Le peptide natriurétique de type B (BNP) est une hormone cardiaque fortement impliquée dans l'insuffisance cardiaque (IC). En clinique, le BNP est un bio-marqueur de diagnostic et de pronostic de l'IC; son taux sanguin augmentant avec la progression du remodelage cardiaque, de la dysfonction du ventricule gauche (VG) et des altérations du couplage excitation-contraction (CEC). Administré sous une forme recombinante, le nésiritide, pour ses effets hémodynamiques vasorelaxants, chez des patients en IC aiguë décompensée, il a montré des effets controversés avec un risque d'augmentation de la mortalité. Pour comprendre l'implication du BNP dans le remodelage cardiaque post-ischémique et son efficacité thérapeutique, nous avons étudié les effets cardiaques in vivo et sur le CEC d'un traitement chronique au BNP (0,03 µg/kg/min) sur deux groupes expérimentaux : i) des souris saines, Sham, pendant 14 jours et ii) des souris PMI (Post-Myocardial Infarction) en stade précoce, après ligature de l'artère coronaire gauche (pendant 7 et 14 jours). Chez les Sham, le BNP a engendré une suractivation du système nerveux sympathique, une hypertrophie cardiaque, des altérations électrophysiologiques in vivo et des mouvements calciques dans les cardiomyocytes du VG, à l'origine d'arythmies cellulaires et cardiaques. Les effets délétères du BNP ont été prévenus par une combinaison de ce traitement avec un β-bloqueur : le métoprolol. Chez les PMI, la supplémentation en BNP a réduit l'inotropisme positif précoce acquis par une modification des mouvements calciques, a accéléré l'apparition des altérations des protéines du CEC et la survenue des arythmies. Le BNP accélère la décompensation cardiaque et pourrait être à déconseiller, du moins en monothérapie, en traitement clinique. / BNP is a natriuretic peptide released in excess in the blood during heart failure (HF) to reduce blood volume and pressure. A recombinant form of human BNP, nesiritide, is used for patients with acute decompensated HF but deleterious cardiac effects have been reported. We aimed to investigate the cardiac effects of chronic BNP supplementation (0.03 µg/kg/min) on: i) healthy mice (Sham) for 14 days and ii) mice subjected to myocardial infarction (MI) induced by coronary artery ligation (PMI) for 7 (D7) and (D14) 14 days. Sham treated animals (Sham-BNP) showed an increase in ventricular arrhythmias occurrence in consequence of sympathetic tone increase and Ca2+ handling alterations observed at cellular and protein levels in the left ventricle (LV). Most of these effects were reduced in Sham-BNP by the selective beta1-adrenergic blocker metoprolol. In the PMI group, at early stages after ligation, we showed an increase in cardiomyocytes contraction and Ca2+ handling at D7 and D14. But this response was attenuated in PMI-BNP. In PMI, alterations in Ca2+ handling proteins, particularly SERCA2a and RyR2 appeared at D14 but not D7. But BNP supplementation accelerated these alterations which appeared since D7 in the PMI-BNP group, in parallel with spontaneous arrhythmias occurrence at D7. BNP infusion attenuates compensatory "inotropism" intrinsic to the LV cardiomyocytes and promotes arrhythmias. Our results show that BNP, at least in monotherapy, may be hazardous for the treatment of patients with decompensated HF.

Background: This study explored the differences between the seasonal mortality rates (by age and gender) between the two jurisdictions (the Republic of Ireland (RoI) and Northern Ireland (NI)). The study assessed the relationship between cold temperatures and daily mortality, and assessed for effect modification of the cold weather-mortality relationship by age and gender. Methods: Mortality rates were calculated for each cause-specific mortality group during various seasons in both jurisdictions. A time-stratified case-crossover approach was applied to examine the cold weather-mortality relationship, 1984-2007. The daily mortality risk was explored in association with exposure to daily maximum temperatures on the same day and up to 6 weeks preceding death, during the winter months and extended cold period (October-March), using distributed lag models. Model stratification by age and gender assessed for modification of the cold weather-mortality relationship. Results: The winter mortality rates were significantly greater than the summer rates. NI experienced higher mortality from cardiovascular disease, respiratory disease and stroke. The impact of cold weather in the winter months persisted up to 35 days in the RoI, with a cumulative mortality increase for all-cause of 6.4% (95%CI: 4.8%-7.9%) with regards to every 1oC drop in the daily maximum temperature with similar associations for cardiovascular disease and stroke with twice as much for respiratory diseases. The associations were less pronounced and less persistent in NI. Conclusions: The study observed excess winter mortality. The cold weather-mortality associations increased with age with some suggestion of gender differences. There were strong cold weather-mortality associations in both jurisdictions, with suggestive differences in associations by age and gender. The findings suggest the potential contribution of societal differences, and require further exploration. These findings will hopefully contribute to the current efforts to modify fuel policy and reduce winter mortality in both jurisdictions.

La réponse de l’organisme contre un agent pathogène nécessite la mise en jeu d’interactions complexes entre cellules immunitaires et environnement. La matrice extra-cellulaire est remodelée au cours de la réponse immunitaire pour permettre la migration des cellules vers le site infectieux. Les peptides issus de la dégradation de la matrice peuvent influencer les fonctions biologiques des cellules immunitaires. Dans les pathologies impliquant des tissus riches en élastine, les cellules de la réponse inflammatoire et immunitaire, notamment les polynucléaires neutrophiles (PN) et les cellules dendritiques se retrouvent dans un environnement riche en produits issus de la dégradation de l’élastine. Le travail de thèse présenté ici nous a permis de montrer que les peptides d’élastine (PE) régulent les fonctions des PN de sujets sains en augmentant de façon significative leur capacité migratoire, leur capacité à produire des cytokines pro-inflammatoire et à phagocyter les agents pathogènes. Les effets régulateurs des PE sont moindres chez les sujets BPCO et varient en fonction de l’état clinique des patients. Les propriétés biologiques des PN de patients BPCO en exacerbation ne sont pas affectées par les PE. Cette différence de réponse aux PE des PN de patients BPCO à l’état stable ou à l’état exacerbé est proportionnellement liée au niveau d’expression du récepteur S-Gal à la surface des PN. Dans un second travail nous avons montré que les PE sont capables d’attirer les CD au niveau du site infectieux sans influencer la maturation des cellules induite par une activation antigénique. L’effet des PE sur la migration des CD met en jeu le récepteur S-Gal présent à la surface des cellules. Par ailleurs, les PE orientent la réponse cytokinique des CD activées par le LPS vers un profil de type Th-2 et favorisent l’émergence d‟un profil tolérogénique des CD. Ces effets régulateurs des PE sont médiés via l’interaction PE/S-Gal et conduisent au développement d’une réponse adaptative T régulatrice. L’ensemble de ces résultats suggère que les PE participent activement à la régulation de la réponse immunitaire innée et adaptative / Organisme defense against pathogens needs complexe interactions interactions between immune cells and environnement. The extracellular matrix is being remodeled to aloww cells to migrate to infectious site. Peptides generated by this degradation can influence biological fonctions of immune cells. In pathologies involving elastin rich tissue degradation inflammatory and immune cells, especially neutrophils and dendritic cells are in an environnement including numbers of matrix degradation products. This work shows that Elastin Peptides (EP) can regulate the fonctions of neutrophils from healthy subjects, by increasing significantly their migration, their cytokines production and their phagocytic capacity. These EP effects are howeever less important en stable COPD subject and depends on the clinical state of these patients. Indeed the biological properties of neutrophils from COPD patients in exacerbation are not affected by EP. This discrepancy considering the clinical state can be explained by the level of the S-Gal receptor expression. In a second part we have shown the ability of the EP to attract dendritic cell (DC) on the infection site without couetracting DC maturation. This effect involves the S-Gal receptor present on the surface of the cells. EP can also oriente the cytokine production by LPS-induced toward a Th-2 profil and favorise the emergence of DC with tolerogenic features. These effects are mediated throug EP/S-Gal interaction and leads to the developement of a T regulatory response. All of these results suggest that EP are involved in the regulation of innate and adaptative immunity.

Organisation’s adaptation to owner’s chronic illness is an important theme for all businesses, but it is especially valuable for small family businesses as well as entrepreneurial couples due to their strong interrelation between family and business. So far family business research has not looked into family businesses’ process of adapting to the disruption caused by the occurence of owner’s severe chronic illness. The purpose of this thesis was to look at what impact an owner’s severe chronic illness has on the organisation’s adaptation. To fulfil the purpose, this study combines family science, and family business research and theories in an interdisciplinary manner, applying family science theory to family business research. Our approach is directed by the Double ABCX Model of Family Stress and the FAAR Model to explore the adaptation process of family businesses and to identify demands and resources connected to the disruption. This multiple case study, utilising semi-structured interviews, observations and secondary data was conducted in a Finnish and German context. The collected qualitative data is presented as narrative case summaries, and analysed by applying in- and cross-case analysis. The findings add to the theoretical understanding of the adaptation process by identifying preconditions, which affect organisations’ adaptation process. Moreover, we identified demands that a chronic illness causes for both the business and the family as well as resources that are used to respond to the new demands. A model illustrating the adaptation process and its dimensions is presented. The findings of the study do not only serve family businesses coping with a chronic illness but provide more implications for businesses in general. Organisations can use the study’s findings to prepare and make their business fit for disruptions of different nature. In addition, organisations in the particular situation researched can benefit by better understanding how they could further improve to stay resilient for possible future disruptions.

M.Tech. / Purpose: To determine what effects flexion distraction will have on males with chronic lumbar facet syndrome, in reference to intersegmental range of motion and pain. Method: Thirty male participants with chronic lumbar facet syndrome received flexion distraction technique. The trail consisted of seven visits over two to three weeks. Treatment was performed on the first to sixth visit, readings and questionnaires were completed on the first, fourth and seventh visits. Data collection was concluded before treatment on the mentioned visits. Subjective data consisted of the Oswestry Disability Index (ODI) and the Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2). Objective data included global lumbar range of motion measurements using the Baseline Digital Inclinometer, and segmental lumbar range of motion by means of the Radiographical Midplane Angle method. Results: Objectively, clinical significance of the intersegmental lumbar range of motion increased from the L1/L2 to the L4/L5 level (2.2% - 17.7%), but showed no statistical significance. In relation to the maximal motion possible at these levels, the increase in motion escalated from 0.8% at the L1/L2 segment to 9.2% at the L4/L5 segment. The global lumbar range of motion showed clinical significant increase in all of the ranges except for extension, however statistical significance was found in right lateral flexion only (p = 0.045). The greatest increase in motion was observed in left lateral flexion (15.72%) and a decrease in extension (3.72%) was illustrated. Subjectively, the group showed statistical significant improvement in both the SF-MPQ-2 (p = 0.000) and ODI (p = 0.000). Clinical meaningful change was noted throughout the subjective data, which resultantly showed a 66% and a 67% change in pain respectively. Conclusion: Flexion distraction has shown to have clinical significant effects on segmental and thus global range of motion, and great clinical meaningful change in pain levels and pain perception. Thus specific segmental mobilisation does affect the segmental motion.

A significant subset of mild traumatic brain injury (mild TBI) and chronic pain (CP) patients report, and sometimes show objective evidence of, persisting cognitive problems. Despite differences in injury mechanisms, there is considerable overlap in the types of persisting cognitive symptoms that are reported by the two populations. Psychogenic, rather than physiogenic, factors are thought to play an important role in the maintenance of these persisting symptoms. The current investigation examined the contributions somatization, depression, and anxiety had on an objective measure of “working attention.” In order to best elucidate the influences these psychological factors had on attentional performance, only individuals who passed well-validated and popular indicators of cognitive and self-report validity were included in the study. Two hundred and forty-nine individuals (n = 116 TBI; n = 133 CP) met the inclusionary criteria for the study. Psychological factors were assessed using Scales 1 (Hypochondriasis), 2 (Depression), 3 (Hysteria), and 7 (Psychasthenia) of the Minnesota Multiphasic Personality Inventory-II. “Working attention” was measured using the demographically-adjusted T-scores for the Working Memory and Processing Speed Indexes of the Wechsler Adult Intelligence Scale- 3. Results indicated that a high rate of psychological complications was observed in the mild TBI and CP groups but not the moderate-severe traumatic brain injury (M/S TBI) comparison group. Analysis indicated that psychological elevations were not significantly related to spontaneously-reported symptoms or working attention deficits for the mild TBI group but were for the CP and M/S TBI groups. The current results are important for understanding the psychological complications that may occur in individuals exhibiting persisting cognitive problems in these clinical populations.

The World Health Organization has called stress-related illness “the health epidemic of the 21st century.” While the biochemical pathways associated with the acute stress response are well-characterized, many of the pathways behave differently under conditions of chronic stress. The purpose of this project is to apply high-sensitivity mass spectrometry (MS)-based targeted and untargeted metabolomics approaches to generate new insights into the biochemical processes and pathways associated with the chronic stress response, and potential mechanisms by which chronic stress produces adverse health effects. Chapter 1 describes the application of sets of targeted and untargeted metabolomics approaches to analyze serum samples from a human epigenetic model of chronic stress in order to identify potential targets for further analysis. To test the resulting hypothesis that oxidative stress is a key feature of chronic stress, a new targeted multiple reaction monitoring (MRM)-MS assay was developed for the accurate quantitation of aldehyde products of lipid peroxidation, as described in Chapter 2. In Chapter 3, the validated method for quantitation of malondialdehyde (MDA) was t applied to mouse plasma samples from a model of chronic social defeat stress to determine whether animals exposed to psychosocial stress show increases in oxidative stress. Mouse plasma samples from this model were also analyzed by untargeted metabolomics using Fourier-transform (FT)-MS to identify other important metabolite features, particularly those that overlap with metabolites identified in the human epigenetic model. Analysis of metabolomic data from two very different models of chronic stress supports the consistent detection of a metabolomic phenotype for chronic stress that is characterized by the dysregulation of energy metabolism associated with decreased concentrations of diacyl-phospholipids in blood. Increased blood concentrations of fatty acids, carnitines, acylcarnitines, and ether phospholipids were also observed. In addition to metabolites associated with energy metabolism, chronic stress also significantly influenced metabolites associated with amino acid metabolism and cell death. This characteristic pattern of differences in metabolite concentrations was observed in the plasma of mice exposed to chronic social defeat stress, irrespective of whether or not they displayed outward signs of a chronic stress response; In fact, mice that were “resilient” to the behavioural effects of chronic social defeat stress displayed an exaggerated phenotype over mice that showed depressive-like symptoms following chronic stress exposure. This may suggest that the observed changes in fatty acid composition are protective against stress. However, changes in fatty acid composition are also known to be associated with a wide variety of pathologies including heart disease, neurodegenerative diseases, and mood disorders, so the lipidomic changes associated with chronic stress may also contribute to its health impact. Overall, the results provide further evidence that changes in energy metabolism are a central part of allostatic adaptation to chronic stress. / Graduate / 0487 / csobsey@gmail.com

<p>Electrostatic interaction is a strong force that attracts positively and negatively charged molecules to each other. Such an interaction is formed between positively charged polycationic polymers and negatively charged nucleic acids. In this dissertation, the electrostatic attraction between polycationic polymers and nucleic acids is exploited for applications in oral gene delivery and nucleic acid scavenging. An enhanced nanoparticle for oral gene delivery of a human Factor IX (hFIX) plasmid is developed using the polycationic polysaccharide, chitosan (Ch), in combination with protamine sulfate (PS) to treat hemophilia B. For nucleic acid scavenging purposes, the development of an effective nucleic acid scavenging nanofiber platform is described for dampening hyper-inflammation and reducing the formation of biofilms.</p><p>Non-viral gene therapy may be an attractive alternative to chronic protein replacement therapy. Orally administered non-viral gene vectors have been investigated for more than one decade with little progress made beyond the initial studies. Oral administration has many benefits over intravenous injection including patient compliance and overall cost; however, effective oral gene delivery systems remain elusive. To date, only chitosan carriers have demonstrated successful oral gene delivery due to chitosan’s stability via the oral route. In this study, we increase the transfection efficiency of the chitosan gene carrier by adding protamine sulfate to the nanoparticle formulation. The addition of protamine sulfate to the chitosan nanoparticles results in up to 42x higher in vitro transfection efficiency than chitosan nanoparticles without protamine sulfate. Therapeutic levels of hFIX protein are detected after oral delivery of Ch/PS/phFIX nanoparticles in 5/12 mice in vivo, ranging from 3 -132 ng/mL, as compared to levels below 4 ng/mL in 1/12 mice given Ch/phFIX nanoparticles. These results indicate the protamine sulfate enhances the transfection efficiency of chitosan and should be considered as an effective ternary component for applications in oral gene delivery.</p><p>Dying cells release nucleic acids (NA) and NA-complexes that activate the inflammatory pathways of immune cells. Sustained activation of these pathways contributes to chronic inflammation related to autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease. Studies have shown that certain soluble, cationic polymers can scavenge extracellular nucleic acids and inhibit RNA-and DNA-mediated activation of Toll-like receptors (TLRs) and inflammation. In this study, the cationic polymers are incorporated onto insoluble nanofibers, enabling local scavenging of negatively charged pro-inflammatory species such as damage-associated molecular pattern (DAMP) molecules in the extracellular space, reducing cytotoxicity related to unwanted internalization of soluble cationic polymers. In vitro data show that electrospun nanofibers grafted with cationic polymers, termed nucleic acid scavenging nanofibers (NASFs), can scavenge nucleic acid-based agonists of TLR 3 and TLR 9 directly from serum and prevent the production of NF-ĸB, an immune system activating transcription factor while also demonstrating low cytotoxicity. NASFs formed from poly (styrene-alt-maleic anhydride) conjugated with 1.8 kDa branched polyethylenimine (bPEI) resulted in randomly aligned fibers with diameters of 486±9 nm. NASFs effectively eliminate the immune stimulating response of NA based agonists CpG (TLR 9) and poly (I:C) (TLR 3) while not affecting the activation caused by the non-nucleic acid TLR agonist pam3CSK4. Results in a more biologically relevant context of doxorubicin-induced cell death in RAW cells demonstrates that NASFs block ~25-40% of NF-ĸβ response in Ramos-Blue cells treated with RAW extracellular debris, ie DAMPs, following doxorubicin treatment. Together, these data demonstrate that the formation of cationic NASFs by a simple, replicable, modular technique is effective and that such NASFs are capable of modulating localized inflammatory responses. </p><p>An understandable way to clinically apply the NASF is as a wound bandage. Chronic wounds are a serious clinical problem that is attributed to an extended period of inflammation as well as the presence of biofilms. An NASF bandage can potentially have two benefits in the treatment of chronic wounds by reducing the inflammation and preventing biofilm formation. NASF can prevent biofilm formation by reducing the NA present in the wound bed, therefore removing large components of what the bacteria use to develop their biofilm matrix, the extracellular polymeric substance, without which the biofilm cannot develop. The NASF described above is used to show the effect of the nucleic acid scavenging technology on in vitro and in vivo biofilm formation of P. aeruginosa, S. aureus, and S. epidermidis biofilms. The in vitro studies demonstrated that the NASFs were able to significantly reduce the biofilm formation in all three bacterial strains. In vivo studies of the NASF on mouse wounds infected with biofilm show that the NASF retain their functionality and are able to scavenge DNA, RNA, and protein from the wound bed. The NASF remove DNA that are maintaining the inflammatory state of the open wound and contributing to the extracellular polymeric substance (EPS), such as mtDNA, and also removing proteins that are required for bacteria/biofilm formation and maintenance such as chaperonin, ribosomal proteins, succinyl CoA-ligase, and polymerases. However, the NASF are not successful at decreasing the wound healing time because their repeated application and removal disrupts the wound bed and removes proteins required for wound healing such as fibronectin, vibronectin, keratin, and plasminogen. Further optimization of NASF treatment duration and potential combination treatments should be tested to reduce the unwanted side effects of increased wound healing time.</p> / Dissertation

<p>Background: Sickle Cell Disease (SCD) is a genetic hematological disorder that affects more than 7 million people globally (NHLBI, 2009). It is estimated that 50% of adults with SCD experience pain on most days, with 1/3 experiencing chronic pain daily (Smith et al., 2008). Persons with SCD also experience higher levels of pain catastrophizing (feelings of helplessness, pain rumination and magnification) than other chronic pain conditions, which is associated with increases in pain intensity, pain behavior, analgesic consumption, frequency and duration of hospital visits, and with reduced daily activities (Sullivan, Bishop, & Pivik, 1995; Keefe et al., 2000; Gil et al., 1992 & 1993). Therefore effective interventions are needed that can successfully be used manage pain and pain-related outcomes (e.g., pain catastrophizing) in persons with SCD. A review of the literature demonstrated limited information regarding the feasibility and efficacy of non-pharmacological approaches for pain in persons with SCD, finding an average effect size of .33 on pain reduction across measurable non-pharmacological studies. Second, a prospective study on persons with SCD that received care for a vaso-occlusive crisis (VOC; N = 95) found: (1) high levels of patient reported depression (29%) and anxiety (34%), and (2) that unemployment was significantly associated with increased frequency of acute care encounters and hospital admissions per person. Research suggests that one promising category of non-pharmacological interventions for managing both physical and affective components of pain are Mindfulness-based Interventions (MBIs; Thompson et al., 2010; Cox et al., 2013). The primary goal of this dissertation was thus to develop and test the feasibility, acceptability, and efficacy of a telephonic MBI for pain catastrophizing in persons with SCD and chronic pain. </p><p>Methods: First, a telephonic MBI was developed through an informal process that involved iterative feedback from patients, clinical experts in SCD and pain management, social workers, psychologists, and mindfulness clinicians. Through this process, relevant topics and skills were selected to adapt in each MBI session. Second, a pilot randomized controlled trial was conducted to test the feasibility, acceptability, and efficacy of the telephonic MBI for pain catastrophizing in persons with SCD and chronic pain. Acceptability and feasibility were determined by assessment of recruitment, attrition, dropout, and refusal rates (including refusal reasons), along with semi-structured interviews with nine randomly selected patients at the end of study. Participants completed assessments at baseline, Week 1, 3, and 6 to assess efficacy of the intervention on decreasing pain catastrophizing and other pain-related outcomes. </p><p>Results: A telephonic MBI is feasible and acceptable for persons with SCD and chronic pain. Seventy-eight patients with SCD and chronic pain were approached, and 76% (N = 60) were enrolled and randomized. The MBI attendance rate, approximately 57% of participants completing at least four mindfulness sessions, was deemed acceptable, and participants that received the telephonic MBI described it as acceptable, easy to access, and consume in post-intervention interviews. The amount of missing data was undesirable (MBI condition, 40%; control condition, 25%), but fell within the range of expected missing outcome data for a RCT with multiple follow-up assessments. Efficacy of the MBI on pain catastrophizing could not be determined due to small sample size and degree of missing data, but trajectory analyses conducted for the MBI condition only trended in the right direction and pain catastrophizing approached statistically significance. </p><p>Conclusion: Overall results showed that at telephonic group-based MBI is acceptable and feasible for persons with SCD and chronic pain. Though the study was not able to determine treatment efficacy nor powered to detect a statistically significant difference between conditions, participants (1) described the intervention as acceptable, and (2) the observed effect sizes for the MBI condition demonstrated large effects of the MBI on pain catastrophizing, mental health, and physical health. Replication of this MBI study with a larger sample size, active control group, and additional assessments at the end of each week (e.g., Week 1 through Week 6) is needed to determine treatment efficacy. Many lessons were learned that will guide the development of future studies including which MBI strategies were most helpful, methods to encourage continued participation, and how to improve data capture.</p> / Dissertation

L´existence d´état douloureux, chronique et sans substrat organique, de maladies de la douleur, sont signalés depuis le XIX siècle. La douleur, comme perception, est une expérience subjective qui intègre des sensations variées. Les différents syndromes de douleur chronique ont la douleur comme symptôme principal et se caractérisent par un ensemble de signes qui ne correspondent pas à un modèle de cause organiques non localisées. Alors que la douleur aigüe est un indicateur précieux dans l´établissement d´un diagnostic, la douleur chronique, pour avoir perdu son caractère de signald´alarme, nous renvoie à une multiplicité de déterminations d´ordre somatique, psychologique et/ou ambiant. L´apport de la psychanalyse, en partenariat avec la médecine se révèle utile dans l´appréhension du sens des symptômes dans laparticularité du cas et en relation avec la singularité du sujet. À la place de soutenir l´idée qu´il est nécessaire, à tout prix, d´éradiquer définitivement un syndrome douloureux quel qu´il soit et la souffrance psychique qui y est associée, il nous semble utile de prendre en considération ce qui est en jeu en termes structurel et inconscient. En d´autres mots, faire « parler » le corps, d´une douleur (psychique) impossible à symboliser. Possiblement, une douleur d´amour, c´est la supposition de base de notre hypothèse / The existence of painful condition, chronic and without organic substrate, disease of pain, are reported from the nineteenth century. Pain, such as perception, which is a subjective experience includes various sensations. Different chronic pain syndromes have pain as the main symptom and is characterized by a set of signs that do not correspond to a modelof organic causes unlocated. While acute pain is a valuable indicator in establishing a diagnosis, chronic pain, to have lost its character as a warning, we refer to a multiplicity of determinations order somatic, psychological and / or ambient. The contribution of psychoanalysis, in partnership with the medicine is useful in understanding the meaning of symptoms in the particularity of the case and in relation to the singularity of the subject. Instead of supporting the idea that it is necessary, at any cost, permanently eradicate a painful syndrome whatsoever and mental suffering associated with it, it is useful to consider what is involved in structural terms and unconscious. In other words, to "speak" the body, pain (psychic) Unable to symbolize. Possibly pain of love is the basic assumption of our hypothesis / A existência de condição dolorosa crônica e sem substrato orgânico , a doença de dor, são relatados a partir do século XIX. Dor, tais como percepção, que é uma experiência subjetiva inclui várias sensações . Diferentes síndromes de dor crônica tem a dor como o principal sintoma e é caracterizada por um conjunto de sinais que não correspondem a um modelo de causas orgânicas não localizados. Enquanto a dor aguda é um indicador valioso para estabelecer um diagnóstico, dor crônica, ter perdido seu caráter de advertência, nos referimos a uma multiplicidade de determinações ordem somática ,psicológica e / ou ambiente . A contribuição da psicanálise, em parceria com o medicamento é útil na compreensão do significado dos sintomas na particularidade do caso e em relação à singularidade do sujeito. Em vez de apoiar a ideia de que é necessário , a qualquer custo, eliminar permanentemente uma síndrome dolorosa que seja e sofrimento mental associado a ele, é útil considerar o que é envolvido em termos estruturais e inconsciente. Em outras palavras, para "falar" do corpo, dor ( psíquica ) Não é possível simbolizar . Possivelmente dor do amor é o pressuposto básico da nossahipótese