Factores socio-demográficos, laborales y factores de riesgo ergonómicos relacionados con la aparición de síntomas osteomusculares de la actividad del bicitaxismo en una localidad de la ciudad de Bogotá (2014)

Resumen Objetivo: Determinar los factores socio-demográficos, laborales y los factores de riesgo ergonómico, relacionados con la aparición de síntomas osteomusculares de la actividad del Bicitaxismo en el barrio Toberín de la Localidad de Usaquén de la Ciudad Bogotá, para recomendar estrategias de prevención. Materiales y métodos: Estudio observacional descriptivo de corte transversal en 150 personas que trabajan en el Bicitaxismo. Se realizó un muestreo simple y aleatorio. La identificación de los factores asociados con síntomas osteomusculares se hizo mediante la aplicación de la metodología Ergopar (Ergonomía Participativa para la prevención de trastornos musculoesqueléticos de origen laboral), en el grupo de personas que trabajan en el Bicitaxismo. Se estimó la proporción de personas con trastornos músculo esqueléticos en este grupo de trabajadores y se exploró asociación mediante la prueba Chi cuadrado de Pearson o prueba exacta de Fisher, usando nivel de significación del 5%, con el programa SPSS 20. Resultados: Los resultados sugirieron que en el bicitaxismo hay asociación estadísticamente significativa con los factores de edad y aparición de dolor en espalda lumbar valor p (0,009), manos/muñecas valor p (0,001), piernas con un valor p (0,022), rodillas valor p (0,001), tiempo de trabajo con la aparición de dolor en codos valor p (0,013), horas de trabajo con la aparición de molestias en codos valor p (0,000), y en piernas valor p (0,002), Días de trabajo, con la aparición de molestias en manos/muñecas valor p (0,003), dolor en piernas valor p (0), y dolor en rodillas valor p (0,014), e igualmente exigencias físicas con la aparición de molestias en manos/muñecas valor p (0,002) y dolor en piernas con un valor p (0,044) Conclusión: Se evidenció asociación entre la actividad del bicitaxismo y la aparición de síntomas osteomusculares de molestia/dolor en los diferentes segmentos musculares, tales como espalda lumbar, codos, manos/muñecas, piernas y rodillas

Individual differences in the effects of perceived controllability on pain perception: critical role of the prefrontal cortex

The degree to which perceived controllability alters the way a stressor is experienced varies greatly among individuals. We used functional magnetic resonance imaging to examine the neural activation associated with individual differences in the impact of perceived controllability on self-reported pain perception. Subjects with greater activation in response to uncontrollable (UC) rather than controllable (C) pain in the pregenual anterior cingulate cortex (pACC), periaqueductal gray (PAG), and posterior insula/SII reported higher levels of pain during the UC versus C conditions. Conversely, subjects with greater activation in the ventral lateral prefrontal cortex (VLPFC) in anticipation of pain in the UC versus C conditions reported less pain in response to UC versus C pain. Activation in the VLPFC was significantly correlated with the acceptance and denial subscales of the COPE inventory [Carver, C. S., Scheier, M. F., & Weintraub, J. K. Assessing coping strategies: A theoretically based approach. Journal of Personality and Social Psychology, 56, 267–283, 1989], supporting the interpretation that this anticipatory activation was associated with an attempt to cope with the emotional impact of uncontrollable pain. A regression model containing the two prefrontal clusters (VLPFC and pACC) predicted 64% of the variance in pain rating difference, with activation in the two additional regions (PAG and insula/SII) predicting almost no additional variance. In addition to supporting the conclusion that the impact of perceived controllability on pain perception varies highly between individuals, these findings suggest that these effects are primarily top-down, driven by processes in regions of the prefrontal cortex previously associated with cognitive modulation of pain and emotion regulation.

A simple two-stage design for quantitative responses with application to a study in diabetic neuropathic pain

Two-stage designs offer substantial advantages for early phase II studies. The interim analysis following the first stage allows the study to he stopped for futility, or more positively, it might lead to early progression to the trials needed for late phase H and phase III. If the study is to continue to its second stage, then there is an opportunity for a revision of the total sample size. Two-stage designs have been implemented widely in oncology studies in which there is a single treatment arm and patient responses are binary. In this paper the case of two-arm comparative studies in which responses are quantitative is considered. This setting is common in therapeutic areas other than oncology. It will be assumed that observations are normally distributed, but that there is some doubt concerning their standard deviation, motivating the need for sample size review. The work reported has been motivated by a study in diabetic neuropathic pain, and the development of the design for that trial is described in detail. Copyright (C) 2008 John Wiley & Sons, Ltd.

Localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) in human gastrointestinal tract

Calcitonin gene-related peptide (CGRP) exerts its diverse effects on vasodilation, nociception, secretion, and motor function through a heterodimeric receptor comprising of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1). Despite the importance of CLR.RAMP1 in human disease, little is known about its distribution in the human gastrointestinal (GI) tract, where it participates in inflammation and pain. In this study, we determined that CLR and RAMP1 mRNAs are expressed in normal human stomach, ileum and colon by RT-PCR. We next characterized antibodies that we generated to rat CLR and RAMP1 in transfected HEK cells. Having characterized these antibodies in vitro, we then localized CLR-, RAMP1-, CGRP- and intermedin-immunoreactivity (IMD-IR) in various human GI segments. In the stomach, nerve bundles in the myenteric plexus and nerve fibers throughout the circular and longitudinal muscle had prominent CLR-IR. In the proximal colon and ileum, CLR was found in nerve varicosities of the myenteric plexus and surrounding submucosal neurons. Interestingly, CGRP expressing fibers did not co-localize, but were in close proximity to CLR. However, CLR and RAMP1, the two subunits of a functional CGRP receptor were clearly localized in myenteric plexus, where they may form functional cell-surface receptors. IMD, another member of calcitonin peptide family was also found in close proximity to CLR, and like CGRP, did not co-localize with either CLR or RAMP1 receptors. Thus, CGRP and IMD appear to be released locally, where they can mediate their effect on their receptors regulating diverse functions such as inflammation, pain and motility.

Agonists of protease-activated receptors 1 and 2 stimulate electrolyte secretion from mouse gallbladder

Cholecystitis is one of the most common gastrointestinal diseases. Inflammation induces the activation of proteases that can signal to cells by cleaving protease-activated receptors (PARs) to induce hemostasis, inflammation, pain, and repair. However, the distribution of PARs in the gallbladder is unknown, and their effects on gallbladder function have not been fully investigated. We localized immunoreactive PAR(1) and PAR(2) to the epithelium, muscle, and serosa of mouse gallbladder. mRNA transcripts corresponding to PAR(1) and PAR(2), but not PAR(4), were detected by RT-PCR and sequencing. Addition of thrombin and a PAR(1)-selective activating peptide (TFLLRN-NH(2)) to the serosal surface of mouse gallbladder mounted in an Ussing chamber stimulated an increase in short-circuit current in wild-type but not PAR(1) knockout mice. Similarly, serosally applied trypsin and PAR(2) activating peptide (SLIGRL-NH(2)) increased short-circuit current in wild-type but not PAR(2) knockout mice. Proteases and activating peptides strongly inhibited electrogenic responses to subsequent stimulation with the same agonist, indicating homologous desensitization. Removal of HCO(3)(-) ions from the serosal buffer reduced responses to thrombin and trypsin by >80%. Agonists of PAR(1) and PAR(2) increase intracellular Ca(2+) concentration in isolated and cultured gallbladder epithelial cells. The COX-2 inhibitor meloxicam and an inhibitor of CFTR prevented the stimulatory effect of PAR(1) but not PAR(2). Thus PAR(1) and PAR(2) are expressed in the epithelium of the mouse gallbladder, and serosally applied proteases cause a HCO(3)(-) secretion. The effects of PAR(1) but not PAR(2) depend on generation of prostaglandins and activation of CFTR. These mechanisms may markedly influence fluid and electrolyte secretion of the inflamed gallbladder when multiple proteases are generated.

Recycling and resensitization of the neurokinin 1 receptor: influence of agonist concentration and Rab GTPases

Substance P (SP) induces endocytosis and recycling of the neurokinin 1 receptor (NK1R) in endothelial cells and spinal neurons at sites of inflammation and pain, and it is thus important to understand the mechanism and function of receptor trafficking. We investigated how the SP concentration affects NK1R trafficking and determined the role of Rab GTPases in trafficking. NK1R trafficking was markedly influenced by the SP concentration. High SP (10 nM) induced translocation of the NK1R and beta-arrestin 1 to perinuclear sorting endosomes containing Rab5a, where NK1R remained for >60 min. Low SP (1 nM) induced translocation of the NK1R to early endosomes located immediately beneath the plasma membrane that also contained Rab5a and beta-arrestin 1, followed by rapid recycling of the NK1R. Overexpression of Rab5a promoted NK1R translocation to perinuclear sorting endosomes, whereas the GTP binding-deficient mutant Rab5aS34N caused retention of the NK1R in superficial early endosomes. NK1R translocated from superficial early endosomes to recycling endosomes containing Rab4a and Rab11a, and Rab11aS25N inhibited NK1R recycling. Rapid NK1R recycling coincided with resensitization of SP-induced Ca2+ mobilization and with the return of surface SP binding sites. Resensitization was minimally affected by inhibition of vacuolar H(+)-ATPase and phosphatases but was markedly suppressed by disruption of Rab4a and Rab11a. Thus, whereas beta-arrestins mediate NK1R endocytosis, Rab5a regulates translocation between early and sorting endosomes, and Rab4a and Rab11a regulate trafficking through recycling endosomes. We have thus identified a new function of Rab5a as a control protein for directing concentration-dependent trafficking of the NK1R into different intracellular compartments and obtained evidence that Rab4a and Rab11a contribute to G-protein-coupled receptor recycling from early endosomes.

Trypsin IV, a novel agonist of protease-activated receptors 2 and 4

Certain serine proteases signal to cells by cleaving protease-activated receptors (PARs) and thereby regulate hemostasis, inflammation, pain and healing. However, in many tissues the proteases that activate PARs are unknown. Although pancreatic trypsin may be a physiological agonist of PAR(2) and PAR(4) in the small intestine and pancreas, these receptors are expressed by cells not normally exposed pancreatic trypsin. We investigated whether extrapancreatic forms of trypsin are PAR agonists. Epithelial cells lines from prostate, colon, and airway and human colonic mucosa expressed mRNA encoding PAR(2), trypsinogen IV, and enteropeptidase, which activates the zymogen. Immunoreactive trypsinogen IV was detected in vesicles in these cells. Trypsinogen IV was cloned from PC-3 cells and expressed in CHO cells, where it was also localized to cytoplasmic vesicles. We expressed trypsinogen IV with an N-terminal Igkappa signal peptide to direct constitutive secretion and allow enzymatic characterization. Treatment of conditioned medium with enteropeptidase reduced the apparent molecular mass of trypsinogen IV from 36 to 30 kDa and generated enzymatic activity, consistent with formation of trypsin IV. In contrast to pancreatic trypsin, trypsin IV was completely resistant to inhibition by polypeptide inhibitors. Exposure of cell lines expressing PAR(2) and PAR(4) to trypsin IV increased [Ca(2+)](i) and strongly desensitized cells to PAR agonists, whereas there were no responses in cells lacking these receptors. Thus, trypsin IV is a potential agonist of PAR(2) and PAR(4) in epithelial tissues where its resistance to endogenous trypsin inhibitors may permit prolonged signaling.

The TGR5 receptor mediates bile acid-induced itch and analgesia

Patients with cholestatic disease exhibit pruritus and analgesia, but the mechanisms underlying these symptoms are unknown. We report that bile acids, which are elevated in the circulation and tissues during cholestasis, cause itch and analgesia by activating the GPCR TGR5. TGR5 was detected in peptidergic neurons of mouse dorsal root ganglia and spinal cord that transmit itch and pain, and in dermal macrophages that contain opioids. Bile acids and a TGR5-selective agonist induced hyperexcitability of dorsal root ganglia neurons and stimulated the release of the itch and analgesia transmitters gastrin-releasing peptide and leucine-enkephalin. Intradermal injection of bile acids and a TGR5-selective agonist stimulated scratching behavior by gastrin-releasing peptide- and opioid-dependent mechanisms in mice. Scratching was attenuated in Tgr5-KO mice but exacerbated in Tgr5-Tg mice (overexpressing mouse TGR5), which exhibited spontaneous pruritus. Intraplantar and intrathecal injection of bile acids caused analgesia to mechanical stimulation of the paw by an opioid-dependent mechanism. Both peripheral and central mechanisms of analgesia were absent from Tgr5-KO mice. Thus, bile acids activate TGR5 on sensory nerves, stimulating the release of neuropeptides in the spinal cord that transmit itch and analgesia. These mechanisms could contribute to pruritus and painless jaundice that occur during cholestatic liver diseases.

Traditional medicine use by cancer patients in Thailand

Ethnobotanical relevance Cancer patients commonly use traditional medicines (TM) and in Thailand these are popular for both self-medication and as prescribed by TM practitioners, and are rarely monitored. A study was conducted at Wat Khampramong, a Thai Buddhist temple herbal medicine hospice, to document some of these practices as well as the hospice regime. Materials and methods Cancer patients (n=286) were surveyed shortly after admission as to which TMs they had previously taken and perceptions of effects experienced. They were also asked to describe their current symptoms. Treatment at the hospice is built upon an 11-herb anti-cancer formula, yod-ya-mareng, prescribed for all patients, and ideally, its effects would have been evaluated. However other herbal medicines and holistic practices are integral to the regime, so instead we attempted to assess the value of the patients׳ stay at the hospice by measuring any change in symptom burden, as they perceived it. Surviving patients (n=270) were therefore asked to describe their symptoms again just before leaving. Results 42% of patients (120/286; 95% CI 36.4%, 47.8%) had used herbal medicines before their arrival, with 31.7% (38/120; 95% CI 24%, 40.4%) using several at once. Mixed effects were reported for these products. After taking the herbal regime at Khampramong, 77% (208/270 95% CI; 71.7%, 81.7%) reported benefit, and a comparison of the incidence of the most common (pain, dyspepsia, abdominal or visceral pain, insomnia, fatigue) showed statistical significance (χ2 57.1, df 7, p<0.001). Conclusions A wide range of TMs is taken by cancer patients in Thailand and considered to provide more benefit than harm, and this perception extends to the temple regime. Patients reported a significant reduction in symptoms after staying at Khampramong, indicating an improvement in quality of life, the aim of hospices everywhere. Based on this evidence, it is not possible to justify the use of TM for cancer in general, but this study suggests that further research is warranted. The uncontrolled use of TMs, many of which are uncharacterised, raises concerns, and this work also highlights the fact that validated, robust methods of assessing holistic medical regimes are urgently needed.

Dyspnea-related cues engage the prefrontal cortex - evidence from functional brain imaging in COPD

Dyspnea is the major source of disability in chronic obstructive pulmonary disease (COPD). In COPD, environmental cues (e.g. the prospect of having to climb stairs) become associated with dyspnea, and may trigger dyspnea even before physical activity commences. We hypothesised that brain activation relating to such cues would be different between COPD patients and healthy controls, reflecting greater engagement of emotional mechanisms in patients. Methods: Using FMRI, we investigated brain responses to dyspnea-related word cues in 41 COPD patients and 40 healthy age-matched controls. We combined these findings with scores of self-report questionnaires thus linking the FMRI task with clinically relevant measures. This approach was adapted from studies in pain that enables identification of brain networks responsible for pain processing despite absence of a physical challenge. Results: COPD patients demonstrate activation in the medial prefrontal cortex (mPFC), and anterior cingulate cortex (ACC) which correlated with the visual analogue scale (VAS) response to word cues. This activity independently correlated with patient-reported questionnaires of depression, fatigue and dyspnea vigilance. Activation in the anterior insula, lateral prefrontal cortex (lPFC) and precuneus correlated with the VAS dyspnea scale but not the questionnaires. Conclusions: Our findings suggest that engagement of the brain's emotional circuitry is important for interpretation of dyspnea-related cues in COPD, and is influenced by depression, fatigue, and vigilance. A heightened response to salient cues is associated with increased symptom perception in chronic pain and asthma, and our findings suggest such mechanisms may be relevant in COPD.

A brief cognitive-behavioural intervention for pain reduces secondary hyperalgesia

Repeated exposure to pain can result in sensitization of the central nervous system, enhancing subsequent pain and potentially leading to chronicity. The ability to reverse this sensitization in a top-down manner would be of tremendous clinical benefit, but the degree that this can be accomplished volitionally remains unknown. Here we investigated whether a brief (~5 min) cognitive-behavioural intervention could modify pain perception and reduce central sensitization (as reflected by secondary hyperalgesia). In each of 8 sessions, 2 groups of healthy human subjects received a series of painful thermal stimuli that resulted in secondary hyperalgesia. One group (regulate) was given brief pain-focused cognitive training at each session, while the other group (control) received a non-pain-focused intervention. The intervention selectively reduced pain unpleasantness but not pain intensity in the regulate group. Furthermore, secondary hyperalgesia was significantly reduced in the regulate group compared with the control group. Reduction in secondary hyperalgesia was associated with reduced pain catastrophizing, suggesting that changes in central sensitization are related to changes in pain-related cognitions. Thus, we demonstrate that central sensitization can be modified volitionally by altering pain-related thoughts.

The “pain matrix” in pain-free individuals

Human functional imaging provides a correlative picture of brain activity during pain. A particular set of central nervous system structures (eg, the anterior cingulate cortex, thalamus, and insula) consistently respond to transient nociceptive stimuli causing pain. Activation of this so-called pain matrix or pain signature has been related to perceived pain intensity, both within and between individuals,1,2 and is now considered a candidate biomarker for pain in medicolegal settings and a tool for drug discovery. The pain-specific interpretation of such functional magnetic resonance imaging (fMRI) responses, although logically flawed,3,4 remains pervasive. For example, a 2015 review states that “the most likely interpretation of activity in the pain matrix seems to be pain.”4 Demonstrating the nonspecificity of the pain matrix requires ruling out the presence of pain when highly salient sensory stimuli are presented. In this study, we administered noxious mechanical stimuli to individuals with congenital insensitivity to pain and sampled their brain activity with fMRI. Loss-of-function SCN9A mutations in these individuals abolishes sensory neuron sodium channel Nav1.7 activity, resulting in pain insensitivity through an impaired peripheral drive that leaves tactile percepts fully intact.5 This allows complete experimental disambiguation of sensory responses and painful sensations

A retrospective study of zygomatico-orbital complex and/or zygomatic arch fractures over a 71-month period

Background/Aim: The aim of this retrospective study was to evaluate the epidemiology, treatment, and complications of zygomatico-orbital complex (ZOC) and/or zygomatic arch (ZA) fractures either associated with other facial fractures or not over a 71-month period. Material and methods: This survey was performed in three hospitals of Ribeirao Preto in Sao Paulo, Brazil, from August 2002 to July 2008. The records of 1575 patients with facial trauma were reviewed. There were 140 cases of ZOC and ZA fractures either associated with other facial fractures or not. Data regarding gender, age, race, addictions, day of trauma, etiology, signs and symptoms, oral hygiene condition, day of initial evaluation, hospital admission, day of surgery, surgery approach, pattern of fractures, treatment performed, post-operative antibiotic therapy, day of hospital discharge, and post-operative complications were collected. The data were subjected to descriptive statistical analyses. Results: The most frequent fractures affected Caucasian men and occurred during the fourth decade of life. The most frequent etiology was traffic accident, and symptoms and signs included pain and edema. Type I fractures were the main injury observed, and the treatment of choice was always rigid internal fixation. Post-operative antibiotic therapy was solely employed when there was an indication. Complications were observed in 13.1% of the cases. Conclusions: The treatment protocol yielded suitable post-operative results and also showed success rates comparable to published data around the world.

Urinary 6-Sulphatoxymelatonin Levels Are Depressed in Chronic Migraine and Several Comorbidities

Objective.- To assess urinary 6-sulphatoxymelatonin levels in a large consecutive series of patients with migraine and several comorbidities (chronic fatigue, fibromyalgia, insomnia, anxiety, and depression) as compared with controls. Background.- Urine analysis is widely used as a measure of melatonin secretion, as it is correlated with the nocturnal profile of plasma melatonin secretion. Melatonin has critical functions in human physiology and substantial evidence points to its importance in the regulation of circadian rhythms, sleep, and headache disorders. Methods.- Urine samples were collected into a single plastic container over a 12-hour period from 8:00 pm to 8:00 am of the next day, and 6-sulphatoxymelatonin was measured by quantitative ELISA. All of the patients were given a detailed questionnaire about headaches and additionally answered the following questionnaires: Chalder fatigue questionnaire, Epworth somnolence questionnaire, State-Trait Anxiety Inventory, and the Beck Depression Inventory. Results.- A total of 220 subjects were evaluated - 73 (33%) had episodic migraine, 73 (33%) had chronic migraine, and 74 (34%) were enrolled as control subjects. There was a strong correlation between the concentration of 6-sulphatoxymelatonin detected and chronic migraine. Regarding the comorbidities, this study objectively demonstrates an inverse relationship between 6-sulphatoxymelatonin levels and depression, anxiety, and fatigue. Conclusions.- To our knowledge, this is the first study to evaluate the relationship between the urinary concentration of melatonin and migraine comorbidities. These results support hypothalamic involvement in migraine pathophysiology.

Differing effects of exogenous and endogenous hydrogen sulphide in carrageenan-induced knee joint synovitis in the rat

Background and purpose: Recent findings suggest that the noxious gas H(2)S is produced endogenously, and that physiological concentrations of H(2)S are able to modulate pain and inflammation in rodents. This study was undertaken to evaluate the ability of endogenous and exogenous H(2)S to modulate carrageenan-induced synovitis in the rat knee. Experimental approach: Synovitis was induced in Wistar rats by intra-articular injection of carrageenan into the knee joint. Sixty minutes prior to carrageenan injection, the rats were pretreated with indomethacin, an inhibitor of H(2)S formation (dl-propargylglycine) or an H(2)S donor [Lawesson`s reagent (LR)]. Key results: Injection of carrageenan evoked knee inflammation, pain as characterized by impaired gait, secondary tactile allodynia of the ipsilateral hindpaw, joint swelling, histological changes, inflammatory cell infiltration, increased synovial myeloperoxidase, protein nitrotyrosine residues, inducible NOS (iNOS) activity and NO production. Pretreatment with LR or indomethacin significantly attenuated the pain responses, and all the inflammatory and biochemical changes, except for the increased iNOS activity, NO production and 3-NT. Propargylglycine pretreatment potentiated synovial iNOS activity (and NO production), and enhanced macrophage infiltration, but had no effect on other inflammatory parameters. Conclusions and implications: Whereas exogenous H(2)S delivered to the knee joint can produce a significant anti-inflammatory and anti-nociceptive effect, locally produced H(2)S exerts little immunomodulatory effect. These data further support the development and use of H(2)S donors as potential alternatives (or complementary therapies) to the available anti-inflammatory compounds used for treatment of joint inflammation or relief of its symptoms.