-01-01

    Full Text Available As a pivotal tool to build interpretive models, variable selection plays an increasingly important role in high-dimensional data analysis. In recent years, variable selection ensembles (VSEs have gained much interest due to their many advantages. Stability selection (Meinshausen and Bühlmann, 2010, a VSE technique based on subsampling in combination with a base algorithm like lasso, is an effective method to control false discovery rate (FDR and to improve selection accuracy in linear regression models. By adopting lasso as a base learner, we attempt to extend stability selection to handle variable selection problems in a Cox model. According to our experience, it is crucial to set the regularization region Λ in lasso and the parameter λmin properly so that stability selection can work well. To the best of our knowledge, however, there is no literature addressing this problem in an explicit way. Therefore, we first provide a detailed procedure to specify Λ and λmin. Then, some simulated and real-world data with various censoring rates are used to examine how well stability selection performs. It is also compared with several other variable selection approaches. Experimental results demonstrate that it achieves better or competitive performance in comparison with several other popular techniques.

  10. Curcumin slows osteoarthritis progression and relieves osteoarthritis-associated pain symptoms in a post-traumatic osteoarthritis mouse model.

    Science.gov (United States)

    Zhang, Zhuo; Leong, Daniel J; Xu, Lin; He, Zhiyong; Wang, Angela; Navati, Mahantesh; Kim, Sun J; Hirsh, David M; Hardin, John A; Cobelli, Neil J; Friedman, Joel M; Sun, Hui B

    2016-06-03

    Curcumin has been shown to have chondroprotective potential in vitro. However, its effect on disease and symptom modification in osteoarthritis (OA) is largely unknown. This study aimed to determine whether curcumin could slow progression of OA and relieve OA-related pain in a mouse model of destabilization of the medial meniscus (DMM). Expression of selected cartilage degradative-associated genes was evaluated in human primary chondrocytes treated with curcumin and curcumin nanoparticles and assayed by real-time PCR. The mice subjected to DMM surgery were orally administered curcumin or topically administered curcumin nanoparticles for 8 weeks. Cartilage integrity was evaluated by Safranin O staining and Osteoarthritis Research Society International (OARSI) score, and by immunohistochemical staining of cleaved aggrecan and type II collagen, and levels of matrix metalloproteinase (MMP)-13 and ADAMTS5. Synovitis and subchondral bone thickness were scored based on histologic images. OA-associated pain and symptoms were evaluated by von Frey assay, and locomotor behavior including distance traveled and rearing. Both curcumin and nanoparticles encapsulating curcumin suppressed mRNA expression of pro-inflammatory mediators IL-1β and TNF-α, MMPs 1, 3, and 13, and aggrecanase ADAMTS5, and upregulated the chondroprotective transcriptional regulator CITED2, in primary cultured chondrocytes in the absence or presence of IL-1β. Oral administration of curcumin significantly reduced OA disease progression, but showed no significant effect on OA pain relief. Curcumin was detected in the infrapatellar fat pad (IPFP) following topical administration of curcumin nanoparticles on the skin of the injured mouse knee. Compared to vehicle-treated controls, topical treatment led to: (1) reduced proteoglycan loss and cartilage erosion and lower OARSI scores, (2) reduced synovitis and subchondral plate thickness, (3) reduced immunochemical staining of type II collagen and aggrecan

  11. Validation of elk resource selection models with spatially independent data

    Science.gov (United States)

    Priscilla K. Coe; Bruce K. Johnson; Michael J. Wisdom; John G. Cook; Marty Vavra; Ryan M. Nielson

    2011-01-01

    Knowledge of how landscape features affect wildlife resource use is essential for informed management. Resource selection functions often are used to make and validate predictions about landscape use; however, resource selection functions are rarely validated with data from landscapes independent of those from which the models were built. This problem has severely...

  12. A Working Model of Natural Selection Illustrated by Table Tennis

    Science.gov (United States)

    Dinc, Muhittin; Kilic, Selda; Aladag, Caner

    2013-01-01

    Natural selection is one of the most important topics in biology and it helps to clarify the variety and complexity of organisms. However, students in almost every stage of education find it difficult to understand the mechanism of natural selection and they can develop misconceptions about it. This article provides an active model of natural…

  13. Augmented Self-Modeling as an Intervention for Selective Mutism

    Science.gov (United States)

    Kehle, Thomas J.; Bray, Melissa A.; Byer-Alcorace, Gabriel F.; Theodore, Lea A.; Kovac, Lisa M.

    2012-01-01

    Selective mutism is a rare disorder that is difficult to treat. It is often associated with oppositional defiant behavior, particularly in the home setting, social phobia, and, at times, autism spectrum disorder characteristics. The augmented self-modeling treatment has been relatively successful in promoting rapid diminishment of selective mutism…

  14. Response to selection in finite locus models with nonadditive effects

    NARCIS (Netherlands)

    Esfandyari, Hadi; Henryon, Mark; Berg, Peer; Thomasen, Jørn Rind; Bijma, Piter; Sørensen, Anders Christian

    2017-01-01

    Under the finite-locus model in the absence of mutation, the additive genetic variation is expected to decrease when directional selection is acting on a population, according to quantitative-genetic theory. However, some theoretical studies of selection suggest that the level of additive

  15. Elementary Teachers' Selection and Use of Visual Models

    Science.gov (United States)

    Lee, Tammy D.; Gail Jones, M.

    2018-02-01

    As science grows in complexity, science teachers face an increasing challenge of helping students interpret models that represent complex science systems. Little is known about how teachers select and use models when planning lessons. This mixed methods study investigated the pedagogical approaches and visual models used by elementary in-service and preservice teachers in the development of a science lesson about a complex system (e.g., water cycle). Sixty-seven elementary in-service and 69 elementary preservice teachers completed a card sort task designed to document the types of visual models (e.g., images) that teachers choose when planning science instruction. Quantitative and qualitative analyses were conducted to analyze the card sort task. Semistructured interviews were conducted with a subsample of teachers to elicit the rationale for image selection. Results from this study showed that both experienced in-service teachers and novice preservice teachers tended to select similar models and use similar rationales for images to be used in lessons. Teachers tended to select models that were aesthetically pleasing and simple in design and illustrated specific elements of the water cycle. The results also showed that teachers were not likely to select images that represented the less obvious dimensions of the water cycle. Furthermore, teachers selected visual models more as a pedagogical tool to illustrate specific elements of the water cycle and less often as a tool to promote student learning related to complex systems.

  16. Cancer Pain Physiology

    DEFF Research Database (Denmark)

    Falk, Sarah; Bannister, Kirsty; Dickenson, Anthony

    2014-01-01

    Mechanisms of inflammatory and neuropathic pains have been elucidated and translated to patient care by the use of animal models of these pain states. Cancer pain has lagged behind since early animal models of cancer-induced bone pain were based on the systemic injection of carcinoma cells....... This precluded systematic investigation of specific neuronal and pharmacological alterations that occur in cancer-induced bone pain. In 1999, Schwei et al. described a murine model of cancer-induced bone pain that paralleled the clinical condition in terms of pain development and bone destruction, confined...... to the mouse femur. This model prompted related approaches and we can now state that cancer pain may include elements of inflammatory and neuropathic pains but also unique changes in sensory processing. Cancer induced bone pain results in progressive bone destruction, elevated osteoclast activity...

  17. The effect of local/topical analgesics on incisional pain in a pig model

    Directory of Open Access Journals (Sweden)

    Castel D

    2017-09-01

    Full Text Available David Castel,1 Itai Sabbag,2 Sigal Meilin3 1The Neufeld Cardiac Research Institute, Sheba Medical Centre, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, 2Lahav Research Institute, Kibutz Lahav, Negev, 3Neurology R&D Division, MD Biosciences, Nes-Ziona, Israel Abstract: Interest in the development of new topical/local drug administration for blocking pain at peripheral sites, with maximum drug activity and minimal systemic effects, is on the rise. In the review article by Kopsky and Stahl, four critical barriers in the process of research and development of topical analgesics were indicated. The active pharmaceutical ingredient (API and the formulation are among the major challenges. The road to the development of such drugs passes through preclinical studies. These studies, if planned correctly, should serve as guidance for choosing the right API and formulation. Although rodent models for pain continue to provide valuable data on the mechanisms driving pain, their use in developing topical and localized treatment approaches is limited for technical (intraplate injection area is small as well as mechanical reasons (non-similarity to human skin and innervation. It has been previously shown that pigs are comparable to humans in ways that make them a better choice for evaluating topical and local analgesics. The aim of this study was to summarize several experiments that used pigs for testing postoperative pain in an incisional pain model (skin incision [SI] and skin and muscle incision [SMI]. At the end of the surgery, the animals were treated with different doses of bupivacaine solution (Marcaine®, bupivacaine liposomal formulation (Exparel® or ropivacaine solution (Naropin. Von Frey testing demonstrated a decrease in the animals’ sensitivity to mechanical stimulation expressed as an increase in the withdrawal force following local treatment. These changes reflect the clinical condition in the level as well as in the duration of

  18. Target Selection Models with Preference Variation Between Offenders

    NARCIS (Netherlands)

    Townsley, Michael; Birks, Daniel; Ruiter, Stijn; Bernasco, Wim; White, Gentry

    2016-01-01

    Objectives: This study explores preference variation in location choice strategies of residential burglars. Applying a model of offender target selection that is grounded in assertions of the routine activity approach, rational choice perspective, crime pattern and social disorganization theories,

  19. COPS model estimates of LLEA availability near selected reactor sites

    International Nuclear Information System (INIS)

    Berkbigler, K.P.

    1979-11-01

    The COPS computer model has been used to estimate local law enforcement agency (LLEA) officer availability in the neighborhood of selected nuclear reactor sites. The results of these analyses are presented both in graphic and tabular form in this report

  20. Molecular modelling of a chemodosimeter for the selective detection ...

    Indian Academy of Sciences (India)

    Wintec

    Molecular modelling of a chemodosimeter for the selective detection of. As(III) ion in water. † ... high levels of arsenic cause severe skin diseases in- cluding skin cancer ..... Special Attention to Groundwater in SE Asia (eds) D. Chakraborti, A ...

  1. Effect of peripheral morphine in a human model of acute inflammatory pain

    DEFF Research Database (Denmark)

    Lillesø, J; Hammer, N A; Pedersen, J L

    2000-01-01

    Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo-controlled, th......Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo......-controlled, three-way crossover design in a human model of acute inflammatory pain (heat injury). We studied 18 healthy volunteers who each received morphine locally (2 mg), morphine systemically (2 mg), or placebo on three separate study days. The subjects received morphine infiltration subcutaneously (s.c.). 1 h......, but local morphine infiltration neither reduced pain during the burn, nor primary or secondary hyperalgesia to mechanical and heat stimuli after the burn. In conclusion, peripherally applied morphine had no acute antinociceptive effects in this human model of acute inflammatory pain....

  2. Acupuncture Treatment of Chronic Low Back Pain by Using the Jingjin (Meridian Sinews) Model.

    Science.gov (United States)

    Legge, David

    2015-10-01

    This case report details the unexpected and sustained relief from chronic low back pain in a patient after a single acupuncture treatment. The treatment administered on that occasion was based on the jingjin (i.e., "meridian sinew") model of traditional acupuncture. Treatments based on the jingjin model involve needling the ah shi (i.e., locally tender) points in myofascial tissue along the jingjin pathway. Tight chains can be needled to treat symptoms that are either close to or at some distance from the site of the needling treatment. In this patient, the points were in the gastrocnemius muscle and the hamstring muscles, which are part of the Bladder jingjin pathway. The patient, a 69-year-old woman, had had back pain for more than 40 years. The relief from the pain occurred within a day after the treatment and, at the time of this report, the relief has persisted for 5 months. This report examines two possible mechanisms for such a result: (1) a local increase in the extensibility of the hamstrings could be responsible or (2) the complex interactions within the central nervous system that are involved in acupuncture treatment could be more important factors. Copyright © 2015. Published by Elsevier B.V.

  3. Spinal astrocytic activation contributes to mechanical allodynia in a rat chemotherapy-induced neuropathic pain model.

    Directory of Open Access Journals (Sweden)

    Xi-Tuan Ji

    Full Text Available Chemotherapy-induced neuropathic pain (CNP is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain enigmatic. Accumulating evidence implicates the involvement of spinal glia in some neuropathic pain models. In this study, using a vincristine-evoked CNP rat model with obvious mechanical allodynia, we found that spinal astrocyte rather than microglia was dramatically activated. The mechanical allodynia was dose-dependently attenuated by intrathecal administratration of L-α-aminoadipate (astrocytic specific inhibitor; whereas minocycline (microglial specific inhibitor had no such effect, indicating that spinal astrocytic activation contributes to allodynia in CNP rat. Furthermore, oxidative stress mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR phosphorylation in spinal neurons to strengthen pain transmission. Taken together, our findings suggest that spinal activated astrocytes may be a crucial component of the pathophysiology of CNP and "Astrocyte-Cytokine-NMDAR-neuron" pathway may be one detailed neural mechanisms underlying CNP. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for treating CNP.

  4. Pulsed magnetic field enhances therapeutic efficiency of mesenchymal stem cells in chronic neuropathic pain model.

    Science.gov (United States)

    Mert, Tufan; Kurt, Akif Hakan; Altun, İdiris; Celik, Ahmet; Baran, Furkan; Gunay, Ismail

    2017-05-01

    Cell-based or magnetic field therapies as alternative approaches to pain management have been tested in several experimental pain models. The aim of this study therefore was to investigate the actions of the cell-based therapy (adipose tissue derived mesenchymal stem cells; ADMSC) or pulsed magnetic field (PMF) therapy and magneto-cell therapy (combination of ADMSC and PMF) in chronic constriction nerve injury model (CCI). The actions of individual ADMSC (route dependent [systemic or local], time-dependent [a day or a week after surgery]), or PMF and their combination (magneto-cell) therapies on hyperalgesia and allodynia were investigated by using thermal plantar test and a dynamic plantar aesthesiometer, respectively. In addition, various cytokine levels (IL-1β, IL-6, and IL-10) of rat sciatic nerve after CCI were analyzed. Following the CCI, both latency and threshold significantly decreased. ADMSC or PMF significantly increased latencies and thresholds. The combination of ADMSC with PMF even more significantly increased latency and threshold when compared with ADMSC alone. However, ADMSC-induced decrease in pro-inflammatory or increase in anti-inflammatory cytokines levels were partially prevented by PMF treatments. Present findings may suggest that both cell-based and magnetic therapies can effectively attenuate chronic neuropathic pain symptoms. Combined magneto-cell therapy may also efficiently reverse neuropathic signs. Bioelectromagnetics. 38:255-264, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. Transcultural adaptation into Portuguese of an instrument for pain evaluation based on the biopsychosocial model

    Directory of Open Access Journals (Sweden)

    Monique Rocha Peixoto dos Santos

    Full Text Available Abstract Introduction: Pain is an individual experience influenced by multiple interacting factors. The “biopsychosocial” care model has gained popularity in response to growing research evidence indicating the influence of biological, psychological, and social factors on the pain experience. The implementation of this model is a challenge in the practice of the health professional. Objective: To perform the transcultural adaptation of the SCEBS method into Brazilian Portuguese. Methods: The instrument was translated and applied to 50 healthy subjects and 50 participants with non-specific chronic pain in the spine. The process of cross-cultural adaptation included the following steps: transcultural adaptation, content analysis of the scale, pre-test, revision, back-translation review, cross-cultural adaptation, revised text correction and final report. Results: The translated and adapted 51-item Portuguese version of the SCEBS method produced an instrument called SCEBS-BR. In the assessment by the target population, 50 adult users of the Brazilian Unified Health System answered the questionnaire and showed good understanding of the instrument on the verbal rating scale. Conclusion: The SCEBS-BR was proved to be easily understandable, showing good semantic validation regardless of schooling level or age, and can be considered adequate for clinical use.

  6. Bone pain caused by swelling of mouse ear capsule static xylene and effects on rat models of cervical spondylosis

    Science.gov (United States)

    Zhang, Xuhui; Xia, Lei; Hao, Shaojun; Chen, Weiliang; Guo, Junyi; Ma, Zhenzhen; Wang, Huamin; Kong, Xuejun; Wang, Hongyu; Zhang, Zhengchen

    2018-04-01

    To observe the effect of intravenous bone pain Capsule on the ear of mice induced by xylene, swelling of rat models of cervical spondylosis. Weighing 18 ˜ 21g 50 mice, male, were randomly divided into for five groups, which were fed with service for bone pain static capsule suspension, Jingfukang granule suspension 0.5%CMC liquid and the same volume of. Respectively to the mice ear drop of xylene 0.05 ml, 4h after cervical dislocation, the mice were sacrificed and the cut two ear, rapid analytical balance weighing, and calculate the ear swelling degree and the other to take the weight of 200 - 60 250g male SD rats, were randomly divided into for 6 groups, 10 rats in each group, of which 5 groups made cervical spondylosis model. Results: with the blank group than bone pain static capsule group and Jingfukang granule group can significantly reduce mouse auricular dimethylbenzene swelling, significantly reduce ear swelling degree (P cervical spondylosis. With the model group ratio, large, medium and small dose of bone pain static capsule group, Jingfukang granule group (P pain static capsule group, Jingfukang granule group can significantly reduce the rat X-ray scores (P pain static capsule can significantly reduce mouse auricular dimethylbenzene swelling. The bone pain capsule has a good effect on the rat model of cervical spondylosis.

  7. Adult emergency department patients with sickle cell pain crisis: a learning collaborative model to improve analgesic management.

    Science.gov (United States)

    Tanabe, Paula; Artz, Nicole; Mark Courtney, D; Martinovich, Zoran; Weiss, Kevin B; Zvirbulis, Elena; Hafner, John W

    2010-04-01

    The objectives were to report the baseline (prior to quality improvement interventions) patient and visit characteristics and analgesic management practices for each site participating in an emergency department (ED) sickle cell learning collaborative. A prospective, multisite longitudinal cohort study in the context of a learning-collaborative model was performed in three midwestern EDs. Each site formed a multidisciplinary team charged with improving analgesic management for patients with sickle cell disease (SCD). Each team developed a nurse-initiated analgesic protocol for SCD patients (implemented after a baseline data collection period of 3.5 months at one site and 10 months at the other two sites). All sites prospectively enrolled adults with an acute pain crisis and SCD. All medical records for patients meeting study criteria were reviewed. Demographic, health services, and analgesic management data were abstracted, including ED visit frequency data, ED disposition, arrival and discharge pain score, and name and route of initial analgesic administered. Ten interviews per quarter per site were conducted with patients within 14 days of their ED discharge, and subjects were queried about the highest level of pain acceptable at discharge. The primary outcome variable was the time to initial analgesic administration. Variable data were described as means and standard deviations (SDs) or medians and interquartile ranges (IQR) for nonnormal data. A total of 155 patients met study criteria (median age = 32 years, IQR = 24-40 years) with a total of 701 ED visits. Eighty-six interviews were conducted. Most patients (71.6%) had between one and three visits to the ED during the study period. However, after removing Site 3 from the analysis because of the short data enrollment period (3.5 months), which influenced the mean number of visits for the entire cohort, 52% of patients had between one and three ED visits over 10 months, 21% had four to nine visits, and 27% had

  8. Descending serotonergic facilitation and the antinociceptive effects of pregabalin in a rat model of osteoarthritic pain

    Directory of Open Access Journals (Sweden)

    Dolphin Annette C

    2009-08-01

    Full Text Available Abstract Background Descending facilitation, from the brainstem, promotes spinal neuronal hyperexcitability and behavioural hypersensitivity in many chronic pain states. We have previously demonstrated enhanced descending facilitation onto dorsal horn neurones in a neuropathic pain model, and shown this to enable the analgesic effectiveness of gabapentin. Here we have tested if this hypothesis applies to other pain states by using a combination of approaches in a rat model of osteoarthritis (OA to ascertain if 1 a role for descending 5HT mediated facilitation exists, and 2 if pregabalin (a newer analogue of gabapentin is an effective antinociceptive agent in this model. Further, quantitative-PCR experiments were undertaken to analyse the α2δ-1 and 5-HT3A subunit mRNA levels in L3–6 DRG in order to assess whether changes in these molecular substrates have a bearing on the pharmacological effects of ondansetron and pregabalin in OA. Results Osteoarthritis was induced via intra-articular injection of monosodium iodoacetate (MIA into the knee joint. Control animals were injected with 0.9% saline. Two weeks later in vivo electrophysiology was performed, comparing the effects of spinal ondansetron (10–100 μg/50 μl or systemic pregabalin (0.3 – 10 mg/kg on evoked responses of dorsal horn neurones to electrical, mechanical and thermal stimuli in MIA or control rats. In MIA rats, ondansetron significantly inhibited the evoked responses to both innocuous and noxious natural evoked neuronal responses, whereas only inhibition of noxious evoked responses was seen in controls. Pregabalin significantly inhibited neuronal responses in the MIA rats only; this effect was blocked by a pre-administration of spinal ondansetron. Analysis of α2δ-1 and 5-HT3A subunit mRNA levels in L3–6 DRG revealed a significant increase in α2δ-1 levels in ipsilateral L3&4 DRG in MIA rats. 5-HT3A subunit mRNA levels were unchanged. Conclusion These data suggest

  9. Characterisation of tramadol, morphine and tapentadol in an acute pain model in Beagle dogs.

    Science.gov (United States)

    Kögel, Babette; Terlinden, Rolf; Schneider, Johannes

    2014-05-01

    To evaluate the analgesic potential of the centrally acting analgesics tramadol, morphine and the novel analgesic tapentadol in a pre-clinical research model of acute nociceptive pain, the tail-flick model in dogs. Prospective part-randomized pre-clinical research trial. Fifteen male Beagle dogs (HsdCpb:DOBE), aged 12-15 months. On different occasions separated by at least 1 week, dogs received intravenous (IV) administrations of tramadol (6.81, 10.0 mg kg(-1) ), tapentadol (2.15, 4.64, 6.81 mg kg(-1) ) or morphine (0.464, 0.681, 1.0 mg kg(-1) ) with subsequent measurement of tail withdrawal latencies from a thermal stimulus (for each treatment n = 5). Blood samples were collected immediately after the pharmacodynamic measurements of tramadol to determine pharmacokinetics and the active metabolite O-demethyltramadol (M1). Tapentadol and morphine induced dose-dependent antinociception with ED50-values of 4.3 mg kg(-1) and 0.71 mg kg(-1) , respectively. In contrast, tramadol did not induce antinociception at any dose tested. Measurements of the serum levels of tramadol and the M1 metabolite revealed only marginal amounts of the M1 metabolite, which explains the absence of the antinociceptive effect of tramadol in this experimental pain model in dogs. Different breeds of dogs might not or only poorly respond to treatment with tramadol due to low metabolism of the drug. Tapentadol and morphine which act directly on μ-opioid receptors without the need for metabolic activation are demonstrated to induce potent antinociception in the experimental model used and should also provide a reliable pain management in the clinical situation. The non-opioid mechanisms of tramadol do not provide antinociception in this experimental setting. This contrasts to many clinical situations described in the literature, where tramadol appears to provide useful analgesia in dogs for post-operative pain relief and in more chronically pain states. © 2014 Association of Veterinary

  10. Model Selection in Continuous Test Norming With GAMLSS.

    Science.gov (United States)

    Voncken, Lieke; Albers, Casper J; Timmerman, Marieke E

    2017-06-01

    To compute norms from reference group test scores, continuous norming is preferred over traditional norming. A suitable continuous norming approach for continuous data is the use of the Box-Cox Power Exponential model, which is found in the generalized additive models for location, scale, and shape. Applying the Box-Cox Power Exponential model for test norming requires model selection, but it is unknown how well this can be done with an automatic selection procedure. In a simulation study, we compared the performance of two stepwise model selection procedures combined with four model-fit criteria (Akaike information criterion, Bayesian information criterion, generalized Akaike information criterion (3), cross-validation), varying data complexity, sampling design, and sample size in a fully crossed design. The new procedure combined with one of the generalized Akaike information criterion was the most efficient model selection procedure (i.e., required the smallest sample size). The advocated model selection procedure is illustrated with norming data of an intelligence test.

  11. Selection Criteria in Regime Switching Conditional Volatility Models

    Directory of Open Access Journals (Sweden)

    Thomas Chuffart

    2015-05-01

    Full Text Available A large number of nonlinear conditional heteroskedastic models have been proposed in the literature. Model selection is crucial to any statistical data analysis. In this article, we investigate whether the most commonly used selection criteria lead to choice of the right specification in a regime switching framework. We focus on two types of models: the Logistic Smooth Transition GARCH and the Markov-Switching GARCH models. Simulation experiments reveal that information criteria and loss functions can lead to misspecification ; BIC sometimes indicates the wrong regime switching framework. Depending on the Data Generating Process used in the experiments, great care is needed when choosing a criterion.

  12. The Use of Evolution in a Central Action Selection Model

    Directory of Open Access Journals (Sweden)

    F. Montes-Gonzalez

    2007-01-01

    Full Text Available The use of effective central selection provides flexibility in design by offering modularity and extensibility. In earlier papers we have focused on the development of a simple centralized selection mechanism. Our current goal is to integrate evolutionary methods in the design of non-sequential behaviours and the tuning of specific parameters of the selection model. The foraging behaviour of an animal robot (animat has been modelled in order to integrate the sensory information from the robot to perform selection that is nearly optimized by the use of genetic algorithms. In this paper we present how selection through optimization finally arranges the pattern of presented behaviours for the foraging task. Hence, the execution of specific parts in a behavioural pattern may be ruled out by the tuning of these parameters. Furthermore, the intensive use of colour segmentation from a colour camera for locating a cylinder sets a burden on the calculations carried out by the genetic algorithm.

  13. A Hybrid Multiple Criteria Decision Making Model for Supplier Selection

    Directory of Open Access Journals (Sweden)

    Chung-Min Wu

    2013-01-01

    Full Text Available The sustainable supplier selection would be the vital part in the management of a sustainable supply chain. In this study, a hybrid multiple criteria decision making (MCDM model is applied to select optimal supplier. The fuzzy Delphi method, which can lead to better criteria selection, is used to modify criteria. Considering the interdependence among the selection criteria, analytic network process (ANP is then used to obtain their weights. To avoid calculation and additional pairwise comparisons of ANP, a technique for order preference by similarity to ideal solution (TOPSIS is used to rank the alternatives. The use of a combination of the fuzzy Delphi method, ANP, and TOPSIS, proposing an MCDM model for supplier selection, and applying these to a real case are the unique features of this study.

  14. Variable selection in Logistic regression model with genetic algorithm.

    Science.gov (United States)

    Zhang, Zhongheng; Trevino, Victor; Hoseini, Sayed Shahabuddin; Belciug, Smaranda; Boopathi, Arumugam Manivanna; Zhang, Ping; Gorunescu, Florin; Subha, Velappan; Dai, Songshi

    2018-02-01

    Variable or feature selection is one of the most important steps in model specification. Especially in the case of medical-decision making, the direct use of a medical database, without a previous analysis and preprocessing step, is often counterproductive. In this way, the variable selection represents the method of choosing the most relevant attributes from the database in order to build a robust learning models and, thus, to improve the performance of the models used in the decision process. In biomedical research, the purpose of variable selection is to select clinically important and statistically significant variables, while excluding unrelated or noise variables. A variety of methods exist for variable selection, but none of them is without limitations. For example, the stepwise approach, which is highly used, adds the best variable in each cycle generally producing an acceptable set of variables. Nevertheless, it is limited by the fact that it commonly trapped in local optima. The best subset approach can systematically search the entire covariate pattern space, but the solution pool can be extremely large with tens to hundreds of variables, which is the case in nowadays clinical data. Genetic algorithms (GA) are heuristic optimization approaches and can be used for variable selection in multivariable regression models. This tutorial paper aims to provide a step-by-step approach to the use of GA in variable selection. The R code provided in the text can be extended and adapted to other data analysis needs.

  15. Evaluation of phenoxybenzamine in the CFA model of pain following gene expression studies and connectivity mapping.

    Science.gov (United States)

    Chang, Meiping; Smith, Sarah; Thorpe, Andrew; Barratt, Michael J; Karim, Farzana

    2010-09-16

    We have previously used the rat 4 day Complete Freund's Adjuvant (CFA) model to screen compounds with potential to reduce osteoarthritic pain. The aim of this study was to identify genes altered in this model of osteoarthritic pain and use this information to infer analgesic potential of compounds based on their own gene expression profiles using the Connectivity Map approach. Using microarrays, we identified differentially expressed genes in L4 and L5 dorsal root ganglia (DRG) from rats that had received intraplantar CFA for 4 days compared to matched, untreated control animals. Analysis of these data indicated that the two groups were distinguishable by differences in genes important in immune responses, nerve growth and regeneration. This list of differentially expressed genes defined a "CFA signature". We used the Connectivity Map approach to identify pharmacologic agents in the Broad Institute Build02 database that had gene expression signatures that were inversely related ('negatively connected') with our CFA signature. To test the predictive nature of the Connectivity Map methodology, we tested phenoxybenzamine (an alpha adrenergic receptor antagonist) - one of the most negatively connected compounds identified in this database - for analgesic activity in the CFA model. Our results indicate that at 10 mg/kg, phenoxybenzamine demonstrated analgesia comparable to that of Naproxen in this model. Evaluation of phenoxybenzamine-induced analgesia in the current study lends support to the utility of the Connectivity Map approach for identifying compounds with analgesic properties in the CFA model.

  16. Applying Four Different Risk Models in Local Ore Selection

    International Nuclear Information System (INIS)

    Richmond, Andrew

    2002-01-01

    Given the uncertainty in grade at a mine location, a financially risk-averse decision-maker may prefer to incorporate this uncertainty into the ore selection process. A FORTRAN program risksel is presented to calculate local risk-adjusted optimal ore selections using a negative exponential utility function and three dominance models: mean-variance, mean-downside risk, and stochastic dominance. All four methods are demonstrated in a grade control environment. In the case study, optimal selections range with the magnitude of financial risk that a decision-maker is prepared to accept. Except for the stochastic dominance method, the risk models reassign material from higher cost to lower cost processing options as the aversion to financial risk increases. The stochastic dominance model usually was unable to determine the optimal local selection

  17. Statistical model selection with “Big Data”

    Directory of Open Access Journals (Sweden)

    Jurgen A. Doornik

    2015-12-01

    Full Text Available Big Data offer potential benefits for statistical modelling, but confront problems including an excess of false positives, mistaking correlations for causes, ignoring sampling biases and selecting by inappropriate methods. We consider the many important requirements when searching for a data-based relationship using Big Data, and the possible role of Autometrics in that context. Paramount considerations include embedding relationships in general initial models, possibly restricting the number of variables to be selected over by non-statistical criteria (the formulation problem, using good quality data on all variables, analyzed with tight significance levels by a powerful selection procedure, retaining available theory insights (the selection problem while testing for relationships being well specified and invariant to shifts in explanatory variables (the evaluation problem, using a viable approach that resolves the computational problem of immense numbers of possible models.

  18. DEET potentiates the development and persistence of anticholinesterase dependent chronic pain signs in a rat model of Gulf War Illness pain

    Energy Technology Data Exchange (ETDEWEB)

    Flunker, L.K., E-mail: lflunker@dental.ufl.edu [Division of Neuroscience, Dept. of Oral and Maxillofacial Surgery, Box 100416, JHMHC, University of Florida College of Dentistry, Gainesville, FL 32610 (United States); Nutter, T.J., E-mail: tnutter@dental.ufl.edu [Division of Neuroscience, Dept. of Oral and Maxillofacial Surgery, Box 100416, JHMHC, University of Florida College of Dentistry, Gainesville, FL 32610 (United States); Johnson, R.D., E-mail: rdjohnso@ufl.edu [Dept. of Physiological Sciences, University of Florida College of Veterinary Science, Gainesville, FL 32610 (United States); Cooper, B.Y., E-mail: bcooper@dental.ufl.edu [Division of Neuroscience, Dept. of Oral and Maxillofacial Surgery, Box 100416, JHMHC, University of Florida College of Dentistry, Gainesville, FL 32610 (United States)

    2017-02-01

    Exposure to DEET (N,N-diethyl-meta-toluamide) may have influenced the pattern of symptoms observed in soldiers with GWI (Gulf War Illness; Haley and Kurt, 1997). We examined how the addition of DEET (400 mg/kg; 50% topical) to an exposure protocol of permethrin (2.6 mg/kg; topical), chlorpyrifos (CP; 120 mg/kg), and pyridostigmine bromide (PB;13 mg/kg) altered the emergence and pattern of pain signs in an animal model of GWI pain (). Rats underwent behavioral testing before, during and after a 4 week exposure: 1) hindlimb pressure withdrawal threshold; 2) ambulation (movement distance and rate); and 3) resting duration. Additional studies were conducted to assess the influence of acute DEET (10–100 μM) on muscle and vascular nociceptor K{sub v}7, K{sub DR}, Na{sub v}1.8 and Na{sub v}1.9. We report that a 50% concentration of DEET enhanced the development and persistence of pain-signs. Rats exposed to all 4 compounds exhibited ambulation deficits that appeared 5–12 weeks post-exposure and persisted through weeks 21–24. Rats exposed to only three agents (CP or PB excluded), did not fully develop ambulation deficits. When PB was excluded, rats also developed rest duration pain signs, in addition to ambulation deficits. There was no evidence that physiological doses of DEET acutely modified nociceptor K{sub v}7, K{sub DR}, Na{sub v}1.8 or Na{sub v}1.9 activities. Nevertheless, DEET augmented protocols decreased the conductance of K{sub v}7 expressed in vascular nociceptors harvested from chronically exposed rats. We concluded that DEET enhanced the development and persistence of pain behaviors, but the anticholinesterases CP and PB played a determinant role. - Highlights: • DEET accelerated and prolonged pain-like behaviors in a rat model of Gulf War Illness. • The development of pain behaviors were dependent upon chlorpyrifos and pyridostigmine. • Conductance of vascular nociceptor Kv7 was diminished 12 weeks following exposures. • DEET did not have any

  19. DEET potentiates the development and persistence of anticholinesterase dependent chronic pain signs in a rat model of Gulf War Illness pain

    International Nuclear Information System (INIS)

    Flunker, L.K.; Nutter, T.J.; Johnson, R.D.; Cooper, B.Y.

    2017-01-01

    Exposure to DEET (N,N-diethyl-meta-toluamide) may have influenced the pattern of symptoms observed in soldiers with GWI (Gulf War Illness; Haley and Kurt, 1997). We examined how the addition of DEET (400 mg/kg; 50% topical) to an exposure protocol of permethrin (2.6 mg/kg; topical), chlorpyrifos (CP; 120 mg/kg), and pyridostigmine bromide (PB;13 mg/kg) altered the emergence and pattern of pain signs in an animal model of GWI pain (). Rats underwent behavioral testing before, during and after a 4 week exposure: 1) hindlimb pressure withdrawal threshold; 2) ambulation (movement distance and rate); and 3) resting duration. Additional studies were conducted to assess the influence of acute DEET (10–100 μM) on muscle and vascular nociceptor K v 7, K DR , Na v 1.8 and Na v 1.9. We report that a 50% concentration of DEET enhanced the development and persistence of pain-signs. Rats exposed to all 4 compounds exhibited ambulation deficits that appeared 5–12 weeks post-exposure and persisted through weeks 21–24. Rats exposed to only three agents (CP or PB excluded), did not fully develop ambulation deficits. When PB was excluded, rats also developed rest duration pain signs, in addition to ambulation deficits. There was no evidence that physiological doses of DEET acutely modified nociceptor K v 7, K DR , Na v 1.8 or Na v 1.9 activities. Nevertheless, DEET augmented protocols decreased the conductance of K v 7 expressed in vascular nociceptors harvested from chronically exposed rats. We concluded that DEET enhanced the development and persistence of pain behaviors, but the anticholinesterases CP and PB played a determinant role. - Highlights: • DEET accelerated and prolonged pain-like behaviors in a rat model of Gulf War Illness. • The development of pain behaviors were dependent upon chlorpyrifos and pyridostigmine. • Conductance of vascular nociceptor Kv7 was diminished 12 weeks following exposures. • DEET did not have any acute influence on nociceptor Kv7

  20. The Ehrlich Tumor Induces Pain-Like Behavior in Mice: A Novel Model of Cancer Pain for Pathophysiological Studies and Pharmacological Screening

    Directory of Open Access Journals (Sweden)

    Cassia Calixto-Campos

    2013-01-01

    Full Text Available The Ehrlich tumor is a mammary adenocarcinoma of mice that can be developed in solid and ascitic forms depending on its administration in tissues or cavities, respectively. The present study investigates whether the subcutaneous plantar administration of the Ehrlich tumor cells induces pain-like behavior and initial pharmacological susceptibility characteristics. The Ehrlich tumor cells (1 × 104–107 cells induced dose-dependent mechanical hyperalgesia (electronic version of the von Frey filaments, paw edema/tumor growth (caliper, and flinches compared with the saline group between days 2 and 12. There was no difference between doses of cells regarding thermal hyperalgesia in the hot-plate test. Indomethacin (a cyclooxygenase inhibitor and amitriptyline hydrochloride (a tricyclic antidepressant treatments did not affect flinches or thermal and mechanical hyperalgesia. On the other hand, morphine (an opioid inhibited the flinch behavior and the thermal and mechanical hyperalgesia. These effects of morphine on pain-like behavior were prevented by naloxone (an opioid receptor antagonist treatment. None of the treatments affected paw edema/tumor growth. The results showed that, in addition to tumor growth, administration of the Ehrlich tumor cells may represent a novel model for the study of cancer pain, specially the pain that is susceptible to treatment with opioids, but not to cyclooxygenase inhibitor or to tricyclic antidepressant.

  1. How Repeated Time To Event (RTTE) modelling of opioid requests after surgery may improve future post-operative pain management

    DEFF Research Database (Denmark)

    Juul, Rasmus Vestergaard; Rasmussen, Sten; Kreilgaard, Mads

    at Orthopaedic Department, Aalborg University Hospital, Denmark during the period May-Dec 2012. Morphine administration times (estimated precision: ±5mins), formulations and doses were extracted from medical journals in the hospitalization period or until 96 hours after surgery. RTTE modelling was performed......Title: How Repeated Time To Event (RTTE) modelling of opioid requests after surgery may improve future post-operative pain management Author: Rasmus Vestergaard Juul (1) Sten Rasmussen (2) Mads Kreilgaard (1) Ulrika S. H. Simonsson (3) Lona Louring Christrup (1) Trine Meldgaard Lund (1) Institution...... of surgery specific, drug concentration related, population specific and/or time-varying covariates of opioid requests and pain events. Conclusions: A framework has been developed based on RTTE modelling that may help improve future pain management by 1) Identification of surgery specific patterns in pain...

  2. Involvement of spinal orexin A in the electroacupuncture analgesia in a rat model of post-laparotomy pain

    Directory of Open Access Journals (Sweden)

    Feng Xiao-Ming

    2012-11-01

    Full Text Available Abstract Background Orexin A (OXA, hypocretin/hcrt 1 is a newly discovered potential analgesic substance. However, whether OXA is involved in acupuncture analgesia remains unknown. The present study was designed to investigate the involvement of spinal OXA in electroacupuncture (EA analgesia. Methods A modified rat model of post-laparotomy pain was adopted and evaluated. Von Frey filaments were used to measure mechanical allodynia of the hind paw and abdomen. EA at 2/15 Hz or 2/100 Hz was performed once on the bilateral ST36 and SP6 for 30 min perioperatively. SB-334867, a selective orexin 1 receptor (OX1R antagonist with a higher affinity for OXA than OXB, was intrathecally injected to observe its effect on EA analgesia. Results OXA at 0.3 nmol and EA at 2/15 Hz produced respective analgesic effects on the model (P0.05. In addition, naloxone, a selective opioid receptor antagonist, failed to antagonize OXA-induced analgesia (P>0.05. Conclusions The results of the present study indicate the involvement of OXA in EA analgesia via OX1R in an opioid-independent way.

  3. Selection, calibration, and validation of models of tumor growth.

    Science.gov (United States)

    Lima, E A B F; Oden, J T; Hormuth, D A; Yankeelov, T E; Almeida, R C

    2016-11-01

    This paper presents general approaches for addressing some of the most important issues in predictive computational oncology concerned with developing classes of predictive models of tumor growth. First, the process of developing mathematical models of vascular tumors evolving in the complex, heterogeneous, macroenvironment of living tissue; second, the selection of the most plausible models among these classes, given relevant observational data; third, the statistical calibration and validation of models in these classes, and finally, the prediction of key Quantities of Interest (QOIs) relevant to patient survival and the effect of various therapies. The most challenging aspects of this endeavor is that all of these issues often involve confounding uncertainties: in observational data, in model parameters, in model selection, and in the features targeted in the prediction. Our approach can be referred to as "model agnostic" in that no single model is advocated; rather, a general approach that explores powerful mixture-theory representations of tissue behavior while accounting for a range of relevant biological factors is presented, which leads to many potentially predictive models. Then representative classes are identified which provide a starting point for the implementation of OPAL, the Occam Plausibility Algorithm (OPAL) which enables the modeler to select the most plausible models (for given data) and to determine if the model is a valid tool for predicting tumor growth and morphology ( in vivo ). All of these approaches account for uncertainties in the model, the observational data, the model parameters, and the target QOI. We demonstrate these processes by comparing a list of models for tumor growth, including reaction-diffusion models, phase-fields models, and models with and without mechanical deformation effects, for glioma growth measured in murine experiments. Examples are provided that exhibit quite acceptable predictions of tumor growth in laboratory

  4. Sexually dimorphic effects of unpredictable early life adversity on visceral pain behavior in a rodent model.

    Science.gov (United States)

    Chaloner, Aaron; Greenwood-Van Meerveld, Beverley

    2013-03-01

    Visceral pain is the hallmark feature of irritable bowel syndrome (IBS), a gastrointestinal disorder, which is more commonly diagnosed in women. Female IBS patients frequently report a history of early life adversity (ELA); however, sex differences in ELA-induced visceral pain and the role of ovarian hormones have yet to be investigated. Therefore, we tested the hypothesis that ELA induces visceral hypersensitivity through a sexually dimorphic mechanism mediated via estradiol. As a model of ELA, neonatal rats were exposed to different pairings of an odor and shock to control for trauma predictability. In adulthood, visceral sensitivity was assessed via a visceromotor response to colorectal distension. Following ovariectomy and estradiol replacement in a separate group of rats, the visceral sensitivity was quantified. We found that females that received unpredictable odor-shock developed visceral hypersensitivity in adulthood. In contrast, visceral sensitivity was not significantly different following ELA in adult males. Ovariectomy reversed visceral hypersensitivity following unpredictable ELA, whereas estradiol replacement reestablished visceral hypersensitivity in the unpredictable group. This study is the first to show sex-related differences in visceral sensitivity following unpredictable ELA. Our data highlight the activational effect of estradiol as a pivotal mechanism in maintaining visceral hypersensitivity. This article directly implicates a critical role for ovarian hormones in maintaining visceral hypersensitivity following ELA, specifically identifying the activational effect of estradiol as a key modulator of visceral sensitivity. These data suggest that ELA induces persistent functional abdominal pain in female IBS patients through an estrogen-dependent mechanism. Copyright © 2013 American Pain Society. All rights reserved.

  5. Comparison of climate envelope models developed using expert-selected variables versus statistical selection

    Science.gov (United States)

    Brandt, Laura A.; Benscoter, Allison; Harvey, Rebecca G.; Speroterra, Carolina; Bucklin, David N.; Romañach, Stephanie; Watling, James I.; Mazzotti, Frank J.

    2017-01-01

    Climate envelope models are widely used to describe potential future distribution of species under different climate change scenarios. It is broadly recognized that there are both strengths and limitations to using climate envelope models and that outcomes are sensitive to initial assumptions, inputs, and modeling methods Selection of predictor variables, a central step in modeling, is one of the areas where different techniques can yield varying results. Selection of climate variables to use as predictors is often done using statistical approaches that develop correlations between occurrences and climate data. These approaches have received criticism in that they rely on the statistical properties of the data rather than directly incorporating biological information about species responses to temperature and precipitation. We evaluated and compared models and prediction maps for 15 threatened or endangered species in Florida based on two variable selection techniques: expert opinion and a statistical method. We compared model performance between these two approaches for contemporary predictions, and the spatial correlation, spatial overlap and area predicted for contemporary and future climate predictions. In general, experts identified more variables as being important than the statistical method and there was low overlap in the variable sets (0.9 for area under the curve (AUC) and >0.7 for true skill statistic (TSS). Spatial overlap, which compares the spatial configuration between maps constructed using the different variable selection techniques, was only moderate overall (about 60%), with a great deal of variability across species. Difference in spatial overlap was even greater under future climate projections, indicating additional divergence of model outputs from different variable selection techniques. Our work is in agreement with other studies which have found that for broad-scale species distribution modeling, using statistical methods of variable

  6. Models of microbiome evolution incorporating host and microbial selection.

    Science.gov (United States)

    Zeng, Qinglong; Wu, Steven; Sukumaran, Jeet; Rodrigo, Allen

    2017-09-25

    Numerous empirical studies suggest that hosts and microbes exert reciprocal selective effects on their ecological partners. Nonetheless, we still lack an explicit framework to model the dynamics of both hosts and microbes under selection. In a previous study, we developed an agent-based forward-time computational framework to simulate the neutral evolution of host-associated microbial communities in a constant-sized, unstructured population of hosts. These neutral models allowed offspring to sample microbes randomly from parents and/or from the environment. Additionally, the environmental pool of available microbes was constituted by fixed and persistent microbial OTUs and by contributions from host individuals in the preceding generation. In this paper, we extend our neutral models to allow selection to operate on both hosts and microbes. We do this by constructing a phenome for each microbial OTU consisting of a sample of traits that influence host and microbial fitnesses independently. Microbial traits can influence the fitness of hosts ("host selection") and the fitness of microbes ("trait-mediated microbial selection"). Additionally, the fitness effects of traits on microbes can be modified by their hosts ("host-mediated microbial selection"). We simulate the effects of these three types of selection, individually or in combination, on microbiome diversities and the fitnesses of hosts and microbes over several thousand generations of hosts. We show that microbiome diversity is strongly influenced by selection acting on microbes. Selection acting on hosts only influences microbiome diversity when there is near-complete direct or indirect parental contribution to the microbiomes of offspring. Unsurprisingly, microbial fitness increases under microbial selection. Interestingly, when host selection operates, host fitness only increases under two conditions: (1) when there is a strong parental contribution to microbial communities or (2) in the absence of a strong

  7. LiCABEDS II. Modeling of ligand selectivity for G-protein-coupled cannabinoid receptors.

    Science.gov (United States)

    Ma, Chao; Wang, Lirong; Yang, Peng; Myint, Kyaw Z; Xie, Xiang-Qun

    2013-01-28

    The cannabinoid receptor subtype 2 (CB2) is a promising therapeutic target for blood cancer, pain relief, osteoporosis, and immune system disease. The recent withdrawal of Rimonabant, which targets another closely related cannabinoid receptor (CB1), accentuates the importance of selectivity for the development of CB2 ligands in order to minimize their effects on the CB1 receptor. In our previous study, LiCABEDS (Ligand Classifier of Adaptively Boosting Ensemble Decision Stumps) was reported as a generic ligand classification algorithm for the prediction of categorical molecular properties. Here, we report extension of the application of LiCABEDS to the modeling of cannabinoid ligand selectivity with molecular fingerprints as descriptors. The performance of LiCABEDS was systematically compared with another popular classification algorithm, support vector machine (SVM), according to prediction precision and recall rate. In addition, the examination of LiCABEDS models revealed the difference in structure diversity of CB1 and CB2 selective ligands. The structure determination from data mining could be useful for the design of novel cannabinoid lead compounds. More importantly, the potential of LiCABEDS was demonstrated through successful identification of newly synthesized CB2 selective compounds.

  8. Use of selected complementary and alternative medicine (CAM) treatments in veterans with cancer or chronic pain: a cross-sectional survey

    OpenAIRE

    McEachrane-Gross, F Patricia; Liebschutz, Jane M; Berlowitz, Dan

    2006-01-01

    Abstract Background Complementary and alternative medicine (CAM) is emerging as an important form of care in the United States. We sought to measure the prevalence of selected CAM use among veterans attending oncology and chronic pain clinics and to describe the characteristics of CAM use in this population. Methods The self-administered, mail-in survey included questions on demographics, health beliefs, medical problems and 6 common CAM treatments (herbs, dietary supplements, chiropractic ca...

  9. Development of an Environment for Software Reliability Model Selection

    Science.gov (United States)

    1992-09-01

    now is directed to other related problems such as tools for model selection, multiversion programming, and software fault tolerance modeling... multiversion programming, 7. Hlardware can be repaired by spare modules, which is not. the case for software, 2-6 N. Preventive maintenance is very important

  10. Fuzzy Investment Portfolio Selection Models Based on Interval Analysis Approach

    Directory of Open Access Journals (Sweden)

    Haifeng Guo

    2012-01-01

    Full Text Available This paper employs fuzzy set theory to solve the unintuitive problem of the Markowitz mean-variance (MV portfolio model and extend it to a fuzzy investment portfolio selection model. Our model establishes intervals for expected returns and risk preference, which can take into account investors' different investment appetite and thus can find the optimal resolution for each interval. In the empirical part, we test this model in Chinese stocks investment and find that this model can fulfill different kinds of investors’ objectives. Finally, investment risk can be decreased when we add investment limit to each stock in the portfolio, which indicates our model is useful in practice.

  11. Diversified models for portfolio selection based on uncertain semivariance

    Science.gov (United States)

    Chen, Lin; Peng, Jin; Zhang, Bo; Rosyida, Isnaini

    2017-02-01

    Since the financial markets are complex, sometimes the future security returns are represented mainly based on experts' estimations due to lack of historical data. This paper proposes a semivariance method for diversified portfolio selection, in which the security returns are given subjective to experts' estimations and depicted as uncertain variables. In the paper, three properties of the semivariance of uncertain variables are verified. Based on the concept of semivariance of uncertain variables, two types of mean-semivariance diversified models for uncertain portfolio selection are proposed. Since the models are complex, a hybrid intelligent algorithm which is based on 99-method and genetic algorithm is designed to solve the models. In this hybrid intelligent algorithm, 99-method is applied to compute the expected value and semivariance of uncertain variables, and genetic algorithm is employed to seek the best allocation plan for portfolio selection. At last, several numerical examples are presented to illustrate the modelling idea and the effectiveness of the algorithm.

  12. A Primer for Model Selection: The Decisive Role of Model Complexity

    Science.gov (United States)

    Höge, Marvin; Wöhling, Thomas; Nowak, Wolfgang

    2018-03-01

    Selecting a "best" model among several competing candidate models poses an often encountered problem in water resources modeling (and other disciplines which employ models). For a modeler, the best model fulfills a certain purpose best (e.g., flood prediction), which is typically assessed by comparing model simulations to data (e.g., stream flow). Model selection methods find the "best" trade-off between good fit with data and model complexity. In this context, the interpretations of model complexity implied by different model selection methods are crucial, because they represent different underlying goals of modeling. Over the last decades, numerous model selection criteria have been proposed, but modelers who primarily want to apply a model selection criterion often face a lack of guidance for choosing the right criterion that matches their goal. We propose a classification scheme for model selection criteria that helps to find the right criterion for a specific goal, i.e., which employs the correct complexity interpretation. We identify four model selection classes which seek to achieve high predictive density, low predictive error, high model probability, or shortest compression of data. These goals can be achieved by following either nonconsistent or consistent model selection and by either incorporating a Bayesian parameter prior or not. We allocate commonly used criteria to these four classes, analyze how they represent model complexity and what this means for the model selection task. Finally, we provide guidance on choosing the right type of criteria for specific model selection tasks. (A quick guide through all key points is given at the end of the introduction.)

  13. Tramadol reduces anxiety-related and depression-associated behaviors presumably induced by pain in the chronic constriction injury model of neuropathic pain in rats.

    Science.gov (United States)

    Caspani, Ombretta; Reitz, Marie-Céline; Ceci, Angelo; Kremer, Andreas; Treede, Rolf-Detlef

    2014-09-01

    Depression and anxiety are common comorbidities of neuropathic pain (NP). Pharmacological preclinical studies on NP have given abundant information on the effects of drugs on reflex measures of stimulus-evoked pain. However, few preclinical studies focus on relief of comorbidities evoked by NP. In this study, we investigated the effects of tramadol on nociceptive reflex, depression-associated and anxiety-related behaviors in a NP model in rats. We used chronic constriction injury (CCI) of the sciatic nerve as an animal model of neuropathic pain. We performed electronic von Frey tests (evF) to measure mechanical sensitivity, elevated plus maze tests (EPM) to record anxiety-related behaviors and forced swimming tests (FST) to evaluate depression-associated behaviors. In the evF, CCI rats showed a decrease of 82% of the paw withdrawal threshold (PWT) compared to sham (Ppain and its indirect consequences and comorbidities, and that this study also is a model for pharmacological studies seeking to investigate the effect of drugs on the major disabling symptoms of NP. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. The influence of children's pain memories on subsequent pain experience.

    Science.gov (United States)

    Noel, Melanie; Chambers, Christine T; McGrath, Patrick J; Klein, Raymond M; Stewart, Sherry H

    2012-08-01

    Healthy children are often required to repeatedly undergo painful medical procedures (eg, immunizations). Although memory is often implicated in children's reactions to future pain, there is a dearth of research directly examining the relationship between the 2. The current study investigated the influence of children's memories for a novel pain stimulus on their subsequent pain experience. One hundred ten healthy children (60 boys) between the ages of 8 and 12 years completed a laboratory pain task and provided pain ratings. Two weeks later, children provided pain ratings based on their memories as well as their expectancies about future pain. One month following the initial laboratory visit, children again completed the pain task and provided pain ratings. Results showed that children's memory of pain intensity was a better predictor of subsequent pain reporting than their actual initial reporting of pain intensity, and mediated the relationship between initial and subsequent pain reporting. Children who had negatively estimated pain memories developed expectations of greater pain prior to a subsequent pain experience and showed greater increases in pain ratings over time than children who had accurate or positively estimated pain memories. These findings highlight the influence of pain memories on healthy children's expectations of future pain and subsequent pain experiences and extend predictive models of subsequent pain reporting. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  15. Music for pain relief.

    Science.gov (United States)

    Cepeda, M S; Carr, D B; Lau, J; Alvarez, H

    2006-04-19

    The efficacy of music for the treatment of pain has not been established. To evaluate the effect of music on acute, chronic or cancer pain intensity, pain relief, and analgesic requirements. We searched The Cochrane Library, MEDLINE, EMBASE, PsycINFO, LILACS and the references in retrieved manuscripts. There was no language restriction. We included randomized controlled trials that evaluated the effect of music on any type of pain in children or adults. We excluded trials that reported results of concurrent non-pharmacological therapies. Data was extracted by two independent review authors. We calculated the mean difference in pain intensity levels, percentage of patients with at least 50% pain relief, and opioid requirements. We converted opioid consumption to morphine equivalents. To explore heterogeneity, studies that evaluated adults, children, acute, chronic, malignant, labor, procedural, or experimental pain were evaluated separately, as well as those studies in which patients chose the type of music. Fifty-one studies involving 1867 subjects exposed to music and 1796 controls met inclusion criteria. In the 31 studies evaluating mean pain intensity there was a considerable variation in the effect of music, indicating statistical heterogeneity ( I(2) = 85.3%). After grouping the studies according to the pain model, this heterogeneity remained, with the exception of the studies that evaluated acute postoperative pain. In this last group, patients exposed to music had pain intensity that was 0.5 units lower on a zero to ten scale than unexposed subjects (95% CI: -0.9 to -0.2). Studies that permitted patients to select the music did not reveal a benefit from music; the decline in pain intensity was 0.2 units, 95% CI (-0.7 to 0.2). Four studies reported the proportion of subjects with at least 50% pain relief; subjects exposed to music had a 70% higher likelihood of having pain relief than unexposed subjects (95% CI: 1.21 to 2.37). NNT = 5 (95% CI: 4 to 13). Three

  16. Optical inactivation of the anterior cingulate cortex modulate descending pain pathway in a rat model of trigeminal neuropathic pain created via chronic constriction injury of the infraorbital nerve

    Directory of Open Access Journals (Sweden)

    Moon HC

    2017-10-01

    facial cold allodynia scores were significantly improved in the TN lesion group during optical stimulation compared to those in the control group. Thalamic neuronal activity, consisting of the firing rate (spikes/s and burst rate (bursts/s, was also decreased during optical stimulation.Conclusion: Reciprocal optical inhibition of the ACC can alleviate pain-associated behavior and decrease abnormal thalamic sensory neuron activity in the trigeminal neuropathic rat model. The descending pain pathway can modulate thalamic neurons from the ACC following optical stimulation. Keywords: optogenetics, trigeminal neuralgia, anterior cingulate cortex, neuropathic pain

  17. Selection of climate change scenario data for impact modelling

    DEFF Research Database (Denmark)

    Sloth Madsen, M; Fox Maule, C; MacKellar, N

    2012-01-01

    Impact models investigating climate change effects on food safety often need detailed climate data. The aim of this study was to select climate change projection data for selected crop phenology and mycotoxin impact models. Using the ENSEMBLES database of climate model output, this study...... illustrates how the projected climate change signal of important variables as temperature, precipitation and relative humidity depends on the choice of the climate model. Using climate change projections from at least two different climate models is recommended to account for model uncertainty. To make...... the climate projections suitable for impact analysis at the local scale a weather generator approach was adopted. As the weather generator did not treat all the necessary variables, an ad-hoc statistical method was developed to synthesise realistic values of missing variables. The method is presented...

  18. A SUPPLIER SELECTION MODEL FOR SOFTWARE DEVELOPMENT OUTSOURCING

    Directory of Open Access Journals (Sweden)

    Hancu Lucian-Viorel

    2010-12-01

    Full Text Available This paper presents a multi-criteria decision making model used for supplier selection for software development outsourcing on e-marketplaces. This model can be used in auctions. The supplier selection process becomes complex and difficult on last twenty years since the Internet plays an important role in business management. Companies have to concentrate their efforts on their core activities and the others activities should be realized by outsourcing. They can achieve significant cost reduction by using e-marketplaces in their purchase process and by using decision support systems on supplier selection. In the literature were proposed many approaches for supplier evaluation and selection process. The performance of potential suppliers is evaluated using multi criteria decision making methods rather than considering a single factor cost.

  19. Can a microscopic stochastic model explain the emergence of pain cycles in patients?

    International Nuclear Information System (INIS)

    Di Patti, Francesca; Fanelli, Duccio

    2009-01-01

    A stochastic model is introduced here to investigate the molecular mechanisms which trigger the perception of pain. The action of analgesic drug compounds is discussed in a dynamical context, where the competition with inactive species is explicitly accounted for. Finite size effects inevitably perturb the mean-field dynamics: oscillations in the amount of bound receptors are spontaneously manifested, driven by the noise which is intrinsic to the system under scrutiny. These effects are investigated both numerically, via stochastic simulations, and analytically, through a large size expansion. The claim that our findings could provide a consistent interpretative framework for explaining the emergence of cyclic behaviors in response to analgesic treatments is substantiated

  20. Optimization of a Pain Model: Effects of Body Temperature and Anesthesia on Bladder Nociception in Mice

    Science.gov (United States)

    Sadler, Katelyn E.; Stratton, Jarred M.; DeBerry, Jennifer J.; Kolber, Benedict J.

    2013-01-01

    Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating urological condition that is resistant to treatment and poorly understood. To determine novel molecular treatment targets and to elucidate the contribution of the nervous system to IC/BPS, many rodent bladder pain models have been developed. In this study we evaluated the effects of anesthesia induction and temperature variation in a mouse model of bladder pain known as urinary bladder distension (UBD). In this model compressed air is used to distend the bladder to distinct pressures while electrodes record the reflexive visceromotor response (VMR) from the overlying abdominal muscle. Two isoflurane induction models are commonly used before UBD: a short method lasting approximately 30 minutes and a long method lasting approximately 90 minutes. Animals were anesthetized with one of the methods then put through three sets of graded bladder distensions. Distensions performed following the short anesthesia protocol were significantly different from one another despite identical testing parameters; this same effect was not observed when the long anesthesia protocol was used. In order to determine the effect of temperature on VMRs, animals were put through three graded distension sets at 37.5 (normal mouse body temperature), 35.5, and 33.5°C. Distensions performed at 33.5 and 35.5°C were significantly lower than those performed at 37.5°C. Additionally, Western blot analysis revealed significantly smaller increases in spinal levels of phosphorylated extracellular-signal regulated kinase 2 (pERK2) following bladder distension in animals whose body temperature was maintained at 33.5°C as opposed to 37.5°C. These results highlight the significance of the dynamic effects of anesthesia on pain-like changes and the importance of close monitoring of temperature while performing UBD. For successful interpretation of VMRs and translation to human disease, body temperature should be maintained at 37.5

  1. Evaluation of Lercanidipine in Paclitaxel-Induced Neuropathic Pain Model in Rat: A Preliminary Study

    OpenAIRE

    Saha, Lekha; Hota, Debasish; Chakrabarti, Amitava

    2012-01-01

    Objective. To demonstrate the antinociceptive effect of lercanidipine in paclitaxel-induced neuropathy model in rat. Materials and Methods. A total of 30 rats were divided into five groups of six rats in each group as follows: Gr I: 0.9% NaCl, Gr II: paclitaxel + 0.9% NaCl, Gr III: paclitaxel + lercanidipine 0.5 μg/kg, Gr IV: paclitaxel + lercanidipine 1 μg/kg, and Gr V: paclitaxel + lercanidipine 2.5 μg/kg. Paclitaxel-induced neuropathic pain in rat was produced by single intraperitoneal (i....

  2. Adverse Selection Models with Three States of Nature

    Directory of Open Access Journals (Sweden)

    Daniela MARINESCU

    2011-02-01

    Full Text Available In the paper we analyze an adverse selection model with three states of nature, where both the Principal and the Agent are risk neutral. When solving the model, we use the informational rents and the efforts as variables. We derive the optimal contract in the situation of asymmetric information. The paper ends with the characteristics of the optimal contract and the main conclusions of the model.

  3. Development and validation of an animal model of prostate inflammation-induced chronic pelvic pain: evaluating from inflammation of the prostate to pain behavioral modifications.

    Directory of Open Access Journals (Sweden)

    Feng Zeng

    Full Text Available BACKGROUND: Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS is the most common type of prostatitis. Due to the lack of a suitable animal model partly, the pathogenesis for this condition is obscure. In the current study we developed and validated an animal model for nonbacterial prostatitis and prostate inflammation-induced chronic pelvic pain in rats with the use of intraprostatic injection of λ-carrageenan. METHODS: Male Sprague-Dawley rats weighing 250-350 g were used for the experiments. After intraprostatic injection of 3% λ-carrageenan, at different time points(after 24 h, 7 d, 14 d and 30 d of injection, radiant heat and von Frey filaments were applied to the scrotum of rats to measure the heat and mechanical thresholds respectively. Then the prostate was removed for histology, and cyclooxygenase (COX 2 protein expression was determined by Western-blot. Evans blue(50 mg/kg was also injected intravenously to assess for plasma protein extravasation at different time points after injection of λ-carrageenan. RESULTS: Compared to control group, inflamed animals showed a significant reduction in mechanical threshold (mechanical allodynia at 24 h and 7d(p = 0.022,0.046, respectively, and a significant reduction in heat threshold (thermal hyperalgesia at 24 h, 7d and 14 d(p = 0.014, 0.018, 0.002, respectively in the scrotal skin. Significant increase of inflammatory cell accumulation, COX2 expression and Evans blue extravasation were observed at 24 h, 7d and 14 d after injection. CONCLUSIONS: Intraprostatic λ-carrageenan injection induced neurogenic prostatitis and prostate inflammation pain, which lasted at least 2 weeks. The current model is expected to be a valuable preclinical tool to study the neurobiological mechanisms of male chronic pelvic pain.

  4. Comparing the staffing models of outsourcing in selected companies

    OpenAIRE

    Chaloupková, Věra

    2010-01-01

    This thesis deals with problems of takeover of employees in outsourcing. The capital purpose is to compare the staffing model of outsourcing in selected companies. To compare in selected companies I chose multi-criteria analysis. This thesis is dividend into six chapters. The first charter is devoted to the theoretical part. In this charter describes the basic concepts as outsourcing, personal aspects, phase of the outsourcing projects, communications and culture. The rest of thesis is devote...

  5. Manipulating the extracellular matrix: an animal model of the bladder pain syndrome.

    Science.gov (United States)

    Offiah, Ifeoma; Didangelos, Athanasios; OʼReilly, Barry A; McMahon, Stephen B

    2017-01-01

    Bladder pain syndrome (BPS) is associated with breakdown of the protective uroepithelial barrier of the urinary bladder allowing urinary constituents access to bladder sensory neurons. Although there are several animal models of cystitis, none specifically relates to BPS. Here, we aimed to create such a model using enzymatic digestion of the barrier proteoglycans (PGs) in the rat. Twenty female Wistar rats were anaesthetized and transurethrally catheterized. Ten animals were treated with 0.25IU of intravesical chondroitinase ABC and heparanase III to digest chondroitin sulphate and heparin sulphate PGs, respectively. Ten animals received saline. Following PG deglycosylation, bladders showed irregular loss of the apical uroplakin and a significant increase in neutrophils, not evident in the control group. Spinal cord sections were also collected for c-fos analysis. A large and significant increase in fos immunoreactivity in the L6/S1 segments in the treatment vs control bladders was observed. Cystometry was performed on 5 treatment and 5 control animals. Analysis revealed a significant increase in micturition reflex excitability postdeglycosylation. On a further group of 10 animals, von Frey mechanical withdrawal thresholds were tested on abdominal skin before and after PG digestions. There was a significant decrease in abdominal mechanical withdrawal threshold postdeglycosylation compared with controls. The results of this animal study suggest that many of the clinical features of BPS are seen after PG digestion from the bladder lumen. This model can be used to further understand mechanisms of pain in patients with BPS and to test new therapeutic strategies.

  6. [Model to predict staffing for anesthesiology and post-anesthesia intensive care units and pain clinics].

    Science.gov (United States)

    Canet, J; Moral, V; Villalonga, A; Pelegrí, D; Gomar, C; Montero, A

    2001-01-01

    Human resources account for a large part of the budgets of anesthesia and post-anesthesia intensive care units and pain clinics (A-PICU-PC). Adequate staffing is a key factor in providing for both effective care and professional staff development. Changes in professional responsibilities have rendered obsolete the concept of one anesthesiologist per operating room. Duties must be analyzed objectively to facilitate understanding between hospital administrators and A-PICU-PC chiefs of service when assigning human resources. The Catalan Society of Anesthesiology, Post-anesthesia Intensive Care and Pain Therapy has developed a model for estimating requirements for A-PICU-PC staffing based on three factors: 1) Definition of staff positions that must be filled and criteria for assigning human resources; 2) Estimation of non-care-related time required by the department for training, teaching, research and internal management, and 3) Estimation of staff required to cover absences from work for vacations, personal leave or illness. The model revealed that the ratio of number of staff positions to number of persons employed by an A-PICU-PC is approximately 1.3. Differences in the nature of services managed by an A-PICU-PC or the type of hospital might change the ratio slightly. The model can be applied universally, independently of differences that might exist among departments. Widespread application would allow adoption of a common language to be used by health care managers and A-PICU-PC departments when discussing a basis for consensus about our specialty.

  7. ERP Software Selection Model using Analytic Network Process

    OpenAIRE

    Lesmana , Andre Surya; Astanti, Ririn Diar; Ai, The Jin

    2014-01-01

    During the implementation of Enterprise Resource Planning (ERP) in any company, one of the most important issues is the selection of ERP software that can satisfy the needs and objectives of the company. This issue is crucial since it may affect the duration of ERP implementation and the costs incurred for the ERP implementation. This research tries to construct a model of the selection of ERP software that are beneficial to the company in order to carry out the selection of the right ERP sof...

  8. Slack channels expressed in sensory neurons control neuropathic pain in mice.

    Science.gov (United States)

    Lu, Ruirui; Bausch, Anne E; Kallenborn-Gerhardt, Wiebke; Stoetzer, Carsten; Debruin, Natasja; Ruth, Peter; Geisslinger, Gerd; Leffler, Andreas; Lukowski, Robert; Schmidtko, Achim

    2015-01-21

    Slack (Slo2.2) is a sodium-activated potassium channel that regulates neuronal firing activities and patterns. Previous studies identified Slack in sensory neurons, but its contribution to acute and chronic pain in vivo remains elusive. Here we generated global and sensory neuron-specific Slack mutant mice and analyzed their behavior in various animal models of pain. Global ablation of Slack led to increased hypersensitivity in models of neuropathic pain, whereas the behavior in models of inflammatory and acute nociceptive pain was normal. Neuropathic pain behaviors were also exaggerated after ablation of Slack selectively in sensory neurons. Notably, the Slack opener loxapine ameliorated persisting neuropathic pain behaviors. In conclusion, Slack selectively controls the sensory input in neuropathic pain states, suggesting that modulating its activity might represent a novel strategy for management of neuropathic pain. Copyright © 2015 the authors 0270-6474/15/351125-11$15.00/0.

  9. Economic assessment model architecture for AGC/AVLIS selection

    International Nuclear Information System (INIS)

    Hoglund, R.L.

    1984-01-01

    The economic assessment model architecture described provides the flexibility and completeness in economic analysis that the selection between AGC and AVLIS demands. Process models which are technology-specific will provide the first-order responses of process performance and cost to variations in process parameters. The economics models can be used to test the impacts of alternative deployment scenarios for a technology. Enterprise models provide global figures of merit for evaluating the DOE perspective on the uranium enrichment enterprise, and business analysis models compute the financial parameters from the private investor's viewpoint

  10. Osteoprotegerin reduces the development of pain behaviour and joint pathology in a model of osteoarthritis.

    Science.gov (United States)

    Sagar, Devi Rani; Ashraf, Sadaf; Xu, Luting; Burston, James J; Menhinick, Matthew R; Poulter, Caroline L; Bennett, Andrew J; Walsh, David A; Chapman, Victoria

    2014-08-01

    Increased subchondral bone turnover may contribute to pain in osteoarthritis (OA). To investigate the analgesic potential of a modified version of osteoprotegerin (osteoprotegerin-Fc (OPG-Fc)) in the monosodium iodoacetate (MIA) model of OA pain. Male Sprague Dawley rats (140-260 g) were treated with either OPG-Fc (3 mg/kg, subcutaneously) or vehicle (phosphate-buffered saline) between days 1 and 27 (pre-emptive treatment) or days 21 and 27 (therapeutic treatment) after an intra-articular injection of MIA (1 mg/50 µl) or saline. A separate cohort of rats received the bisphosphonate zoledronate (100 µg/kg, subcutaneously) between days 1 and 25 post-MIA injection. Incapacitance testing and von Frey (1-15 g) hind paw withdrawal thresholds were used to assess pain behaviour. At the end of the study, rats were killed and the knee joints and spinal cord removed for analysis. Immunohistochemical studies using Iba-1 and GFAP quantified levels of activation of spinal microglia and astrocytes, respectively. Joint sections were stained with haematoxylin and eosin or Safranin-O fast green and scored for matrix proteoglycan and overall joint morphology. The numbers of tartrate-resistant acid phosphatase-positive osteoclasts were quantified. N=10 rats/group. Pre-emptive treatment with OPG-Fc significantly attenuated the development of MIA-induced changes in weightbearing, but not allodynia. OPG-Fc decreased osteoclast number, inhibited the formation of osteophytes and improved structural pathology within the joint similarly to the decrease seen after pretreatment with the bisphosphonate, zoledronate. Therapeutic treatment with OPG-Fc decreased pain behaviour, but did not improve pathology in rats with established joint damage. Our data suggest that early targeting of osteoclasts may reduce pain associated with OA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. IT vendor selection model by using structural equation model & analytical hierarchy process

    Science.gov (United States)

    Maitra, Sarit; Dominic, P. D. D.

    2012-11-01

    Selecting and evaluating the right vendors is imperative for an organization's global marketplace competitiveness. Improper selection and evaluation of potential vendors can dwarf an organization's supply chain performance. Numerous studies have demonstrated that firms consider multiple criteria when selecting key vendors. This research intends to develop a new hybrid model for vendor selection process with better decision making. The new proposed model provides a suitable tool for assisting decision makers and managers to make the right decisions and select the most suitable vendor. This paper proposes a Hybrid model based on Structural Equation Model (SEM) and Analytical Hierarchy Process (AHP) for long-term strategic vendor selection problems. The five steps framework of the model has been designed after the thorough literature study. The proposed hybrid model will be applied using a real life case study to assess its effectiveness. In addition, What-if analysis technique will be used for model validation purpose.

  12. Model Selection in Historical Research Using Approximate Bayesian Computation

    Science.gov (United States)

    Rubio-Campillo, Xavier

    2016-01-01

    Formal Models and History Computational models are increasingly being used to study historical dynamics. This new trend, which could be named Model-Based History, makes use of recently published datasets and innovative quantitative methods to improve our understanding of past societies based on their written sources. The extensive use of formal models allows historians to re-evaluate hypotheses formulated decades ago and still subject to debate due to the lack of an adequate quantitative framework. The initiative has the potential to transform the discipline if it solves the challenges posed by the study of historical dynamics. These difficulties are based on the complexities of modelling social interaction, and the methodological issues raised by the evaluation of formal models against data with low sample size, high variance and strong fragmentation. Case Study This work examines an alternate approach to this evaluation based on a Bayesian-inspired model selection method. The validity of the classical Lanchester’s laws of combat is examined against a dataset comprising over a thousand battles spanning 300 years. Four variations of the basic equations are discussed, including the three most common formulations (linear, squared, and logarithmic) and a new variant introducing fatigue. Approximate Bayesian Computation is then used to infer both parameter values and model selection via Bayes Factors. Impact Results indicate decisive evidence favouring the new fatigue model. The interpretation of both parameter estimations and model selection provides new insights into the factors guiding the evolution of warfare. At a methodological level, the case study shows how model selection methods can be used to guide historical research through the comparison between existing hypotheses and empirical evidence. PMID:26730953

  13. Sample selection and taste correlation in discrete choice transport modelling

    DEFF Research Database (Denmark)

    Mabit, Stefan Lindhard

    2008-01-01

    explain counterintuitive results in value of travel time estimation. However, the results also point at the difficulty of finding suitable instruments for the selection mechanism. Taste heterogeneity is another important aspect of discrete choice modelling. Mixed logit models are designed to capture...... the question for a broader class of models. It is shown that the original result may be somewhat generalised. Another question investigated is whether mode choice operates as a self-selection mechanism in the estimation of the value of travel time. The results show that self-selection can at least partly...... of taste correlation in willingness-to-pay estimation are presented. The first contribution addresses how to incorporate taste correlation in the estimation of the value of travel time for public transport. Given a limited dataset the approach taken is to use theory on the value of travel time as guidance...

  14. Short-Run Asset Selection using a Logistic Model

    Directory of Open Access Journals (Sweden)

    Walter Gonçalves Junior

    2011-06-01

    Full Text Available Investors constantly look for significant predictors and accurate models to forecast future results, whose occasional efficacy end up being neutralized by market efficiency. Regardless, such predictors are widely used for seeking better (and more unique perceptions. This paper aims to investigate to what extent some of the most notorious indicators have discriminatory power to select stocks, and if it is feasible with such variables to build models that could anticipate those with good performance. In order to do that, logistical regressions were conducted with stocks traded at Bovespa using the selected indicators as explanatory variables. Investigated in this study were the outputs of Bovespa Index, liquidity, the Sharpe Ratio, ROE, MB, size and age evidenced to be significant predictors. Also examined were half-year, logistical models, which were adjusted in order to check the potential acceptable discriminatory power for the asset selection.

  15. Anti-hyperalgesic effect of electroacupuncture in a model of post-incisional pain in rats

    Directory of Open Access Journals (Sweden)

    R. Oliveira

    2000-08-01

    Full Text Available Electroacupuncture has been proposed to be a low cost and practical method that allows effective pain management with minimal collateral effects. In this study we have examined the effect of electroacupuncture against the hyperalgesia developed in a model of post-incisional pain in rats. A 1-cm longitudinal incision was made through the skin and fascia of the plantar region of the animal hind paw. Mechanical hyperalgesia in the incision was evaluated 135 min after the surgery with von Frey filaments. The tension threshold was reduced from 75 g (upper limit of the test to 1.36 ± 0.36 g (mean ± SEM in control rats. It is shown that a 15-min period of electroacupuncture applied 120 min after surgery to the Zusanli (ST36 and Sanyinjiao (SP6 points, but not to non-acupoints, produces a significant and long-lasting reduction of the mechanical hyperalgesia induced by the surgical incision of the plantar surface of the ipsilateral hind paw. The tension threshold was reduced from 75 to 27.6 ± 4.2 g in animals soon after the end of electroacupuncture. The mechanical threshold in this group was about 64% less than in control. Electroacupuncture was ineffective in rats treated 10 min earlier with naloxone (1 mg/kg, ip, thus confirming the involvement of opioid mechanisms in the antinociceptive effects of such procedure. The results indicate that post-incisional pain is a useful model for studying the anti-hyperalgesic properties of electroacupuncture in laboratory animals.

  16. Uncertain programming models for portfolio selection with uncertain returns

    Science.gov (United States)

    Zhang, Bo; Peng, Jin; Li, Shengguo

    2015-10-01

    In an indeterminacy economic environment, experts' knowledge about the returns of securities consists of much uncertainty instead of randomness. This paper discusses portfolio selection problem in uncertain environment in which security returns cannot be well reflected by historical data, but can be evaluated by the experts. In the paper, returns of securities are assumed to be given by uncertain variables. According to various decision criteria, the portfolio selection problem in uncertain environment is formulated as expected-variance-chance model and chance-expected-variance model by using the uncertainty programming. Within the framework of uncertainty theory, for the convenience of solving the models, some crisp equivalents are discussed under different conditions. In addition, a hybrid intelligent algorithm is designed in the paper to provide a general method for solving the new models in general cases. At last, two numerical examples are provided to show the performance and applications of the models and algorithm.

  17. Ear acupuncture in the control of migraine pain: selecting the right acupoints by the "needle-contact test".

    Science.gov (United States)

    Romoli, M; Allais, G; Airola, G; Benedetto, C

    2005-05-01

    There is increasing evidence that somatic acupuncture can be helpful in migraine treatment, but substantial data on ear acupuncture (EAP) are still lacking. EAP can be useful both in the diagnosis and in the treatment of many medical conditions. As regards the control of migrainous pain, we present a case report in which a procedure called the "needle-contact test" is described in detail. During a migraine attack, the patient undergoes an accurate search for tender points of the outer ear by means of a specific pressure algometer. Once the most sensitive point has been identified, an acupuncture needle is placed in contact with it for about 10 s, without skin penetration. The expected effect is a quick and evident reduction of acute pain. If no appreciable variation in pain intensity occurs within the following 60 s, a second or third attempt is made on other previously identified tender points, until the point at which the patient notices a clear remission of pain is found. In this positive case, the same testing needle can be immediately used for therapy, completely penetrating the skin, and then extracted after about 30 min. Alternatively, a temporary needle can be implanted and left in situ for a variable period of time (1-15 days). This innovative technique allows the identification, with maximum accuracy, of the most effective ear acupoints on migraine pain during acute attacks.

  18. Sympathetic regulation and anterior cingulate cortex volume are altered in a rat model of chronic back pain.

    Science.gov (United States)

    Touj, Sara; Houle, Sébastien; Ramla, Djamel; Jeffrey-Gauthier, Renaud; Hotta, Harumi; Bronchti, Gilles; Martinoli, Maria-Grazia; Piché, Mathieu

    2017-06-03

    Chronic pain is associated with autonomic disturbance. However, specific effects of chronic back pain on sympathetic regulation remain unknown. Chronic pain is also associated with structural changes in the anterior cingulate cortex (ACC), which may be linked to sympathetic dysregulation. The aim of this study was to determine whether sympathetic regulation and ACC surface and volume are affected in a rat model of chronic back pain, in which complete Freund Adjuvant (CFA) is injected in back muscles. Sympathetic regulation was assessed with renal blood flow (RBF) changes induced by electrical stimulation of a hind paw, while ACC structure was examined by measuring cortical surface and volume. RBF changes and ACC volume were compared between control rats and rats injected with CFA in back muscles segmental (T10) to renal sympathetic innervation or not (T2). In rats with CFA, chronic inflammation was observed in the affected muscles in addition to increased nuclear factor-kappa B (NF-kB) protein expression in corresponding spinal cord segments (p=0.01) as well as decreased ACC volume (pchronic pain at T2 (p'schronic back pain alters sympathetic functions through non-segmental mechanisms, possibly by altering descending regulatory pathways from ACC. Yet, segmental somato-sympathetic reflexes may compete with non-segmental processes depending on the back region affected by pain and according to the segmental organization of the sympathetic nervous system. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. The Properties of Model Selection when Retaining Theory Variables

    DEFF Research Database (Denmark)

    Hendry, David F.; Johansen, Søren

    Economic theories are often fitted directly to data to avoid possible model selection biases. We show that embedding a theory model that specifies the correct set of m relevant exogenous variables, x{t}, within the larger set of m+k candidate variables, (x{t},w{t}), then selection over the second...... set by their statistical significance can be undertaken without affecting the estimator distribution of the theory parameters. This strategy returns the theory-parameter estimates when the theory is correct, yet protects against the theory being under-specified because some w{t} are relevant....

  20. The involvement of peripheral alpha 2-adrenoceptors in the antihyperalgesic effect of oxcarbazepine in a rat model of inflammatory pain.

    Science.gov (United States)

    Tomić, Maja A; Vucković, Sonja M; Stepanović-Petrović, Radica M; Ugresić, Nenad D; Paranos, Sonja Lj; Prostran, Milica S; Bosković, Bogdan

    2007-11-01

    We studied whether peripheral alpha2-adrenergic receptors are involved in the antihyperalgesic effects of oxcarbazepine by examining the effects of yohimbine (selective alpha2-adrenoceptor antagonist), BRL 44408 (selective alpha(2A)-adrenoceptor antagonist), MK-912 (selective alpha2C-adrenoceptor antagonist), and clonidine (alpha2-adrenoceptor agonist) on the antihyperalgesic effect of oxcarbazepine in the rat model of inflammatory pain. Rats were intraplantarly (i.pl.) injected with the proinflammatory compound concanavalin A (Con A). A paw-pressure test was used to determine: 1) the development of hyperalgesia induced by Con A; 2) the effects of oxcarbazepine (i.pl.) on Con A-induced hyperalgesia; and 3) the effects of i.pl. yohimbine, BRL 44408, MK-912 and clonidine on the oxcarbazepine antihyperalgesia. Both oxcarbazepine (1000-3000 nmol/paw; i.pl.) and clonidine (1.9-7.5 nmol/paw; i.pl.) produced a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by Con A. Yohimbine (260 and 520 nmol/paw; i.pl.), BRL 44408 (100 and 200 nmol/paw; i.pl.) and MK-912 (10 and 20 nmol/paw; i.pl.) significantly depressed the antihyperalgesic effects of oxcarbazepine (2000 nmol/paw; i.pl.) in a dose-dependent manner. The effects of antagonists were due to local effects since they were not observed after administration into the contralateral hindpaw. Oxcarbazepine and clonidine administered jointly in fixed-dose fractions of the ED(50) (1/4, 1/2, and 3/4) caused significant and dose-dependent reduction of hyperalgesia induced by Con A. Isobolographic analysis revealed an additive antihyperalgesic effect. Our results indicate that the peripheral alpha2A and alpha2C adrenoceptors could be involved in the antihyperalgesic effects of oxcarbazepine in a rat model of inflammatory hyperalgesia.

  1. Methyl-orvinol-Dual activity opioid receptor ligand inhibits gastrointestinal transit and alleviates abdominal pain in the mouse models mimicking diarrhea-predominant irritable bowel syndrome.

    Science.gov (United States)

    Zielińska, Marta; Jarmuż, Agata; Wasilewski, Andrzej; Cami-Kobeci, Gerta; Husbands, Stephen; Fichna, Jakub

    2017-04-01

    Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional disorder of the gastrointestinal (GI) tract. The major IBS-D symptoms include diarrhea, abdominal pain and discomfort. High density of opioid receptors (ORs) in the GI tract and their participation in the maintenance of GI homeostasis make ORs ligands an attractive option for developing new anti-IBS-D treatments. The aim of this study was to characterize the effect of methyl-orvinol on the GI motility and secretion and in mouse models mimicking symptoms of IBS-D. In vitro, the effects of methyl-orvinol on electrical field stimulated smooth muscle contractility and epithelial ion transport were characterized in the mouse colon. In vivo, the following tests were used to determine methyl-orvinol effect on mouse GI motility: colonic bead expulsion, whole GI transit and fecal pellet output. An antinociceptive action of methyl-orvinol was assessed in the mouse model of visceral pain induced by mustard oil. Methyl-orvinol (10 -10 to 10 -6 M) inhibited colonic smooth muscle contractions in a concentration-dependent manner. This effect was reversed by naloxone (non-selective opioid antagonist) and β-funaltrexamine (selective MOP antagonist). Experiments with a selective KOP receptor agonist, U50488 revealed that methyl-orvinol is a KOP receptor antagonist in the GI tract. Methyl-orvinol enhanced epithelial ion transport. In vivo, methyl-orvinol inhibited colonic bead expulsion and prolonged GI transit. Methyl-orvinol improved hypermotility and reduced abdominal pain in the mouse models mimicking IBS-D symptoms. Methyl-orvinol could become a promising drug candidate in chronic therapy of functional GI diseases such as IBS-D. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  2. Physiotherapy and low back pain - part iii: outcomes research utilising the biosychosocial model: psychosocial outcomes

    Directory of Open Access Journals (Sweden)

    L. D. Bardin

    2003-02-01

    has evolved that necessitates the use of a biopsychosocial model, focusing on illness rather than disease and incorporating the biological, psychological and social aspects that are important to understand and to study LBP in its chronic form. Traditional outcome measures that measure elements within the biological component are limited to assess the spectrum of impacts caused by chronic low back pain (CLBP and the validity, reliability and sensitivity of some of these measures has been questioned.Few physiologic tests of spine function are clinically meaningful to patients, objective physical findings can be absent, and in CLBP disability and activity intolerance are often disproportional to the original injury. Biological outcomes should be complemented by outcomes of the psychosocial aspects of back pain that measure the considerable functional and emotional impact on the quality of life of patients experiencing low back dysfunction. Outcomes research is an analysis of clinical practice as it actually occurs and can  make a valuable contribution to understanding the multidimensional impact of LBP. Psychosocial aspects of the biopsychosocial model for outcomes research are discussed in part III: functional status/disability, psychological impairment, patient satisfaction, health related quality of life

  3. Effects of Electroacupuncture Treatment on Bone Cancer Pain Model with Morphine Tolerance

    Directory of Open Access Journals (Sweden)

    Lei Sima

    2016-01-01

    Full Text Available Objective. To explore the efficacy of electroacupuncture treatment in cancer induced bone pain (CIBP rat model with morphine tolerance and explore changes of calcitonin-gene related peptide (CGRP expression in dorsal root ganglion (DRG. Methods. Forty SD rats were divided into five groups: sham, CIBP (B, CIBP + morphine (BM, CIBP + electroacupuncture (BE, and CIBP + morphine + electroacupuncture (BME. B, BM, BE, and BME groups were prepared CIBP model. The latter three groups then accepted morphine, electroacupuncture, and morphine combined electroacupuncture, separately, nine days consecutively (M1 to M9. Mechanical withdraw threshold (MWT was evaluated. Results. BE group only had differences in M1, M2, and M3 compared to B group (P<0.01. From M5, BM group showed significantly decreased MWT. Electroacupuncture could obtain analgesic effects only at early stage (M1 to M5. From M5 to M9, BME had the differences with BM group (P<0.01. IOD value of CGRP in BM and BME was substantially less than in B group. CGRP in BME was significantly lower than that in BM group (P<0.01. Conclusion. When used in combination with electroacupuncture, morphine could result in improving analgesic effects and reducing tolerance. CGRP may be associated with pain behaviors.

  4. Fixation probability in a two-locus intersexual selection model.

    Science.gov (United States)

    Durand, Guillermo; Lessard, Sabin

    2016-06-01

    We study a two-locus model of intersexual selection in a finite haploid population reproducing according to a discrete-time Moran model with a trait locus expressed in males and a preference locus expressed in females. We show that the probability of ultimate fixation of a single mutant allele for a male ornament introduced at random at the trait locus given any initial frequency state at the preference locus is increased by weak intersexual selection and recombination, weak or strong. Moreover, this probability exceeds the initial frequency of the mutant allele even in the case of a costly male ornament if intersexual selection is not too weak. On the other hand, the probability of ultimate fixation of a single mutant allele for a female preference towards a male ornament introduced at random at the preference locus is increased by weak intersexual selection and weak recombination if the female preference is not costly, and is strong enough in the case of a costly male ornament. The analysis relies on an extension of the ancestral recombination-selection graph for samples of haplotypes to take into account events of intersexual selection, while the symbolic calculation of the fixation probabilities is made possible in a reasonable time by an optimizing algorithm. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Sustained analgesic effect of clonidine co-polymer depot in a porcine incisional pain model

    Directory of Open Access Journals (Sweden)

    Wilsey JT

    2018-04-01

    Full Text Available Jared T Wilsey, Julie H Block Medtronic Spine Division, Memphis, TN, USA Background: Previous research suggests that the α2 adrenergic agonist clonidine, a centrally acting analgesic and antihypertensive, may also have direct effects on peripheral pain generators. However, aqueous injections are limited by rapid systemic absorption leading to off target effects and a brief analgesic duration of action. Purpose: The aim of this study was to examine the efficacy of a sustained-release clonidine depot, placed in the wound bed, in a pig incisional pain model. Methods: The depot was a 15 mm ×5 mm ×0.3 mm poly(lactide-co-caprolactone polymer film containing 3% (w/w clonidine HCl (MDT3. Fifty-two young adult mix Landrace pigs (9–11 kg were divided into seven groups. All subjects received a 6 cm, full-thickness, linear incision into the left lateral flank. Group 1 served as a Sham control group (Sham, n=8. Group 2 received three placebo strips (PBO, n=8, placed end-to-end in the subcutaneous wound bed before wound closure. Group 3 received one MDT3 and two PBO (n=8, Group 4 received two MDT3 and one PBO (n=8, and Group 5 received three MDT3 (n=8. Positive control groups received peri-incisional injections of bupivacaine solution (Group 6, 30 mg/day bupivacaine, n=8 or clonidine solution (Group 7, 225 µg/day, n=4. Results: The surgical procedure was associated with significant peri-incisional tactile allodynia. There was a dose-dependent effect of MDT3 in partially reversing the peri-incisional tactile allodynia, with maximum pain relief relative to Sham at 72 hours. Daily injections of bupivacaine (30 mg, but not clonidine (up to 225 µg, completely reversed allodynia within 48 hours. There was a statistically significant correlation between the dose of MDT3 and cumulative withdrawal threshold from 4 hours through the conclusion of the study on day 7. Conclusion: These data suggest that a sustained-release clonidine depot may be a

  6. Implementing the Keele stratified care model for patients with low back pain: an observational impact study.

    Science.gov (United States)

    Bamford, Adrian; Nation, Andy; Durrell, Susie; Andronis, Lazaros; Rule, Ellen; McLeod, Hugh

    2017-02-03

    The Keele stratified care model for management of low back pain comprises use of the prognostic STarT Back Screening Tool to allocate patients into one of three risk-defined categories leading to associated risk-specific treatment pathways, such that high-risk patients receive enhanced treatment and more sessions than medium- and low-risk patients. The Keele model is associated with economic benefits and is being widely implemented. The objective was to assess the use of the stratified model following its introduction in an acute hospital physiotherapy department setting in Gloucestershire, England. Physiotherapists recorded data on 201 patients treated using the Keele model in two audits in 2013 and 2014. To assess whether implementation of the stratified model was associated with the anticipated range of treatment sessions, regression analysis of the audit data was used to determine whether high- or medium-risk patients received significantly more treatment sessions than low-risk patients. The analysis controlled for patient characteristics, year, physiotherapists' seniority and physiotherapist. To assess the physiotherapists' views on the usefulness of the stratified model, audit data on this were analysed using framework methods. To assess the potential economic consequences of introducing the stratified care model in Gloucestershire, published economic evaluation findings on back-related National Health Service (NHS) costs, quality-adjusted life years (QALYs) and societal productivity losses were applied to audit data on the proportion of patients by risk classification and estimates of local incidence. When the Keele model was implemented, patients received significantly more treatment sessions as the risk-rating increased, in line with the anticipated impact of targeted treatment pathways. Physiotherapists were largely positive about using the model. The potential annual impact of rolling out the model across Gloucestershire is a gain in approximately 30

  7. Percutaneous sciatic nerve block with tramadol induces analgesia and motor blockade in two animal pain models

    International Nuclear Information System (INIS)

    Sousa, A.M.; Ashmawi, H.A.; Costa, L.S.; Posso, I.P.; Slullitel, A.

    2011-01-01

    Local anesthetic efficacy of tramadol has been reported following intradermal application. Our aim was to investigate the effect of perineural tramadol as the sole analgesic in two pain models. Male Wistar rats (280-380 g; N = 5/group) were used in these experiments. A neurostimulation-guided sciatic nerve block was performed and 2% lidocaine or tramadol (1.25 and 5 mg) was perineurally injected in two different animal pain models. In the flinching behavior test, the number of flinches was evaluated and in the plantar incision model, mechanical and heat thresholds were measured. Motor effects of lidocaine and tramadol were quantified and a motor block score elaborated. Tramadol, 1.25 mg, completely blocked the first and reduced the second phase of the flinching behavior test. In the plantar incision model, tramadol (1.25 mg) increased both paw withdrawal latency in response to radiant heat (8.3 ± 1.1, 12.7 ± 1.8, 8.4 ± 0.8, and 11.1 ± 3.3 s) and mechanical threshold in response to von Frey filaments (459 ± 82.8, 447.5 ± 91.7, 320.1 ± 120, 126.43 ± 92.8 mN) at 5, 15, 30, and 60 min, respectively. Sham block or contralateral sciatic nerve block did not differ from perineural saline injection throughout the study in either model. The effect of tramadol was not antagonized by intraperitoneal naloxone. High dose tramadol (5 mg) blocked motor function as well as 2% lidocaine. In conclusion, tramadol blocks nociception and motor function in vivo similar to local anesthetics

  8. Percutaneous sciatic nerve block with tramadol induces analgesia and motor blockade in two animal pain models

    Directory of Open Access Journals (Sweden)

    A.M. Sousa

    2012-02-01

    Full Text Available Local anesthetic efficacy of tramadol has been reported following intradermal application. Our aim was to investigate the effect of perineural tramadol as the sole analgesic in two pain models. Male Wistar rats (280-380 g; N = 5/group were used in these experiments. A neurostimulation-guided sciatic nerve block was performed and 2% lidocaine or tramadol (1.25 and 5 mg was perineurally injected in two different animal pain models. In the flinching behavior test, the number of flinches was evaluated and in the plantar incision model, mechanical and heat thresholds were measured. Motor effects of lidocaine and tramadol were quantified and a motor block score elaborated. Tramadol, 1.25 mg, completely blocked the first and reduced the second phase of the flinching behavior test. In the plantar incision model, tramadol (1.25 mg increased both paw withdrawal latency in response to radiant heat (8.3 ± 1.1, 12.7 ± 1.8, 8.4 ± 0.8, and 11.1 ± 3.3 s and mechanical threshold in response to von Frey filaments (459 ± 82.8, 447.5 ± 91.7, 320.1 ± 120, 126.43 ± 92.8 mN at 5, 15, 30, and 60 min, respectively. Sham block or contralateral sciatic nerve block did not differ from perineural saline injection throughout the study in either model. The effect of tramadol was not antagonized by intraperitoneal naloxone. High dose tramadol (5 mg blocked motor function as well as 2% lidocaine. In conclusion, tramadol blocks nociception and motor function in vivo similar to local anesthetics.

  9. Spatial Fleming-Viot models with selection and mutation

    CERN Document Server

    Dawson, Donald A

    2014-01-01

    This book constructs a rigorous framework for analysing selected phenomena in evolutionary theory of populations arising due to the combined effects of migration, selection and mutation in a spatial stochastic population model, namely the evolution towards fitter and fitter types through punctuated equilibria. The discussion is based on a number of new methods, in particular multiple scale analysis, nonlinear Markov processes and their entrance laws, atomic measure-valued evolutions and new forms of duality (for state-dependent mutation and multitype selection) which are used to prove ergodic theorems in this context and are applicable for many other questions and renormalization analysis for a variety of phenomena (stasis, punctuated equilibrium, failure of naive branching approximations, biodiversity) which occur due to the combination of rare mutation, mutation, resampling, migration and selection and make it necessary to mathematically bridge the gap (in the limit) between time and space scales.

  10. Uniform design based SVM model selection for face recognition

    Science.gov (United States)

    Li, Weihong; Liu, Lijuan; Gong, Weiguo

    2010-02-01

    Support vector machine (SVM) has been proved to be a powerful tool for face recognition. The generalization capacity of SVM depends on the model with optimal hyperparameters. The computational cost of SVM model selection results in application difficulty in face recognition. In order to overcome the shortcoming, we utilize the advantage of uniform design--space filling designs and uniformly scattering theory to seek for optimal SVM hyperparameters. Then we propose a face recognition scheme based on SVM with optimal model which obtained by replacing the grid and gradient-based method with uniform design. The experimental results on Yale and PIE face databases show that the proposed method significantly improves the efficiency of SVM model selection.

  11. How Many Separable Sources? Model Selection In Independent Components Analysis

    DEFF Research Database (Denmark)

    Woods, Roger P.; Hansen, Lars Kai; Strother, Stephen

    2015-01-01

    among potential model categories with differing numbers of Gaussian components. Based on simulation studies, the assumptions and approximations underlying the Akaike Information Criterion do not hold in this setting, even with a very large number of observations. Cross-validation is a suitable, though....../Principal Components Analysis (mixed ICA/PCA) model described here accommodates one or more Gaussian components in the independent components analysis model and uses principal components analysis to characterize contributions from this inseparable Gaussian subspace. Information theory can then be used to select from...... might otherwise be questionable. Failure of the Akaike Information Criterion in model selection also has relevance in traditional independent components analysis where all sources are assumed non-Gaussian....

  12. Selecting an optimal mixed products using grey relationship model

    Directory of Open Access Journals (Sweden)

    Farshad Faezy Razi

    2013-06-01

    Full Text Available This paper presents an integrated supplier selection and inventory management using grey relationship model (GRM as well as multi-objective decision making process. The proposed model of this paper first ranks different suppliers based on GRM technique and then determines the optimum level of inventory by considering different objectives. To show the implementation of the proposed model, we use some benchmark data presented by Talluri and Baker [Talluri, S., & Baker, R. C. (2002. A multi-phase mathematical programming approach for effective supply chain design. European Journal of Operational Research, 141(3, 544-558.]. The preliminary results indicate that the proposed model of this paper is capable of handling different criteria for supplier selection.

  13. Model selection and inference a practical information-theoretic approach

    CERN Document Server

    Burnham, Kenneth P

    1998-01-01

    This book is unique in that it covers the philosophy of model-based data analysis and an omnibus strategy for the analysis of empirical data The book introduces information theoretic approaches and focuses critical attention on a priori modeling and the selection of a good approximating model that best represents the inference supported by the data Kullback-Leibler information represents a fundamental quantity in science and is Hirotugu Akaike's basis for model selection The maximized log-likelihood function can be bias-corrected to provide an estimate of expected, relative Kullback-Leibler information This leads to Akaike's Information Criterion (AIC) and various extensions and these are relatively simple and easy to use in practice, but little taught in statistics classes and far less understood in the applied sciences than should be the case The information theoretic approaches provide a unified and rigorous theory, an extension of likelihood theory, an important application of information theory, and are ...

  14. Working covariance model selection for generalized estimating equations.

    Science.gov (United States)

    Carey, Vincent J; Wang, You-Gan

    2011-11-20

    We investigate methods for data-based selection of working covariance models in the analysis of correlated data with generalized estimating equations. We study two selection criteria: Gaussian pseudolikelihood and a geodesic distance based on discrepancy between model-sensitive and model-robust regression parameter covariance estimators. The Gaussian pseudolikelihood is found in simulation to be reasonably sensitive for several response distributions and noncanonical mean-variance relations for longitudinal data. Application is also made to a clinical dataset. Assessment of adequacy of both correlation and variance models for longitudinal data should be routine in applications, and we describe open-source software supporting this practice. Copyright © 2011 John Wiley & Sons, Ltd.

  15. Alteration of cancer pain-related signals by radiation: Proteomic analysis in an animal model with cancer bone invasion

    International Nuclear Information System (INIS)

    Park, Hee Chul; Seong, Jinsil; An, Jung Hee; Kim, Jiyoung; Kim, Un Jung; Lee, Bae Whan

    2005-01-01

    Purpose: Although radiotherapy is highly effective in relieving bone pain due to cancer invasion, its mechanism remains unclear. The aim of this study was to explore this mechanism in an animal model system. Methods and Materials: A hind paw model of cancer pain was developed by transplanting a murine hepatocarcinoma, HCa-1, into the periosteal membrane of the foot dorsum of C3H/HeJ mice. Bone invasion from HCa-1 was histopathologically confirmed from sequential tumor sampling. For three experimental groups, a control (N), tumor without radiation (T), and tumor with radiation (TR), the development and level of pain were objectively examined in mice with a growing tumor by assessing pain-associated behavior. The differential expression of pain-related signals in the spinal cord was analyzed by proteomic analysis using high-resolution two-dimensional gel electrophoresis (2-DE) and mass spectrometry, and those of proteins by Western blotting. The pain-mediating neurotransmitters in the spinal cord were also examined by immunohistochemical staining for calcitonin gene-related peptide (CGRP) and substance P. Results: In the histopathologic examinations, bone invasion from HCa-1 was seen from Day 7 and was evident at Day 14 after transplantation, and measurable pain-associated behaviors were developed from Day 7. After 25 Gy of radiation to the tumors, the objective level of pain in the TR group decreased, with higher thresholds to mechanical and thermal stimulation than in the T group. From the 2-DE of spinal cord, 107 spots were identified; 12 proteins were changed more than fivefold because of tumor formation but then reversed after radiation in the tumor-bearing mice. The proteins involved included secretagogin, syntenin, P2X purinoreceptor 6 (P2X6), and Ca 2+ /Calmodulin-dependent protein kinase 1 (CaM kinase 1), the functions of which have been known to be involved in the Ca 2+ -signaling cascade, ATP-mediated fast synaptic transmission, or control of vesicular

  16. Alteration of cancer pain-related signals by radiation: Proteomic analysis in an animal model with cancer bone invasion

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hee Chul [Department of Radiation Oncology, Hallym University, Chuncheon (Korea, Republic of); Seong, Jinsil [Department of Radiation Oncology, Brain Korea 21 Project for Medicine, Yonsei University, Seoul (Korea, Republic of); An, Jung Hee [Department of Radiation Oncology, Brain Korea 21 Project for Medicine, Yonsei University, Seoul (Korea, Republic of); Kim, Jiyoung [Department of Radiation Oncology, Brain Korea 21 Project for Medicine, Yonsei University, Seoul (Korea, Republic of); Kim, Un Jung [Yonsei Medical Research Center, Brain Korea 21 Project for Medicine, Yonsei University, Seoul (Korea, Republic of); Lee, Bae Whan [Yonsei Medical Research Center, Brain Korea 21 Project for Medicine, Yonsei University, Seoul (Korea, Republic of)

    2005-04-01

    Purpose: Although radiotherapy is highly effective in relieving bone pain due to cancer invasion, its mechanism remains unclear. The aim of this study was to explore this mechanism in an animal model system. Methods and Materials: A hind paw model of cancer pain was developed by transplanting a murine hepatocarcinoma, HCa-1, into the periosteal membrane of the foot dorsum of C3H/HeJ mice. Bone invasion from HCa-1 was histopathologically confirmed from sequential tumor sampling. For three experimental groups, a control (N), tumor without radiation (T), and tumor with radiation (TR), the development and level of pain were objectively examined in mice with a growing tumor by assessing pain-associated behavior. The differential expression of pain-related signals in the spinal cord was analyzed by proteomic analysis using high-resolution two-dimensional gel electrophoresis (2-DE) and mass spectrometry, and those of proteins by Western blotting. The pain-mediating neurotransmitters in the spinal cord were also examined by immunohistochemical staining for calcitonin gene-related peptide (CGRP) and substance P. Results: In the histopathologic examinations, bone invasion from HCa-1 was seen from Day 7 and was evident at Day 14 after transplantation, and measurable pain-associated behaviors were developed from Day 7. After 25 Gy of radiation to the tumors, the objective level of pain in the TR group decreased, with higher thresholds to mechanical and thermal stimulation than in the T group. From the 2-DE of spinal cord, 107 spots were identified; 12 proteins were changed more than fivefold because of tumor formation but then reversed after radiation in the tumor-bearing mice. The proteins involved included secretagogin, syntenin, P2X purinoreceptor 6 (P2X6), and Ca{sup 2+}/Calmodulin-dependent protein kinase 1 (CaM kinase 1), the functions of which have been known to be involved in the Ca{sup 2+}-signaling cascade, ATP-mediated fast synaptic transmission, or control of

  17. Evidence accumulation as a model for lexical selection.

    Science.gov (United States)

    Anders, R; Riès, S; van Maanen, L; Alario, F X

    2015-11-01

    We propose and demonstrate evidence accumulation as a plausible theoretical and/or empirical model for the lexical selection process of lexical retrieval. A number of current psycholinguistic theories consider lexical selection as a process related to selecting a lexical target from a number of alternatives, which each have varying activations (or signal supports), that are largely resultant of an initial stimulus recognition. We thoroughly present a case for how such a process may be theoretically explained by the evidence accumulation paradigm, and we demonstrate how this paradigm can be directly related or combined with conventional psycholinguistic theory and their simulatory instantiations (generally, neural network models). Then with a demonstrative application on a large new real data set, we establish how the empirical evidence accumulation approach is able to provide parameter results that are informative to leading psycholinguistic theory, and that motivate future theoretical development. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Integrated model for supplier selection and performance evaluation

    Directory of Open Access Journals (Sweden)

    Borges de Araújo, Maria Creuza

    2015-08-01

    Full Text Available This paper puts forward a model for selecting suppliers and evaluating the performance of those already working with a company. A simulation was conducted in a food industry. This sector has high significance in the economy of Brazil. The model enables the phases of selecting and evaluating suppliers to be integrated. This is important so that a company can have partnerships with suppliers who are able to meet their needs. Additionally, a group method is used to enable managers who will be affected by this decision to take part in the selection stage. Finally, the classes resulting from the performance evaluation are shown to support the contractor in choosing the most appropriate relationship with its suppliers.

  19. Attention-based Memory Selection Recurrent Network for Language Modeling

    OpenAIRE

    Liu, Da-Rong; Chuang, Shun-Po; Lee, Hung-yi

    2016-01-01

    Recurrent neural networks (RNNs) have achieved great success in language modeling. However, since the RNNs have fixed size of memory, their memory cannot store all the information about the words it have seen before in the sentence, and thus the useful long-term information may be ignored when predicting the next words. In this paper, we propose Attention-based Memory Selection Recurrent Network (AMSRN), in which the model can review the information stored in the memory at each previous time ...

  20. Chronic administration of the selective P2X3, P2X2/3 receptor antagonist, A-317491, transiently attenuates cancer-induced bone pain in mice

    DEFF Research Database (Denmark)

    Hansen, Rikke Rie; Nasser, Arafat; Falk, Sarah

    2012-01-01

    The purinergic P2X3 and P2X2/3 receptors are in the peripheral nervous system almost exclusively confined to afferent sensory neurons, where they are found both at peripheral and central synapses. The P2X3 receptor is implicated in both neuropathic and inflammatory pain. However, the role of the ......X3 receptor in chronic cancer-induced bone pain is less known. Here we investigated the effect of systemic acute and chronic administration of the selective P2X3, P2X2/3 receptor antagonist (5-[[[(3-Phenoxyphenyl)methyl][(1S)-1,2,3,4-tetrahydro-1-naphthalenyl]amino]carbonyl]-1...

  1. The Selection of ARIMA Models with or without Regressors

    DEFF Research Database (Denmark)

    Johansen, Søren; Riani, Marco; Atkinson, Anthony C.

    We develop a $C_{p}$ statistic for the selection of regression models with stationary and nonstationary ARIMA error term. We derive the asymptotic theory of the maximum likelihood estimators and show they are consistent and asymptotically Gaussian. We also prove that the distribution of the sum...

  2. Model selection for contingency tables with algebraic statistics

    NARCIS (Netherlands)

    Krampe, A.; Kuhnt, S.; Gibilisco, P.; Riccimagno, E.; Rogantin, M.P.; Wynn, H.P.

    2009-01-01

    Goodness-of-fit tests based on chi-square approximations are commonly used in the analysis of contingency tables. Results from algebraic statistics combined with MCMC methods provide alternatives to the chi-square approximation. However, within a model selection procedure usually a large number of

  3. Computationally efficient thermal-mechanical modelling of selective laser melting

    NARCIS (Netherlands)

    Yang, Y.; Ayas, C.; Brabazon, Dermot; Naher, Sumsun; Ul Ahad, Inam

    2017-01-01

    The Selective laser melting (SLM) is a powder based additive manufacturing (AM) method to produce high density metal parts with complex topology. However, part distortions and accompanying residual stresses deteriorates the mechanical reliability of SLM products. Modelling of the SLM process is

  4. Multivariate time series modeling of selected childhood diseases in ...

    African Journals Online (AJOL)

    This paper is focused on modeling the five most prevalent childhood diseases in Akwa Ibom State using a multivariate approach to time series. An aggregate of 78,839 reported cases of malaria, upper respiratory tract infection (URTI), Pneumonia, anaemia and tetanus were extracted from five randomly selected hospitals in ...

  5. Rank-based model selection for multiple ions quantum tomography

    International Nuclear Information System (INIS)

    Guţă, Mădălin; Kypraios, Theodore; Dryden, Ian

    2012-01-01

    The statistical analysis of measurement data has become a key component of many quantum engineering experiments. As standard full state tomography becomes unfeasible for large dimensional quantum systems, one needs to exploit prior information and the ‘sparsity’ properties of the experimental state in order to reduce the dimensionality of the estimation problem. In this paper we propose model selection as a general principle for finding the simplest, or most parsimonious explanation of the data, by fitting different models and choosing the estimator with the best trade-off between likelihood fit and model complexity. We apply two well established model selection methods—the Akaike information criterion (AIC) and the Bayesian information criterion (BIC)—two models consisting of states of fixed rank and datasets such as are currently produced in multiple ions experiments. We test the performance of AIC and BIC on randomly chosen low rank states of four ions, and study the dependence of the selected rank with the number of measurement repetitions for one ion states. We then apply the methods to real data from a four ions experiment aimed at creating a Smolin state of rank 4. By applying the two methods together with the Pearson χ 2 test we conclude that the data can be suitably described with a model whose rank is between 7 and 9. Additionally we find that the mean square error of the maximum likelihood estimator for pure states is close to that of the optimal over all possible measurements. (paper)

  6. Novel orally available salvinorin A analog PR-38 inhibits gastrointestinal motility and reduces abdominal pain in mouse models mimicking irritable bowel syndrome.

    Science.gov (United States)

    Sałaga, M; Polepally, P R; Sobczak, M; Grzywacz, D; Kamysz, W; Sibaev, A; Storr, M; Do Rego, J C; Zjawiony, J K; Fichna, J

    2014-07-01

    The opioid and cannabinoid systems play a crucial role in multiple physiological processes in the central nervous system and in the periphery. Selective opioid as well as cannabinoid (CB) receptor agonists exert a potent inhibitory action on gastrointestinal (GI) motility and pain. In this study, we examined (in vitro and in vivo) whether PR-38 (2-O-cinnamoylsalvinorin B), a novel analog of salvinorin A, can interact with both systems and demonstrate therapeutic effects. We used mouse models of hypermotility, diarrhea, and abdominal pain. We also assessed the influence of PR-38 on the central nervous system by measurement of motoric parameters and exploratory behaviors in mice. Subsequently, we investigated the pharmacokinetics of PR-38 in mouse blood samples after intraperitoneal and oral administration. PR-38 significantly inhibited mouse colonic motility in vitro and in vivo. Administration of PR-38 significantly prolonged the whole GI transit time, and this effect was mediated by µ- and κ-opioid receptors and the CB1 receptor. PR-38 reversed hypermotility and reduced pain in mouse models mimicking functional GI disorders. These data expand our understanding of the interactions between opioid and cannabinoid systems and their functions in the GI tract. We also provide a novel framework for the development of future potential treatments of functional GI disorders. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  7. PREVALENCE OF LOW BACK PAIN AND BACK ERGONOMICS AWARENESS AMONG TEACHERS OF SELECTED SECONDARY SCHOOLS IN KANO METROPOLIS

    Directory of Open Access Journals (Sweden)

    Farida Garba Sumaila

    2015-12-01

    Full Text Available Background: Low back pain (LBP is regarded as the commonest musculoskeletal problem in the world which affects people across various strata of the society from lay men on the street to teachers as well as health care providers in health institutions. Therefore the purpose of this study is to determine the prevalence of low back pain and back education awareness among secondary school teachers in Kano Metropolis. Methodos: 200 questionnaires were distributed and only 157 were retrieved, one out of which 4 were invalid because of incomplete data so that only 153 were relevant and used for analysis giving a return rate of 76.5%. The study revealed that 96 out of 153 respondents have low back pain implying 62.7% prevalence. The level of back ergonomic awareness on the other hand was found to be moderate (43.1%. Results: Based on the outcomes of the study, it was concluded that there is a high prevalence of low back pain among secondary school teachers in Kano metropolis. However, the level of back ergonomic awareness is moderate. Conclusion: Therefore proper intervention to prevent exposure to LBP among school teachers should be enhanced and teachers should be well educated on the importance of ergonomic intervention in their working environments.

  8. The Sensitization Model to Explain How Chronic Pain Exists Without Tissue Damage

    NARCIS (Netherlands)

    van Wilgen, C. Paul; Keizer, Doeke

    The interaction of nurses with chronic pain patients is often difficult. One of the reasons is that chronic pain is difficult to explain, because no obvious anatomic defect or tissue damage is present. There is now enough evidence available indicating that chronic pain syndromes such as low back

  9. Measures and limits of models of fixation selection.

    Directory of Open Access Journals (Sweden)

    Niklas Wilming

    Full Text Available Models of fixation selection are a central tool in the quest to understand how the human mind selects relevant information. Using this tool in the evaluation of competing claims often requires comparing different models' relative performance in predicting eye movements. However, studies use a wide variety of performance measures with markedly different properties, which makes a comparison difficult. We make three main contributions to this line of research: First we argue for a set of desirable properties, review commonly used measures, and conclude that no single measure unites all desirable properties. However the area under the ROC curve (a classification measure and the KL-divergence (a distance measure of probability distributions combine many desirable properties and allow a meaningful comparison of critical model performance. We give an analytical proof of the linearity of the ROC measure with respect to averaging over subjects and demonstrate an appropriate correction of entropy-based measures like KL-divergence for small sample sizes in the context of eye-tracking data. Second, we provide a lower bound and an upper bound of these measures, based on image-independent properties of fixation data and between subject consistency respectively. Based on these bounds it is possible to give a reference frame to judge the predictive power of a model of fixation selection. We provide open-source python code to compute the reference frame. Third, we show that the upper, between subject consistency bound holds only for models that predict averages of subject populations. Departing from this we show that incorporating subject-specific viewing behavior can generate predictions which surpass that upper bound. Taken together, these findings lay out the required information that allow a well-founded judgment of the quality of any model of fixation selection and should therefore be reported when a new model is introduced.

  10. Antiallodynic Effects of Bee Venom in an Animal Model of Complex Regional Pain Syndrome Type 1 (CRPS-I).

    Science.gov (United States)

    Lee, Sung Hyun; Lee, Jae Min; Kim, Yun Hong; Choi, Jung Hyun; Jeon, Seung Hwan; Kim, Dong Kyu; Jeong, Hyeon Do; Lee, You Jung; Park, Hue Jung

    2017-09-15

    Neuropathic pain in a chronic post-ischaemic pain (CPIP) model mimics the symptoms of complex regional pain syndrome type I (CRPS I). The administration of bee venom (BV) has been utilized in Eastern medicine to treat chronic inflammatory diseases accompanying pain. However, the analgesic effect of BV in a CPIP model remains unknown. The application of a tight-fitting O-ring around the left ankle for a period of 3 h generated CPIP in C57/Bl6 male adult mice. BV (1 mg/kg ; 1, 2, and 3 times) was administered into the SC layer of the hind paw, and the antiallodynic effects were investigated using the von Frey test and by measuring the expression of neurokinin type 1 (NK-1) receptors in dorsal root ganglia (DRG). The administration of BV dose-dependently reduced the pain withdrawal threshold to mechanical stimuli compared with the pre-administration value and with that of the control group. After the development of the CPIP model, the expression of NK-1 receptors in DRG increased and then decreased following the administration of BV. SC administration of BV results in the attenuation of allodynia in a mouse model of CPIP. The antiallodynic effect was objectively proven through a reduction in the increased expression of NK-1 receptors in DRG.

  11. Generalized Selectivity Description for Polymeric Ion-Selective Electrodes Based on the Phase Boundary Potential Model.

    Science.gov (United States)

    Bakker, Eric

    2010-02-15

    A generalized description of the response behavior of potentiometric polymer membrane ion-selective electrodes is presented on the basis of ion-exchange equilibrium considerations at the sample-membrane interface. This paper includes and extends on previously reported theoretical advances in a more compact yet more comprehensive form. Specifically, the phase boundary potential model is used to derive the origin of the Nernstian response behavior in a single expression, which is valid for a membrane containing any charge type and complex stoichiometry of ionophore and ion-exchanger. This forms the basis for a generalized expression of the selectivity coefficient, which may be used for the selectivity optimization of ion-selective membranes containing electrically charged and neutral ionophores of any desired stoichiometry. It is shown to reduce to expressions published previously for specialized cases, and may be effectively applied to problems relevant in modern potentiometry. The treatment is extended to mixed ion solutions, offering a comprehensive yet formally compact derivation of the response behavior of ion-selective electrodes to a mixture of ions of any desired charge. It is compared to predictions by the less accurate Nicolsky-Eisenman equation. The influence of ion fluxes or any form of electrochemical excitation is not considered here, but may be readily incorporated if an ion-exchange equilibrium at the interface may be assumed in these cases.

  12. The Role of the Fear-avoidance Model in Female Workers With Neck-shoulder Pain related to Computer Work

    NARCIS (Netherlands)

    Huis in 't Veld, M.H.A.; Vollenbroek-Hutten, Miriam Marie Rosé; Groothuis-Oudshoorn, Catharina Gerarda Maria; Hermens, Hermanus J.

    Objective: This study explores the fear-avoidance model in a sample of women with neck-shoulder pain related to computer work who were still functioning at the workplace. Exploring this model in this population could produce starting points for new treatment approaches in occupational health.

  13. Fisher-Wright model with deterministic seed bank and selection.

    Science.gov (United States)

    Koopmann, Bendix; Müller, Johannes; Tellier, Aurélien; Živković, Daniel

    2017-04-01

    Seed banks are common characteristics to many plant species, which allow storage of genetic diversity in the soil as dormant seeds for various periods of time. We investigate an above-ground population following a Fisher-Wright model with selection coupled with a deterministic seed bank assuming the length of the seed bank is kept constant and the number of seeds is large. To assess the combined impact of seed banks and selection on genetic diversity, we derive a general diffusion model. The applied techniques outline a path of approximating a stochastic delay differential equation by an appropriately rescaled stochastic differential equation. We compute the equilibrium solution of the site-frequency spectrum and derive the times to fixation of an allele with and without selection. Finally, it is demonstrated that seed banks enhance the effect of selection onto the site-frequency spectrum while slowing down the time until the mutation-selection equilibrium is reached. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Forecasting house prices in the 50 states using Dynamic Model Averaging and Dynamic Model Selection

    DEFF Research Database (Denmark)

    Bork, Lasse; Møller, Stig Vinther

    2015-01-01

    We examine house price forecastability across the 50 states using Dynamic Model Averaging and Dynamic Model Selection, which allow for model change and parameter shifts. By allowing the entire forecasting model to change over time and across locations, the forecasting accuracy improves substantia......We examine house price forecastability across the 50 states using Dynamic Model Averaging and Dynamic Model Selection, which allow for model change and parameter shifts. By allowing the entire forecasting model to change over time and across locations, the forecasting accuracy improves...

  15. Evaluation of Lercanidipine in Paclitaxel-Induced Neuropathic Pain Model in Rat: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Lekha Saha

    2012-01-01

    Full Text Available Objective. To demonstrate the antinociceptive effect of lercanidipine in paclitaxel-induced neuropathy model in rat. Materials and Methods. A total of 30 rats were divided into five groups of six rats in each group as follows: Gr I: 0.9% NaCl, Gr II: paclitaxel + 0.9% NaCl, Gr III: paclitaxel + lercanidipine 0.5 μg/kg, Gr IV: paclitaxel + lercanidipine 1 μg/kg, and Gr V: paclitaxel + lercanidipine 2.5 μg/kg. Paclitaxel-induced neuropathic pain in rat was produced by single intraperitoneal (i.p. injection of 1 mg/kg of paclitaxel on four alternate days (0, 2, 4, and 6. The tail flick and cold allodynia methods were used for assessing the pain threshold, and the assessments were done on days 0 (before first dose of paclitaxel and on days 7, 14, 21, and 28. Results. There was a significant decrease (P<0.001 in the tail flick and cold allodynia latency in the paclitaxel-alone group from day 14 onward when compared with day 0. In the lercanidipine groups, the decrease in the tail flick and cold allodynia latency was not observed in 1.0 and 2.5 μg/kg groups and it was statistically significant (P<0.01 when compared with paclitaxel-alone group.

  16. Is the Experience of Thermal Pain Genetics Dependent?

    Directory of Open Access Journals (Sweden)

    Emilia Horjales-Araujo

    2015-01-01

    Full Text Available It is suggested that genetic variations explain a significant portion of the variability in pain perception; therefore, increased understanding of pain-related genetic influences may identify new targets for therapies and treatments. The relative contribution of the different genes to the variance in clinical and experimental pain responses remains unknown. It is suggested that the genetic contributions to pain perception vary across pain modalities. For example, it has been suggested that more than 60% of the variance in cold pressor responses can be explained by genetic factors; in comparison, only 26% of the variance in heat pain responses is explained by these variations. Thus, the selection of pain model might markedly influence the magnitude of the association between the pain phenotype and genetic variability. Thermal pain sensation is complex with multiple molecular and cellular mechanisms operating alone and in combination within the peripheral and central nervous system. It is thus highly probable that the thermal pain experience is affected by genetic variants in one or more of the pathways involved in the thermal pain signaling. This review aims to present and discuss some of the genetic variations that have previously been associated with different experimental thermal pain models.

  17. How Many Separable Sources? Model Selection In Independent Components Analysis

    Science.gov (United States)

    Woods, Roger P.; Hansen, Lars Kai; Strother, Stephen

    2015-01-01

    Unlike mixtures consisting solely of non-Gaussian sources, mixtures including two or more Gaussian components cannot be separated using standard independent components analysis methods that are based on higher order statistics and independent observations. The mixed Independent Components Analysis/Principal Components Analysis (mixed ICA/PCA) model described here accommodates one or more Gaussian components in the independent components analysis model and uses principal components analysis to characterize contributions from this inseparable Gaussian subspace. Information theory can then be used to select from among potential model categories with differing numbers of Gaussian components. Based on simulation studies, the assumptions and approximations underlying the Akaike Information Criterion do not hold in this setting, even with a very large number of observations. Cross-validation is a suitable, though computationally intensive alternative for model selection. Application of the algorithm is illustrated using Fisher's iris data set and Howells' craniometric data set. Mixed ICA/PCA is of potential interest in any field of scientific investigation where the authenticity of blindly separated non-Gaussian sources might otherwise be questionable. Failure of the Akaike Information Criterion in model selection also has relevance in traditional independent components analysis where all sources are assumed non-Gaussian. PMID:25811988

  18. A model for the sustainable selection of building envelope assemblies

    Energy Technology Data Exchange (ETDEWEB)

    Huedo, Patricia, E-mail: huedo@uji.es [Universitat Jaume I (Spain); Mulet, Elena, E-mail: emulet@uji.es [Universitat Jaume I (Spain); López-Mesa, Belinda, E-mail: belinda@unizar.es [Universidad de Zaragoza (Spain)

    2016-02-15

    The aim of this article is to define an evaluation model for the environmental impacts of building envelopes to support planners in the early phases of materials selection. The model is intended to estimate environmental impacts for different combinations of building envelope assemblies based on scientifically recognised sustainability indicators. These indicators will increase the amount of information that existing catalogues show to support planners in the selection of building assemblies. To define the model, first the environmental indicators were selected based on the specific aims of the intended sustainability assessment. Then, a simplified LCA methodology was developed to estimate the impacts applicable to three types of dwellings considering different envelope assemblies, building orientations and climate zones. This methodology takes into account the manufacturing, installation, maintenance and use phases of the building. Finally, the model was validated and a matrix in Excel was created as implementation of the model. - Highlights: • Method to assess the envelope impacts based on a simplified LCA • To be used at an earlier phase than the existing methods in a simple way. • It assigns a score by means of known sustainability indicators. • It estimates data about the embodied and operating environmental impacts. • It compares the investment costs with the costs of the consumed energy.

  19. A model for the sustainable selection of building envelope assemblies

    International Nuclear Information System (INIS)

    Huedo, Patricia; Mulet, Elena; López-Mesa, Belinda

    2016-01-01

    The aim of this article is to define an evaluation model for the environmental impacts of building envelopes to support planners in the early phases of materials selection. The model is intended to estimate environmental impacts for different combinations of building envelope assemblies based on scientifically recognised sustainability indicators. These indicators will increase the amount of information that existing catalogues show to support planners in the selection of building assemblies. To define the model, first the environmental indicators were selected based on the specific aims of the intended sustainability assessment. Then, a simplified LCA methodology was developed to estimate the impacts applicable to three types of dwellings considering different envelope assemblies, building orientations and climate zones. This methodology takes into account the manufacturing, installation, maintenance and use phases of the building. Finally, the model was validated and a matrix in Excel was created as implementation of the model. - Highlights: • Method to assess the envelope impacts based on a simplified LCA • To be used at an earlier phase than the existing methods in a simple way. • It assigns a score by means of known sustainability indicators. • It estimates data about the embodied and operating environmental impacts. • It compares the investment costs with the costs of the consumed energy.

  20. On selection of optimal stochastic model for accelerated life testing

    International Nuclear Information System (INIS)

    Volf, P.; Timková, J.

    2014-01-01

    This paper deals with the problem of proper lifetime model selection in the context of statistical reliability analysis. Namely, we consider regression models describing the dependence of failure intensities on a covariate, for instance, a stressor. Testing the model fit is standardly based on the so-called martingale residuals. Their analysis has already been studied by many authors. Nevertheless, the Bayes approach to the problem, in spite of its advantages, is just developing. We shall present the Bayes procedure of estimation in several semi-parametric regression models of failure intensity. Then, our main concern is the Bayes construction of residual processes and goodness-of-fit tests based on them. The method is illustrated with both artificial and real-data examples. - Highlights: • Statistical survival and reliability analysis and Bayes approach. • Bayes semi-parametric regression modeling in Cox's and AFT models. • Bayes version of martingale residuals and goodness-of-fit test

  1. Model building strategy for logistic regression: purposeful selection.

    Science.gov (United States)

    Zhang, Zhongheng

    2016-03-01

    Logistic regression is one of the most commonly used models to account for confounders in medical literature. The article introduces how to perform purposeful selection model building strategy with R. I stress on the use of likelihood ratio test to see whether deleting a variable will have significant impact on model fit. A deleted variable should also be checked for whether it is an important adjustment of remaining covariates. Interaction should be checked to disentangle complex relationship between covariates and their synergistic effect on response variable. Model should be checked for the goodness-of-fit (GOF). In other words, how the fitted model reflects the real data. Hosmer-Lemeshow GOF test is the most widely used for logistic regression model.

  2. Statistical modelling in biostatistics and bioinformatics selected papers

    CERN Document Server

    Peng, Defen

    2014-01-01

    This book presents selected papers on statistical model development related mainly to the fields of Biostatistics and Bioinformatics. The coverage of the material falls squarely into the following categories: (a) Survival analysis and multivariate survival analysis, (b) Time series and longitudinal data analysis, (c) Statistical model development and (d) Applied statistical modelling. Innovations in statistical modelling are presented throughout each of the four areas, with some intriguing new ideas on hierarchical generalized non-linear models and on frailty models with structural dispersion, just to mention two examples. The contributors include distinguished international statisticians such as Philip Hougaard, John Hinde, Il Do Ha, Roger Payne and Alessandra Durio, among others, as well as promising newcomers. Some of the contributions have come from researchers working in the BIO-SI research programme on Biostatistics and Bioinformatics, centred on the Universities of Limerick and Galway in Ireland and fu...

  3. Modeling and Solving the Liner Shipping Service Selection Problem

    DEFF Research Database (Denmark)

    Karsten, Christian Vad; Balakrishnan, Anant

    We address a tactical planning problem, the Liner Shipping Service Selection Problem (LSSSP), facing container shipping companies. Given estimated demand between various ports, the LSSSP entails selecting the best subset of non-simple cyclic sailing routes from a given pool of candidate routes...... to accurately model transshipment costs and incorporate routing policies such as maximum transit time, maritime cabotage rules, and operational alliances. Our hop-indexed arc flow model is smaller and easier to solve than path flow models. We outline a preprocessing procedure that exploits both the routing...... requirements and the hop limits to reduce problem size, and describe techniques to accelerate the solution procedure. We present computational results for realistic problem instances from the benchmark suite LINER-LIB....

  4. Variable Selection for Regression Models of Percentile Flows

    Science.gov (United States)

    Fouad, G.

    2017-12-01

    Percentile flows describe the flow magnitude equaled or exceeded for a given percent of time, and are widely used in water resource management. However, these statistics are normally unavailable since most basins are ungauged. Percentile flows of ungauged basins are often predicted using regression models based on readily observable basin characteristics, such as mean elevation. The number of these independent variables is too large to evaluate all possible models. A subset of models is typically evaluated using automatic procedures, like stepwise regression. This ignores a large variety of methods from the field of feature (variable) selection and physical understanding of percentile flows. A study of 918 basins in the United States was conducted to compare an automatic regression procedure to the following variable selection methods: (1) principal component analysis, (2) correlation analysis, (3) random forests, (4) genetic programming, (5) Bayesian networks, and (6) physical understanding. The automatic regression procedure only performed better than principal component analysis. Poor performance of the regression procedure was due to a commonly used filter for multicollinearity, which rejected the strongest models because they had cross-correlated independent variables. Multicollinearity did not decrease model performance in validation because of a representative set of calibration basins. Variable selection methods based strictly on predictive power (numbers 2-5 from above) performed similarly, likely indicating a limit to the predictive power of the variables. Similar performance was also reached using variables selected based on physical understanding, a finding that substantiates recent calls to emphasize physical understanding in modeling for predictions in ungauged basins. The strongest variables highlighted the importance of geology and land cover, whereas widely used topographic variables were the weakest predictors. Variables suffered from a high

  5. Topical gabapentin gel alleviates allodynia and hyperalgesia in the chronic sciatic nerve constriction injury neuropathic pain model.

    Science.gov (United States)

    Shahid, M; Subhan, F; Ahmad, N; Ali, G; Akbar, S; Fawad, K; Sewell, R D E

    2017-04-01

    Systemic gabapentin is a mainstay treatment for neuropathic pain though there are side-effects. Localized therapy may curtail such side-effects so a topical gabapentin dermal application was examined in the chronic constriction injury (CCI) model of neuropathic pain. Partial denervation CCI was achieved by rat sciatic nerve ligation. Gabapentin gel (10% w/w) was applied three times daily on the ipsilateral or contralateral plantar surface of the hind-paw, whereas in a concurrent systemic study, gabapentin was intraperitoneally administered daily (75 mg/kg) for 30 days. Tests for static- and dynamic-mechano-allodynia [paw withdrawal threshold (PWT) to von Frey filament application and latency (PWL) to light brushing], cold-allodynia [paw withdrawal duration (PWD) to acetone], heat- (PWL and PWD) and mechano-hyperalgesia (PWD to pin prick) were utilized to assess pain, whereas effects on locomotion (open field) and motor balance (rotarod and footprint analysis) were measured on days 5-30 post surgery. Topical application of gabapentin gel ipsilaterally but not contralaterally alleviated CCI-induced static- (days 10-30) and dynamic-allodynia (days 15-30), suppressed cold-allodynia (days 10-30), heat- (days 15-30) and mechano-hyperalgesia (days 5-30) indicating a local action. Systemic gabapentin exhibited similar pain profiles but was associated with motor impairment. The gabapentin gel formulation afforded desirable neuropathic pain alleviating effects devoid of unwanted systemic side-effects. These outcomes disclose an expedient pharmacological validation of the effectiveness of topical gabapentin gel against an extensive range of nociceptive stimulus modalities utilizing the CCI-induced neuropathic pain model. They also advocate further clinical studies on topical gabapentin with regard to certain neuropathic pain syndromes. Systemic gabapentin neuropathic pain management carries side-effects ostensibly preventable by localized therapy. This study validates the

  6. Wen-Luo-Tong Prevents Glial Activation and Nociceptive Sensitization in a Rat Model of Oxaliplatin-Induced Neuropathic Pain.

    Science.gov (United States)

    Deng, Bo; Jia, Liqun; Pan, Lin; Song, Aiping; Wang, Yuanyuan; Tan, Huangying; Xiang, Qing; Yu, Lili; Ke, Dandan

    2016-01-01

    One of the main dose-limiting complications of the chemotherapeutic agent oxaliplatin (OXL) is painful neuropathy. Glial activation and nociceptive sensitization may be responsible for the mechanism of neuropathic pain. The Traditional Chinese Medicine (TCM) Wen-luo-tong (WLT) has been widely used in China to treat chemotherapy induced neuropathic pain. However, there is no study on the effects of WLT on spinal glial activation induced by OXL. In this study, a rat model of OXL-induced chronic neuropathic pain was established and WLT was administrated. Pain behavioral tests and morphometric examination of dorsal root ganglia (DRG) were conducted. Glial fibrillary acidic protein (GFAP) immunostaining was performed, glial activation was evaluated, and the excitatory neurotransmitter substance P (SP) and glial-derived proinflammatory cytokine tumor necrosis factor-α (TNF-α) were analyzed. WLT treatment alleviated OXL-induced mechanical allodynia and mechanical hyperalgesia. Changes in the somatic, nuclear, and nucleolar areas of neurons in DRG were prevented. In the spinal dorsal horn, hypertrophy and activation of GFAP-positive astrocytes were averted, and the level of GFAP mRNA decreased significantly. Additionally, TNF-α mRNA and protein levels decreased. Collectively, these results indicate that WLT reversed both glial activation in the spinal dorsal horn and nociceptive sensitization during OXL-induced chronic neuropathic pain in rats.

  7. Vitamin D and ferritin correlation with chronic neck pain using standard statistics and a novel artificial neural network prediction model.

    Science.gov (United States)

    Eloqayli, Haytham; Al-Yousef, Ali; Jaradat, Raid

    2018-02-15

    Despite the high prevalence of chronic neck pain, there is limited consensus about the primary etiology, risk factors, diagnostic criteria and therapeutic outcome. Here, we aimed to determine if Ferritin and Vitamin D are modifiable risk factors with chronic neck pain using slandered statistics and artificial intelligence neural network (ANN). Fifty-four patients with chronic neck pain treated between February 2016 and August 2016 in King Abdullah University Hospital and 54 patients age matched controls undergoing outpatient or minor procedures were enrolled. Patients and control demographic parameters, height, weight and single measurement of serum vitamin D, Vitamin B12, ferritin, calcium, phosphorus, zinc were obtained. An ANN prediction model was developed. The statistical analysis reveals that patients with chronic neck pain have significantly lower serum Vitamin D and Ferritin (p-value artificial neural network can be of future benefit in classification and prediction models for chronic neck pain. We hope this initial work will encourage a future larger cohort study addressing vitamin D and iron correction as modifiable factors and the application of artificial intelligence models in clinical practice.

  8. Inhibition of the cAMP/PKA/CREB Pathway Contributes to the Analgesic Effects of Electroacupuncture in the Anterior Cingulate Cortex in a Rat Pain Memory Model.

    Science.gov (United States)

    Shao, Xiao-Mei; Sun, Jing; Jiang, Yong-Liang; Liu, Bo-Yi; Shen, Zui; Fang, Fang; Du, Jun-Ying; Wu, Yuan-Yuan; Wang, Jia-Ling; Fang, Jian-Qiao

    2016-01-01

    Pain memory is considered as endopathic factor underlying stubborn chronic pain. Our previous study demonstrated that electroacupuncture (EA) can alleviate retrieval of pain memory. This study was designed to observe the different effects between EA and indomethacin (a kind of nonsteroid anti-inflammatory drugs, NSAIDs) in a rat pain memory model. To explore the critical role of protein kinase A (PKA) in pain memory, a PKA inhibitor was microinjected into anterior cingulate cortex (ACC) in model rats. We further investigated the roles of the cyclic adenosine monophosphate (cAMP), PKA, cAMP response element-binding protein (CREB), and cAMP/PKA/CREB pathway in pain memory to explore the potential molecular mechanism. The results showed that EA alleviates the retrieval of pain memory while indomethacin failed. Intra-ACC microinjection of a PKA inhibitor blocked the occurrence of pain memory. EA reduced the activation of cAMP, PKA, and CREB and the coexpression levels of cAMP/PKA and PKA/CREB in the ACC of pain memory model rats, but indomethacin failed. The present findings identified a critical role of PKA in ACC in retrieval of pain memory. We propose that the proper mechanism of EA on pain memory is possibly due to the partial inhibition of cAMP/PKA/CREB signaling pathway by EA.

  9. Few promising multivariable prognostic models exist for recovery of people with non-specific neck pain in musculoskeletal primary care: A systematic review

    NARCIS (Netherlands)

    R.W. Wingbermühle (Roel); E. van Trijffel (Emiel); Nelissen, P.M. (Paul M.); B.W. Koes (Bart); A.P. Verhagen (Arianne)

    2017-01-01

    markdownabstractQuestion: Which multivariable prognostic model(s) for recovery in people with neck pain can be used in primary care? Design: Systematic review of studies evaluating multivariable prognostic models. Participants: People with non-specific neck pain presenting at primary care.

  10. Numerical Model based Reliability Estimation of Selective Laser Melting Process

    DEFF Research Database (Denmark)

    Mohanty, Sankhya; Hattel, Jesper Henri

    2014-01-01

    Selective laser melting is developing into a standard manufacturing technology with applications in various sectors. However, the process is still far from being at par with conventional processes such as welding and casting, the primary reason of which is the unreliability of the process. While...... of the selective laser melting process. A validated 3D finite-volume alternating-direction-implicit numerical technique is used to model the selective laser melting process, and is calibrated against results from single track formation experiments. Correlation coefficients are determined for process input...... parameters such as laser power, speed, beam profile, etc. Subsequently, uncertainties in the processing parameters are utilized to predict a range for the various outputs, using a Monte Carlo method based uncertainty analysis methodology, and the reliability of the process is established....

  11. Modelling Technical and Economic Parameters in Selection of Manufacturing Devices

    Directory of Open Access Journals (Sweden)

    Naqib Daneshjo

    2017-11-01

    Full Text Available Sustainable science and technology development is also conditioned by continuous development of means of production which have a key role in structure of each production system. Mechanical nature of the means of production is complemented by controlling and electronic devices in context of intelligent industry. A selection of production machines for a technological process or technological project has so far been practically resolved, often only intuitively. With regard to increasing intelligence, the number of variable parameters that have to be considered when choosing a production device is also increasing. It is necessary to use computing techniques and decision making methods according to heuristic methods and more precise methodological procedures during the selection. The authors present an innovative model for optimization of technical and economic parameters in the selection of manufacturing devices for industry 4.0.

  12. Selection of Models for Ingestion Pathway and Relocation Radii Determination

    International Nuclear Information System (INIS)

    Blanchard, A.

    1998-01-01

    The distance at which intermediate phase protective actions (such as food interdiction and relocation) may be needed following postulated accidents at three Savannah River Site nonreactor nuclear facilities will be determined by modeling. The criteria used to select dispersion/deposition models are presented. Several models were considered, including ARAC, MACCS, HOTSPOT, WINDS (coupled with PUFF-PLUME), and UFOTRI. Although ARAC and WINDS are expected to provide more accurate modeling of atmospheric transport following an actual release, analyses consistent with regulatory guidance for planning purposes may be accomplished with comparatively simple dispersion models such as HOTSPOT and UFOTRI. A recommendation is made to use HOTSPOT for non-tritium facilities and UFOTRI for tritium facilities

  13. Selection of Models for Ingestion Pathway and Relocation

    International Nuclear Information System (INIS)

    Blanchard, A.; Thompson, J.M.

    1998-01-01

    The area in which intermediate phase protective actions (such as food interdiction and relocation) may be needed following postulated accidents at three Savannah River Site nonreactor nuclear facilities will be determined by modeling. The criteria used to select dispersion/deposition models are presented. Several models are considered, including ARAC, MACCS, HOTSPOT, WINDS (coupled with PUFF-PLUME), and UFOTRI. Although ARAC and WINDS are expected to provide more accurate modeling of atmospheric transport following an actual release, analyses consistent with regulatory guidance for planning purposes may be accomplished with comparatively simple dispersion models such as HOTSPOT and UFOTRI. A recommendation is made to use HOTSPOT for non-tritium facilities and UFOTRI for tritium facilities. The most recent Food and Drug Administration Derived Intervention Levels (August 1998) are adopted as evaluation guidelines for ingestion pathways

  14. Selection of Models for Ingestion Pathway and Relocation

    International Nuclear Information System (INIS)

    Blanchard, A.; Thompson, J.M.

    1999-01-01

    The area in which intermediate phase protective actions (such as food interdiction and relocation) may be needed following postulated accidents at three Savannah River Site nonreactor nuclear facilities will be determined by modeling. The criteria used to select dispersion/deposition models are presented. Several models are considered, including ARAC, MACCS, HOTSPOT, WINDS (coupled with PUFF-PLUME), and UFOTRI. Although ARAC and WINDS are expected to provide more accurate modeling of atmospheric transport following an actual release, analyses consistent with regulatory guidance for planning purposes may be accomplished with comparatively simple dispersion models such as HOTSPOT and UFOTRI. A recommendation is made to use HOTSPOT for non-tritium facilities and UFOTRI for tritium facilities. The most recent Food and Drug Administration Derived Intervention Levels (August 1998) are adopted as evaluation guidelines for ingestion pathways

  15. Predicting artificailly drained areas by means of selective model ensemble

    DEFF Research Database (Denmark)

    Møller, Anders Bjørn; Beucher, Amélie; Iversen, Bo Vangsø

    . The approaches employed include decision trees, discriminant analysis, regression models, neural networks and support vector machines amongst others. Several models are trained with each method, using variously the original soil covariates and principal components of the covariates. With a large ensemble...... out since the mid-19th century, and it has been estimated that half of the cultivated area is artificially drained (Olesen, 2009). A number of machine learning approaches can be used to predict artificially drained areas in geographic space. However, instead of choosing the most accurate model....... The study aims firstly to train a large number of models to predict the extent of artificially drained areas using various machine learning approaches. Secondly, the study will develop a method for selecting the models, which give a good prediction of artificially drained areas, when used in conjunction...

  16. ASYMMETRIC PRICE TRANSMISSION MODELING: THE IMPORTANCE OF MODEL COMPLEXITY AND THE PERFORMANCE OF THE SELECTION CRITERIA

    Directory of Open Access Journals (Sweden)

    Henry de-Graft Acquah

    2013-01-01

    Full Text Available Information Criteria provides an attractive basis for selecting the best model from a set of competing asymmetric price transmission models or theories. However, little is understood about the sensitivity of the model selection methods to model complexity. This study therefore fits competing asymmetric price transmission models that differ in complexity to simulated data and evaluates the ability of the model selection methods to recover the true model. The results of Monte Carlo experimentation suggest that in general BIC, CAIC and DIC were superior to AIC when the true data generating process was the standard error correction model, whereas AIC was more successful when the true model was the complex error correction model. It is also shown that the model selection methods performed better in large samples for a complex asymmetric data generating process than with a standard asymmetric data generating process. Except for complex models, AIC's performance did not make substantial gains in recovery rates as sample size increased. The research findings demonstrate the influence of model complexity in asymmetric price transmission model comparison and selection.

  17. An Improved Nested Sampling Algorithm for Model Selection and Assessment

    Science.gov (United States)

    Zeng, X.; Ye, M.; Wu, J.; WANG, D.

    2017-12-01

    Multimodel strategy is a general approach for treating model structure uncertainty in recent researches. The unknown groundwater system is represented by several plausible conceptual models. Each alternative conceptual model is attached with a weight which represents the possibility of this model. In Bayesian framework, the posterior model weight is computed as the product of model prior weight and marginal likelihood (or termed as model evidence). As a result, estimating marginal likelihoods is crucial for reliable model selection and assessment in multimodel analysis. Nested sampling estimator (NSE) is a new proposed algorithm for marginal likelihood estimation. The implementation of NSE comprises searching the parameters' space from low likelihood area to high likelihood area gradually, and this evolution is finished iteratively via local sampling procedure. Thus, the efficiency of NSE is dominated by the strength of local sampling procedure. Currently, Metropolis-Hasting (M-H) algorithm and its variants are often used for local sampling in NSE. However, M-H is not an efficient sampling algorithm for high-dimensional or complex likelihood function. For improving the performance of NSE, it could be feasible to integrate more efficient and elaborated sampling algorithm - DREAMzs into the local sampling. In addition, in order to overcome the computation burden problem of large quantity of repeating model executions in marginal likelihood estimation, an adaptive sparse grid stochastic collocation method is used to build the surrogates for original groundwater model.

  18. Stochastic isotropic hyperelastic materials: constitutive calibration and model selection

    Science.gov (United States)

    Mihai, L. Angela; Woolley, Thomas E.; Goriely, Alain

    2018-03-01

    Biological and synthetic materials often exhibit intrinsic variability in their elastic responses under large strains, owing to microstructural inhomogeneity or when elastic data are extracted from viscoelastic mechanical tests. For these materials, although hyperelastic models calibrated to mean data are useful, stochastic representations accounting also for data dispersion carry extra information about the variability of material properties found in practical applications. We combine finite elasticity and information theories to construct homogeneous isotropic hyperelastic models with random field parameters calibrated to discrete mean values and standard deviations of either the stress-strain function or the nonlinear shear modulus, which is a function of the deformation, estimated from experimental tests. These quantities can take on different values, corresponding to possible outcomes of the experiments. As multiple models can be derived that adequately represent the observed phenomena, we apply Occam's razor by providing an explicit criterion for model selection based on Bayesian statistics. We then employ this criterion to select a model among competing models calibrated to experimental data for rubber and brain tissue under single or multiaxial loads.

  19. Spontaneous inflammatory pain model from a mouse line with N-ethyl-N-nitrosourea mutagenesis

    Directory of Open Access Journals (Sweden)

    Chen Tsung-Chieh

    2012-05-01

    in pstpip2 causes autoinflammatory disease in an N-ethyl-N-nitrosourea mutagenesis mouse model. Thus, our pstpip2 mutant mice provide a new model for investigating the potential mechanisms of inflammatory pain.

  20. Carbamazepine potentiates the effectiveness of morphine in a rodent model of neuropathic pain.

    Directory of Open Access Journals (Sweden)

    Michael R Due

    Full Text Available Approximately 60% of morphine is glucuronidated to morphine-3-glucuronide (M3G which may aggravate preexisting pain conditions. Accumulating evidence indicates that M3G signaling through neuronal Toll-like receptor 4 (TLR4 may be central to this proalgesic signaling event. These events are known to include elevated neuronal excitability, increased voltage-gated sodium (NaV current, tactile allodynia and decreased opioid analgesic efficacy. Using an in vitro ratiometric-based calcium influx analysis of acutely dissociated small and medium-diameter neurons derived from lumbar dorsal root ganglion (DRG, we observed that M3G-sensitive neurons responded to lipopolysaccharide (LPS and over 35% of these M3G/LPS-responsive cells exhibited sensitivity to capsaicin. In addition, M3G-exposed sensory neurons significantly increased excitatory activity and potentiated NaV current as measured by current and voltage clamp, when compared to baseline level measurements. The M3G-dependent excitability and potentiation of NaV current in these sensory neurons could be reversed by the addition of carbamazepine (CBZ, a known inhibitor of several NaV currents. We then compared the efficacy between CBZ and morphine as independent agents, to the combined treatment of both drugs simultaneously, in the tibial nerve injury (TNI model of neuropathic pain. The potent anti-nociceptive effects of morphine (5 mg/kg, i.p. were observed in TNI rodents at post-injury day (PID 7-14 and absent at PID21-28, while administration of CBZ (10 mg/kg, i.p. alone failed to produce anti-nociceptive effects at any time following TNI (PID 7-28. In contrast to either drug alone at PID28, the combination of morphine and CBZ completely attenuated tactile hyperalgesia in the rodent TNI model. The basis for the potentiation of morphine in combination with CBZ may be due to the effects of a latent upregulation of NaV1.7 in the DRG following TNI. Taken together, our observations demonstrate a

  1. The Effect of 8 Weeks of the Selected Combined Exercises on Balance and Pain of Patients Suffering from Arthritis of Knee

    Directory of Open Access Journals (Sweden)

    Elnaz Karimi

    2016-11-01

    Full Text Available Osteoarthritis is considered as the most common joint disease of humans and one of the most common causes of chronic disability among elderly people in the developed countries. The main objective of the present research was to determine the impact of 8 weeks of the combined exercises on the balance and the amount of pain of patients with knee osteoarthritis. 15 patients with knee arthritis were selected purposefully and in form of convenience and they participated in this research. The patients implemented the Training Protocol of walking in water and land and the knee locking and the front thigh exercises for 8 weeks. Dynamic balance (Y test and pain (McGill questionnaire of patients with knee arthritis were measured and evaluated before and after eight weeks of combined exercises. The data were analyzed by use of the t-dependent (P˂0.05. In the dynamic balance of patients with knee arthritis, there was significant difference regarding the anterior side between before-exercises (39.9 7.2 and after-exercises (50.76.8, regarding the internal posterior side between before-exercises (28.8 9.2 and after-exercises (38.0 8.7, regarding the external posterior direction between before-exercises (37.5 7.2 and after-exercises (44.4 7.4. (P˂0.05. Regarding sense perception of pain by patients, there was significant difference between before-exercises (2.2 0.6 and after-exercises (1.8 0.5, regarding the emotional perception of pain by patients between beforeexercises (1.5 0.3 and after-exercises (1.2 0.3 and on perceiving variety of pain by patients between before- (2.10.8 and after-practices (1.8 0.7 (P˂0.05. From the findings of the present research we can conclude that the hydrotherapy exercises combined with exercises on land can cause to improve the dynamic balance and the pain of patients with knee arthritis; therefore we can recommend it as a modality for these patients.

  2. Patient-centered professional practice models for managing low back pain in older adults: a pilot randomized controlled trial.

    Science.gov (United States)

    Goertz, Christine M; Salsbury, Stacie A; Long, Cynthia R; Vining, Robert D; Andresen, Andrew A; Hondras, Maria A; Lyons, Kevin J; Killinger, Lisa Z; Wolinsky, Fredric D; Wallace, Robert B

    2017-10-13

    Low back pain is a debilitating condition for older adults, who may seek healthcare from multiple providers. Few studies have evaluated impacts of different healthcare delivery models on back pain outcomes in this population. The purpose of this study was to compare clinical outcomes of older adults receiving back pain treatment under 3 professional practice models that included primary medical care with or without chiropractic care. We conducted a pilot randomized controlled trial with 131 community-dwelling, ambulatory older adults with subacute or chronic low back pain. Participants were randomly allocated to 12 weeks of individualized primary medical care (Medical Care), concurrent medical and chiropractic care (Dual Care), or medical and chiropractic care with enhanced interprofessional collaboration (Shared Care). Primary outcomes were low back pain intensity rated on the numerical rating scale and back-related disability measured with the Roland-Morris Disability Questionnaire. Secondary outcomes included clinical measures, adverse events, and patient satisfaction. Statistical analyses included mixed-effects regression models and general estimating equations. At 12 weeks, participants in all three treatment groups reported improvements in mean average low back pain intensity [Shared Care: 1.8; 95% confidence interval (CI) 1.0 to 2.6; Dual Care: 3.0; 95% CI 2.3 to 3.8; Medical Care: 2.3; 95% CI 1.5 to 3.2)] and back-related disability (Shared Care: 2.8; 95% CI 1.6 to 4.0; Dual Care: 2.5; 95% CI 1.3 to 3.7; Medical Care: 1.5; 95% CI 0.2 to 2.8). No statistically significant differences were noted between the three groups on the primary measures. Participants in both models that included chiropractic reported significantly better perceived low back pain improvement, overall health and quality of life, and greater satisfaction with healthcare services than patients who received medical care alone. Professional practice models that included primary care and

  3. Modeling selective pressures on phytoplankton in the global ocean.

    Directory of Open Access Journals (Sweden)

    Jason G Bragg

    Full Text Available Our view of marine microbes is transforming, as culture-independent methods facilitate rapid characterization of microbial diversity. It is difficult to assimilate this information into our understanding of marine microbe ecology and evolution, because their distributions, traits, and genomes are shaped by forces that are complex and dynamic. Here we incorporate diverse forces--physical, biogeochemical, ecological, and mutational--into a global ocean model to study selective pressures on a simple trait in a widely distributed lineage of picophytoplankton: the nitrogen use abilities of Synechococcus and Prochlorococcus cyanobacteria. Some Prochlorococcus ecotypes have lost the ability to use nitrate, whereas their close relatives, marine Synechococcus, typically retain it. We impose mutations for the loss of nitrogen use abilities in modeled picophytoplankton, and ask: in which parts of the ocean are mutants most disadvantaged by losing the ability to use nitrate, and in which parts are they least disadvantaged? Our model predicts that this selective disadvantage is smallest for picophytoplankton that live in tropical regions where Prochlorococcus are abundant in the real ocean. Conversely, the selective disadvantage of losing the ability to use nitrate is larger for modeled picophytoplankton that live at higher latitudes, where Synechococcus are abundant. In regions where we expect Prochlorococcus and Synechococcus populations to cycle seasonally in the real ocean, we find that model ecotypes with seasonal population dynamics similar to Prochlorococcus are less disadvantaged by losing the ability to use nitrate than model ecotypes with seasonal population dynamics similar to Synechococcus. The model predictions for the selective advantage associated with nitrate use are broadly consistent with the distribution of this ability among marine picocyanobacteria, and at finer scales, can provide insights into interactions between temporally varying

  4. Modeling selective pressures on phytoplankton in the global ocean.

    Science.gov (United States)

    Bragg, Jason G; Dutkiewicz, Stephanie; Jahn, Oliver; Follows, Michael J; Chisholm, Sallie W

    2010-03-10

    Our view of marine microbes is transforming, as culture-independent methods facilitate rapid characterization of microbial diversity. It is difficult to assimilate this information into our understanding of marine microbe ecology and evolution, because their distributions, traits, and genomes are shaped by forces that are complex and dynamic. Here we incorporate diverse forces--physical, biogeochemical, ecological, and mutational--into a global ocean model to study selective pressures on a simple trait in a widely distributed lineage of picophytoplankton: the nitrogen use abilities of Synechococcus and Prochlorococcus cyanobacteria. Some Prochlorococcus ecotypes have lost the ability to use nitrate, whereas their close relatives, marine Synechococcus, typically retain it. We impose mutations for the loss of nitrogen use abilities in modeled picophytoplankton, and ask: in which parts of the ocean are mutants most disadvantaged by losing the ability to use nitrate, and in which parts are they least disadvantaged? Our model predicts that this selective disadvantage is smallest for picophytoplankton that live in tropical regions where Prochlorococcus are abundant in the real ocean. Conversely, the selective disadvantage of losing the ability to use nitrate is larger for modeled picophytoplankton that live at higher latitudes, where Synechococcus are abundant. In regions where we expect Prochlorococcus and Synechococcus populations to cycle seasonally in the real ocean, we find that model ecotypes with seasonal population dynamics similar to Prochlorococcus are less disadvantaged by losing the ability to use nitrate than model ecotypes with seasonal population dynamics similar to Synechococcus. The model predictions for the selective advantage associated with nitrate use are broadly consistent with the distribution of this ability among marine picocyanobacteria, and at finer scales, can provide insights into interactions between temporally varying ocean processes and

  5. High-frequency electroacupuncture versus carprofen in an incisional pain model in rats

    Energy Technology Data Exchange (ETDEWEB)

    Teixeira, F.M.; Castro, L.L.; Ferreira, R.T.; Pires, P.A.; Vanderlinde, F.A.; Medeiros, M.A. [Departamento de Ciências Fisiológicas, Universidade Federal Rural do Rio de Janeiro, Rio de Janeiro, RJ (Brazil)

    2012-08-24

    The objective of the present study was to compare the effect of electroacupuncture (EA) and carprofen (CP) on postoperative incisional pain using the plantar incision (PI) model in rats. A 1-cm longitudinal incision was made through skin, fascia and muscles of a hind paw of male Wistar rats and the development of mechanical and thermal hypersensitivity was determined over 4 days using the von Frey and Hargreaves methods, respectively. Based on the experimental treatments received on the third postoperative day, the animals were divided into the following groups: PI+CP (CP, 2 mg/kg, po); PI+EAST36 (100-Hz EA applied bilaterally at the Zusanli point (ST36)); PI+EANP (EA applied to a non-acupoint region); PI+IMMO (immobilization only); PI (vehicle). In the von Frey test, the PI+EAST36 group had higher withdrawal force thresholds in response to mechanical stimuli than the PI, PI+IMMO and PI+EANP groups at several times studied. Furthermore, the PI+EAST36 group showed paw withdrawal thresholds in response to mechanical stimuli that were similar to those of the PI+CP group. In the Hargreaves test, all groups had latencies higher than those observed with PI. The PI+EAST36 group was similar to the PI+IMMO, PI+EANP and PI+CP groups. We conclude that 100-Hz EA at the ST36 point, but not at non-acupoints, can reduce mechanical nociception in the rat model of incisional pain, and its effectiveness is comparable to that of carprofen.

  6. High-frequency electroacupuncture versus carprofen in an incisional pain model in rats

    Directory of Open Access Journals (Sweden)

    F.M. Teixeira

    2012-12-01

    Full Text Available The objective of the present study was to compare the effect of electroacupuncture (EA and carprofen (CP on postoperative incisional pain using the plantar incision (PI model in rats. A 1-cm longitudinal incision was made through skin, fascia and muscles of a hind paw of male Wistar rats and the development of mechanical and thermal hypersensitivity was determined over 4 days using the von Frey and Hargreaves methods, respectively. Based on the experimental treatments received on the third postoperative day, the animals were divided into the following groups: PI+CP (CP, 2 mg/kg, po; PI+EAST36 (100-Hz EA applied bilaterally at the Zusanli point (ST36; PI+EANP (EA applied to a non-acupoint region; PI+IMMO (immobilization only; PI (vehicle. In the von Frey test, the PI+EAST36 group had higher withdrawal force thresholds in response to mechanical stimuli than the PI, PI+IMMO and PI+EANP groups at several times studied. Furthermore, the PI+EAST36 group showed paw withdrawal thresholds in response to mechanical stimuli that were similar to those of the PI+CP group. In the Hargreaves test, all groups had latencies higher than those observed with PI. The PI+EAST36 group was similar to the PI+IMMO, PI+EANP and PI+CP groups. We conclude that 100-Hz EA at the ST36 point, but not at non-acupoints, can reduce mechanical nociception in the rat model of incisional pain, and its effectiveness is comparable to that of carprofen.

  7. High-frequency electroacupuncture versus carprofen in an incisional pain model in rats

    International Nuclear Information System (INIS)

    Teixeira, F.M.; Castro, L.L.; Ferreira, R.T.; Pires, P.A.; Vanderlinde, F.A.; Medeiros, M.A.

    2012-01-01

    The objective of the present study was to compare the effect of electroacupuncture (EA) and carprofen (CP) on postoperative incisional pain using the plantar incision (PI) model in rats. A 1-cm longitudinal incision was made through skin, fascia and muscles of a hind paw of male Wistar rats and the development of mechanical and thermal hypersensitivity was determined over 4 days using the von Frey and Hargreaves methods, respectively. Based on the experimental treatments received on the third postoperative day, the animals were divided into the following groups: PI+CP (CP, 2 mg/kg, po); PI+EAST36 (100-Hz EA applied bilaterally at the Zusanli point (ST36)); PI+EANP (EA applied to a non-acupoint region); PI+IMMO (immobilization only); PI (vehicle). In the von Frey test, the PI+EAST36 group had higher withdrawal force thresholds in response to mechanical stimuli than the PI, PI+IMMO and PI+EANP groups at several times studied. Furthermore, the PI+EAST36 group showed paw withdrawal thresholds in response to mechanical stimuli that were similar to those of the PI+CP group. In the Hargreaves test, all groups had latencies higher than those observed with PI. The PI+EAST36 group was similar to the PI+IMMO, PI+EANP and PI+CP groups. We conclude that 100-Hz EA at the ST36 point, but not at non-acupoints, can reduce mechanical nociception in the rat model of incisional pain, and its effectiveness is comparable to that of carprofen

  8. High-frequency electroacupuncture versus carprofen in an incisional pain model in rats.

    Science.gov (United States)

    Teixeira, F M; Castro, L L; Ferreira, R T; Pires, P A; Vanderlinde, F A; Medeiros, M A

    2012-12-01

    The objective of the present study was to compare the effect of electroacupuncture (EA) and carprofen (CP) on postoperative incisional pain using the plantar incision (PI) model in rats. A 1-cm longitudinal incision was made through skin, fascia and muscles of a hind paw of male Wistar rats and the development of mechanical and thermal hypersensitivity was determined over 4 days using the von Frey and Hargreaves methods, respectively. Based on the experimental treatments received on the third postoperative day, the animals were divided into the following groups: PI+CP (CP, 2 mg/kg, po); PI+EAST36 (100-Hz EA applied bilaterally at the Zusanli point (ST36)); PI+EANP (EA applied to a non-acupoint region); PI+IMMO (immobilization only); PI (vehicle). In the von Frey test, the PI+EAST36 group had higher withdrawal force thresholds in response to mechanical stimuli than the PI, PI+IMMO and PI+EANP groups at several times studied. Furthermore, the PI+EAST36 group showed paw withdrawal thresholds in response to mechanical stimuli that were similar to those of the PI+CP group. In the Hargreaves test, all groups had latencies higher than those observed with PI. The PI+EAST36 group was similar to the PI+IMMO, PI+EANP and PI+CP groups. We conclude that 100-Hz EA at the ST36 point, but not at non-acupoints, can reduce mechanical nociception in the rat model of incisional pain, and its effectiveness is comparable to that of carprofen.

  9. Use of Liposomal Bupivacaine for Postoperative Analgesia in an Incisional Pain Model in Rats (Rattus norvegicus).

    Science.gov (United States)

    Kang, Stacey C; Jampachaisri, Katechan; Seymour, Travis L; Felt, Stephen A; Pacharinsak, Cholawat

    2017-01-01

    The local anesthetic bupivacaine is valuable for perioperative analgesia, but its use in the postoperative period is limited by its short duration of action. Here, we evaluated the application of a slow-release liposomal formulation of bupivacaine for postoperative analgesia. The aim was to assess whether liposomal bupivacaine effectively attenuates postoperative mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats (n = 36) were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC every 12 h for 2 d; buprenorphine HCl, 0.05 mg/kg SC every 12 h for 2 d (Bup HCl); 0.5% bupivacaine, 2 mg/kg SC local infiltration once (Bupi); liposomal bupivacaine, 1 mg/kg SC local infiltration once (Exp1); and liposomal bupivacaine, 6 mg/kg SC local infiltration once (Exp6). Mechanical and thermal hypersensitivity were evaluated daily on days -1, 0, 1, 2, 3, and 4. The saline group exhibited both hypersensitivities through all 4 evaluated postoperative days. Bup HCl attenuated mechanical hypersensitivity for 2 d and thermal hypersensitivity for 1 d. Bupi attenuated only thermal hypersensitivity for 4 d. Rats in the Exp1 group showed attenuation of both mechanical and thermal hypersensitivity for 4 d, and those in the Exp6 group had attenuation of mechanical hypersensitivity on day 0 and thermal hypersensitivity for 4 d. These data suggest that a single local infiltration of liposomal bupivacaine at a dose of 1 mg/kg SC effectively attenuates postoperative mechanical and thermal hypersensitivity for 4 d in a rat model of incisional pain.

  10. Factors Associated with Increased Pain in Primary Dysmenorrhea: Analysis Using a Multivariate Ordered Logistic Regression Model.

    Science.gov (United States)

    Tomás-Rodríguez, María I; Palazón-Bru, Antonio; Martínez-St John, Damian R J; Navarro-Cremades, Felipe; Toledo-Marhuenda, José V; Gil-Guillén, Vicente F

    2017-04-01

    In the literature about primary dysmenorrhea (PD), either a pain gradient has been studied just in women with PD or pain was assessed as a binary variable (presence or absence). Accordingly, we decided to carry out a study in young women to determine possible factors associated with intense pain. A cross-sectional observational study. A Spanish University in 2016. A total of 306 women, aged 18-30 years. A questionnaire was filled in by the participants to assess associated factors with dysmenorrhoea. Our outcome measure was the Andersch and Milsom scale (grade from 0 to 3). grade 0 (menstruation is not painful and daily activity is unaffected), grade 1 (menstruation is painful but seldom inhibits normal activity, analgesics are seldom required, and mild pain), grade 2 (daily activity affected, analgesics required and give relief so that absence from work or school is unusual, and moderate pain), and grade 3 (activity clearly inhibited, poor effect of analgesics, vegetative symptoms and severe pain). Factors significantly associated with more extreme pain: a higher menstrual flow (odds ratio [OR], 2.11; P < .001), a worse quality of life (OR, 0.97; P < .001) and use of medication for PD (OR, 8.22; P < .001). We determined factors associated with extreme pain in PD in a novel way. Further studies are required to corroborate our results. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  11. Modeling selective attention using a neuromorphic analog VLSI device.

    Science.gov (United States)

    Indiveri, G

    2000-12-01

    Attentional mechanisms are required to overcome the problem of flooding a limited processing capacity system with information. They are present in biological sensory systems and can be a useful engineering tool for artificial visual systems. In this article we present a hardware model of a selective attention mechanism implemented on a very large-scale integration (VLSI) chip, using analog neuromorphic circuits. The chip exploits a spike-based representation to receive, process, and transmit signals. It can be used as a transceiver module for building multichip neuromorphic vision systems. We describe the circuits that carry out the main processing stages of the selective attention mechanism and provide experimental data for each circuit. We demonstrate the expected behavior of the model at the system level by stimulating the chip with both artificially generated control signals and signals obtained from a saliency map, computed from an image containing several salient features.

  12. Genomic Selection in Plant Breeding: Methods, Models, and Perspectives.

    Science.gov (United States)

    Crossa, José; Pérez-Rodríguez, Paulino; Cuevas, Jaime; Montesinos-López, Osval; Jarquín, Diego; de Los Campos, Gustavo; Burgueño, Juan; González-Camacho, Juan M; Pérez-Elizalde, Sergio; Beyene, Yoseph; Dreisigacker, Susanne; Singh, Ravi; Zhang, Xuecai; Gowda, Manje; Roorkiwal, Manish; Rutkoski, Jessica; Varshney, Rajeev K

    2017-11-01

    Genomic selection (GS) facilitates the rapid selection of superior genotypes and accelerates the breeding cycle. In this review, we discuss the history, principles, and basis of GS and genomic-enabled prediction (GP) as well as the genetics and statistical complexities of GP models, including genomic genotype×environment (G×E) interactions. We also examine the accuracy of GP models and methods for two cereal crops and two legume crops based on random cross-validation. GS applied to maize breeding has shown tangible genetic gains. Based on GP results, we speculate how GS in germplasm enhancement (i.e., prebreeding) programs could accelerate the flow of genes from gene bank accessions to elite lines. Recent advances in hyperspectral image technology could be combined with GS and pedigree-assisted breeding. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Efficacy and tolerability of lumiracoxib, a highly selective cyclo-oxygenase-2 (COX2 inhibitor, in the management of pain and osteoarthritis

    Directory of Open Access Journals (Sweden)

    Piet Geusens

    2008-04-01

    Full Text Available Piet Geusens1, Willem Lems21Department of Internal Medicine, Subdivision of Rheumatology, University Hospital, Maastricht, The Netherlands and Biomedical Research Institute, University Hasselt, Belgium; 2Vrije Universiteit Medical Centre, Department of Rheumatology, Amsterdam, the NetherlandsAbstract: Lumiracoxib is a COX2 inhibitor that is highly selective, is more effective than placebo on pain in osteoarthritis (OA, with similar analgesic and anti-inflammatory effects as non-selective NSAIDs and the selective COX2 inhibitor celecoxib, has a lower incidence of upper gastrointestinal (GI side effects in patients not taking aspirin, and a similar incidence of cardiovascular (CV side effects compared to naproxen or ibuprofen. In the context of earlier guidelines and taking into account the GI and CV safety results of the TARGET study, lumiracoxib had secured European Medicines Agency (EMEA approval with as indication symptomatic treatment of OA as well as short-term management of acute pain associated with primary dysmenorrhea and following orthopedic or dental surgery. In the complex clinical context of efficiency and safety of selective and non-selective COX inhibitors, its prescription and use should be based on the risk and safety profile of the patient. In addition, there is further need for long-term GI and CV safety studies and general post-marketing safety on its use in daily practice. Meanwhile, at the time of submission of this manuscript, the EMEA has withdrawn lumiracoxib throughout Europe because of the risk of serious side effects affecting the liver.Keywords: lumiracoxib, NSAIDs, COX2 inhibitors, gastro-intestinal and cardiovascular safety

  14. A Model of Social Selection and Successful Altruism

    Science.gov (United States)

    1989-10-07

    D., The evolution of social behavior. Annual Reviews of Ecological Systems, 5:325-383 (1974). 2. Dawkins , R., The selfish gene . Oxford: Oxford...alive and well. it will be important to re- examine this striking historical experience,-not in terms o, oversimplified models of the " selfish gene ," but...Darwinian Analysis The acceptance by many modern geneticists of the axiom that the basic unit of selection Is the " selfish gene " quickly led to the

  15. Pareto-Optimal Model Selection via SPRINT-Race.

    Science.gov (United States)

    Zhang, Tiantian; Georgiopoulos, Michael; Anagnostopoulos, Georgios C

    2018-02-01

    In machine learning, the notion of multi-objective model selection (MOMS) refers to the problem of identifying the set of Pareto-optimal models that optimize by compromising more than one predefined objectives simultaneously. This paper introduces SPRINT-Race, the first multi-objective racing algorithm in a fixed-confidence setting, which is based on the sequential probability ratio with indifference zone test. SPRINT-Race addresses the problem of MOMS with multiple stochastic optimization objectives in the proper Pareto-optimality sense. In SPRINT-Race, a pairwise dominance or non-dominance relationship is statistically inferred via a non-parametric, ternary-decision, dual-sequential probability ratio test. The overall probability of falsely eliminating any Pareto-optimal models or mistakenly returning any clearly dominated models is strictly controlled by a sequential Holm's step-down family-wise error rate control method. As a fixed-confidence model selection algorithm, the objective of SPRINT-Race is to minimize the computational effort required to achieve a prescribed confidence level about the quality of the returned models. The performance of SPRINT-Race is first examined via an artificially constructed MOMS problem with known ground truth. Subsequently, SPRINT-Race is applied on two real-world applications: 1) hybrid recommender system design and 2) multi-criteria stock selection. The experimental results verify that SPRINT-Race is an effective and efficient tool for such MOMS problems. code of SPRINT-Race is available at https://github.com/watera427/SPRINT-Race.

  16. Establishment of selected acute pulmonary thromboembolism model in experimental sheep

    International Nuclear Information System (INIS)

    Fan Jihai; Gu Xiulian; Chao Shengwu; Zhang Peng; Fan Ruilin; Wang Li'na; Wang Lulu; Wang Ling; Li Bo; Chen Taotao

    2010-01-01

    Objective: To establish a selected acute pulmonary thromboembolism model in experimental sheep suitable for animal experiment. Methods: By using Seldinger's technique the catheter sheath was placed in both the femoral vein and femoral artery in ten sheep. Under C-arm DSA guidance the catheter was inserted through the catheter sheath into the pulmonary artery. Via the catheter appropriate amount of sheep autologous blood clots was injected into the selected pulmonary arteries. The selected acute pulmonary thromboembolism model was thus established. Pulmonary angiography was performed to check the results. The pulmonary arterial pressure, femoral artery pressure,heart rates and partial pressure of oxygen in arterial blood (PaO 2 ) were determined both before and after the treatment. The above parameters obtained after the procedure were compared with the recorded parameters measured before the procedure, and the sheep model quality was evaluated. Results: The baseline of pulmonary arterial pressure was (27.30 ± 9.58) mmHg,femoral artery pressure was (126.4 ± 13.72) mmHg, heart rate was (103 ± 15) bpm and PaO 2 was (87.7 ± 12.04) mmHg. Sixty minutes after the injection of (30 ± 5) ml thrombotic agglomerates, the pulmonary arterial pressures rose to (52 ± 49) mmHg, femoral artery pressures dropped to (100 ± 21) mmHg. The heart rates went up to (150 ± 26) bpm. The PaO 2 fell to (25.3 ± 11.2) mmHg. After the procedure the above parameters were significantly different from that measured before the procedure in all ten animals (P < 0.01). The pulmonary arteriography clearly demonstrated that the selected pulmonary arteries were successfully embolized. Conclusion: The anatomy of sheep's femoral veins,vena cava system, pulmonary artery and right heart system are suitable for the establishment of the catheter passage, for this reason, selected acute pulmonary thromboembolism model can be easily created in experimental sheep. The technique is feasible and the model

  17. Selection of key terrain attributes for SOC model

    DEFF Research Database (Denmark)

    Greve, Mogens Humlekrog; Adhikari, Kabindra; Chellasamy, Menaka

    As an important component of the global carbon pool, soil organic carbon (SOC) plays an important role in the global carbon cycle. SOC pool is the basic information to carry out global warming research, and needs to sustainable use of land resources. Digital terrain attributes are often use...... was selected, total 2,514,820 data mining models were constructed by 71 differences grid from 12m to 2304m and 22 attributes, 21 attributes derived by DTM and the original elevation. Relative importance and usage of each attributes in every model were calculated. Comprehensive impact rates of each attribute...

  18. A decision model for energy resource selection in China

    International Nuclear Information System (INIS)

    Wang Bing; Kocaoglu, Dundar F.; Daim, Tugrul U.; Yang Jiting

    2010-01-01

    This paper evaluates coal, petroleum, natural gas, nuclear energy and renewable energy resources as energy alternatives for China through use of a hierarchical decision model. The results indicate that although coal is still the major preferred energy alternative, it is followed closely by renewable energy. The sensitivity analysis indicates that the most critical criterion for energy selection is the current energy infrastructure. A hierarchical decision model is used, and expert judgments are quantified, to evaluate the alternatives. Criteria used for the evaluations are availability, current energy infrastructure, price, safety, environmental impacts and social impacts.

  19. The peer effect on pain tolerance.

    Science.gov (United States)

    Engebretsen, Solveig; Frigessi, Arnoldo; Engø-Monsen, Kenth; Furberg, Anne-Sofie; Stubhaug, Audun; de Blasio, Birgitte Freiesleben; Nielsen, Christopher Sivert

    2018-05-19

    Twin studies have found that approximately half of the variance in pain tolerance can be explained by genetic factors, while shared family environment has a negligible effect. Hence, a large proportion of the variance in pain tolerance is explained by the (non-shared) unique environment. The social environment beyond the family is a potential candidate for explaining some of the variance in pain tolerance. Numerous individual traits have previously shown to be associated with friendship ties. In this study, we investigate whether pain tolerance is associated with friendship ties. We study the friendship effect on pain tolerance by considering data from the Tromsø Study: Fit Futures I, which contains pain tolerance measurements and social network information for adolescents attending first year of upper secondary school in the Tromsø area in Northern Norway. Pain tolerance was measured with the cold-pressor test (primary outcome), contact heat and pressure algometry. We analyse the data by using statistical methods from social network analysis. Specifically, we compute pairwise correlations in pain tolerance among friends. We also fit network autocorrelation models to the data, where the pain tolerance of an individual is explained by (among other factors) the average pain tolerance of the individual's friends. We find a significant and positive relationship between the pain tolerance of an individual and the pain tolerance of their friends. The estimated effect is that for every 1 s increase in friends' average cold-pressor tolerance time, the expected cold-pressor pain tolerance of the individual increases by 0.21 s (p-value: 0.0049, sample size n=997). This estimated effect is controlled for sex. The friendship effect remains significant when controlling for potential confounders such as lifestyle factors and test sequence among the students. Further investigating the role of sex on this friendship effect, we only find a significant peer effect of male friends

  20. Patients speak out: development of an evidence-based model for managing orthopaedic postoperative pain.

    Science.gov (United States)

    Pulido, Pamela; Hardwick, Mary E; Munro, Michelle; May, Laura; Dupies-Rosa, Denise

    2010-01-01

    Perioperative pain management after total joint replacement continues to be a concern for orthopaedic nurses. In our institution, the results of routine post-hospital stay surveys had shown below average scores in the area of pain management. This began as a quality management issue, became a pain subcommittee issue, and drew in the research nurses to ask what we can learn from this process. Changing the method of handling pain management is not easy, but it makes a difference in patients' hospital experiences. We learned that cooperation and expertise from multiple departments within the institution and some organizations outside the institution is needed to bring about change. We learned that education of not just staff members but also patients on pain management affected the outcome. This article describes our journey to enhance pain management in our institution.

  1. Covariate selection for the semiparametric additive risk model

    DEFF Research Database (Denmark)

    Martinussen, Torben; Scheike, Thomas

    2009-01-01

    This paper considers covariate selection for the additive hazards model. This model is particularly simple to study theoretically and its practical implementation has several major advantages to the similar methodology for the proportional hazards model. One complication compared...... and study their large sample properties for the situation where the number of covariates p is smaller than the number of observations. We also show that the adaptive Lasso has the oracle property. In many practical situations, it is more relevant to tackle the situation with large p compared with the number...... of observations. We do this by studying the properties of the so-called Dantzig selector in the setting of the additive risk model. Specifically, we establish a bound on how close the solution is to a true sparse signal in the case where the number of covariates is large. In a simulation study, we also compare...

  2. Optimal foraging in marine ecosystem models: selectivity, profitability and switching

    DEFF Research Database (Denmark)

    Visser, Andre W.; Fiksen, Ø.

    2013-01-01

    ecological mechanics and evolutionary logic as a solution to diet selection in ecosystem models. When a predator can consume a range of prey items it has to choose which foraging mode to use, which prey to ignore and which ones to pursue, and animals are known to be particularly skilled in adapting...... to the preference functions commonly used in models today. Indeed, depending on prey class resolution, optimal foraging can yield feeding rates that are considerably different from the ‘switching functions’ often applied in marine ecosystem models. Dietary inclusion is dictated by two optimality choices: 1...... by letting predators maximize energy intake or more properly, some measure of fitness where predation risk and cost are also included. An optimal foraging or fitness maximizing approach will give marine ecosystem models a sound principle to determine trophic interactions...

  3. Selection of productivity improvement techniques via mathematical modeling

    Directory of Open Access Journals (Sweden)

    Mahassan M. Khater

    2011-07-01

    Full Text Available This paper presents a new mathematical model to select an optimal combination of productivity improvement techniques. The proposed model of this paper considers four-stage cycle productivity and the productivity is assumed to be a linear function of fifty four improvement techniques. The proposed model of this paper is implemented for a real-world case study of manufacturing plant. The resulted problem is formulated as a mixed integer programming which can be solved for optimality using traditional methods. The preliminary results of the implementation of the proposed model of this paper indicate that the productivity can be improved through a change on equipments and it can be easily applied for both manufacturing and service industries.

  4. An Introduction to Model Selection: Tools and Algorithms

    Directory of Open Access Journals (Sweden)

    Sébastien Hélie

    2006-03-01

    Full Text Available Model selection is a complicated matter in science, and psychology is no exception. In particular, the high variance in the object of study (i.e., humans prevents the use of Popper’s falsification principle (which is the norm in other sciences. Therefore, the desirability of quantitative psychological models must be assessed by measuring the capacity of the model to fit empirical data. In the present paper, an error measure (likelihood, as well as five methods to compare model fits (the likelihood ratio test, Akaike’s information criterion, the Bayesian information criterion, bootstrapping and cross-validation, are presented. The use of each method is illustrated by an example, and the advantages and weaknesses of each method are also discussed.

  5. Chronic Pain

    Science.gov (United States)

    ... pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain. × ... pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain. ...