Clinical rearfoot and knee static alignment measurements are not associated with patellofemoral pain syndrome

The aim of the present study was to investigate the association between the patellofemoral pain syndrome and the clinical static measurements: the rearfoot and the Q angles. The design was a cross-sectional, observational, case-control study. We evaluated 77 adults (both genders), 30 participants with patellofemoral pain syndrome, and 47 controls. We measured the rearfoot and Q angles by photogrammetry. Independent t-tests were used to compare outcome continuous measures between groups. Outcome continuous data were also transformed into categorical clinical classifications, in order to verify their statistical association with the dysfunction, and χ2 tests for multiple responses were used. There were no differences between groups for rearfoot angle [mean differences: 0.2º (95%CI -1.4-1.8)] and Q angle [mean differences: -0.3º (95%CI -3.0-2.4). No associations were found between increased rearfoot valgus [Odds Ratio: 1.29 (95%CI 0.51-3.25)], as well as increased Q angle [Odds Ratio: 0.77 (95%CI 0.31-1.93)] and the patellofemoral pain syndrome occurrence. Although widely used in clinical practice and theoretically thought, it cannot be affirmed that increased rearfoot valgus and increased Q angle, when statically measured in relaxed stance, are associated with patellofemoral pain syndrome (PFPS). These measures may have limited applicability in screening of the PFPS development.

Pain in preterm infants: effects of sex, gestational age, and neonatal illness severity

Neonates hospitalized in a neonatal intensive care unit are exposed to many painful and stressful procedures. Biobehavioral pain reactivity in preterm infants during the neonatal period may reflect the capacity of the central nervous system to regulate arousal and neurobiological organization. We review empirical studies on the effects of sex, gestational age, and neonatal illness severity on pain reactivity in children born preterm. A literature search was conducted using PubMed, Institute of Scientific Information Web of Science, PsycINFO, Latin American and Caribbean Health Sciences Literature, and Scientific Electronic Library Online databases. Additionally, a special search was performed in online journals that publish pain studies including Pain, Early Human Development, European Journal of Pain, and Pain Management Nursing. The literature search covered the period from 2004 to 2009. Data were extracted according to predefined inclusion and exclusion criteria. Of the 18 studies reviewed, 16 analyzed gestational age, 13 examined neonatal illness severity, and eight focused on sex. Most of the studies analyzed more than one of these three variables. The majority of the studies found effects of gestational age (n = 14) and neonatal illness severity (n = 11) on pain responses. Only two studies found an influence of sex on infant pain responses. In conclusion, gestational age and neonatal illness severity influence pain responses in infants born preterm. Further studies should be conducted to examine the influence of sex on pain responses.

Laser therapy and pain-related behavior after injury of the inferior alveolar nerve: possible involvement of neurotrophins

Nerve-related complications have been frequently reported in dental procedures, and a very frequent type of occurrence involves the inferior alveolar nerve (IAN). The nerve injury in humans often results in persistent pain accompanied by allodynia and hyperalgesia. In this investigation, we used an experimental IAN injury in rats, which was induced by a Crile hemostatic clamp, to evaluate the effects of laser therapy on nerve repair. We also studied the nociceptive behavior (von Frey hair test) before and after the injury and the behavioral effects of treatment with laser therapy (emitting a wavelength of 904 nm, output power of 70 Wpk, a spot area of *0.1 cm2, frequency of 9500 Hz, pulse time 60 ns and an energy density of 6 J/cm2). As neurotrophins are essential for the process of nerve regeneration, we used immunoblotting techniques to preliminarily examine the effects of laser therapy on the expression of nerve growth factor (NGF) and brainderived neurotrophic factor (BDNF). The injured animals treated with laser exhibited an improved nociceptive behavior. In irradiated animals, there was an enhanced expression of NGF (53%) and a decreased BDNF expression (40%) after laser therapy. These results indicate that BDNF plays a locally crucial role in pain-related behavior development after IAN injury, increasing after lesions (in parallel to the installation of pain behavior) and decreasing with laser therapy (in parallel to the improvement of pain behavior). On the other hand, NGF probably contributes to the repair of nerve tissue, in addition to improving the pain-related behavior.

Why do arms extract less oxygen than legs during exercise?

[EN] To determine whether conditions for O2 utilization and O2 off-loading from the hemoglobin are different in exercising arms and legs, six cross-country skiers participated in this study. Femoral and subclavian vein blood flow and gases were determined during skiing on a treadmill at approximately 76% maximal O2 uptake (V(O2)max) and at V(O2)max with different techniques: diagonal stride (combined arm and leg exercise), double poling (predominantly arm exercise), and leg skiing (predominantly leg exercise). The percentage of O2 extraction was always higher for the legs than for the arms. At maximal exercise (diagonal stride), the corresponding mean values were 93 and 85% (n = 3; P < 0.05). During exercise, mean arm O2 extraction correlated with the P(O2) value that causes hemoglobin to be 50% saturated (P50: r = 0.93, P < 0.05), but for a given value of P50, O2 extraction was always higher in the legs than in the arms. Mean capillary muscle O2 conductance of the arm during double poling was 14.5 (SD 2.6) ml.min(-1).mmHg(-1), and mean capillary P(O2) was 47.7 (SD 2.6) mmHg. Corresponding values for the legs during maximal exercise were 48.3 (SD 13.0) ml.min(-1).mmHg(-1) and 33.8 (SD 2.6) mmHg, respectively. Because conditions for O2 off-loading from the hemoglobin are similar in leg and arm muscles, the observed differences in maximal arm and leg O2 extraction should be attributed to other factors, such as a higher heterogeneity in blood flow distribution, shorter mean transit time, smaller diffusing area, and larger diffusing distance, in arms than in legs.

La Restless Legs Syndrome aumenta il rischio cardiovascolare e la mortalità a breve termine nei pazienti emodializzati

Abstract Restless legs syndrome (RLS) is a sensori-motor neurological disorder characterzed by paraesthesia, dysaesthesia and irresistibile urge to move the legs especially at night. Its prevalence is much higher among dialysis patients at 12 to 62% compared to 3 to 9% in the general population. In our study we investigated the association between RLS and cardiovascular events risk and laboratory parameters in End-stage kidney disease (ESKD) patients on dialysis. We studied 100 ESKD patients undergoing hemodialysis that were enrolled in an 18-months prospective observational study. The main outcomes were the association of RLS with new cardiovascular events and cardiovascular mortality. RLS affected 31% of the study population. It was associated with female gender, gradual reduction in residual dieresis, lower albumin (P=0.039) and inflammation, but not the dialysis parameters spKt/V and URR. During observation, 47% of patients experienced new cardiovascular events (64.5% with and 39.1% without RLS; P=0.019). Mortality was 20.0% in all patients, 32.3% in those with and 14.5% in patients without RLS (P=0.04). This study confirmed the high prevalence of RLS among dialysis patients and the associations between the severity of RLS and the risk of new cardiovascular events and higher short-term mortality. Abstract Restless legs syndrome (RLS) is a sensori-motor neurological disorder characterzed by paraesthesia, dysaesthesia and irresistibile urge to move the legs especially at night. Its prevalence is much higher among dialysis patients at 12 to 62% compared to 3 to 9% in the general population. In our study we investigated the association between RLS and cardiovascular events risk and laboratory parameters in End-stage kidney disease (ESKD) patients on dialysis. We studied 100 ESKD patients undergoing hemodialysis that were enrolled in an 18-months prospective observational study. The main outcomes were the association of RLS with new cardiovascular events and cardiovascular mortality. RLS affected 31% of the study population. It was associated with female gender, gradual reduction in residual dieresis, lower albumin (P=0.039) and inflammation, but not the dialysis parameters spKt/V and URR. During observation, 47% of patients experienced new cardiovascular events (64.5% with and 39.1% without RLS; P=0.019). Mortality was 20.0% in all patients, 32.3% in those with and 14.5% in patients without RLS (P=0.04). This study confirmed the high prevalence of RLS among dialysis patients and the associations between the severity of RLS and the risk of new cardiovascular events and higher short-term mortality.

Psychiatric comorbidity, Restless Legs Syndrome and Nocturnal Eating Disorder: a case-control study

Objective: to evaluate the psychopathological profile in primary Restless Legs Syndrome (p-RLS) patients with and without nocturnal eating disorder (NED), analysing obsessive-compulsive traits, mood and anxiety disorder, and the two domains of personality proposed by Cloninger, temperament and character. Methods: we tested ten p-RLS patients without NED, ten p-RLS patients with NED and ten healthy control subjects, age and sex-matched, using Hamilton Depression and Anxiety Rating Scales, State-Trait Anxiety Inventory, Maudsley Obsessive Compulsive Inventory (MOCI) and Temperament and Character Inventory - revised (TCI). Results: p-RLS patients, particularly those with NED, had increased anxiety factor scores. MOCI-total, doubting and checking compulsion, and TCI-harm avoidance scores were significantly higher in p-RLS patients with NED. p-RLS patients without NED had significantly higher MOCI-doubting scores and a trend toward higher checking compulsion and harm avoidance scores with an apparent grading from controls to p-RLS patients without NED to p-RLS with NED. Conclusions: higher harm avoidance might predispose to display obsessive-compulsive symptoms, RLS and then, with increasing severity, compulsive nocturnal eating. RLS and NED could represent a pathological continuum in which a dysfunction in the limbic system, possibly driven by a dopaminergic dysfunction, could be the underlying pathophysiological mechanism.

Relationship between pain and anxiety in rats

Clinically, it is well known that neuropathic pain often induces comorbid symptoms such as anxiety. In turn, also anxiety has been associated with a heightened experience of pain. Although, the link between pain and anxiety is well recognized in humans, the neurobiological basis of this relationship remains unclear. Therefore, the aim of the current study was to investigate the influence of neuropathic pain on anxiety and vice versa in rats by assessing not only pain-related behaviour but also by discovering possible key substrates which are responsible for the interrelation of pain and anxiety.rnIn rats with a chronic constriction of the sciatic nerve (CCI model) anxiety-like behaviour was observed. Since anxiety behaviour could be completely abolished after the treatment of the pure analgesic drugs gabapentin and morphine, we concluded that anxiety was caused by the strong persistent pain. Furthermore, we found that the neuropeptides oxytocin and vasopressin were upregulated in the amygdala of CCI rats, and the intra-amygdala treatment of an oxytocin antagonist but not the vasopressin antagonist could reduce anxiety-like behaviour in these animals, while no effect on mechanical hypersensitivity was observed. These data indicate that oxytocin is implicated in the underlying neuronal processes of pain-induced anxiety and helps to elucidate the pathophysiological mechanisms of neuropathic pain. rnTo assess the influence of trait anxiety on pain sensation in rats, we determined mechanical hypersensitivity after sciatic nerve lesion (CCI) in animals selectively bred for high anxiety or low anxiety behaviour. The paw withdrawal thresholds were significantly decreased in high anxiety animals in comparison to low anxiety animals 2 and 3 weeks after surgery. In a second model state anxiety was induced by the sub-chronic injection of the anxiogenic drug pentylentetrazol in naive rats. Pain response to mechanical stimuli was increased after pharmacologically-induced anxiety. These results provided evidence for the influence of both trait and state anxiety on pain sensation. rnThe studies contribute to the elucidation of the relationship between pain and anxiety. We investigated that the neuropathic pain model displays sensory as well as emotional factors of peripheral neuropathy. Changes in expression levels of neuropeptides in the central nervous system due to neuropathic pain may contribute to the pathophysiology of neuropathic pain and its related symptoms in animals which might also be relevant for human scenarios. The results of the current study also confirm that anxiety plays an important role in the perception of pain. rnA better understanding of pain behaviour in animals might improve the preclinical profiling of analgesic drugs during development. The study highlights the potential use of the rat model as a new preclinical tool to further investigate the link between pain and anxiety by determining not only the sensory reflexes after painful stimuli but also the more complex pain-related behaviour such as anxiety.rn

Biomedicine and pain

The focus of my research is on contemporary biomedical construction of pain as an object, i.e. the different ways in which pain has been conceptualized and approached as a specific site of investigation in biomedicine. A significant shift in the scientific conception of pain occured in the second half of XXth century. In 1965, Ronald Melzack and Patrick D. Wall propose the Gate Control theory of pain mechanism. This theory denies a fixed and direct relationship between stimulus and pain perception, and emphazises the role played by psychological factors in pain. The IASP utilizes this perspective on the phenomenon, describing pain as “an unpleasant sensory and emotional experience associated to an actual or potential tissue damage or described in the terms of such a damage.” The relationship between pain and damage is pivotal in the definition of pain as a pathological entity. In particular, the biomedical approach to pain appears to be strongly characterized by a dualistic view of its aetiology. Disease conceptions such as “psychogenic pain” and chronic pain are deeply influenced by the ways in which psychological factors have been interpreted as components, or as causes of pain. In the second part of my dissertation, I focus on fibromyalgia, which is emblematic of the problematic acknowledgment of chronic pain as a disease. Even if fibromyalgia is actually treated in Rheumatology, its status as a disease is blurred, mainly because of its complex symptomatology including both physiological manifestations and psychological ones. In the conclusion, I present a scenario of the different ways in which this disease is dealt with in biomedical knowledge, through medical literature, clinical practice, and patients’ accounts. The findings of an ethnographic enquiry in the Rheumatology Division of a local clinic and a visual research on patients’ experiences are analyzed and discussed.

Involvement of the opioid system and BDNF in neuroplastic alterations occurring in neuropathic pain conditions

Chronic pain affects one in five adults, reducing quality of life and increasing risk of developing co-morbidities such as depression. Neuropathic pain results by lesions to the nervous system that alter its structure and function leading to spontaneous pain and amplified responses to noxious and innocuous stimuli. The Opioid System is probably the most important system involved in control of nociceptive transmission. Dynorphin and nociceptin systems have been suggested key mediators of some neuropathic pain aspects. An important role also for BDNF has been recently suggested since its involvement in the peripheral and central sensitization phenomena is known. We studied neuroplastic alterations occurring in chronic pain in mice subjected to the chronic constriction injury (CCI). We investigated gene expression alterations of both BDNF and Opioid System at spinal level at different intervals of time. A transient upregulation of pBDNF and pDYN was observed in spinal cord, while increasing upregulation of ppN/OFQ was found in the DRGs of injured mice. Development of neuropathic behavioral signs has been observed in ICR/CD-1 and BDNF+/+ mice, subjected to CCI. A different development of these signs was observed in BDNF+/-. We also studied gene expression changes of investigated systems in different brain areas fourteen days after surgery. We found pBDNF, pDYN, pKOP, ppN/OFQ and pNOP gene expression alterations in several areas of CCI mice. In the same brain regions we also determined bioactive nociceptin peptide levels, and elevated N/OFQ levels were observed in the amygdala area. Histone modifications studies have been performed in BDNF and DYN gene promoters of CCI animal spinal cord showing selected alterations in pDYN gene promoter. In addition, a preliminary characterization of the innovative NOP-EGFP mice was performed. Overall, our results could be useful to understand which and how neuropeptidergic systems are involved in neuroplastic mechanism occurring in neuropathic pain.

Efficient calculation of gluon amplitudes with n legs and an implementation of parton showers using the dipole formalism

The conventional way to calculate hard scattering processes in perturbation theory using Feynman diagrams is not efficient enough to calculate all necessary processes - for example for the Large Hadron Collider - to a sufficient precision. Two alternatives to order-by-order calculations are studied in this thesis.rnrnIn the first part we compare the numerical implementations of four different recursive methods for the efficient computation of Born gluon amplitudes: Berends-Giele recurrence relations and recursive calculations with scalar diagrams, with maximal helicity violating vertices and with shifted momenta. From the four methods considered, the Berends-Giele method performs best, if the number of external partons is eight or bigger. However, for less than eight external partons, the recursion relation with shifted momenta offers the best performance. When investigating the numerical stability and accuracy, we found that all methods give satisfactory results.rnrnIn the second part of this thesis we present an implementation of a parton shower algorithm based on the dipole formalism. The formalism treats initial- and final-state partons on the same footing. The shower algorithm can be used for hadron colliders and electron-positron colliders. Also massive partons in the final state were included in the shower algorithm. Finally, we studied numerical results for an electron-positron collider, the Tevatron and the Large Hadron Collider.

PPAR-gamma expression in peritoneal endometriotic lesions correlates with pain experienced by patients

Endometriosis is a significant gynecologic condition that can cause both pain and infertility and affects up to 15% of women during their reproductive years. In peritoneal endometriotic lesions, the expression of peroxisome proliferation-activated receptor gamma, a nuclear receptor with antiinflammatory and neuroprotective roles, is positively correlated with the pain reported by patients.

MicroRNAs may mediate the down-regulation of neurokinin-1 receptor in chronic bladder pain syndrome

Bladder pain syndrome (BPS) is a clinical syndrome of pelvic pain and urinary urgency-frequency in the absence of a specific cause. Investigating the expression levels of genes involved in the regulation of epithelial permeability, bladder contractility, and inflammation, we show that neurokinin (NK)1 and NK2 tachykinin receptors were significantly down-regulated in BPS patients. Tight junction proteins zona occludens-1, junctional adherins molecule -1, and occludin were similarly down-regulated, implicating increased urothelial permeability, whereas bradykinin B(1) receptor, cannabinoid receptor CB1 and muscarinic receptors M3-M5 were up-regulated. Using cell-based models, we show that prolonged exposure of NK1R to substance P caused a decrease of NK1R mRNA levels and a concomitant increase of regulatory micro(mi)RNAs miR-449b and miR-500. In the biopsies of BPS patients, the same miRNAs were significantly increased, suggesting that BPS promotes an attenuation of NK1R synthesis via activation of specific miRNAs. We confirm this hypothesis by identifying 31 differentially expressed miRNAs in BPS patients and demonstrate a direct correlation between miR-449b, miR-500, miR-328, and miR-320 and a down-regulation of NK1R mRNA and/or protein levels. Our findings further the knowledge of the molecular mechanisms of BPS, and have relevance for other clinical conditions involving the NK1 receptor.