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Sample records for visceral hyperalgesia serotonin

  1. Effect of electroacupuncture on visceral hyperalgesia, serotonin and fos expression in an animal model of irritable bowel syndrome.

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    Wu, Justin Cy; Ziea, Eric Tc; Lao, Lixing; Lam, Emma Fc; Chan, Catherine Sm; Liang, Angela Yq; Chu, Sunny Lh; Yew, David Tw; Berman, Brian M; Sung, Joseph Jy

    2010-07-01

    While it is well established that acupuncture relieves somatic pain, its therapeutic effect on visceral pain such as irritable bowel syndrome (IBS) is unclear. We evaluated the effect of acupuncture in treating visceral hyperalgesia in an animal model. Sprague-Dawley rats (n = 8 per group) with prior neonatal maternal separation stress were randomly allocated to receive 3-day treatment of either electroacupuncture (EA) or sham acupuncture at acupoint ST-36. Another group of rats without prior maternal separation was included as non-handled controls. Colorectal distension was performed on the day after acupuncture treatment. The 3 groups were compared for pain threshold as determined by abdominal withdrawal reflex and visceromotor response as measured by electromyogram. Colon, spinal cord, and brainstem were sampled for topographic distribution and quantitative assessment of serotonin and Fos expression by immunohistochemistry. Rats in EA group had significantly higher pain threshold compared to those in sham acpuncture group (25.0 +/- 5.7 mmHg vs 18.7 +/- 5.2 mmHg, p = 0.01) and it was comparable with that of non-handled treatment naïve controls (29.4 +/- 9.3 mmHg, p = 0.28). They also had lower visceromotor response as measured by electromyogram compared to those received sham acupuncture at all colorectal distension pressures. EA significantly suppressed Fos expression in doral raphe nuclei of brainstem, superficial dorsal horn of spinal cord and colonic epithelium but suppressed 5-HT expression only in brainstem and spinal cord. Electro acupuncture attenuates visceral hyperlagesia through down-regulation of central serotonergic activities in the brain-gut axis.

  2. Effect of Electroacupuncture on Visceral Hyperalgesia, Serotonin and Fos Expression in an Animal Model of Irritable Bowel Syndrome

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    Wu, Justin CY; Ziea, Eric TC; Lao, Lixing; Lam, Emma FC; Chan, Catherine SM; Liang, Angela YQ; Chu, Sunny LH; Yew, David TW; Berman, Brian M.; Sung, Joseph JY

    2010-01-01

    Background/Aims While it is well established that acupuncture relieves somatic pain, its therapeutic effect on visceral pain such as irritable bowel syndrome (IBS) is unclear. We evaluated the effect of acupuncture in treating visceral hyperalgesia in an animal model. Methods Sprague-Dawley rats (n = 8 per group) with prior neonatal maternal separation stress were randomly allocated to receive 3-day treatment of either electroacupuncture (EA) or sham acupuncture at acupoint ST-36. Another gro...

  3. Neuroplastic alteration of TTX-resistant sodium channel with visceral pain and morphine-induced hyperalgesia

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    Chen J

    2012-11-01

    Full Text Available Jinghong Chen,1,2,4 Ze-hui Gong,4 Hao Yan,2 Zhijun Qiao,3 Bo-yi Qin41Department of Internal Medicine, Neuroscience Program, The University of Texas Medical Branch, Galveston, TX, USA; 2The Divisions of Pharmacy, Pharmacology core lab, MD Anderson Cancer Center, Houston, TX, USA; 3University of Texas-Pan American, Edinburg, TX, USA; 4Beijing Institute of Pharmacology and Toxicology, Beijing, China Abstract: The discovery of the tetrodotoxin-resistant (TTX-R Na+ channel in nociceptive neurons has provided a special target for analgesic intervention. In a previous study we found that both morphine tolerance and persistent visceral inflammation resulted in visceral hyperalgesia. It has also been suggested that hyperexcitability of sensory neurons due to altered TTX-R Na+ channel properties and expression contributes to hyperalgesia; however, we do not know if some TTX-R Na+ channel property changes can be triggered by visceral hyperalgesia and morphine tolerance, or whether there are similar molecular or channel mechanisms in both situations. To evaluate the effects of morphine tolerance and visceral inflammation on the channel, we investigated the dorsal root ganglia (DRG neuronal change following these chronic treatments. Using whole-cell patch clamp recording, we recorded TTX-R Na+ currents in isolated adult rat lumbar and sacral (L6-S2 DRG neurons from normal and pathologic rats with colon inflammatory pain or chronic morphine treatment. We found that the amplitudes of TTX-R Na+ currents were signiflcantly increased in small-diameter DRG neurons with either morphine tolerance or visceral inflammatory pain. Meanwhile, the result also showed that those treatments altered the kinetics properties of the electrical current (ie, the activating and inactivating speed of the channel was accelerated. Our current results suggested that in both models, visceral chronic inflammatory pain and morphine tolerance causes electrophysiological changes in voltage

  4. Widespread hyperalgesia in irritable bowel syndrome is dynamically maintained by tonic visceral impulse input and placebo/nocebo factors: evidence from human psychophysics, animal models, and neuroimaging.

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    Price, Donald D; Craggs, Jason G; Zhou, QiQi; Verne, G Nicholas; Perlstein, William M; Robinson, Michael E

    2009-09-01

    Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder that is often accompanied by both visceral and somatic hyperalgesia (enhanced pain from colorectal and somatic stimuli). Neural mechanisms of both types of hyperalgesia have been analyzed by neuroimaging studies of IBS patients and animal analog studies of "IBS-like" rats with delayed rectal and somatic hypersensitivity. Results from these studies suggest that pains associated with both visceral and widespread secondary cutaneous hyperalgesia are dynamically maintained by tonic impulse input from the non-inflamed colon and/or rectum and by brain-to-spinal cord facilitation. Enhanced visceral and somatic pains are accompanied by enhanced pain-related brain activity in IBS patients as compared to normal control subjects; placebos can normalize both their hyperalgesia and enhanced brain activity. That pain in IBS which is likely to be at least partly maintained by peripheral impulse input from the colon/rectum is supported by results showing that local rectal-colonic anesthesia normalizes visceral and somatic hyperalgesia in IBS patients and visceral and somatic hypersensitivity in "IBS-like" rats. Yet these forms of hyperalgesia are also highly modifiable by placebo and nocebo factors (e.g., expectations of relief or distress, respectively). Our working hypothesis is that synergistic interactions occur between placebo/nocebo factors and enhanced afferent processing so as to enhance, maintain, or reduce hyperalgesia in IBS. This explanatory model may be relevant to other persistent pain conditions.

  5. Widespread hyperalgesia in irritable bowel syndrome is dynamically maintained by tonic visceral impulse input and placebo/nocebo factors: Evidence from human psychophysics, animal models, and neuroimaging

    OpenAIRE

    Price, Donald D.; Craggs, Jason G.; Zhou, QiQi; Verne, G Nicholas; Perlstein, William M.; Robinson, Michael E

    2009-01-01

    Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder that is often accompanied by both visceral and somatic hyperalgesia (enhanced pain from colorectal and somatic stimuli). Neural mechanisms of both types of hyperalgesia have been analyzed by neuroimaging studies of IBS patients and animal analog studies of “IBS-like” rats with delayed rectal and somatic hypersensitivity. Results from these studies suggest that pains associated with both visceral and widespread seco...

  6. Visceral hyperalgesia induced by forebrain-specific suppression of native Kv7/KCNQ/M-current in mice

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    Bian Xiling

    2011-10-01

    Full Text Available Abstract Background Dysfunction of brain-gut interaction is thought to underlie visceral hypersensitivity which causes unexplained abdominal pain syndromes. However, the mechanism by which alteration of brain function in the brain-gut axis influences the perception of visceral pain remains largely elusive. In this study we investigated whether altered brain activity can generate visceral hyperalgesia. Results Using a forebrain specific αCaMKII promoter, we established a line of transgenic (Tg mice expressing a dominant-negative pore mutant of the Kv7.2/KCNQ2 channel which suppresses native KCNQ/M-current and enhances forebrain neuronal excitability. Brain slice recording of hippocampal pyramidal neurons from these Tg mice confirmed the presence of hyperexcitable properties with increased firing. Behavioral evaluation of Tg mice exhibited increased sensitivity to visceral pain induced by intraperitoneal (i.p. injection of either acetic acid or magnesium sulfate, and intracolon capsaicin stimulation, but not cutaneous sensation for thermal or inflammatory pain. Immunohistological staining showed increased c-Fos expression in the somatosensory SII cortex and insular cortex of Tg mice that were injected intraperitoneally with acetic acid. To mimic the effect of cortical hyperexcitability on visceral hyperalgesia, we injected KCNQ/M channel blocker XE991 into the lateral ventricle of wild type (WT mice. Intracerebroventricular injection of XE991 resulted in increased writhes of WT mice induced by acetic acid, and this effect was reversed by co-injection of the channel opener retigabine. Conclusions Our findings provide evidence that forebrain hyperexcitability confers visceral hyperalgesia, and suppression of central hyperexcitability by activation of KCNQ/M-channel function may provide a therapeutic potential for treatment of abdominal pain syndromes.

  7. Early life stress elicits visceral hyperalgesia and functional reorganization of pain circuits in adult rats

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    D.P. Holschneider

    2016-06-01

    Full Text Available Early life stress (ELS is a risk factor for developing functional gastrointestinal disorders, and has been proposed to be related to a central amplification of sensory input and resultant visceral hyperalgesia. We sought to characterize ELS-related changes in functional brain responses during acute noxious visceral stimulation. Neonatal rats (males/females were exposed to limited bedding (ELS or standard bedding (controls on postnatal days 2–9. Age 10–11 weeks, animals were implanted with venous cannulas and transmitters for abdominal electromyography (EMG. Cerebral blood flow (rCBF was mapped during colorectal distension (CRD using [14C]-iodoantipyrine autoradiography, and analyzed in three-dimensionally reconstructed brains by statistical parametric mapping and functional connectivity. EMG responses to CRD were increased after ELS, with no evidence of a sex difference. ELS rats compared to controls showed a greater significant positive correlation of EMG with amygdalar rCBF. Factorial analysis revealed a significant main effect of ‘ELS’ on functional activation of nodes within the pain pathway (somatosensory, insular, cingulate and prefrontal cortices, locus coeruleus/lateral parabrachial n. [LC/LPB], periaqueductal gray, sensory thalamus, as well as in the amygdala, hippocampus and hypothalamus. In addition, ELS resulted in an increase in the number of significant functional connections (i.e. degree centrality between regions within the pain circuit, including the amygdala, LC/LPB, insula, anterior ventral cingulate, posterior cingulate (retrosplenium, and stria terminalis, with decreases noted in the sensory thalamus and the hippocampus. Sex differences in rCBF were less broadly expressed, with significant differences noted at the level of the cortex, amygdala, dorsal hippocampus, raphe, sensory thalamus, and caudate-putamen. ELS showed a sexually dimorphic effect (‘Sex x ELS’ interaction at the LC/LPB complex, globus pallidus

  8. Effect of the 5-HT{sub 4} receptor and serotonin transporter on visceral hypersensitivity in rats

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    Chi, Yan; Liu, Xin-Guang; Wang, Hua-Hong; Li, Jun-Xia; Li, Yi-Xuan [Department of Gastroenterology, Peking University First Hospital, Beijing (China)

    2012-07-27

    Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT{sub 4} receptor and the serotonin transporter (SERT) as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times) between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT{sub 4} receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05) and increased 5-HT{sub 4} receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05). Treatment with fluoxetine (10 mg·kg{sup −1}·day{sup −1}, days 36-42), tegaserod (1 mg·kg{sup −1}·day{sup −1}, day 43), or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT{sub 4} receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01) but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654). These results indicate that both the 5-HT{sub 4} receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT

  9. Visceral hypersensitivity induced by activation of transient receptor potential vanilloid type 1 is mediated through the serotonin pathway in rat colon.

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    Qin, Hong-yan; Luo, Jia-lie; Qi, Sheng-da; Xu, Hong-xi; Sung, Joseph J Y; Bian, Zhao-xiang

    2010-11-25

    This study aimed to clarify the relationship between TRPV1 activation-induced visceral pain and the serotonin pathway in the colon of rats. The effects of para-chlorophenylalanine (pCPA) on visceral pain threshold pressure were assessed in capsaicin -induced visceral pain of rats. The expression of TRPV1 in the colon was examined by immunohistochemistry and Western blot analysis, and TRPV1 excitability in dorsal root ganglion (DRG) neurons was examined by whole-cell patch-clamp recording in pCPA-treated rats. Calcineurin and Ca(2+)-calmodulin-dependent kinase II (CaMKII), the important proteins in maintaining TRPV1 function in the colon, were also tested by Western blot analysis and immunofluorescence staining. Results showed that pCPA significantly increased the capsaicin-induced visceral pain threshold by 2.3-fold, and the enhanced visceral pain threshold corresponded with decreased 5-HT content (58% depleted) and enterochromaffin cell number (80% reduced). The reduced excitability of TRPV1 in DRG neurons, instead of changed TRPV1 expression, is responsible for the enhanced visceral pain threshold in 5-HT-depleted rats, and the mechanism may be related to the decreased expression of pCaMKII. These results indicate that visceral hypersensitivity induced by TRPV1 activation is modulated through 5-HT pathways and the attenuated function of TRPV1 and decreased protein expression of pCaMKII may play an important role in capsaicin-induced TRPV1 desensitization under 5-HT-depleted condition. The important role of TRPV1 and 5-HT in generating and maintaining visceral hypersensitivity may provide insights for the treatment of visceral hypersensitivity. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Hiperalgesia visceral e dor abdominal crônica: abordagem diagnóstica e terapêutica Hiperalgesia visceral y dolor abdominal crónico: abordaje diagnóstica y terapéutica Visceral hyperalgesia and chronic abdominal pain: diagnostic and therapeutic approach

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    Durval Campos Kraychete

    2003-12-01

    nociception mechanisms seem to be involved in visceral hyperalgesia. Diagnosis requires detailed history and clinical evaluation, taking into consideration Rome II criteria. Based on known or assumed pathophysiological mechanisms, new drugs have been researched, and some have been more recently used to control abdominal pain, such as 5-HT4 receptor agonists and sodium channel blockers. CONCLUSIONS: Chronic pathophysiological abdominal pain mechanisms are still not well understood. Therapy and diagnosis require the understanding of such mechanisms, as well as of Rome II criteria. On the other hand, good patient-physician relationship and multidisciplinary team’s performance seem to be critical in improving treatment response and patients’ quality of life.

  11. Trigeminal-Rostral Ventromedial Medulla circuitry is involved in orofacial hyperalgesia contralateral to tissue injury

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    Chai Bryan

    2012-10-01

    Full Text Available Abstract Background Our previous studies have shown that complete Freund’s adjuvant (CFA-induced masseter inflammation and microinjection of the pro-inflammatory cytokine interleukin-1β (IL-1β into the subnucleus interpolaris/subnucleus caudalis transition zone of the spinal trigeminal nucleus (Vi/Vc can induce contralateral orofacial hyperalgesia in rat models. We have also shown that contralateral hyperalgesia is attenuated with a lesion of the rostral ventromedial medulla (RVM, a critical site of descending pain modulation. Here we investigated the involvement of the RVM-Vi/Vc circuitry in mediating contralateral orofacial hyperalgesia after an injection of CFA into the masseter muscle. Results Microinjection of the IL-1 receptor antagonist (5 nmol, n=6 into the ipsilateral Vi/Vc attenuated the CFA-induced contralateral hyperalgesia but not the ipsilateral hyperalgesia. Intra-RVM post-treatment injection of the NK1 receptor antagonists, RP67580 (0.5-11.4 nmol and L-733,060 (0.5-11.4 nmol, attenuated CFA-induced bilateral hyperalgesia and IL-1β induced bilateral hyperalgesia. Serotonin depletion in RVM neurons prior to intra-masseter CFA injection prevented the development of contralateral hyperalgesia 1–3 days after CFA injection. Inhibition of 5-HT3 receptors in the contralateral Vi/Vc with direct microinjection of the select 5-HT3 receptor antagonist, Y-25130 (2.6-12.9 nmol, attenuated CFA-induced contralateral hyperalgesia. Lesions to the ipsilateral Vc prevented the development of ipsilateral hyperalgesia but did not prevent the development of contralateral hyperalgesia. Conclusions These results suggest that the development of CFA-induced contralateral orofacial hyperalgesia is mediated through descending facilitatory mechanisms of the RVM-Vi/Vc circuitry.

  12. Serotonin syndrome

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    Hyperserotonemia; Serotonergic syndrome; Serotonin toxicity; SSRI - serotonin syndrome; MAO - serotonin syndrome ... brain area. For example, you can develop this syndrome if you take migraine medicines called triptans together ...

  13. Serotonin Transporter Gene Polymorphism Modulates Activity and Connectivity within an Emotional Arousal Network of Healthy Men during an Aversive Visceral Stimulus.

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    Kilpatrick, Lisa A; Mayer, Emeran A; Labus, Jennifer S; Gupta, Arpana; Hamaguchi, Toyohiro; Mizuno, Tomoko; Komuro, Hazuki; Kano, Michiko; Kanazawa, Motoyori; Aoki, Masashi; Fukudo, Shin

    2015-01-01

    The 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) has been linked to increased stress responsiveness and negative emotional states. During fearful face recognition individuals with the s allele of 5-HTTLPR show greater amygdala activation. We aimed to test the hypothesis that the 5-HTTLPR polymorphism differentially affects connectivity within brain networks during an aversive visceral stimulus. Twenty-three healthy male subjects were enrolled. DNA was extracted from the peripheral blood. The genotype of 5-HTTLPR was determined using polymerase chain reaction. Subjects with the s/s genotype (n = 13) were compared to those with the l allele (genotypes l/s, l/l, n = 10). Controlled rectal distension from 0 to 40 mmHg was delivered in random order using a barostat. Radioactive H2[15-O] saline was injected at time of distension followed by positron emission tomography (PET). Changes in regional cerebral blood flow (rCBF) were analyzed using partial least squares (PLS) and structural equation modeling (SEM). During baseline, subjects with s/s genotype demonstrated a significantly increased negative influence of pregenual ACC (pACC) on amygdala activity compared to l-carriers. During inflation, subjects with s/s genotype demonstrated a significantly greater positive influence of hippocampus on amygdala activity compared to l-carriers. In male Japanese subjects, individuals with s/s genotype show alterations in the connectivity of brain regions involved in stress responsiveness and emotion regulation during aversive visceral stimuli compared to those with l carriers.

  14. Demarcation of secondary hyperalgesia zones

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    Ringsted, Thomas K; Enghuus, Casper; Petersen, Morten A

    2015-01-01

    BACKGROUND: Secondary hyperalgesia is increased sensitivity in normal tissue near an injury, and it is a measure of central sensitization reflecting injury-related effects on the CNS. Secondary hyperalgesia areas (SHAs), usually assessed by polyamide monofilaments, are important outcomes in studies...... of analgesic drug effects in humans. However, since the methods applied in demarcating the secondary hyperalgesia zone seem inconsistent across studies, we examined the effect of a standardized approach upon the measurement of SHA following a first degree burn injury (BI). NEW METHOD: The study was a two......-observer, test-retest study with the two sessions separated by 6wk. An observer-blinded design adjusted to examine day-to-day and observer-to-observer variability in SHA was used. In 23 healthy volunteers (12 females/11 males) a BI was induced by a contact thermode (47.0°C, 420s, 2.5×5.0cm(2)). The SHA...

  15. Visceral pain originating from the upper urinary tract

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    Pedersen, Katja Venborg; Drewes, Asbjørn Mohr; Frimodt-Møller, Poul Christian

    2010-01-01

    -visceral hyperalgesia. However, further studies are needed to better understand these visceral pain mechanisms with regard to optimising pain management. This review gives an introduction to visceral pain in general and upper urinary tract pain in particular, with special reference to pain pathways and pharmacological......Pain originating from the upper urinary tract is a common problem and stone colic is one of the most intense pain conditions that can be experienced in the clinic. The pain is difficult to alleviate and often leads to medical attention. In humans, pain mechanisms of the upper urinary tract pain...... are still poorly understood, which often leads to a trial and error approach in clinical pain management. Pain from the upper urinary tract seems to have all the characteristics of pure visceral pain, including referred pain with or without hyperalgesia/trophic changes in somatic tissues and viscero...

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

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    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

  17. Nocebo Hyperalgesia, Partial Reinforcement, and Extinction.

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    Colagiuri, Ben; Quinn, Veronica F; Colloca, Luana

    2015-10-01

    Many studies have found evidence of conditioning-induced nocebo hyperalgesia. However, these studies have exclusively involved continuous reinforcement (CRF) schedules. Thus, it is currently unknown whether nocebo hyperalgesia can result after partial reinforcement (PRF). We tested this using electrodermal pain stimulation in healthy volunteers. Undergraduates (N = 135) received nocebo treatment under the guise of a hyperalgesic. Participants were randomly allocated to CRF, PRF, or control (no conditioning). Conditioning involved surreptitiously increasing pain stimulation on nocebo trials relative to control trials. During training, the CRF group always had the nocebo paired with the surreptitious pain increase, whereas the PRF group experienced the increase on only 62.5% of nocebo trials. In the test phase, pain stimulation was equivalent across nocebo and control trials. PRF was sufficient to induce nocebo hyperalgesia; however, this was weaker than CRF. Nocebo hyperalgesia failed to extinguish irrespective of the training schedule. Additional assessment of expectancies indicated strong concordance between expectancy and nocebo hyperalgesia. Overall, these findings suggest that once established, nocebo hyperalgesia may be difficult to disrupt. PRF may be a novel method of reducing the intensity of nocebo hyperalgesia in the clinic, which may be particularly important given its persistence. This study provides novel evidence that partial reinforcement results in weaker nocebo hyperalgesia than continuous reinforcement and that nocebo hyperalgesia fails to extinguish, irrespective of the training schedule. As a result, partial reinforcement may serve as a method for reducing the intensity of nocebo hyperalgesia in the clinic. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  18. Chronic Stress and Peripheral Pain: Evidence for Distinct, Region-specific Changes in Visceral and Somatosensory Pain Regulatory Pathways

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    Zheng, Gen; Hong, Shuangsong; Hayes, John M; Wiley, John W

    2015-01-01

    Chronic stress alters the hypothalamic-pituitary-adrenal (HPA) axis and enhances visceral and somatosensory pain perception. It is unresolved whether chronic stress has distinct effects on visceral and somatosensory pain regulatory pathways. Previous studies reported that stress-induced visceral hyperalgesia is associated with reciprocal alterations of endovanilloid and endocannabinoid pain pathways in DRG neurons innervating the pelvic viscera. In this study, we compared somatosensory and visceral hyperalgesia with respect to differential responses of peripheral pain regulatory pathways in a rat model of chronic, intermittent stress. We found that chronic stress induced reciprocal changes in the endocannabinoid 2-AG (increased) and endocannabinoid degradation enzymes COX-2 and FAAH (decreased), associated with down-regulation of CB1 and up-regulation of TRPV1 receptors in L6-S2 DRG but not L4-L5 DRG neurons. In contrast, sodium channels Nav1.7 and Nav1.8 were up-regulated in L4-L5 but not L6-S2 DRGs in stressed rats, which was reproduced in control L4-L5 DRGs treated with corticosterone in vitro. The reciprocal changes of CB1, TRPV1 and sodium channels were cell-specific and observed in the sub-population of nociceptive neurons. Behavioral assessment showed that visceral hyperalgesia persisted, whereas somatosensory hyperalgesia and enhanced expression of Nav1.7 and Nav1.8 sodium channels in L4-L5 DRGs normalized 3 days after completion of the stress phase. These data indicate that chronic stress induces visceral and somatosensory hyperalgesia that involves differential changes in endovanilloid and endocannabinoid pathways, and sodium channels in DRGs innervating the pelvic viscera and lower extremities. These results suggest that chronic stress-induced visceral and lower extremity somatosensory hyperalgesia can be treated selectively at different levels of the spinal cord. PMID:26408049

  19. Acute tryptophan depletion alters the effective connectivity of emotional arousal circuitry during visceral stimuli in healthy women.

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    Labus, J S; Mayer, E A; Jarcho, J; Kilpatrick, L A; Kilkens, T O C; Evers, E A T; Backes, W H; Brummer, R-J M; van Nieuwenhoven, M A

    2011-09-01

    Alterations in serotonin signalling within the brain-gut axis have been implicated in the pathophysiology of irritable bowel syndrome (IBS) and is a treatment target. Acute tryptophan depletion (ATD) decreases brain serotonin (5-hydroxytryptamine; 5-HT) levels, and increases visceral perception and negative emotional bias in patients with IBS. The aim of the present study was to determine the effect of ATD on brain activity and connectivity during visceral stimuli in healthy women, and to compare the ATD-induced brain connectivity of an arousal circuit in female patients with IBS without ATD. 12 healthy females (19-25 years) were studied under placebo (PLA) conditions and ATD. Functional MRI measurements were performed during a rectal barostat protocol, consisting of random non-painful and maximal tolerable distensions. Partial least squares analyses and structural equation modelling were used to evaluate the effect of ATD on functional and effective brain connectivity during distension. Results in healthy controls under ATD were compared with the effective connectivity of brain responses to 45 mm Hg rectal distension in 14 female patients with constipation-predominant IBS (IBS-C) (24-50 years). In healthy controls, ATD resulted in increased response of an extensive brain network to balloon distension, including the amygdala and nodes of emotional arousal and homeostatic afferent networks. The effect was greater during high inflation, suggesting greater engagement of the central serotonion system with more aversive visceral stimuli. Effective connectivity analysis revealed a profound effect of ATD on coupling between emotional arousal network nodes, resulting in loss of negative feedback inhibition of the amygdala. A near-identical pattern was identified in the patients with IBS-C. The findings are consistent with an ATD-induced disinhibition of and increased connectivity within an emotional arousal network during aversive stimulation. Together with the previous

  20. Visceral Leishmaniasis

    Science.gov (United States)

    2011-06-01

    Autoclaved Leishmania major vaccine for prevention of visceral leishmaniasis: a randomised, double-blind, BCG -controlled trial in Sudan. Lancet...nitric oxide killing. These properties of sandfly saliva are the focus of current research on an antileishmania vaccine .11 At the site of inoculation...these campaigns, incidence has returned to high levels. No VL vaccine is currently licensed or commercially available. A variety of vaccine

  1. Serotonin & Depression

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    Axholm, Ida; Haxgart, Nina; Ranum, Kasper; Svendsen, Astrid Helmer

    2014-01-01

    350.000.000 people worldwide have a depression and 150.000 Danes are affected every year. Depresion is defined by WHO from it’s syptoms. The diagnose is given from a point system for the patient’s symptoms, for instance HAM-D scale and MADRS scale Serotonin in the brain is synthesized from L-tryptophan in the presynaptic parts of the neuron and is released into the synapse as a transmitter drug. According to the serotonin theory, the concentration of serotonin in the brain is low in depressio...

  2. Secondary hyperalgesia to heat stimuli after burn injury in man

    DEFF Research Database (Denmark)

    Pedersen, J L; Kehlet, H

    1998-01-01

    .006) and was more intense (P = 0.001) within the zone of secondary hyperalgesia than on the lateral part of the crus. Further, the heat pain response was more intense in the zone of primary hyperalgesia than in the zone of secondary hyperalgesia (P = 0.004), in contrast to the mechanical pain response, which...... was not significantly different between the two zones of hyperalgesia. In conclusion, secondary hyperalgesia in man is not restricted to mechanical stimuli, as significant hyperalgesia to heat developed within the zone of secondary hyperalgesia to punctate mechanical stimuli. The data, combined with other evidence......, suggest differences in the mechanisms accounting for primary hyperalgesia to heat and mechanical stimuli, whereas secondary hyperalgesia to heat and mechanical stimuli may be explained by a common central mechanism....

  3. Serotonin Test

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    ... acute myocardial infarction ( heart attack ), cystic fibrosis , and dumping syndrome . The serotonin test is not usually ordered ... Thank you. Contact a Scientist Find Us On Social Media: Facebook Twitter Google Plus Footer Menu Home ...

  4. Serotonin Test

    Science.gov (United States)

    ... High-sensitivity C-reactive Protein (hs-CRP) Histamine Histone Antibody HIV Antibody and HIV Antigen (p24) HIV ... 282515-overview. Accessed December 2010. (© 1995-2010). Unit Code 84395: Serotonin, Serum. Mayo Clinic, Mayo Medical Laboratories [ ...

  5. Review article: intestinal serotonin signalling in irritable bowel syndrome.

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    Mawe, G M; Coates, M D; Moses, P L

    2006-04-15

    Alterations in motility, secretion and visceral sensation are hallmarks of irritable bowel syndrome. As all of these aspects of gastrointestinal function involve serotonin signalling between enterochromaffin cells and sensory nerve fibres in the mucosal layer of the gut, potential alterations in mucosal serotonin signalling have been explored as a possible mechanism of altered function and sensation in irritable bowel syndrome. Literature related to intestinal serotonin signalling in normal and pathophysiological conditions has been searched and summarized. Elements of serotonin signalling that are altered in irritable bowel syndrome include: enterochromaffin cell numbers, serotonin content, tryptophan hydroxylase message levels, 5-hydroxyindoleacedic acid levels, serum serotonin levels and expression of the serotonin-selective reuptake transporter. Both genetic and epigenetic factors could contribute to decreased serotonin-selective reuptake transporter in irritable bowel syndrome. A serotonin-selective reuptake transporter gene promoter polymorphism may cause a genetic predisposition, and inflammatory mediators can induce serotonin-selective reuptake transporter downregulation. While a psychiatric co-morbidity exists with IBS, changes in mucosal serotonin handling support the concept that there is a gastrointestinal component to the aetiology of irritable bowel syndrome. Additional studies will be required to gain a more complete understanding of changes in serotonin signalling that are occurring, their cause and effect relationship, and which of these changes have pathophysiological consequences.

  6. Targeting fatty acid amide hydrolase and transient receptor potential vanilloid-1 simultaneously to modulate colonic motility and visceral sensation in the mouse: A pharmacological intervention with N-arachidonoyl-serotonin (AA-5-HT).

    Science.gov (United States)

    Bashashati, M; Fichna, J; Piscitelli, F; Capasso, R; Izzo, A A; Sibaev, A; Timmermans, J-P; Cenac, N; Vergnolle, N; Di Marzo, V; Storr, M

    2017-12-01

    Endocannabinoid anandamide (AEA) inhibits intestinal motility and visceral pain, but it may also be proalgesic through transient receptor potential vanilloid-1 (TRPV1). AEA is degraded by fatty acid amide hydrolase (FAAH). This study explored whether dual inhibition of FAAH and TRPV1 reduces diarrhea and abdominal pain. Immunostaining was performed on myenteric plexus of the mouse colon. The effects of the dual FAAH/TRPV1 inhibitor AA-5-HT on electrically induced contractility, excitatory junction potential (EJP) and fast (f) and slow (s) inhibitory junction potentials (IJP) in the mouse colon, colonic propulsion and visceromotor response (VMR) to rectal distension were studied. The colonic levels of endocannabinoids and fatty acid amides were measured. CB1-positive neurons exhibited TRPV1; only some TRPV1 positive neurons did not express CB1. CB1 and FAAH did not colocalize. AA-5-HT (100 nM-10 μM) decreased colonic contractility by ~60%; this effect was abolished by TRPV1 antagonist 5'-IRTX, but not by CB1 antagonist, SR141716. AA-5-HT (1 μM-10 μM) inhibited EJP by ~30% and IJPs by ~50%. The effects of AA-5-HT on junction potentials were reversed by SR141716 and 5`-IRTX. AA-5-HT (20 mg/kg; i.p.) inhibited colonic propulsion by ~30%; SR141716 but not 5`-IRTX reversed this effect. AA-5-HT decreased VMR by ~50%-60%; these effects were not blocked by SR141716 or 5`-IRTX. AA-5-HT increased AEA in the colon. The effects of AA-5-HT on visceral sensation and colonic motility are differentially mediated by CB1, TRPV1 and non-CB1/TRPV1 mechanisms, possibly reflecting the distinct neuromodulatory roles of endocannabinoid and endovanilloid FAAH substrates in the mouse intestine. © 2017 John Wiley & Sons Ltd.

  7. Visceral larva migrans

    Science.gov (United States)

    Parasite infection - visceral larva migrans; VLM; Toxocariasis; Ocular larva migrans; Larva migrans visceralis ... Saunders; 2016:chap 39. Nash TE. Visceral larvae migrans and other uncommon helminth infections. In: Bennett JE, ...

  8. 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

  9. Fear of pain potentiates nocebo hyperalgesia

    Directory of Open Access Journals (Sweden)

    Aslaksen PM

    2015-10-01

    Full Text Available Per M Aslaksen,1 Peter S Lyby2 1Department of Psychology, Research Group for Cognitive Neuroscience, The Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway; 2Catosenteret Rehabilitation Center, Son, Norway Abstract: Nocebo hyperalgesia has received sparse experimental attention compared to placebo analgesia. The aim of the present study was to investigate if personality traits and fear of pain could predict experimental nocebo hyperalgesia. One hundred and eleven healthy volunteers (76 females participated in an experimental study in which personality traits and fear of pain were measured prior to induction of thermal heat pain. Personality traits were measured by the Big-Five Inventory-10. Fear of pain was measured by the Fear of Pain Questionnaire III. Heat pain was induced by a PC-controlled thermode. Pain was measured by a computerized visual analog scale. Stress levels during the experiment were measured by numerical rating scales. The participants were randomized to a Nocebo group or to a no-treatment Natural History group. The results revealed that pain and stress levels were significantly higher in the Nocebo group after nocebo treatment. Mediation analysis showed that higher levels of the Fear of Pain Questionnaire III factor "fear of medical pain" significantly increased stress levels after nocebo treatment and that higher stress levels were associated with increased nocebo hyperalgesic responses. There were no significant associations between any of the personality factors and the nocebo hyperalgesic effect. The results from the present study suggest that dispositional fear of pain might be a useful predictor for nocebo hyperalgesia and emotional states concomitant with expectations of increased pain. Furthermore, measurement of traits that are specific to pain experience is probably better suited for prediction of nocebo hyperalgesic responses compared to broad measures of personality

  10. [Psychophysiology of visceral pain].

    Science.gov (United States)

    Horing, B; Enck, P

    2014-06-01

    The psychophysiology of visceral pain is--different from cardiac psychophysiology--much less well investigated due to the invasiveness of its methods and problems associated with reliably and reproducibly stimulating as well as recording of the gastrointestinal tract. Despite these problems, the last 30 years have documented a number of psychophysiological phenomena such as the perception (interoception) of visceral stimuli, the effect of emotions and stress on visceral sensations, and the effect of visceral processes on cortical processing. This was mainly due to the application of neurophysiological techniques (cortical imaging and stimulation) in these investigations.

  11. Acute restraint stress induces hyperalgesia via non-adrenergic ...

    African Journals Online (AJOL)

    ... the non-involvement of adrenergic mechanisms. The hyperalgesia may however result from a change in the affective state of the animal and not from a change in sensory processing of noxious stimulus. Keywords: stress, hyperalgesia, tail-flick test, sympathetic nervous system. African Journal of Biomedical Research Vol.

  12. Opioid induced hyperalgesia in anesthetic settings.

    Science.gov (United States)

    Lee, Hyeon Jeong; Yeomans, David C

    2014-11-01

    Pain is difficult to investigate and difficult to treat, in part, because of problems in quantification and assessment. The use of opioids, combined with classic anesthetics to maintain hemodynamic stability by controlling responses to intraoperative painful events has gained significant popularity in the anesthetic field. However, several side effects profiles concerning perioperative use of opioid have been published. Over the past two decades, many concerns have arisen with respect to opioid-induced hyperalgesia (OIH), which is the paradoxical effect wherein opioid usage may decrease pain thresholds and increase atypical pain unrelated to the original, preexisting pain. This brief review focuses on the evidence, mechanisms, and modulatory and pharmacologic management of OIH in order to elaborate on the clinical implication of OIH.

  13. Visceral sensitivity testing.

    Science.gov (United States)

    Andresen, Viola

    2009-01-01

    Visceral hypersensitivity is regarded as an important factor in the pathogenesis of functional gastrointestinal disorders. Assessment of visceral sensitivity has several important aims: increasing the understanding of normal and abnormal visceral sensory mechanisms and participating sensory pathways, serving as diagnostic tool to detect patients with abnormal visceral sensitivity, and evaluating therapeutic interventions directed towards modification of visceral sensitivity. Current stimulation modes in sensitivity tests include mechanical distension by barostat or tensostat, nutrient drink or water load, chemical stimulation, e.g. acid provocation or capsaicin ingestion, electrical, or thermal stimulation. Multimodal probes incorporating several stimulation modes in one device have recently been developed. Assessment of visceral sensation can be based on subjective responses of conscious perception or on objective parameters such as visceromotoric responses or central sensory processing patterns. All methods face the challenge that visceral sensitivity may be influenced by a wide spectrum of different factors, including the test techniques themselves, and improved, preferably non-invasive sensitivity tests with a greater standardisation and a broader applicability are still needed.

  14. Sustained Morphine Administration Induces TRPM8-Dependent Cold Hyperalgesia.

    Science.gov (United States)

    Gong, Kerui; Jasmin, Luc

    2017-02-01

    It is not uncommon for patients chronically treated with opioids to exhibit opioid-induced hyperalgesia, and this has been widely reported clinically and experimentally. The molecular substrate for this hyperalgesia is multifaceted, and associated with a complex neural reorganization even in the periphery. For instance, we have recently shown that chronic morphine-induced heat hyperalgesia is associated with an increased expression of GluN2B containing N-methyl-D-aspartate receptors, as well as of the neuronal excitatory amino acid transporter 3/excitatory amino acid carrier 1, in small-diameter primary sensory neurons only. Cold allodynia is also a common complaint of patients chronically treated with opioids, yet its molecular mechanisms remain to be understood. Here we present evidence that the cold sensor TRPM8 channel is involved in opioid-induced hyperalgesia. After 7 days of morphine administration, we observed an upregulation of TRPM8 channels using patch clamp recording on sensory neurons and Western blot analysis on dorsal root ganglia. The selective TRPM8 antagonist RQ-00203078 blocked cold hyperalgesia in morphine-treated rats. Also, TRPM8 knockout mice failed to develop cold hyperalgesia after chronic administration of morphine. Our results show that chronic morphine upregulates TRPM8 channels, which is in contrast with the previous finding that acute morphine triggers TRPM8 internalization. Patients receiving chronic opioid are sensitive to cold. We show in mice and rats that sustained morphine administration induces cold hyperalgesia and an upregulation of TRPM8. Knockout or selectively blocking TRPM8 reduces morphine-induced cold hyperalgesia suggesting TRPM8 is regulated by opioids. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  15. Immunity to Visceral Leishmaniasis

    OpenAIRE

    Ali, Nahid; Mekuria, Asrat Hailu; Requena, José María; Engwerda, Christian

    2012-01-01

    Leishmaniasis is a major vector-borne parasitic disease affecting 12 million people worldwide. With a broad range of clinical manifestations, ranging from self-healing skin ulcers to disfiguring mucosal lesions to life-threatening infections of visceral organs (liver and spleen), the disease has become a serious human health issue, particularly in developing countries. Among all of its forms, visceral leishmaniasis (VL, also known as kala-azar), caused by the Leishmania donovani complex (i.e....

  16. Secondary hyperalgesia to heat stimuli after burn injury in man

    DEFF Research Database (Denmark)

    Pedersen, J L; Kehlet, H

    1998-01-01

    ), and assessments were made 70 min and 40 min before, and 0, 1, and 2 h after the burn injury. Hyperalgesia to mechanical and heat stimuli were examined by von Frey hairs and contact thermodes (3.75 and 12.5 cm2), and pain responses were rated with a visual analog scale (0-100). The area of secondary hyperalgesia......The aim of the study was to examine the presence of hyperalgesia to heat stimuli within the zone of secondary hyperalgesia to punctate mechanical stimuli. A burn was produced on the medial part of the non-dominant crus in 15 healthy volunteers with a 50 x 25 mm thermode (47 degrees C, 7 min...... to punctate stimuli was assessed with a rigid von Frey hair (462 mN). The heat pain responses to 45 degrees C in 5 s (3.75 cm2) were tested in the area just outside the burn, where the subjects developed secondary hyperalgesia, and on the lateral crus where no subject developed secondary hyperalgesia (control...

  17. Serotonin receptor 3A polymorphism c.-42C > T is associated with severe dyspepsia.

    OpenAIRE

    Mujakovic, S.; Linde, J.J. ter; Wit, N.J. de; Marrewijk, C.J. van; Fransen, G.A.J.; Onland-Moret, N.C.; Laheij, R.J.F.; Muris, J.W.M.; Grobbee, D.E.; Samsom, M.; Jansen, J.B.M.J.; Knottnerus, J.A.; Numans, M.E.

    2011-01-01

    Abstract Background The association between anxiety and depression related traits and dyspepsia may reflect a common genetic predisposition. Furthermore, genetic factors may contribute to the risk of having increased visceral sensitivity, which has been implicated in dyspeptic symptom generation. Serotonin (5-HT) modulates visceral sensitivity by its action on 5-HT3 receptors. Interestingly, a functional polymorphism in HTR3A, encoding the 5-HT3 receptor A subunit, has been reported to be ass...

  18. Role of sympathetic nervous system in rat model of chronic visceral pain.

    Science.gov (United States)

    Gil, D W; Wang, J; Gu, C; Donello, J E; Cabrera, S; Al-Chaer, E D

    2016-03-01

    Changes in central pain modulation have been implicated in generalized pain syndromes such as irritable bowel syndrome (IBS). We have previously demonstrated that reduced descending inhibition unveils a role of sympathoneuronal outflow in decreasing peripheral sensory thresholds, resulting in stress-induced hyperalgesia. We investigated whether sympathetic nervous system (SNS) exacerbation of pain sensation when central pain inhibition is reduced is relevant to chronic pain disorders using a rat colon irritation (CI) model of chronic visceral hypersensitivity with hallmarks of IBS. Rats were treated to a series of colorectal balloon distensions (CRD) as neonates resulting in visceral and somatic hypersensitivity and altered stool function that persists into adulthood. The visceral sensitivity was assessed by recording electromyographic (EMG) responses to CRD. Somatic sensitivity was assessed by paw withdrawal thresholds to radiant heat. The effects on the hypersensitivity of (i) inhibiting sympathoneuronal outflow with pharmacological and surgical interventions and (ii) enhancing the outflow with water avoidance stress (WAS) were tested. The alpha2-adrenergic agonist, clonidine, and the alpha1-adrenergic antagonist, prazosin, reduced the visceral hypersensitivity and WAS enhanced the pain. Chemical sympathectomy with guanethidine and surgical sympathectomy resulted in a loss of the chronic visceral hypersensitivity. The results support a role of the SNS in driving the chronic visceral and somatic hypersensitivity seen in CI rats. The findings further suggest that treatments that decrease sympathetic outflow or block activation of adrenergic receptors on sensory nerves could be beneficial in the treatment of generalized pain syndromes. © 2015 John Wiley & Sons Ltd.

  19. Nocebo hyperalgesia induced by social observational learning.

    Science.gov (United States)

    Vögtle, Elisabeth; Barke, Antonia; Kröner-Herwig, Birgit

    2013-08-01

    Nocebo effects can be acquired by verbal suggestion, but it is unknown whether they can be induced through observational learning and whether they are influenced by factors known to influence pain perception, such as pain anxiety or pain catastrophizing. Eighty-five female students (aged 22.5 ± 4.4 years) were randomly assigned to one of three conditions. Participants in the control condition (CC) received information that an ointment had no effect on pain perception. Participants in the verbal suggestion condition (VSC) received information that it increased pain sensitivity. Participants in the social observational learning condition (OLC) watched a video in which a model displayed more pain when ointment was applied. Subsequently, all participants received three pressure pain stimuli (60 seconds) on each hand. On one hand, the ointment was applied prior to the stimulation. Numerical pain ratings were collected at 20-second intervals during pain stimulation. The participants filled in questionnaires regarding pain-related attitudes (Pain Anxiety Symptoms Scale, Pain Catastrophizing Scale, and Somatosensory Amplification Scale). Participants in the OLC showed higher pain ratings with than without ointment. Pain ratings within the CC and the VSC were at the same level with and without ointment. In the VSC, the pain ratings were higher than in the CC with and without ointment. The nocebo response correlated with pain catastrophizing but not with pain anxiety or somatosensory amplification. A nocebo response to pressure pain was induced by observational learning but not by verbal suggestion. This finding highlights the importance of investigating the influence of observational learning on nocebo hyperalgesia. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  20. Duration and distribution of experimental muscular hyperalgesia in humans following combined infusions of serotonin and bradykinin

    DEFF Research Database (Denmark)

    Babenko, Victor; Svensson, Peter; Graven-Nielsen, Thomas

    2000-01-01

    -infusions interval of 3 min. Infusions of isotonic saline (NaCl, 0.9%) were given as control. Pain intensity was continuously scored on a visual analogue scale (VAS), and subjects drew the distribution of the pain areas on an anatomical map. Pressure pain thresholds (PPTs) were assessed with an electronic algometer...... min after infusions. The VAS-peak after BKN was significantly higher (PVAS after 5-HT+BKN was significantly longer (P

  1. Electroacupuncture Reduces Hyperalgesia after Injections of Acidic Saline in Rats

    Directory of Open Access Journals (Sweden)

    Leonardo Yung dos Santos Maciel

    2014-01-01

    Full Text Available Background. Injections of acidic saline into the gastrocnemius muscle in rats produce a bilateral long-lasting hyperalgesia similar to fibromyalgia in humans. No previous study investigated the effect of electroacupuncture (EA on this acidic saline model. This study aimed to identify the effects of EA in the hyperalgesia produced by repeated intramuscular injections of acidic saline. Methods. Rats were divided into four groups (n=6, each group: control, acupuncture, EA 15 Hz, and 100 Hz. Left gastrocnemius muscle was injected with 100 μL of pH 4.0 sterile saline twice five days apart. EA, acupuncture, or control therapy was daily administered (20 min for 5 consecutive days under anesthesia. Needles were placed in the St36 and Sp6 acupoints. The assessment of secondary mechanical hyperalgesia, thermal hyperalgesia, and motor performance was performed before injections and before and after the treatment performed on each day. The paw withdrawal threshold was tested using the nonparametric Kruskal-Wallis test and differences within the group Wilcoxon Matched Pairs. The latency and motor performance were tested for ANOVA parametric test for independent measures, and for differences in the group, we used t-test for paired samples. Post hoc Tukey test was used for multiple corrections. P values ​​less than 0.05 were considered statistically significant. Results. Indicate that there was a significant reduction of mechanical withdrawal threshold and paw withdrawal latency 24 hours following the second injection. Moreover, mechanical and thermal hyperalgesia were significantly reversed by EA 15, 100 Hz, and acupuncture. Conclusions. The results suggest that EA high and low frequency as well as acupuncture are effective in reducing hyperalgesia in chronic muscle pain model.

  2. Chronic vitamin C administration induces thermal hyperalgesia in ...

    African Journals Online (AJOL)

    Against a backdrop of neurological effects, the effects of acute and chronic administration of vitamin C (600mg/kg) on pain processing were investigated in male rats. Chronic administration of vitamin C induced significant thermal hyperalgesia while acute administration had no effect. In addition, the intraperitoneal ...

  3. Peripheral Receptor Mechanisms Underlying Orofacial Muscle Pain and Hyperalgesia

    Science.gov (United States)

    Saloman, Jami L.

    Musculoskeletal pain conditions, particularly those associated with temporomandibular joint and muscle disorders (TMD) are severely debilitating and affect approximately 12% of the population. Identifying peripheral nociceptive mechanisms underlying mechanical hyperalgesia, a prominent feature of persistent muscle pain, could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. This study provides evidence of functional interactions between ligand-gated channels, P2X3 and TRPV1/TRPA1, in trigeminal sensory neurons, and proposes that these interactions underlie the development of mechanical hyperalgesia. In the masseter muscle, direct P2X3 activation, via the selective agonist αβmeATP, induced a dose- and time-dependent hyperalgesia. Importantly, the αβmeATP-induced hyperalgesia was prevented by pretreatment of the muscle with a TRPV1 antagonist, AMG9810, or the TRPA1 antagonist, AP18. P2X3 was co-expressed with both TRPV1 and TRPA1 in masseter muscle afferents confirming the possibility for intracellular interactions. Moreover, in a subpopulation of P2X3 /TRPV1 positive neurons, capsaicin-induced Ca2+ transients were significantly potentiated following P2X3 activation. Inhibition of Ca2+-dependent kinases, PKC and CaMKII, prevented P2X3-mechanical hyperalgesia whereas blockade of Ca2+-independent PKA did not. Finally, activation of P2X3 induced phosphorylation of serine, but not threonine, residues in TRPV1 in trigeminal sensory neurons. Significant phosphorylation was observed at 15 minutes, the time point at which behavioral hyperalgesia was prominent. Similar data were obtained regarding another nonselective cation channel, the NMDA receptor (NMDAR). Our data propose P2X3 and NMDARs interact with TRPV1 in a facilitatory manner, which could contribute to the peripheral sensitization underlying masseter hyperalgesia. This study offers novel mechanisms by which individual pro-nociceptive ligand

  4. Immunobiology of visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Susanne eNylén

    2012-08-01

    Full Text Available Visceral leishmaniasis (VL, commonly known as kala-azar, is caused by Leishmania donovani and Leishmania infantum (Leishmania chagasi in the Americas. These Leishmania species infect macrophages throughout the viscera, and parasites are typically found in the spleen, liver and bone marrow. Patients with active disease typically exhibit marked immunosuppression, lack reactivity to the Leishmania skin test (LST, a delayed type hypersensitivity test, and their peripheral blood mononuclear cells (PBMC fail to respond when stimulated with leishmanial antigens in vitro. However, most people infected with visceralizing species of Leishmania never develop disease. Understanding immune failure and the underlying immune mechanism that lead to disease as well as control of infection are key questions for research in this field. In this review we discuss immunological events described in human and experimental VL and how these can affect the outcome of infection.

  5. Serotonin Receptors in Hippocampus

    Science.gov (United States)

    Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

    2012-01-01

    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. PMID:22629209

  6. Mifepristone modulates serotonin transporter function

    OpenAIRE

    Li, Chaokun; Shan, Linlin; Li, Xinjuan; Wei, Linyu; Li, Dongliang

    2014-01-01

    Regulating serotonin expression can be used to treat psychotic depression. Mifepristone, a glucocorticoid receptor antagonist, is an effective candidate for psychotic depression treatment. However, the underlying mechanism related to serotonin transporter expression is poorly understood. In this study, we cloned the human brain serotonin transporter into Xenopus oocytes, to establish an in vitro expression system. Two-electrode voltage clamp recordings were used to detect serotonin transporte...

  7. Pregabalin Suppresses Spinal Neuronal Hyperexcitability and Visceral Hypersensitivity in the Absence of Peripheral Pathophysiology

    Science.gov (United States)

    Bannister, Kirsty; Sikandar, Shafaq; Bauer, Claudia S.; Dolphin, Annette C.; Porreca, Frank; Dickenson, Anthony H.

    2011-01-01

    Background Opioid induced hyperalgesia is recognised in the laboratory and the clinic, generating central hyperexcitability in the absence of peripheral pathology. We investigated pregabalin, indicated for neuropathic pain, and ondansetron, a drug that disrupts descending serotonergic processing in the central nervous system, on spinal neuronal hyperexcitability and visceral hypersensitivity in a rat model of opioid induced hyperalgesia. Methods Sprague-Dawley rats (180-200 g) were implanted with morphine (90μg · μl−1 · hr−1) or saline (0.9% w/v) filled osmotic mini-pumps. On days 7-10 in isoflurane anaesthetized animals we evaluated the effects of (a) systemic pregabalin on spinal neuronal and visceromotor responses and (b) spinal ondansetron on dorsal horn neuronal responses. The messenger RNA levels of α2δ-1, 5HT3A and mu-opioid receptor in the dorsal root ganglia of all animals were analysed. Results In morphine-treated animals the evoked spinal neuronal responses were enhanced to a sub-set of thermal and mechanical stimuli. This activity was attenuated by pregabalin (by at least 71%) and ondansetron (37%), and the visceromotor response to a sub-set of colorectal distension pressures was attenuated by pregabalin (52.8%) (n = 8 for all measures, P pregabalin in opioid induced hyperalgesia animals is not neuropathy-dependent nor reliant on up-regulation of the α2δ-1 subunit of voltage gated calcium channels, mechanisms proposed essential for pregabalin’s efficacy in neuropathy. In opioid induced hyperalgesia, which extends to colonic distension, a serotonergic facilitatory system may be upregulated creating an environment that’s permissive for pregabalin-mediated analgesia without peripheral pathology. PMID:21602662

  8. Does naloxone reinstate secondary hyperalgesia in humans after resolution of a burn injury?

    DEFF Research Database (Denmark)

    Pereira, Manuel P; Werner, Mads U; Ringsted, Thomas K

    2013-01-01

    Development of secondary hyperalgesia following a cutaneous injury is a centrally mediated, robust phenomenon. The pathophysiological role of endogenous opioid signalling to the development of hyperalgesia is unclear. Recent animal studies, carried out after the resolution of inflammatory pain, h......, have demonstrated reinstatement of tactile hypersensitivity following administration of μ-opioid-receptor-antagonists. In the present study in humans, we analyzed the effect of naloxone when given after the resolution of secondary hyperalgesia following a first-degree burn injury....

  9. Visceral leishmaniasis in Brazil

    Directory of Open Access Journals (Sweden)

    Mary Marcondes

    2013-10-01

    Full Text Available Visceral leishmaniasis (VL is among the most important vector-borne diseases that occur in Brazil, mainly due to its zoonotic nature. It is currently present in almost all Brazilian territory, and its control is a challenge both for veterinarians and for public health officials. The etiologic agent is Leishmania infantum (syn chagasi, and the main vector in Brazil is Lutzomyia longipalpis. Of all animals identified as reservoirs of VL, the dog is considered the most important domestic reservoir. Although the disease has already been identified in cats, the epidemiological role of this animal species is still unclear. This article presents a brief review of the epidemiological situation of the disease, its mode of transmission, clinical features in dogs and cats as well as possible risk factors associated with the occurrence of the disease in Brazil.

  10. Serotonin receptor modulators in the treatment of irritable bowel syndrome

    Directory of Open Access Journals (Sweden)

    Mohammad Fayyaz

    2008-03-01

    Full Text Available Mohammad Fayyaz, Jeffrey M LacknerDivision of Gastroenterology, Department of Medicine, University at Buffalo School of Medicine, SUNY, Buffalo, NY, USAAbstract: The aim of this article is to review the pathophysiology and clinical role of serotonin receptor modulators used in the treatment of irritable bowel syndrome. Serotonin is an important monoamine neurotransmitter that plays a key role in the initiation of peristaltic and secretory reflexes, and in modulation of visceral sensations. Several serotonin receptor subtypes have been characterized, of which 5HT3, 5HT4, and 5HT1b are the most important for GI function. 5HT4 agonists (eg, tegaserod potentiate peristalsis initiated by 5HT1 receptor stimulation. 5HT4 agonists are therefore useful in constipation predominant form of IBS and in chronic constipation. 5HT3 antagonists (Alosetron and Cilansetron prevent the activation of 5HT3 receptors on extrinsic afferent neurons and can decrease the visceral pain associated with IBS. These agents also retard small intestinal and colonic transit, and are therefore useful in diarrhea-predominant IBS. Tegaserod has been demonstrated in several randomized, placebo controlled trials to relieve global IBS symptoms as well as individual symptoms of abdominal discomfort, number of bowel movements and stool consistency. Several randomized, controlled trials have shown that alosetron relieves pain, improves bowel function, and provides global symptom improvement in women with diarrhea-predominant irritable bowel syndrome. However, ischemic colitis and severe complications of constipation have been major concerns leading to voluntary withdrawal of Alosetron from the market followed by remarketing with a comprehensive risk management program.Keywords: serotonin, irritable bowel syndrome, tegaserod

  11. Muscle Fatigue Increases the Probability of Developing Hyperalgesia in Mice

    OpenAIRE

    Yokoyama, Takeshi; Lisi, Tammy L.; Moore, Steven A.; Sluka, Kathleen A.

    2007-01-01

    Chronic muscle pain is a major clinical problem that is often associated with fatigue. Conversely, chronic fatigue conditions are commonly associated with muscle pain. We tested the hypothesis that muscle fatigue enhances hyperalgesia associated with injection of acidic saline into muscle. We evaluated mechanical sensitivity of the paw (von Frey) in mice after 2 intramuscular injections of saline (20 µL; pH 4, pH 5, pH 6, pH 7.2) in a fatigue and a control group. To induce fatigue, mice were ...

  12. Generalized deep-tissue hyperalgesia in patients with chronic low-back pain

    DEFF Research Database (Denmark)

    O'Neill, Søren; Manniche, Claus; Graven-Nielsen, Thomas

    2007-01-01

    Some chronic painful conditions including e.g. fibromyalgia, whiplash associated disorders, endometriosis, and irritable bowel syndrome are associated with generalized musculoskeletal hyperalgesia. The aim of the present study was to determine whether generalized deep-tissue hyperalgesia could be...... management regimes....

  13. [Visceral leishmaniasis: an update].

    Science.gov (United States)

    Faucher, B; Piarroux, R

    2011-09-01

    During the last decade, visceral leishmaniasis has been reconsidered in its epidemiology and strategies for diagnosis, treatment and prevention. This vectorial disease, responsible for more than 50,000 deaths each year across India, East Africa, South America, the Mediterranean area, Central Asia and China, is currently spreading over new territories. This formerly rural disease has even reached cities in South America. This spreading is caused by environmental changes due to global warming or human activity, and by the movement of workers and refugees. As a consequence, the burden of HIV/Leishmania coinfection is increasing in many developing countries even though effective antiretroviral therapy has led to a marked decrease in its incidence in Europe. The disease is now handled differently than it was 10 years ago: PCR has become the most accurate tool for diagnosis and follow-up in developed countries, and field diagnostic tools have been developed (antigenuria, rK39 dipstick). While resistance to antimoniate has appeared in India and Europe, new therapies have been evaluated such as miltefosine, the first oral therapy, or short treatment with liposomal amphotericin B. In France, liposomal amphotericin B has supplanted antimoniate meglumine because of better tolerance and shorter hospitalization duration. Protecting dogs through immunization or collars impregnated with deltamethrin proved effective to prevent zoonotic leishmaniasis due to Leishmania infantum. Copyright © 2010 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  14. Anterior herniation of lumbar disc induces persistent visceral pain: discogenic visceral pain: discogenic visceral pain.

    Science.gov (United States)

    Tang, Yuan-Zhang; Shannon, Moore-Langston; Lai, Guang-Hui; Li, Xuan-Ying; Li, Na; Ni, Jia-Xiang

    2013-01-01

    Visceral pain is a common cause for seeking medical attention. Afferent fibers innervating viscera project to the central nervous system via sympathetic nerves. The lumbar sympathetic nerve trunk lies in front of the lumbar spine. Thus, it is possible for patients to suffer visceral pain originating from sympathetic nerve irritation induced by anterior herniation of the lumbar disc. This study aimed to evaluate lumbar discogenic visceral pain and its treatment. Twelve consecutive patients with a median age of 56.4 years were enrolled for investigation between June 2012 and December 2012. These patients suffered from long-term abdominal pain unresponsive to current treatment options. Apart from obvious anterior herniation of the lumbar discs and high signal intensity anterior to the herniated disc on magnetic resonance imaging, no significant pathology was noted on gastroscopy, vascular ultrasound, or abdominal computed tomography (CT). To prove that their visceral pain originated from the anteriorly protruding disc, we evaluated whether pain was relieved by sympathetic block at the level of the anteriorly protruding disc. If the block was effective, CT-guided continuous lumbar sympathetic nerve block was finally performed. All patients were positive for pain relief by sympathetic block. Furthermore, the average Visual Analog Scale of visceral pain significantly improved after treatment in all patients (P herniation of the lumbar disc when forming a differential diagnosis for seemingly idiopathic abdominal pain. Continuous lumbar sympathetic nerve block is an effective and safe therapy for patients with discogenic visceral pain.

  15. Is heat pain detection threshold associated with the area of secondary hyperalgesia following brief thermal sensitization?

    DEFF Research Database (Denmark)

    Hansen, Morten Sejer; Wetterslev, Jørn; Pipper, Christian Bressen

    2016-01-01

    investigates different aspects of the human pain response. Brief thermal sensitization induces a mild burn injury, resulting in development of primary hyperalgesia at the site of stimulation, and secondary hyperalgesia surrounding the site of stimulation. Central sensitization is believed to play an important...... if HPDT, a known quantitative sensory test, is associated with areas of secondary hyperalgesia following brief thermal sensitization TRIAL REGISTRATION: Clinicaltrials.gov (Identifier: NCT02527395 ). Danish Research Ethics Committee (Identifier: H-8-2014-012). Danish Data Protection Agency (Identifier: 30-1436)....... role in the development of secondary hyperalgesia; however, a possible association of secondary hyperalgesia following brief thermal sensitization and other heat pain models remains unknown. Our aim with this study is to investigate how close the heat pain detection threshold is associated...

  16. Heat pain detection threshold is associated with the area of secondary hyperalgesia following brief thermal sensitization

    DEFF Research Database (Denmark)

    Hansen, Morten Sejer; Wetterslev, Jørn; Pipper, Christian Bressen

    2017-01-01

    participants was included and tested on 2 separate study days with BTS (45°C, 3 minutes), HPDT, and pain during thermal stimulation (45°C, 1 minute). Areas of secondary hyperalgesia were quantified after monofilament pinprick stimulation. The pain catastrophizing scale (PCS) and hospital anxiety and depression......INTRODUCTION: The area of secondary hyperalgesia following brief thermal sensitization (BTS) of the skin and heat pain detection thresholds (HPDT) may both have predictive abilities in regards to pain sensitivity and clinical pain states. The association between HPDT and secondary hyperalgesia...... scale (HADS) were also applied. RESULTS: A significant association between HPDT and the size of the area of secondary hyperalgesia (parea of secondary hyperalgesia due to a 1-degree increase in HPDT was estimated to be -27.38 cm(2), 95% confidence interval (CI...

  17. Laparoscopic Cholecystectomy for Gallbladder Calculosis in Fibromyalgia Patients: Impact on Musculoskeletal Pain, Somatic Hyperalgesia and Central Sensitization

    Science.gov (United States)

    Costantini, Raffaele; Affaitati, Giannapia; Massimini, Francesca; Tana, Claudio; Innocenti, Paolo; Giamberardino, Maria Adele

    2016-01-01

    Fibromyalgia, a chronic syndrome of diffuse musculoskeletal pain and somatic hyperalgesia from central sensitization, is very often comorbid with visceral pain conditions. In fibromyalgia patients with gallbladder calculosis, this study assessed the short and long-term impact of laparoscopic cholecystectomy on fibromyalgia pain symptoms. Fibromyalgia pain (VAS scale) and pain thresholds in tender points and control areas (skin, subcutis and muscle) were evaluated 1week before (basis) and 1week, 1,3,6 and 12months after laparoscopic cholecystectomy in fibromyalgia patients with symptomatic calculosis (n = 31) vs calculosis patients without fibromyalgia (n. 26) and at comparable time points in fibromyalgia patients not undergoing cholecystectomy, with symptomatic (n = 27) and asymptomatic (n = 28) calculosis, and no calculosis (n = 30). At basis, fibromyalgia+symptomatic calculosis patients presented a significant linear correlation between the number of previously experienced biliary colics and fibromyalgia pain (direct) and muscle thresholds (inverse)(pfibromyalgia pain significantly increased and all thresholds significantly decreased at 1week and 1month (1-way ANOVA, pFibromyalgia pain and thresholds returned to preoperative values at 3months, then pain significantly decreased and thresholds significantly increased at 6 and 12months (pfibromyalgia patients undergoing cholecystectomy thresholds did not change; in all other fibromyalgia groups not undergoing cholecystectomy fibromyalgia pain and thresholds remained stable, except in fibromyalgia+symptomatic calculosis at 12months when pain significantly increased and muscle thresholds significantly decreased (pfibromyalgia symptoms and that laparoscopic cholecystectomy produces only a transitory worsening of these symptoms, largely compensated by the long-term improvement/desensitization due to gallbladder removal. This study provides new insights into the role of visceral pain comorbidities and the effects of

  18. Laparoscopic Cholecystectomy for Gallbladder Calculosis in Fibromyalgia Patients: Impact on Musculoskeletal Pain, Somatic Hyperalgesia and Central Sensitization.

    Science.gov (United States)

    Costantini, Raffaele; Affaitati, Giannapia; Massimini, Francesca; Tana, Claudio; Innocenti, Paolo; Giamberardino, Maria Adele

    2016-01-01

    Fibromyalgia, a chronic syndrome of diffuse musculoskeletal pain and somatic hyperalgesia from central sensitization, is very often comorbid with visceral pain conditions. In fibromyalgia patients with gallbladder calculosis, this study assessed the short and long-term impact of laparoscopic cholecystectomy on fibromyalgia pain symptoms. Fibromyalgia pain (VAS scale) and pain thresholds in tender points and control areas (skin, subcutis and muscle) were evaluated 1week before (basis) and 1week, 1,3,6 and 12months after laparoscopic cholecystectomy in fibromyalgia patients with symptomatic calculosis (n = 31) vs calculosis patients without fibromyalgia (n. 26) and at comparable time points in fibromyalgia patients not undergoing cholecystectomy, with symptomatic (n = 27) and asymptomatic (n = 28) calculosis, and no calculosis (n = 30). At basis, fibromyalgia+symptomatic calculosis patients presented a significant linear correlation between the number of previously experienced biliary colics and fibromyalgia pain (direct) and muscle thresholds (inverse)(pfibromyalgia pain significantly increased and all thresholds significantly decreased at 1week and 1month (1-way ANOVA, pFibromyalgia pain and thresholds returned to preoperative values at 3months, then pain significantly decreased and thresholds significantly increased at 6 and 12months (pfibromyalgia patients undergoing cholecystectomy thresholds did not change; in all other fibromyalgia groups not undergoing cholecystectomy fibromyalgia pain and thresholds remained stable, except in fibromyalgia+symptomatic calculosis at 12months when pain significantly increased and muscle thresholds significantly decreased (pfibromyalgia symptoms and that laparoscopic cholecystectomy produces only a transitory worsening of these symptoms, largely compensated by the long-term improvement/desensitization due to gallbladder removal. This study provides new insights into the role of visceral pain comorbidities and the effects of

  19. The modulation role of serotonin in Pacific oyster Crassostrea gigas in response to air exposure.

    Science.gov (United States)

    Dong, Wenjing; Liu, Zhaoqun; Qiu, Limei; Wang, Weilin; Song, Xiaorui; Wang, Xiudan; Li, Yiqun; Xin, Lusheng; Wang, Lingling; Song, Linsheng

    2017-03-01

    Serotonin, also known as 5-hydroxytryptamine (5-HT), is a critical neurotransmitter in the neuroendocrine-immune regulatory network and involved in regulation of the stress response in vertebrates and invertebrates. In the present study, serotonin was found to be widely distributed in the tissues of Pacific oyster Crassostrea gigas, including haemolymph, gonad, visceral ganglion, mantle, gill, labial palps and hepatopancreas, and its concentration increased significantly in haemolymph and mantle after the oysters were exposed to air for 1 d. The apoptosis rate of haemocytes was significantly declined after the oysters received an injection of extra serotonin, while the activity of superoxide dismutase (SOD) in haemolymph increased significantly. After the stimulation of serotonin during air exposure, the apoptosis rate of oyster haemocytes and the concentration of H2O2 in haemolymph were significantly decreased, while the SOD activity was significantly elevated. Furthermore, the survival rate of oysters from 4(th) to 6(th) d after injection of serotonin was higher than that of FSSW group and air exposure group. The results clearly indicated that serotonin could modulate apoptotic effect and redox during air exposure to protect oysters from stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Serotonin-Induced Hypersensitivity via Inhibition of Catechol O-Methyltransferase Activity

    Science.gov (United States)

    2012-01-01

    The subcutaneous and systemic injection of serotonin reduces cutaneous and visceral pain thresholds and increases responses to noxious stimuli. Different subtypes of 5-hydroxytryptamine (5-HT) receptors are suggested to be associated with different types of pain responses. Here we show that serotonin also inhibits catechol O-methyltransferase (COMT), an enzyme that contributes to modultion the perception of pain, via non-competitive binding to the site bound by catechol substrates with a binding affinity comparable to the binding affinity of catechol itself (Ki = 44 μM). Using computational modeling, biochemical tests and cellular assays we show that serotonin actively competes with the methyl donor S-adenosyl-L-methionine (SAM) within the catalytic site. Binding of serotonin to the catalytic site inhibits the access of SAM, thus preventing methylation of COMT substrates. The results of in vivo animal studies show that serotonin-induced pain hypersensitivity in mice is reduced by either SAM pretreatment or by the combined administration of selective antagonists for β2- and β3-adrenergic receptors, which have been previously shown to mediate COMT-dependent pain signaling. Our results suggest that inhibition of COMT via serotonin binding contributes to pain hypersensitivity, providing additional strategies for the treatment of clinical pain conditions. PMID:22500608

  1. Serotonin-Induced Hypersensitivity via Inhibition of Catechol O-Methyltransferase Activity

    Directory of Open Access Journals (Sweden)

    Tsao Douglas

    2012-04-01

    Full Text Available Abstract The subcutaneous and systemic injection of serotonin reduces cutaneous and visceral pain thresholds and increases responses to noxious stimuli. Different subtypes of 5-hydroxytryptamine (5-HT receptors are suggested to be associated with different types of pain responses. Here we show that serotonin also inhibits catechol O-methyltransferase (COMT, an enzyme that contributes to modultion the perception of pain, via non-competitive binding to the site bound by catechol substrates with a binding affinity comparable to the binding affinity of catechol itself (Ki = 44 μM. Using computational modeling, biochemical tests and cellular assays we show that serotonin actively competes with the methyl donor S-adenosyl-L-methionine (SAM within the catalytic site. Binding of serotonin to the catalytic site inhibits the access of SAM, thus preventing methylation of COMT substrates. The results of in vivo animal studies show that serotonin-induced pain hypersensitivity in mice is reduced by either SAM pretreatment or by the combined administration of selective antagonists for β2- and β3-adrenergic receptors, which have been previously shown to mediate COMT-dependent pain signaling. Our results suggest that inhibition of COMT via serotonin binding contributes to pain hypersensitivity, providing additional strategies for the treatment of clinical pain conditions.

  2. The Effects of Serotonin in Immune Cells

    OpenAIRE

    Nadine Herr; Christoph Bode; Daniel Duerschmied

    2017-01-01

    Serotonin [5-hydroxytryptamine (5-HT)] plays an important role in many organs as a peripheral hormone. Most of the body’s serotonin is circulating in the bloodstream, transported by blood platelets and is released upon activation. The functions of serotonin are mediated by members of the 7 known mammalian serotonin receptor subtype classes (15 known subtypes), the serotonin transporter (SERT), and by covalent binding of serotonin to different effector proteins. Almost all immune cells express...

  3. Management of chronic visceral pain

    DEFF Research Database (Denmark)

    Olesen, Anne E; Farmer, Adam D; Olesen, Søren S

    2016-01-01

    Despite marked differences in underlying pathophysiology, the current management of visceral pain largely follows the guidelines derived from the somatic pain literature. The effective management of patients with chronic visceral pain should be multifaceted, including both pharmacological...... and psychological interventions, thereby providing a mechanism-orientated approach to treatment. Patients can frequently become disenfranchised, and subsequently disengaged, with healthcare providers leading to repeated consultations. Thus, a key aspect of management is to break this cycle by validating patients......' symptoms, adopting an empathic approach and taking time to educate patients. To optimize treatment and outcomes in chronic visceral pain we need to move away from approaches exclusively based on dealing with peripheral nociceptive input toward more holistic strategies, taking into account alterations...

  4. Differential effects of systemically administered ketamine and lidocaine on dynamic and static hyperalgesia induced by intradermal capsaicin in humans

    DEFF Research Database (Denmark)

    Gottrup, Hanne; Hansen, Peter Orm; Arendt-Nielsen, Lars

    2000-01-01

    were measured: spontaneous pain, pain evoked by punctate and brush stimuli (VAS), and areas of brush-evoked and punctate-evoked hyperalgesia. Ketamine reduced both the area of brush-evoked and punctate-evoked hyperalgesia significantly and it tended to reduce brush-evoked pain. Lidocaine reduced...... the area of punctate-evoked hyperalgesia significantly. It tended to reduce VAS scores of spontaneous pain but had no effect on evoked pain. The differential effects of ketamine and lidocaine on static and dynamic hyperalgesia suggest that the two types of hyperalgesia are mediated by separate mechanisms...

  5. Treatment of visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    E M Moore

    2010-01-01

    Full Text Available The available treatment options for visceral leishmaniasis (VL have problems relating to efficacy, adverse effects and cost, making treatment a complex issue. We review the evidence relating to the different methods of treatment in relation to - efficacy and toxicity of the drugs in different areas of the world; ability to monitor side effects, length of treatment; ability of patients to pay for and stay safe during treatment, ability of the healthcare services to give intramuscular, intravenous or oral therapy; the sex and child-bearing potential of the patient and the immune status of the patient. The high mortality of untreated/ poorly treated VL infection makes the decisions paramount, but a unified and coordinated response by each area is likely to be more effective and informative to future policies than an ad hoc response. For patients in resource-rich countries, liposomal amphotericin B appears to be the optimal treatment. In South Asia, miltefosine is being used; the combination of single dose liposomal amphotericin B and short course miltefosine looks encouraging but has the problem of potential reproductive toxicities in females. In Africa, the evidence to switch from SSG is not yet compelling. The need to monitor and plan for evolving drug failure, secondary to leishmania parasite resistance, is paramount. With a few drugs the options may be limited; however, we await key ongoing trials in both Africa and India to explore the effects of combination treatment. If safe and reliable combinations are revealed by the ongoing studies, it is far from clear as to whether this will avoid leishmania parasite resistance. The development of new drugs to add to the armamentarium is paramount. Lessons can be learnt from the management of diseases such as tuberculosis and malaria in terms of planning the switch to combination treatment. As important as establishing the best choice for specific antileishmanial agent is ensuring treatment centers

  6. Classical conditioning and pain: conditioned analgesia and hyperalgesia.

    Science.gov (United States)

    Miguez, Gonzalo; Laborda, Mario A; Miller, Ralph R

    2014-01-01

    This article reviews situations in which stimuli produce an increase or a decrease in nociceptive responses through basic associative processes and provides an associative account of such changes. Specifically, the literature suggests that cues associated with stress can produce conditioned analgesia or conditioned hyperalgesia, depending on the properties of the conditioned stimulus (e.g., contextual cues and audiovisual cues vs. gustatory and olfactory cues, respectively) and the proprieties of the unconditioned stimulus (e.g., appetitive, aversive, or analgesic, respectively). When such cues are associated with reducers of exogenous pain (e.g., opiates), they typically increase sensitivity to pain. Overall, the evidence concerning conditioned stress-induced analgesia, conditioned hyperalagesia, conditioned tolerance to morphine, and conditioned reduction of morphine analgesia suggests that selective associations between stimuli underlie changes in pain sensitivity. © 2013 Elsevier B.V. All rights reserved.

  7. Ranolazine attenuation of CFA-induced mechanical hyperalgesia.

    Science.gov (United States)

    Casey, Gregory P; Roberts, Jomar S; Paul, Dennis; Diamond, Ivan; Gould, Harry J

    2010-01-01

    To determine whether ranolazine, a new anti-angina medication, could be an effective analgesic agent in complete Freund's adjuvant-induced inflammatory pain. Plantar injection of complete Freund's adjuvant (CFA) produces an extended period of hyperalgesia that is associated with a dramatic up-regulation of Na(v) 1.7 sodium channels in populations of large and small dorsal root ganglion neurons related to the injection site. Ranolazine appears to produce its anti-angina effect through blocking the late sodium current associated with the voltage-gated sodium channel, Na(v) 1.5. Because ranolazine also inhibits Na(v) 1.7, and 1.8, we sought to determine whether it could be an effective analgesic agent in CFA-induced inflammatory pain. Baseline determinations of withdrawal from thermal and mechanical stimulation were made in Sprague-Dawley rats ( approximately 300-350 x g). Following determination of baseline, one hindpaw in each group was injected with 0.1 mL of CFA. The contralateral paw received saline. Thermal and mechanical stimulation was repeated on the third day post-injection. Vehicle (0.9% isotonic saline; pH 3.0) or ranolazine was then administered in randomized and blinded doses either by intraperitoneal (ip) injection (0, 10, 20, and 50 mg/kg) or by oral gavage (po; 0, 20, 50, 100, and 200 mg/kg). Animals were again tested 30 minutes (ip) and 1 hour (po) after drug administration. Ranolazine produced dose-dependant analgesia on mechanical allodynia induced by CFA injection, but had no effect on thermal hyperalgesia. Ranolazine's potential as a new option for managing both angina and chronic inflammatory pain warrants further study.

  8. Gender differences in pain and secondary hyperalgesia after heat/capsaicin sensitization in healthy volunteers

    DEFF Research Database (Denmark)

    Jensen, Magnus Thorsten; Petersen, Karin Lottrup

    2006-01-01

    In most published studies women are more sensitive to experimental pain than men. Enhanced central pain processing in women has been suggested, but psychosocial factors might also have affected the findings. Data from five completed healthy volunteer studies were analyzed to investigate gender...... differences in development of secondary hyperalgesia. Cutaneous hyperalgesia was induced with the heat/capsaicin sensitization model. Outcome measures were areas of secondary hyperalgesia to brush and von Frey hair stimulation after heat and capsaicin sensitization, rating of pain during heat...

  9. Spatial and temporal aspects of muscle hyperalgesia induced by nerve growth factor in humans

    DEFF Research Database (Denmark)

    Andersen, H.; Arendt-Nielsen, L.; Svensson, P.

    2008-01-01

    distribution of muscle hyperalgesia over time (immediately after, 3 h, 1, 4, 7 and 21 days) after injecting NGF (5 mu g) into the tibialis anterior (TA) muscle, to explore possibly involved central pain mechanisms and to investigate the effect of gender on development of hyperalgesia. Totally 20 healthy...... 1. Hypertonic saline evoked more pain in men when injected in the NGF treated TA compared to the control leg. Injection of NGF increased muscle soreness during muscle activity for 7 days. In this material there was no gender effect of NGF-induced muscle hyperalgesia. The expansion of muscle...

  10. The selective serotonin reuptake inhibitor fluoxetine does not change rectal sensitivity and symptoms in patients with irritable bowel syndrome: a double blind, randomized, placebo-controlled study

    NARCIS (Netherlands)

    Kuiken, Sjoerd D.; Tytgat, Guido N. J.; Boeckxstaens, Guy E. E.

    2003-01-01

    BACKGROUND & AIMS: Although widely prescribed, the evidence for the use of antidepressants for the treatment of irritable bowel syndrome (IBS) is limited. In this study, we hypothesized that fluoxetine (Prozac), a selective serotonin reuptake inhibitor, has visceral analgesic properties, leading to

  11. Visceral leishmaniasis: an update of laboratory diagnosis

    Directory of Open Access Journals (Sweden)

    Zineb Tlamcani

    2016-07-01

    Full Text Available Visceral leishmaniasis, is an infection due to obligate intracellular protozoa of the genus Leishmania. There exist two varieties of visceral leishmaniasis, that vary in their transmission aspects: zoonotic visceral leishmaniasis and anthroponotic visceral leishmaniasis. Their clinical features are comparable with sevral differences. Laboratory diagnosis of visceral leishmaniasis consists of microscopic observation of parasite, culture from appropriate samples, detection of antigen, serological tests, and identification of parasite DNA. In this review, we will discuss the different techniques of diagnosis and the interet of the recent methods such as rapid diagnostic test and direct agglutination test.

  12. NMDA receptor mediates chronic visceral pain induced by neonatal noxious somatic stimulation.

    Science.gov (United States)

    Miranda, Adrian; Mickle, Aaron; Bruckert, Mitchell; Kannampalli, Pradeep; Banerjee, Banani; Sengupta, Jyoti N

    2014-12-05

    NMDA receptors (NMDAR) are important in the development and maintenance of central sensitization. Our objective was to investigate the role of spinal neurons and NMDAR in the maintenance of chronic visceral pain. Neonatal rats were injected with acidic saline adjusted to pH 4.0 in the gastrocnemius muscle every other day for 12 days. In adult rats, NR1 and NR2B subunits were examined in the lumbo-sacral (LS) spinal cord. A baseline, visceromotor response (VMR) to graded colorectal distension (CRD) was recorded before and after administration of the NMDA antagonist, CGS-19755. Extracellular recordings were performed from CRD-sensitive LS spinal neurons and pelvic nerve afferents (PNA) before and after CGS-19755. Rats that received pH 4.0 saline injections demonstrated a significant increase in the expression NR2B subunits and VMR response to CRD>20 mmHg. CGS-19755 (i.v. or i.t.) had no effect in naïve rats, but significantly decreased the response to CRD in pH 4.0 saline injected rats. CGS-19755 had no effect on the spontaneous firing of SL-A, but decreased that of SL-S. Similarly, CGS-19755 attenuates the responses of SL-S neurons to CRD, but had no effect on SL-A neurons or on the response characteristics of PNA fibers. Neonatal noxious somatic stimulation results in chronic visceral hyperalgesia and sensitizes a specific subpopulation of CRD-sensitive spinal neurons. The sensitization of these SL-S spinal neurons is attenuated by the NMDAR antagonist. The results of this study suggest that spinal NMDARs play an important role in the development of hyperalgesia early in life. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Sciatic nerve block with bupivacaine-loaded microspheres prevents hyperalgesia in an inflammatory animal model

    National Research Council Canada - National Science Library

    Estèbe, Jean-Pierre; Gentili, Marc E; Le Corre, Pascal; Le Verge, Roger; Moulinoux, Jacques-Philippe; Ecoffey, Claude

    2002-01-01

    ... model.Inflammation was obtained by injection of carrageenan in the righ hind paw. Hyperalgesia was determined by measuring the threshold of response to increasing mechanical stimuli on the contralateral and on the ipsilateral paw...

  14. Learning by experience? Visceral pain-related neural and behavioral responses in a classical conditioning paradigm.

    Science.gov (United States)

    Icenhour, A; Labrenz, F; Ritter, C; Theysohn, N; Forsting, M; Bingel, U; Elsenbruch, S

    2017-06-01

    Studies investigating mechanisms underlying nocebo responses in pain have mainly focused on negative expectations induced by verbal suggestions. Herein, we addressed neural and behavioral correlates of nocebo responses induced by classical conditioning in a visceral pain model. In two independent studies, a total of 40 healthy volunteers underwent classical conditioning, consisting of repeated pairings of one visual cue (CS High ) with rectal distensions of high intensity, while a second cue (CS Low ) was always followed by low-intensity distensions. During subsequent test, only low-intensity distensions were delivered, preceded by either CS High or CS Low . Distension intensity ratings were assessed in both samples and functional magnetic resonance imaging data were available from one study (N=16). As a consequence of conditioning, we hypothesized CS High -cued distensions to be perceived as more intense and expected enhanced cue- and distension-related neural responses in regions encoding sensory and affective dimensions of pain and in structures associated with pain-related fear memory. During test, distension intensity ratings did not differ depending on preceding cue. Greater distension-induced neural activation was observed in somatosensory, prefrontal, and cingulate cortices and caudate when preceded by CS High . Analysis of cue-related responses revealed strikingly similar activation patterns. We report changes in neural activation patterns during anticipation and visceral stimulation induced by prior conditioning. In the absence of behavioral effects, markedly altered neural responses may indicate conditioning with visceral signals to induce hypervigilance rather than hyperalgesia, involving altered attention, reappraisal, and perceptual acuity as processes contributing to the pathophysiology of visceral pain. © 2017 John Wiley & Sons Ltd.

  15. Inflammation mobilizes local resources to control hyperalgesia: the role of endogenous opioid peptides.

    Science.gov (United States)

    Alves, Daniela P; da Motta, Patrícia G; Lima, Patrícia P; Queiroz-Junior, Celso M; Caliari, Marcelo V; Pacheco, Daniela F; Pacheco, Cinthia F; Francischi, Janetti N; Duarte, Igor D G

    2012-01-01

    The aim of the present study was to investigate the mechanisms underlying the endogenous control of nociception at a peripheral level during inflammation. Using a pharmacological approach and the rat paw pressure test, we assessed the effect of an intraplantar injection of naloxone, an opioid receptor antagonist, and bestatin, an aminopeptidase inhibitor, on hyperalgesia induced by carrageenan, which mimics an inflammatory process, or prostaglandin E(2) (PGE(2)), which directly sensitizes nociceptors. Naloxone induced a significant and dose-dependent (25, 50 or 100 μg) increase in carrageenan-induced hyperalgesia, but not PGE(2)-induced hyperalgesia. Bestatin (400 μg/paw) significantly counteracted carrageenan-induced hyperalgesia, inducing an increase in the nociceptive threshold compared to control, but it did not modify hyperalgesia induced by PGE(2) injection into the rat paw. Positive β-endorphin immunoreactivity was increased in paw inflammation induced by carrageenan in comparison with the control group. However, PGE(2) did not significantly alter the immunostained area. These results provide evidence for activation of the endogenous opioidergic system during inflammation and indicate that this system regulates hyperalgesia through a negative feedback mechanism, modulating it at a peripheral level. Copyright © 2012 S. Karger AG, Basel.

  16. Modulation of musculoskeletal hyperalgesia by brown adipose tissue activity in mice.

    Science.gov (United States)

    Goudie-DeAngelis, Elizabeth M; Abdelhamid, Ramy E; Nunez, Myra G; Kissel, Casey L; Kovács, Katalin J; Portoghese, Philip S; Larson, Alice A

    2016-11-01

    Cold exposure and a variety of types of mild stress increase pain in patients with painful disorders such as fibromyalgia syndrome. Acutely, stress induces thermogenesis by increasing sympathetic activation of beta-3 (β3) adrenergic receptors in brown adipose tissue. Chronic stress leads to the hypertrophy of brown adipose, a phenomenon termed adaptive thermogenesis. Based on the innervation of skeletal muscle by collaterals of nerves projecting to brown adipose, we theorized an association between brown adipose tissue activity and musculoskeletal hyperalgesia and tested this hypothesis in mice. Exposure to a cold swim or injection of BRL37344 (β3 adrenergic agonist) each enhanced musculoskeletal hyperalgesia, as indicated by morphine-sensitive decreases in grip force responses, whereas SR59230A (β3 adrenergic antagonist) attenuated swim-induced hyperalgesia. Chemical ablation of interscapular brown adipose, using Rose Bengal, attenuated the development of hyperalgesia in response to either swim stress or BRL37344. In addition, elimination of the gene expressing uncoupling protein-1 (UCP1), the enzyme responsible for thermogenesis, prevented musculoskeletal hyperalgesia in response to either a swim or BRL37344, as documented in UCP1-knockout (UCP1-KO) mice compared with wild-type controls. Together, these data provide a convergence of evidence suggesting that activation of brown adipose contributes to stress-induced musculoskeletal hyperalgesia.

  17. Multiple Visceral and Peritoneal Anomalies

    Directory of Open Access Journals (Sweden)

    Gayathri Prabhu S

    2016-07-01

    Full Text Available Visceral and peritoneal anomalies are frequently encountered during cadaveric dissections and surgical procedures of abdomen. A thorough knowledge of the same is required for the success of diagnostic, surgical and radiological procedures of abdomen. We report multiple peritoneal and visceral anomalies noted during dissection classes for medical undergraduates. The anomalies were found in an adult male cadaver aged approximately 70 years. The right iliac fossa was empty due to the sub-hepatic position of caecum and appendix. The sigmoid colon formed an inverted “U” shaped loop above the sacral promontory in the median position. It entered the pelvis from the right side and descended along the lateral wall of the pelvis. The sigmoid mesocolon was attached obliquely to the posterior abdominal wall, just above the sacral promontory. Further there was a cysto-colic fold of peritoneum extending from the right colic flexure. We discuss the clinical significance of the variations.

  18. Epigenetic Mechanisms of Serotonin Signaling.

    Science.gov (United States)

    Holloway, Terrell; González-Maeso, Javier

    2015-07-15

    Histone modifications and DNA methylation represent central dynamic and reversible processes that regulate gene expression and contribute to cellular phenotypes. These epigenetic marks have been shown to play fundamental roles in a diverse set of signaling and behavioral outcomes. Serotonin is a monoamine that regulates numerous physiological responses including those in the central nervous system. The cardinal signal transduction mechanisms via serotonin and its receptors are well established, but fundamental questions regarding complex interactions between the serotonin system and heritable epigenetic modifications that exert control on gene function remain a topic of intense research and debate. This review focuses on recent advances and contributions to our understanding of epigenetic mechanisms of serotonin receptor-dependent signaling, with focus on psychiatric disorders such as schizophrenia and depression.

  19. Serotonin, inhibition, and negative mood

    National Research Council Canada - National Science Library

    Dayan, Peter; Huys, Quentin J M

    2008-01-01

    .... There is considerable evidence for the involvement of serotonin in both the learning of these predictions and the inhibitory consequences that ensue, although less for a causal relationship between the two...

  20. Selective Serotonin Reuptake Inhibitors (SSRIs)

    Science.gov (United States)

    ... Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects. http://www.uptodate.com/home. Accessed June 2, 2016. Mental health medications. National Institute of Mental Health. http://www. ...

  1. SOMATIC PAIN OF VISCERAL ORIGIN

    Science.gov (United States)

    Reggars, John W.

    1994-01-01

    It is not uncommon, within general practice, for patients to present with somatic or musculoskeletal pain of visceral origin. Furthermore patients may present with two separate and co-existing conditions within the same anatomical region making the clinical diagnosis confusing and complex. The following case study describes one such case which presented to a chiropractor. A discussion of examination findings, diagnostic dilemmas in such cases, differential diagnoses considered, diagnostic tests and appropriate therapy are discussed.

  2. Chronic Monosodium Glutamate Administration Induced Hyperalgesia in Mice

    Directory of Open Access Journals (Sweden)

    Anca Zanfirescu

    2017-12-01

    Full Text Available Monosodium glutamate (MSG is a widely used food additive. Although it is generally considered safe, some questions regarding the impact of its use on general health have arisen. Several reports correlate MSG consumption with a series of unwanted reactions, including headaches and mechanical sensitivity in pericranial muscles. Endogenous glutamate plays a significant role in nociceptive processing, this neurotransmitter being associated with hyperalgesia and central sensitization. One of the mechanisms underlying these phenomena is the stimulation of Ca2+/calmodulin sensitive nitric oxide synthase, and a subsequent increase in nitric oxide production. This molecule is a key player in nociceptive processing, with implications in acute and chronic pain states. Our purpose was to investigate the effect of this food additive on the nociceptive threshold when given orally to mice. Hot-plate and formalin tests were used to assess nociceptive behaviour. We also tried to determine if a correlation between chronic administration of MSG and variations in central nitric oxide (NO concentration could be established. We found that a dose of 300 mg/kg MSG given for 21 days reduces the pain threshold and is associated with a significant increase in brain NO level. The implications of these findings on food additive-drug interaction, and on pain perception in healthy humans, as well as in those suffering from affections involving chronic pain, are still to be investigated.

  3. Experimental forearm immobilization in humans induces cold and mechanical hyperalgesia.

    Science.gov (United States)

    Terkelsen, Astrid J; Bach, Flemming W; Jensen, Troels S

    2008-08-01

    Complex regional pain syndrome is a painful condition of unknown etiology. Clinical and experimental observations suggest that limb immobilization may induce symptoms and signs characteristic of complex regional pain syndrome. This study examined the effect of forearm immobilization on regional sensory and autonomic functions in healthy subjects. Thermal and mechanical sensitivity, skin temperature, and vasoconstrictor responses were measured in 30 healthy subjects before and 0, 3, and 28 days after scaphoid cast immobilization. Fifteen subjects served as nonimmobilized controls. At cast removal, 27 subjects experienced pain at joint movement. Cast immobilization induced cold hyperalgesia in glabrous and hairy skin on the immobilized hand and induced significant skin temperature differences between the control and the immobilized hand at cast removal and after 3 days. Immobilization also reduced pain threshold at skin fold testing at all time points after cast removal. All measures except pain threshold at skin fold testing were normalized after 28 days. Immobilization did not affect thermal detection, heat pain, and pressure pain thresholds; resting skin perfusion; or vasoconstrictor responses induced by mental stress or deep inspirations. Four weeks of forearm immobilization caused transient changes in skin temperature, mechanosensitivity, and thermosensitivity, without alteration in the sympathetically mediated vascular tone.

  4. The serotonin reuptake inhibitor citalopram does not affect colonic sensitivity or compliance in rats.

    Science.gov (United States)

    Käll, Erika; Lindström, Erik; Martinez, Vicente

    2007-09-10

    Altered serotonin signaling has been implicated in the pathophysiology of irritable bowel syndrome (IBS). Selective serotonin reuptake inhibitors (SSRI) improve IBS symptoms, although the mechanism of action remains unclear. We assessed the effects of the SSRI, citalopram, on colonic sensitivity and compliance in rats after acute and repeated administration. Colorectal distension was performed in conscious rats. Pressure-volume relationships during colorectal distension (2-20 mmHg), fitted using a power exponential model [Vol=V(max)xexp[-(kappaxRelP)(beta)], were used as a measure of colonic compliance. The visceral pain-related visceromotor response during colorectal distension (10-80 mmHg) was used to assess visceral sensitivity. Pressure-volume curves and visceromotor responses were assessed after acute citalopram (3 or 10 mg/kg, ip) or vehicle and after repeated treatment (7 and 14 days; 3 or 10 mg/kg/day). In vehicle-treated animals, pressure-volume curves were similar over time. Citalopram (acute or repeated treatment) did not affect neither the pressure-volume curves nor the visceromotor response to colorectal distension. Thus, citalopram, after acute or repeated administration, had no significant effects on colon compliance or visceral pain during colorectal distension in rats. These results agree with recent observations in humans suggesting that the therapeutic actions of citalopram in IBS are independent of any effects on colonic sensorimotor function.

  5. Immunity and immunosuppression in experimental visceral leishmaniasis

    OpenAIRE

    Goto H; Lindoso J.A.L.

    2004-01-01

    Leishmaniasis is a disease caused by protozoa of the genus Leishmania, and visceral leishmaniasis is a form in which the inner organs are affected. Since knowledge about immunity in experimental visceral leishmaniasis is poor, we present here a review on immunity and immunosuppression in experimental visceral leishmaniasis in mouse and hamster models. We show the complexity of the mechanisms involved and differences when compared with the cutaneous form of leishmaniasis. Resistance in viscera...

  6. The role of PAF/PAFR signaling in zymosan-induced articular inflammatory hyperalgesia.

    Science.gov (United States)

    Guerrero, Ana T; Zarpelon, Ana C; Zaperlon, Ana C; Vieira, Silvio M; Pinto, Larissa G; Ferreira, Sérgio H; Cunha, Fernando Q; Verri, Waldiceu A; Cunha, Thiago M

    2013-01-01

    Platelet-activating factor (PAF) and its receptor (PAFR) have been shown to be involved in several inflammatory events, including neutrophil chemoattraction and nociception. The present study addressed the role of PAF in the genesis of articular hyperalgesia in a model of joint inflammation. Zymosan-induced articular hyperalgesia, oedema and neutrophil migration were dose-dependently reduced following pretreatment with selective PAFR antagonists, UK74505 (5, 10 and 20 mg/kg) and PCA4248 (3, 10, 30 mg/kg). These parameters were also reduced in PAF receptor-deficient mice (PAFR(-/-)). The hyperalgesic action of PAF was further confirmed by the demonstration that joint injection of PAF induces a dose- (0.3, 1 and 3 μg/joint), time- and PAFR-dependent articular hyperalgesia and oedema. The PAF hyperalgesic mechanisms were dependent on prostaglandins, leukotrienes and neutrophils, as PAF-induced articular hyperalgesia was inhibited by indomethacin (COX inhibitor), MK886 (leukotrienes synthesis inhibitor) or fucoidan (leukocyte rolling inhibitor). Furthermore, PAF-induced hyperalgesia was reduced in 5-lypoxigenase-null mice. In corroboration of these findings, intra-articular injection of PAF promotes the production of LTB(4) as well as the recruitment of neutrophils to the joint. These results suggest that PAF may participate in the cascade of events involved in the genesis of articular inflammatory hyperalgesia via stimulation of prostaglandins, leukotrienes and neutrophil migration. Finally, targeting PAF action (e.g., with a PAFR antagonist) might provide a useful therapeutic approach to inhibit articular inflammatory hyperalgesia.

  7. Pathophysiology of human visceral obesity: an update

    National Research Council Canada - National Science Library

    Tchernof, André; Després, Jean-Pierre

    2013-01-01

    Excess intra-abdominal adipose tissue accumulation, often termed visceral obesity, is part of a phenotype including dysfunctional subcutaneous adipose tissue expansion and ectopic triglyceride storage...

  8. Laparoscopic Cholecystectomy for Gallbladder Calculosis in Fibromyalgia Patients: Impact on Musculoskeletal Pain, Somatic Hyperalgesia and Central Sensitization.

    Directory of Open Access Journals (Sweden)

    Raffaele Costantini

    Full Text Available Fibromyalgia, a chronic syndrome of diffuse musculoskeletal pain and somatic hyperalgesia from central sensitization, is very often comorbid with visceral pain conditions. In fibromyalgia patients with gallbladder calculosis, this study assessed the short and long-term impact of laparoscopic cholecystectomy on fibromyalgia pain symptoms. Fibromyalgia pain (VAS scale and pain thresholds in tender points and control areas (skin, subcutis and muscle were evaluated 1week before (basis and 1week, 1,3,6 and 12months after laparoscopic cholecystectomy in fibromyalgia patients with symptomatic calculosis (n = 31 vs calculosis patients without fibromyalgia (n. 26 and at comparable time points in fibromyalgia patients not undergoing cholecystectomy, with symptomatic (n = 27 and asymptomatic (n = 28 calculosis, and no calculosis (n = 30. At basis, fibromyalgia+symptomatic calculosis patients presented a significant linear correlation between the number of previously experienced biliary colics and fibromyalgia pain (direct and muscle thresholds (inverse(p<0.0001. After cholecystectomy, fibromyalgia pain significantly increased and all thresholds significantly decreased at 1week and 1month (1-way ANOVA, p<0.01-p<0.001, the decrease in muscle thresholds correlating linearly with the peak postoperative pain at surgery site (p<0.003-p<0.0001. Fibromyalgia pain and thresholds returned to preoperative values at 3months, then pain significantly decreased and thresholds significantly increased at 6 and 12months (p<0.05-p<0.0001. Over the same 12-month period: in non-fibromyalgia patients undergoing cholecystectomy thresholds did not change; in all other fibromyalgia groups not undergoing cholecystectomy fibromyalgia pain and thresholds remained stable, except in fibromyalgia+symptomatic calculosis at 12months when pain significantly increased and muscle thresholds significantly decreased (p<0.05-p<0.0001. The results of the study show that biliary colics from

  9. Therapeutic options for visceral leishmaniasis.

    Science.gov (United States)

    Monge-Maillo, Begoña; López-Vélez, Rogelio

    2013-11-01

    Visceral leishmaniasis (VL), also known as Kala-Azar, is a disseminated protozoal infection caused principally by Leishmania donovani and Leishmania infantum (known as Leishmania chagasi in South America). The therapeutic options for VL are diverse and depend on different factors, such as the geographical area of the infection, development of resistance to habitual treatments, HIV co-infection, malnourishment and other concomitant infections. This article provides an exhaustive review of the literature regarding studies published on the treatment of VL, and gives therapeutic recommendations stratified according to their level of evidence, the species of Leishmania implicated and the geographical location of the infection.

  10. Deletion of the serotonin transporter in rats disturbs serotonin homeostasis without impairing liver regeneration

    NARCIS (Netherlands)

    Matondo, R.B.; Punt, C.; Homberg, J.R.; Toussaint, M.J.; Kisjes, R.; Korporaal, S.J.; Akkerman, J.W.; Cuppen, E.; de Bruin, A.

    2009-01-01

    The serotonin transporter is implicated in the uptake of the vasoconstrictor serotonin from the circulation into the platelets, where 95% of all blood serotonin is stored and released in response to vascular injury. In vivo studies indicated that platelet-derived serotonin mediates liver

  11. Deletion of the serotonin transporter in rats disturbs serotonin homeostasis without impairing liver regeneration.

    NARCIS (Netherlands)

    Matondo, R.B.; Punt, C.; Homberg, J.R.; Toussaint, M.J.; Kisjes, R.; Korporaal, S.J.; Akkerman, J.W.; Cuppen, E.; Bruin, A. de

    2009-01-01

    The serotonin transporter is implicated in the uptake of the vasoconstrictor serotonin from the circulation into the platelets, where 95% of all blood serotonin is stored and released in response to vascular injury. In vivo studies indicated that platelet-derived serotonin mediates liver

  12. Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

    Science.gov (United States)

    ... Effexor XR) ― also approved to treat anxiety and panic disorder All SNRIs work in a similar way ... such as aspirin or warfarin (Coumadin, Jantoven). Serotonin syndrome. Rarely, serotonin syndrome can occur when you take ...

  13. Pathophysiology of stress-induced visceral hypersensitivity

    NARCIS (Netherlands)

    Stanisor, O.I.

    2014-01-01

    Visceral hypersensitivity is observed in the majority of patients with IBS and considered a pathophysiological mechanism. The aim of the work described in this thesis was to obtain a better understanding of the stress-related pathophysiology of visceral hypersensitivity. Investigations were carried

  14. Molecular diagnosis of visceral herpes zoster

    NARCIS (Netherlands)

    de Jong, M. D.; Weel, J. F.; van Oers, M. H.; Boom, R.; Wertheim-van Dillen, P. M.

    2001-01-01

    Patients with disseminated herpes zoster may present with severe abdominal pain that results from visceral involvement of varicella-zoster-virus infection. In the absence of cutaneous eruptions of herpes zoster, visceral herpes zoster is extremely difficult to diagnose. This diagnostic difficulty

  15. Blood platelet serotonin following enterectomy in rats.

    Science.gov (United States)

    Osim, E E; Wyllie, J H

    1991-01-01

    The role of the intestine as a source of platelet serotonin was investigated. Radioactive serotonin precursor. 5-Hydroxytryptophan was injected into enterectomised and sham-operated rats. Blood samples were taken at time intervals and serotonin uptake was estimated by radioactive counting. Soon (1-2 hrs) after surgery and under sodium pentobarbital anaesthesia, platelet 5HT activity was higher in enterectomised rats than in controls. The intestine may not be the major source of platelet serotonin.

  16. Secondary hyperalgesia phenotypes exhibit differences in brain activation during noxious stimulation

    DEFF Research Database (Denmark)

    Asghar, Mohammad Sohail; Pereira, Manuel Pedro; Werner, Mads Utke

    2015-01-01

    . To study differences in the propensity to develop central sensitization we examined differences in brain activity and anatomy according to individual phenotypical expression of secondary hyperalgesia by magnetic resonance imaging. Forty healthy volunteers received a first-degree burn-injury (47 °C, 7 min...... to central neuronal sensitization. Some individuals develop large areas of secondary hyperalgesia (high-sensitization responders), while others develop small areas (low-sensitization responders). The magnitude of each area is reproducible within individuals, and can be regarded as a phenotypic characteristic...... hyperalgesia areas after burn-injury. In addition, T1-weighted images were used to measure differences in gray-matter density in cortical and subcortical regions of the brain. We found significant differences in neuronal activity between high- and low-sensitization responders at baseline (before application...

  17. Effect of sympathetic nerve block on acute inflammatory pain and hyperalgesia

    DEFF Research Database (Denmark)

    Pedersen, J L; Rung, G W; Kehlet, H

    1997-01-01

    BACKGROUND: Sympathetic nerve blocks relieve pain in certain chronic pain states, but the role of the sympathetic pathways in acute pain is unclear. Thus the authors wanted to determine whether a sympathetic block could reduce acute pain and hyperalgesia after a heat injury in healthy volunteers....... acute inflammatory pain or hyperalgesia after a heat injury in human skin.......BACKGROUND: Sympathetic nerve blocks relieve pain in certain chronic pain states, but the role of the sympathetic pathways in acute pain is unclear. Thus the authors wanted to determine whether a sympathetic block could reduce acute pain and hyperalgesia after a heat injury in healthy volunteers....... The duration and quality of blocks were evaluated by the sympatogalvanic skin response and skin temperature. Bilateral heat injuries were produced on the medial surfaces of the calves with a 50 x 25 mm thermode (47 degrees C, 7 min) 45 min after the blocks. Pain intensity induced by heat, pain thresholds...

  18. Is the Volume of the Caudate Nuclei Associated With Area of Secondary Hyperalgesia?

    DEFF Research Database (Denmark)

    Hansen, Morten Sejer; Asghar, Mohammad Sohail; Wetterslev, Jørn

    2016-01-01

    volunteers with differences in size of the area of secondary hyperalgesia following a standardized burn injury. OBJECTIVE: We aim to investigate the degree of association between the volume of pain-relevant structures in the brain and the size of the area of secondary hyperalgesia following brief thermal...... sensitization. METHODS: The study consists of one experimental day, in which whole-brain magnetic resonance imaging (MRI) scans will be conducted including T1-weighed three-dimensional anatomy scan, diffusion tensor imaging, and resting state functional MRI. Before the experimental day, all included......: The association between the volume of pain-relevant structures in the brain and the area of secondary hyperalgesia will be investigated by linear regression of the estimated best linear unbiased predictors on the individual volumes of the pain relevant brain structures. CONCLUSIONS: We plan to investigate...

  19. Thermal hyperalgesia and light touch allodynia after intradermal Mycobacterium butyricum administration in rat.

    Science.gov (United States)

    Arévalo, Maria Isabel; Escribano, Elvira; Calpena, Ana; Domenech, Josep; Queralt, Josep

    2003-10-01

    We examined the time course (7 weeks) of thermal hyperalgesia and light touch allodynia in rats after intradermal administration of Mycobacterium butyricum. Nociceptive thresholds to heat and light touch were assessed. Paw edema and temperature, motor function, body weight, and propioception were also tested. Some rats developed arthritis (named AA rats) but others did not (named non-AA rats). Both groups were compared with healthy animals. Persistent hyperalgesia was found in both groups; in AA rats it appeared before clinical evidence of arthritis. Transient allodynia ocurred only after edema development and fell when edema decreased. Motor function was impaired only in AA rats. The results of this study demonstrate that hyperalgesia, but not allodynia, appeared after Mycobacterium butyricum in both groups, suggesting that changes in sensitivity were not merely the result of local hypersensitivity of the inflamed tissue, but may also be due to alterations in nociception in the central nervous system.

  20. Drug Resistance in Visceral Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Helena C. Maltezou

    2010-01-01

    Full Text Available Visceral leishmaniasis remains a public health problem worldwide. This illness was included by the World Health Organization in the list of neglected tropical diseases targeted for elimination by 2015. The widespread emergence of resistance to pentavalent antimonials in India where half cases occur globally and the unavailability of a vaccine in clinical use constitute major obstacles in achieving this goal. The last decade new antileishmanials became available, including the oral agent miltefosine. However, in poor endemic countries their wide use was curtailed because of the high costs, and also due to concerns of toxicity and emergence of resistance. Various mechanisms of antileishmanial resistance were identified recently in field isolates. Their elucidation will boost the design of new drugs and the molecular surveillance of resistance. Combination regimens should be evaluated in large trials. Overall, the development of antileishmanials has been generally slow; new drugs are needed. In order to control visceral leishmaniasis worldwide, treatment advances should become affordable in the poorest countries, where they are needed most.

  1. [Visceral leishmaniasis. Pediatric case report].

    Science.gov (United States)

    Gomila H, Andrés; Vanzo, Carolina; Garnero, Analía; Peruzzo, Luisina; Badalotti, Mónica

    2017-08-01

    La leishmaniasis es una enfermedad causada por parásitos obligados intracelulares pertenecientes al género Leishmania y que reconoce tres formas clínicas principales: cutánea, visceral y mucocutánea. Es una patología del grupo de las "enfermedades desatendidas". Es la única enfermedad tropical transmitida a través de vectores que se ha mantenido endémica por décadas en el sur de Europa. La leishmaniasis visceral representa la forma más grave. Se caracteriza por fiebre, pérdida de peso, anemia y hepatoesplenomegalia. Su período de incubación oscila entre 2 semanas y 18 meses. La leishmaniasis se considera una enfermedad reemergente a nivel mundial. Algunos de los factores que favorecen esta situación son los cambios en las condiciones climáticas, migraciones y urbanizaciones deficitarias en saneamiento ambiental. Se presenta el caso de un niño europeo que estaba vacacionando en Córdoba y fue derivado a nuestro Hospital por fiebre y pancitopenia, lo que generó un abordaje multidisciplinario con resolución clínica favorable. Sociedad Argentina de Pediatría.

  2. Sphingosine 1-phosphate mediates hyperalgesia via a neutrophil-dependent mechanism.

    Directory of Open Access Journals (Sweden)

    Amanda Finley

    Full Text Available Novel classes of pain-relieving molecules are needed to fill the void between non-steroidal anti-inflammatory agents and narcotics. We have recently shown that intraplantar administration of sphingosine 1-phosphate (S1P in rats causes peripheral sensitization and hyperalgesia through the S1P(1 receptor subtype (S1PR(1: the mechanism(s involved are largely unknown and were thus explored in the present study. Intraplantar injection of carrageenan in rats led to a time-dependent development of thermal hyperalgesia that was associated with pronounced edema and infiltration of neutrophils in paw tissues. Inhibition of 1 S1P formation with SK-I, a sphingosine kinase inhibitor, 2 S1P bioavailability with the S1P blocking antibody Sphingomab, LT1002 (but not its negative control, LT1017 or 3 S1P actions through S1PR(1 with the selective S1PR(1 antagonist, W146 (but not its inactive enantiomer, W140 blocked thermal hyperalgesia and infiltration of neutrophils. Taken together, these findings identify S1P as an important contributor to inflammatory pain acting through S1PR(1 to elicit hyperalgesia in a neutrophil-dependant manner. In addition and in further support, we demonstrate that the development of thermal hyperalgesia following intraplantar injection of S1P or SEW2871 (an S1PR(1 agonist was also associated with neutrophilic infiltration in paw tissues as these events were attenuated by fucoidan, an inhibitor of neutrophilic infiltration. Importantly, FTY720, an FDA-approved S1P receptor modulator known to block S1P-S1PR(1 signaling, attenuated carrageenan-induced thermal hyperalgesia and associated neutrophil infiltration. Targeting the S1P/S1PR(1 axis opens a therapeutic strategy for the development of novel non-narcotic anti-hyperalgesic agents.

  3. SR 141716A, a cannabinoid receptor antagonist, produces hyperalgesia in untreated mice.

    Science.gov (United States)

    Richardson, J D; Aanonsen, L; Hargreaves, K M

    1997-01-29

    Antinociceptive effects of cannabinoids are well documented. However, the physiological role of endogenous cannabinoids in nociception is unknown. We evaluated the effects of the cannabinoid receptor antagonist SR 141716A (N-piperidino-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-3-pyrazolecarboxamide) on mouse hot plate latencies. Intrathecal injection of SR 141716A evoked a significant thermal hyperalgesia. These results suggest that the cannabinoid system tonically regulates thermal nociceptive thresholds. Furthermore, the absence of this regulation results in hyperalgesia suggesting that hypoactivity of this system may be involved in certain types of chronic pain.

  4. Pharmacokinetic/Pharmacodynamic Relationship of Gabapentin in a CFA-induced Inflammatory Hyperalgesia Rat Model

    DEFF Research Database (Denmark)

    Larsen, Malte Selch; Keizer, Ron; Munro, Gordon

    2016-01-01

    PURPOSE: Gabapentin displays non-linear drug disposition, which complicates dosing for optimal therapeutic effect. Thus, the current study was performed to elucidate the pharmacokinetic/pharmacodynamic (PKPD) relationship of gabapentin's effect on mechanical hypersensitivity in a rat model of CFA......-induced inflammatory hyperalgesia. METHODS: A semi-mechanistic population-based PKPD model was developed using nonlinear mixed-effects modelling, based on gabapentin plasma and brain extracellular fluid (ECF) time-concentration data and measurements of CFA-evoked mechanical hyperalgesia following administration...

  5. Pharmacogenetic workup of perioperative serotonin syndrome.

    Science.gov (United States)

    Beatty, Nicole C; Nicholson, Wayne T; Langman, Loralie J; Curry, Timothy B; Eisenach, John H

    2013-12-01

    Serotonin syndrome is gaining attention in perioperative and chronic pain settings due to the growing prevalence of multimodal therapies that increase serotonin levels and thereby heighten patient risk. A patient's genetic make-up may further increase the risk of serotonin syndrome. A case of serotonin syndrome on emergence after general anesthesia is presented. A subsequent cytochrome P4502D6 genetic test result suggested a potential alteration in metabolism. For this patient, who was taking combination antidepressant medications and receiving common perioperative medicines, additive pharmacodynamic effects converged with a pharmacogenetic predisposition, resulting in serotonin syndrome. © 2013 Elsevier Inc. All rights reserved.

  6. Serotonin and Blood Pressure Regulation

    Science.gov (United States)

    Morrison, Shaun F.; Davis, Robert Patrick; Barman, Susan M.

    2012-01-01

    5-Hydroxytryptamine (5-HT; serotonin) was discovered more than 60 years ago as a substance isolated from blood. The neural effects of 5-HT have been well investigated and understood, thanks in part to the pharmacological tools available to dissect the serotonergic system and the development of the frequently prescribed selective serotonin-reuptake inhibitors. By contrast, our understanding of the role of 5-HT in the control and modification of blood pressure pales in comparison. Here we focus on the role of 5-HT in systemic blood pressure control. This review provides an in-depth study of the function and pharmacology of 5-HT in those tissues that can modify blood pressure (blood, vasculature, heart, adrenal gland, kidney, brain), with a focus on the autonomic nervous system that includes mechanisms of action and pharmacology of 5-HT within each system. We compare the change in blood pressure produced in different species by short- and long-term administration of 5-HT or selective serotonin receptor agonists. To further our understanding of the mechanisms through which 5-HT modifies blood pressure, we also describe the blood pressure effects of commonly used drugs that modify the actions of 5-HT. The pharmacology and physiological actions of 5-HT in modifying blood pressure are important, given its involvement in circulatory shock, orthostatic hypotension, serotonin syndrome and hypertension. PMID:22407614

  7. ROLE OF SEROTONIN IN FISH REPRODUCTION

    Directory of Open Access Journals (Sweden)

    Parvathy ePrasad

    2015-06-01

    Full Text Available The neuroendocrine mechanism regulates reproduction through the hypothalamo-pituitary-gonadal (HPG axis which is evolutionarily conserved in vertebrates. The HPG axis is regulated by a variety of internal as well as external factors. Serotonin, a monoamine neurotransmitter, is involved in a wide range of reproductive functions. In mammals, serotonin regulates sexual behaviours, gonadotropin release and gonadotropin-release hormone (GnRH secretion. However, the serotonin system in teleost may play unique role in the control of reproduction as the mechanism of reproductive control in teleosts is not always the same as in the mammalian models. In fish, the serotonin system is also regulated by natural environmental factors as well as chemical substances. In particular, selective serotonin reuptake inhibitors (SSRIs are commonly detected as pharmaceutical contaminants in the natural environment. Those factors may influence fish reproductive functions via the serotonin system. This review summarizes the functional significance of serotonin in the teleosts reproduction.

  8. [A case report of visceral leishmaniasis].

    Science.gov (United States)

    Popov, G; Andreeva, N; Georgiev, A; Kuzmanova, E

    1991-01-01

    A brief review of the spread of visceral leishmaniasis in Bulgaria and data about the disease are presented. A case of probably nonautochtonous form of visceral leishmaniasis is described. The clinical evolution of the disease is followed up and the large number of examinations which were carried out for the etiological diagnosis are presented. The diagnosis is based on the characteristic clinical symptoms, epidemiological history, positive serologic tests but with a negative myelogram. The diagnosis was proved ex juvantibus by the antimony treatment and the full recovery of the patient. This is the first case of visceral leishmaniasis in the 40 year history of the hospital.

  9. ASICs Do Not Play a Role in Maintaining Hyperalgesia Induced by Repeated Intramuscular Acid Injections

    Directory of Open Access Journals (Sweden)

    Mamta Gautam

    2012-01-01

    Full Text Available Repeated intramuscular acid injections produce long-lasting mechanical hyperalgesia that depends on activation of ASICs. The present study investigated if pH-activated currents in sensory neurons innervating muscle were altered in response to repeated acid injections, and if blockade of ASICs reverses existing hyperalgesia. In muscle sensory neurons, the mean acid-evoked current amplitudes and the biophysical properties of the ASIC-like currents were unchanged following acidic saline injections when compared to neutral pH saline injections or uninjected controls. Moreover, increased mechanical sensitivity of the muscle and paw after the second acid injection was unaffected by local blockade of ASICs (A-317567 in the muscle. As a control, electron microscopic analysis showed that the tibial nerve was undamaged after acid injections. Our previous studies demonstrated that ASICs are important in the development of hyperalgesia to repeated acid injections. However, the current data suggest that ASICs are not involved in maintaining hyperalgesia to repeated intramuscular acid injections.

  10. Hyperalgesia and temporal summation of pain after heat injury in man

    DEFF Research Database (Denmark)

    Pedersen, J L; Andersen, O K; Arendt-Nielsen, L

    1998-01-01

    Temporal summation of pain occurs when repeated stimuli become increasingly painful in spite of unchanged stimulus intensity. Summation can be quantified as the difference in pain between the first and the last stimulus in a train of stimuli. The aim of the study was to compare temporal summation...... and pain intensity during the induction of heat injury. We conclude that the development of primary and secondary mechanical hyperalgesia after heat injury in man was not associated with changes in temporal summation of painful electrical stimuli....... of pain in normal skin with summation of pain in skin with primary and secondary hyperalgesia evoked by a heat injury. A heat injury was produced on the crus of 12 volunteers with a 50 x 25 mm thermode (47 degrees C, 7 min). Measurements were made before, and 0, 1, 2, and 4 h after the heat injury......, in three areas: primary and secondary mechanical hyperalgesia induced by the heat injury, and in a mirror image of the injury on the opposite leg. Temporal summation of pain was induced by repeated electrical stimuli (five stimuli at 2 Hz) and assessed by visual analog scale (VAS). Primary hyperalgesia...

  11. Activated spinal astrocytes are involved in the maintenance of chronic widespread mechanical hyperalgesia after cast immobilization

    Science.gov (United States)

    2014-01-01

    Background In the present study, we examined spinal glial cell activation as a central nervous system mechanism of widespread mechanical hyperalgesia in rats that experienced chronic post-cast pain (CPCP) 2 weeks after cast immobilization. Activated spinal microglia and astrocytes were investigated immunohistologically in lumbar and coccygeal spinal cord segments 1 day, 5 weeks, and 13 weeks following cast removal. Results In the lumbar cord, astrocytes were activated after microglia. Astrocytes also were activated after microglia in the coccygeal cord, but with a delay that was longer than that observed in the lumbar cord. This activation pattern paralleled the observation that mechanical hyperalgesia occurred in the hindleg or the hindpaw before the tail. The activating transcription factor 3 (ATF3) immune response in dorsal root ganglia (DRG) on the last day of cast immobilization suggested that nerve damage might not occur in CPCP rats. The neural activation assessed by the phosphorylated extracellular signal-regulated kinase (pERK) immune response in DRG arose 1 day after cast removal. In addition, L-α-aminoadipate (L-α-AA), an inhibitor of astrocyte activation administered intrathecally 5 weeks after cast removal, inhibited mechanical hyperalgesia in several body parts including the lower leg skin and muscles bilaterally, hindpaws, and tail. Conclusions These findings suggest that activation of lumbar cord astrocytes is an important factor in widespread mechanical hyperalgesia in CPCP. PMID:24456903

  12. Is development of hyperalgesia, allodynia and myoclonus related to morphine metabolism during long-term administration?

    DEFF Research Database (Denmark)

    Sjøgren, P; Thunedborg, L P; Christrup, Lona Louring

    1998-01-01

    Recently, clinical reports have suggested a relationship between the occurrence of hyperalgesia, allodynia and/or myoclonus and treatment with high doses of morphine in humans. Although few clinical descriptions of these phenomena are available, experimental work supports the notion that high dos...

  13. Evaluation of antivenoms in the neutralization of hyperalgesia and edema induced by Bothrops jararaca and Bothrops asper snake venoms

    Directory of Open Access Journals (Sweden)

    Picolo G.

    2002-01-01

    Full Text Available Neutralization of hyperalgesia induced by Bothrops jararaca and B. asper venoms was studied in rats using bothropic antivenom produced at Instituto Butantan (AVIB, 1 ml neutralizes 5 mg B. jararaca venom and polyvalent antivenom produced at Instituto Clodomiro Picado (AVCP, 1 ml neutralizes 2.5 mg B. aspar venom. The intraplantar injection of B. jararaca and B. asper venoms caused hyperalgesia, which peaked 1 and 2 h after injection, respectively. Both venoms also induced edema with a similar time course. When neutralization assays involving the independent injection of venom and antivenom were performed, the hyperalgesia induced by B. jararaca venom was neutralized only when bothropic antivenom was administered iv 15 min before venom injection, whereas edema was neutralized when antivenom was injected 15 min or immediately before venom injection. On the other hand, polyvalent antivenom did not interfere with hyperalgesia or edema induced by B. asper venom, even when administered prior to envenomation. The lack of neutralization of hyperalgesia and edema induced by B. asper venom is not attributable to the absence of neutralizing antibodies in the antivenom, since neutralization was achieved in assays involving preincubation of venom and antivenom. Cross-neutralization of AVCP or AVIB against B. jararaca and B. asper venoms, respectively, was also evaluated. Only bothropic antivenom partially neutralized hyperalgesia induced by B. asper venom in preincubation experiments. The present data suggest that hyperalgesia and edema induced by Bothrops venoms are poorly neutralized by commercial antivenoms even when antibodies are administered immediately after envenomation.

  14. Visceral leishmaniasis complicating systemic lupus erythematosus

    OpenAIRE

    Wallis, P. J. W.; Clark, C. J. M.

    1983-01-01

    Active systemic lupus erythematosus in a 32-year-old Chinese woman was successfully controlled by plasmapheresis and steroids. However, occult visceral leishmaniasis was uncovered during therapy and responded to appropriate treatment.

  15. The endogenous hydrogen sulfide producing enzyme cystathionine-β synthase contributes to visceral hypersensitivity in a rat model of irritable bowel syndrome

    Directory of Open Access Journals (Sweden)

    Chen Jiande DZ

    2009-08-01

    Full Text Available Abstract Background The pathogenesis of visceral hypersensitivity, a characteristic pathophysiological feature of irritable bowel syndrome (IBS, remains elusive. Recent studies suggest a role for hydrogen sulfide (H2S in pain signaling but this has not been well studied in visceral models of hyperalgesia. We therefore determined the role for the endogenous H2S producing enzyme cystathionine-β-synthetase (CBS in a validated rat model of IBS-like chronic visceral hyperalgesia (CVH. CVH was induced by colonic injection of 0.5% acetic acid (AA in 10-day-old rats and experiments were performed at 8–10 weeks of age. Dorsal root ganglion (DRG neurons innervating the colon were labeled by injection of DiI (1,1'-dioleyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate into the colon wall. Results In rat DRG, CBS-immunoreactivity was observed in approximately 85% of predominantly small- and medium-sized neurons. Colon specific DRG neurons revealed by retrograde labeling DiI were all CBS-positive. CBS-positive colon neurons co-expressed TRPV1 or P2X3 receptors. Western blotting analysis showed that CBS expression was significantly increased in colon DRGs 8 weeks after neonatal AA-treatment. Furthermore, the CBS inhibitor hydroxylamine markedly attenuated the abdominal withdrawal reflex scores in response to colorectal distention in rats with CVH. By contrast, the H2S donor NaHS significantly enhanced the frequency of action potentials of colon specific DRG neurons evoked by 2 times rheobase electrical stimulation. Conclusion Our results suggest that upregulation of CBS expression in colonic DRG neurons and H2S signaling may play an important role in developing CVH, thus identifying a specific neurobiological target for the treatment of CVH in functional bowel syndromes.

  16. Traumatic Stress Promotes Hyperalgesia via Corticotropin-Releasing Factor-1 Receptor (CRFR1) Signaling in Central Amygdala.

    Science.gov (United States)

    Itoga, Christy A; Roltsch Hellard, Emily A; Whitaker, Annie M; Lu, Yi-Ling; Schreiber, Allyson L; Baynes, Brittni B; Baiamonte, Brandon A; Richardson, Heather N; Gilpin, Nicholas W

    2016-09-01

    Hyperalgesia is an exaggerated response to noxious stimuli produced by peripheral or central plasticity. Stress modifies nociception, and humans with post-traumatic stress disorder (PTSD) exhibit co-morbid chronic pain and amygdala dysregulation. Predator odor stress produces hyperalgesia in rodents. Systemic blockade of corticotropin-releasing factor (CRF) type 1 receptors (CRFR1s) reduces stress-induced thermal hyperalgesia. We hypothesized that CRF-CRFR1 signaling in central amygdala (CeA) mediates stress-induced hyperalgesia in rats with high stress reactivity. Adult male Wistar rats were exposed to predator odor stress in a conditioned place avoidance paradigm and indexed for high (Avoiders) and low (Non-Avoiders) avoidance of predator odor-paired context, or were unstressed Controls. Rats were tested for the latency to withdraw hindpaws from thermal stimuli (Hargreaves test). We used pharmacological, molecular, and immunohistochemical techniques to assess the role of CRF-CRFR1 signaling in CeA in stress-induced hyperalgesia. Avoiders exhibited higher CRF peptide levels in CeA that did not appear to be locally synthesized. Intra-CeA CRF infusion mimicked stress-induced hyperalgesia. Avoiders exhibited thermal hyperalgesia that was reversed by systemic or intra-CeA injection of a CRFR1 antagonist. Finally, intra-CeA infusion of tetrodotoxin produced thermal hyperalgesia in unstressed rats and blocked the anti-hyperalgesic effect of systemic CRFR1 antagonist in stressed rats. These data suggest that rats with high stress reactivity exhibit hyperalgesia that is mediated by CRF-CRFR1 signaling in CeA.

  17. Mechanisms of Stress-induced Visceral Pain

    OpenAIRE

    Greenwood-Van Meerveld, Beverley; Johnson, Anthony C

    2018-01-01

    Evidence suggests that long-term stress facilitates visceral pain through sensitization of pain pathways and promotes chronic visceral pain disorders such as the irritable bowel syndrome (IBS). This review will describe the importance of stress in exacerbating IBS-induced abdominal pain. Additionally, we will briefly review our understanding of the activation of the hypothalamic-pituitary-adrenal axis by both chronic adult stress and following early life stress in the pathogenesis of IBS. The...

  18. Characterization of migraineurs presenting interictal widespread pressure hyperalgesia identified using a tender point count: a cross-sectional study.

    Science.gov (United States)

    Toriyama, Toshihide; Horiuchi, Tetsuyoshi; Hongo, Kazuhiro

    2017-12-28

    Migraineurs exhibit pain hypersensitivity throughout the body during and between migraine headaches. Migraine is classified as a central sensitivity syndrome, typified by fibromyalgia showing widespread pressure hyperalgesia determined by a tender point. This study was performed to examine whether: 1) there is a subgroup of episodic migraineurs with widespread pressure hyperalgesia during and between attacks; 2) if such a subgroup exists, what is the prevalence and what is the difference between groups with interictal widespread hyperalgesia and acute allodynia regarding the demographic and clinical characteristics of migraine. This was a cross-sectional study. A total of 176 consecutive episodic migraineurs and 132 age- and sex-matched controls were recruited. The presence of widespread pressure hyperalgesia was investigated using manual tender point survey. To classify a subject's response as widespread pressure hyperalgesia, the cutoff value for responders was defined as the positive tender point count below which 95% of controls responded. Based on the number of positive tender points in controls, the cutoff value of tender point count for pressure hyperalgesia responders was 7. Of the 176 subjects, interictal widespread pressure hyperalgesia and acute allodynia were observed in 74 (42%) and 115 (65.3%) patients, respectively. Univariate analysis indicated that risk factors associated with interictal widespread pressure hyperalgesia were female gender, younger age at migraine onset, higher frequency of migraine attacks, severe headache impact, cutaneous allodynia and depression. Multivariate logistic regression analysis confirmed that independent risk factors associated with interictal widespread pressure hyperalgesia were female gender, higher frequency of migraine attack and younger age at onset. Interictal widespread pressure hyperalgesia was common (42%) in the episodic migraineurs and was associated with younger age at onset, female gender, and higher

  19. Serotonin in fear conditioning processes.

    Science.gov (United States)

    Bauer, Elizabeth P

    2015-01-15

    This review describes the latest developments in our understanding of how the serotonergic system modulates Pavlovian fear conditioning, fear expression and fear extinction. These different phases of classical fear conditioning involve coordinated interactions between the extended amygdala, hippocampus and prefrontal cortices. Here, I first define the different stages of learning involved in cued and context fear conditioning and describe the neural circuits underlying these processes. The serotonergic system can be manipulated by administering serotonin receptor agonists and antagonists, as well as selective serotonin reuptake inhibitors (SSRIs), and these can have significant effects on emotional learning and memory. Moreover, variations in serotonergic genes can influence fear conditioning and extinction processes, and can underlie differential responses to pharmacological manipulations. This research has considerable translational significance as imbalances in the serotonergic system have been linked to anxiety and depression, while abnormalities in the mechanisms of conditioned fear contribute to anxiety disorders. Copyright © 2014. Published by Elsevier B.V.

  20. Visceral sensitivity perturbation integration in the brain-gut axis in functional digestive disorders.

    Science.gov (United States)

    Bonaz, B

    2003-12-01

    Chronic abdominal pain is the most distressing symptom in patients with functional digestive disorders (FDD). IBS is the most common gastrointestinal disorder seen in primary care and gastroenterology practice. IBS is a functional bowel disorder in which abdominal pain is associated with defaecation or a change in bowel habit, with features of disordered defecation and with distension. The underlying pathophysiology of IBS is unknown but a chronic visceral hyperalgesia, in the absence of detectable organic disease, is implicated. The exact location of abnormality of visceral pain processing is not known. Theories of its etiology have range widely from the original view that the disease represents a primary disturbance of gut mucosa to emerging conception of the syndrome as emanating from a complex disordered interaction between the digestive and nervous systems. Several lines of evidence suggest a strong modulatory or etiologic role of the central nervous system in the pathophysiology of IBS. A major advance in the understanding of the central mechanisms of pain processing has evolved from application of functional imaging techniques, as represented by positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). In humans, multiple components are involved in somato-visceral pain processings, including sensory-discriminative components, affective components, and cognitive components. Silverman et al, using PET, were the first to explore neural correlates of abdominal pain induced by rectal distension. If healthy subjects activated the ACC, the IBS patients did not while they presented an activation of the left PFC. These findings were consistent with an IBS model that includes both the exaggerated activation of a vigilance network (dorsolateral PFC) and a failure in pain inhibition network anterior cingulate cortex (ACC). In contrast, Mertz et al., using fMRI, observed that pain led to a greater activation of the ACC than did non

  1. SEROTONIN METABOLISM FOLLOWING PLATINUM-BASED CHEMOTHERAPY COMBINED WITH THE SEROTONIN TYPE-3 ANTAGONIST TROPISETRON

    NARCIS (Netherlands)

    SCHRODER, CP; VANDERGRAAF, WTA; KEMA, IP; GROENEWEGEN, A; SLEIJFER, DT; DEVRIES, EGE

    1995-01-01

    The administration of platinum-based chemotherapy induces serotonin release from the enterochromaffin cells, causing nausea and vomiting. This study was conducted to evaluate parameters of serotonin metabolism following platinum-based chemotherapy given in combination with the serotonin type-3

  2. Interleukin-10 limits intense acute swimming-induced muscle mechanical hyperalgesia in mice.

    Science.gov (United States)

    Borghi, Sergio M; Pinho-Ribeiro, Felipe A; Zarpelon, Ana C; Cunha, Thiago M; Alves-Filho, Jose C; Ferreira, Sergio H; Cunha, Fernando Q; Casagrande, Rubia; Verri, Waldiceu A

    2015-04-20

    What is the central question of this study? This study investigated the role of the endogenous anti-inflammatory cytokine interleukin-10 in intense acute swimming-induced muscle mechanical hyperalgesia in mice. What is the main finding and its importance? Endogenous interleukin-10 has a key role in limiting exercise-induced muscle pain in a model presenting similarities to delayed-onset muscle soreness in mice. Interleukin-10 reduced muscle pain by diminishing leucocyte recruitment, hyperalgesic cytokine production, oxidative stress and myocyte damage. Interleukin-10 (IL-10) is an antihyperalgesic cytokine. In this study, IL-10-deficient (IL-10(-/-) ) mice were used to investigate the role of endogenous IL-10 in intense acute swimming-induced muscle mechanical hyperalgesia, which presents similarities with delayed-onset muscle soreness. An intense acute swimming session of 1 or 2 h induced significant muscle mechanical hyperalgesia in a time-dependent manner in wild-type mice compared with the sham group 24 h after the session, which was further increased in IL-10(-/-) mice (P ˂ 0.05). Intraperitoneal treatment of wild-type mice with IL-10 (1-10 ng) reduced muscle mechanical hyperalgesia in a dose-dependent manner and reversed the enhanced muscle hyperalgesia in IL-10(-/-) mice (P ˂ 0.05). The 2 h swimming session induced increases in tumour necrosis factor-α, interleukin-1β and IL-10 production in the soleus muscle. However, tumour necrosis factor-α and interleukin-1β production in the soleus muscle were even higher in IL-10(-/-) mice between 2 and 6 h after the stimulus (P ˂ 0.05). There was no statistical difference in the levels of the antihyperalgesic cytokines interleukin-4, interleukin-5, interleukin-13 and transforming growth factor-β between wild-type and IL-10(-/-) mice (P ˃ 0.05). Interleukin-10 deficiency also resulted in increased myeloperoxidase activity, greater depletion of reduced glutathione levels, increased superoxide anion

  3. Role of voltage gated Ca2+ channels in rat visceral hypersensitivity change induced by 2,4,6-trinitrobenzene sulfonic acid.

    Science.gov (United States)

    Qian, Aihua; Song, Dandan; Li, Yong; Liu, Xinqiu; Tang, Dong; Yao, Weiyan; Yuan, Yaozong

    2013-03-28

    Visceral pain is common symptom involved in many gastrointestinal disorders such as inflammatory bowel disease. The underlying molecular mechanisms remain elusive. We investigated the molecular mechanisms and the role for voltage gated calcium channel (VGCC) in the pathogenesis in a rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced visceral inflammatory hypersensitivity. Using Agilent cDNA arrays, we found 172 genes changed significantly in dorsal root ganglia (DRG) of TNBS treated rats. Among these changed genes, Cav1.2 and Cav2.3 were significantly up-regulated. Then the RT-PCR and Western blot further confirmed the up-regulation of Cav1.2 and Cav2.3. The whole cell patch clamp recording of acutely dissociated colonic specific DRG neurons showed that the peak IBa density was significantly increased in colonic neurons of TNBS treated rats compared with control rats (-127.82 ± 20.82 pA/pF Vs -91.67 ± 19.02 pA/pF, n = 9, *P type of calcium currents with the corresponding selective channel blockers, we found that L-type (-38.56 ± 3.97 pA/pF Vs -25.75 ± 3.35 pA/pF, n = 9, * P type (-13.31 ± 1.36 pA/pF Vs -8.60 ± 1.25 pA/pF, n = 9, * P type antagonist (nimodipine) and R-type antagonist (SNX-482) with intrathecal injection attenuates visceral pain in TNBS induced inflammatory visceral hypersensitivity. Cav1.2 and Cav2.3 in colonic primary sensory neurons play an important role in visceral inflammatory hyperalgesia, which maybe the potential therapeutic targets.

  4. Endogenous tumor necrosis factor alpha (TNFalpha) requires TNF receptor type 2 to generate heat hyperalgesia in a mouse cancer model

    National Research Council Canada - National Science Library

    Constantin, Cristina E; Mair, Norbert; Sailer, Claudia A; Andratsch, Manfred; Xu, Zhen-Zhong; Blumer, Michael J F; Scherbakov, Nadja; Davis, John B; Bluethmann, Horst; Ji, Ru-Rong; Kress, Michaela

    2008-01-01

    To provide a tool to investigate the mechanisms inducing and maintaining cancer-related pain and hyperalgesia, a soft tissue tumor/metastasis model was developed that is applicable in C57BL/6J wild...

  5. Increased capsaicin-induced secondary hyperalgesia as a marker of abnormal sensory activity in patients with fibromyalgia.

    Science.gov (United States)

    Morris, V; Cruwys, S; Kidd, B

    1998-07-10

    In this study, capsaicin-induced secondary hyperalgesia was assessed as a marker of abnormal nociceptive processing in patients with fibromyalgia (FM). The area of mechanical secondary hyperalgesia induced by a standard solution of capsaicin placed on the volar forearm was measured in ten patients with FM and the results compared to those obtained in ten patients with rheumatoid arthritis (RA) and ten normal subjects. The area of secondary hyperalgesia was found to be substantially increased in both the FM and RA groups compared with controls. In the FM group the area of hyperalgesia correlated with the overall pain score and with the joint tenderness score. The results suggest that in FM there is enhanced sensitivity of nociceptive neurones at a spinal level, thereby supporting the concept of a generalised disturbance of pain modulation in this disorder.

  6. Effects of different electroacupuncture scheduling regimens on murine bone tumor-induced hyperalgesia: sex differences and role of inflammation

    National Research Council Canada - National Science Library

    Smeester, Branden A; Al-Gizawiy, Mona; Beitz, Alvin J

    2012-01-01

    ... about the analgesic effects and potential sex differences of different EA treatment regimens. In the present study, we examined the effects of five different EA treatments on tumor-induced hyperalgesia in male and female mice...

  7. Effects of Different Electroacupuncture Scheduling Regimens on Murine Bone Tumor-Induced Hyperalgesia: Sex Differences and Role of Inflammation

    National Research Council Canada - National Science Library

    Smeester, Branden A; Al-Gizawiy, Mona; Beitz, Alvin J

    2012-01-01

    ... about the analgesic effects and potential sex differences of different EA treatment regimens. In the present study, we examined the effects of five different EA treatments on tumor-induced hyperalgesia in male and female mice...

  8. Visceral Adiposity and Sarcopenic Visceral Obesity are Associated with Poor Prognosis After Resection of Pancreatic Cancer.

    Science.gov (United States)

    Okumura, Shinya; Kaido, Toshimi; Hamaguchi, Yuhei; Kobayashi, Atsushi; Shirai, Hisaya; Yao, Siyuan; Yagi, Shintaro; Kamo, Naoko; Hatano, Etsuro; Okajima, Hideaki; Takaori, Kyoichi; Uemoto, Shinji

    2017-11-01

    Visceral fat accumulation and muscle depletion have been identified as poor prognostic factors for various cancers. However, the significance of visceral adiposity and sarcopenic visceral obesity on outcomes after resection of pancreatic cancer remains unclear. A retrospective analysis of 301 patients who underwent resection for localized pancreatic cancer between 2004 and 2015 was performed. The extent of visceral adiposity [visceral to subcutaneous adipose tissue area ratio (VSR)] and visceral obesity [visceral fat area (VFA)] were measured on preoperative computed tomography images, together with skeletal muscle index (SMI) and muscle attenuation (MA). The impacts of these body composition parameters on outcomes after pancreatic resection were investigated. The overall survival (OS) and recurrence-free survival (RFS) rates in patients with high VSR were significantly lower than those in patients with low VSR (P = 0.001, P = 0.007, respectively). There were no differences in OS and RFS between high VFA and low VFA group; however, when analyzed together with sarcopenic factors, OS and RFS rates of the patients with sarcopenic visceral obesity were significantly lower compared with those of the others. Multivariate analyses revealed that high VSR was an independent risk factor for mortality (hazard ratio (HR) 1.58, P = 0.009) and recurrence (HR 1.41, P = 0.026) together with low SMI, low MA, high CA19-9, microvascular invasion, and nodal metastasis. Visceral adiposity and sarcopenic visceral obesity, as well as low muscle mass and quality, were closely associated with mortality and recurrence after resection of pancreatic cancer.

  9. Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sojin; Jin, Zhenhua; Lee, Goeun [Department of Physiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Park, Yong Seek; Park, Cheung-Seog [Department of Microbiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Jin, Young-Ho, E-mail: jinyh@khu.ac.kr [Department of Physiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of)

    2015-01-02

    Highlights: • Prostaglandin E2 (PGE{sub 2}) effect was tested on visceral afferent neurons. • PGE{sub 2} did not evoke response but potentiated serotonin (5-HT) currents up to 167%. • PGE{sub 2}-induced potentiation was blocked by E-prostanoid type 4 receptors antagonist. • PGE{sub 2} effect on 5-HT response was also blocked by protein kinase A inhibitor KT5720. • Thus, PGE{sub 2} modulate visceral afferent neurons via synergistic signaling with 5-HT. - Abstract: Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E{sub 2} (PGE{sub 2}) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE{sub 2} induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE{sub 2} effect on visceral afferent sensory neurons of the rat. Interestingly, PGE{sub 2} itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE{sub 2}-induced potentiation were blocked by a selective E-prostanoid type4 (EP{sub 4}) receptors antagonist, L-161,982, but type1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE{sub 2} effects. PGE{sub 2} induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE{sub 2} potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal prostaglandin

  10. [Sleep, emotions and the visceral control].

    Science.gov (United States)

    Pigarev, I N; Pigareva, M L

    2013-01-01

    It is known that sleep is connected with sensory isolation of the brain, inactivation of the consciousness and reorganization of the electrical activity in all cerebral cortical areas. On the other hand, sleep deprivation leads to pathology in visceral organs and finally to the death of animals, while there are no obvious changes in the brain itself. It stays the opened question how the changes in the brain activity during sleep could be con- nected with the visceral health? We proposed that the same brain areas and the same neurons, which in wakefulness process the information coming from the distant and proprioreceptors, switch during sleep to the processing of the interoceptive information. Thus, central nervous system is involved into the regulation of the life support functions of the body during sleep. Results of our experiments supported this hypothesis, explained many observations obtained in somnology and offered the mechanisms of several pathological states connected with sleep. However, at the present level of the visceral sleep theory there were no understanding of the well known link between the emotional states of the organisms and transition from wakefulness to sleep, and sleep quality. In this study the attempt is undertaken to combine the visceral theory of sleep with the need- informational theory ofemotions, proposed by P. Simonov. The visceral theory of sleep proposes that in living organisms there is a constant monitoring of the correspondence of the visceral parameters to the genetically determined values. Mismatch signals evoke the feeling of tiredness and the need of sleep. This sleep need en- ters the competition with the other actual needs of the organism. In according with the theory of P. Simonov emotions connected with a particular need play important role in their ranking for satisfaction. We propose that emotional estimation of the sleep need, based on the visceral signals, is realized in the same brain structures which undertake this

  11. [Treatment of visceral leishmaniasis in children].

    Science.gov (United States)

    Minodier, P; Noël, G; Blanc, P; Uters, M; Retornaz, K; Garnier, J M

    2007-02-01

    Visceral Leishmania infantum leishmaniasis is endemic in the south of France. For many years the mainstay for treatment of infected children was pentavalent antimony: meglumine antimoniate (Glucantime) or sodium stibogluconate (Pentostam). However these drugs are poorly tolerated and resistance similar to that observed in the treatment of Indian visceral Leishmania donovani leishmaniasis has been reported. Currently liposomal amphotericin B is being used instead of antimony for treatment of visceral leishmaniasis in children in France. In addition to being well tolerated, liposomal amphotericin B is almost 100% effective. It can be administered in six intravenous injections of 3-4 mg/kg each (days 1 to 5 then day 10). A two-day protocol (10 mg/kg/d) that would reduce overall cost by shortening the duration of hospitalization is now being studied. Another oral drug, i.e., miltefosine, has been successfully used for treatment of visceral leishmaniasis in India. However it has not been evaluated for treatment of Mediterranean visceral leishmaniasis.

  12. Correlation between Complicated Diverticulitis and Visceral Fat

    Science.gov (United States)

    Jeong, Jong Heon; Kim, Jin Ok; Tae, Hye Jin; Jung, Suk Hyun; Lee, Kang Nyeong; Jun, Dae Won; Lee, Oh Young; Yoon, Byung Chul; Choi, Ho Soon; Hahm, Joon Soo; Song, Soon Young

    2011-01-01

    The aim of this study was to examine the relationship of complications related to diverticulitis and visceral obesity. The study was based on a retrospective case note review conducted at the Hanyang University Hospital. Patients were diagnosed with diverticulitis based on clinical symptoms and abdominal computed tomography (CT) findings and divided into two groups: those admitted with complicated diverticulitis and those with a simple diverticulitis episode. We compared the body mass index (BMI) and degree of visceral obesity, measured by abdominal CT. The study included 140 patients, 87 (62.1%) were simple diverticulitis and 53 (37.9%) were complicated diverticulitis. In the complicated diverticulitis group, 9 (6.4%) cases were recurrent, 29 (20.7%) were perforation or abscess patients, and 28 (20%) were patients with systemic inflammatory response syndrome (SIRS). Of the SIRS patients, 13 were involved in other complication groups. When comparing in the two groups, the complicated diverticulitis group had a significantly higher visceral fat area (128.57 cm2 vs 102.80 cm2, P = 0.032) and a higher ratio of visceral fat area/subcutaneous fat area (0.997 vs 0.799, P = 0.014). Visceral obesity is significantly associated with complications of diverticulitis. PMID:22022188

  13. Vaccines for visceral leishmaniasis: A review.

    Science.gov (United States)

    Jain, Keerti; Jain, N K

    2015-07-01

    Visceral leishmaniasis, which is also known as Kala-Azar, is one of the most severely neglected tropical diseases recognized by the World Health Organization (WHO). The threat of this debilitating disease continues due to unavailability of promising drug therapy or human vaccine. An extensive research is undergoing to develop a promising vaccine to prevent this devastating disease. In this review we compiled the findings of recent research with a view to facilitate knowledge on experimental vaccinology for visceral leishmaniasis. Various killed or attenuated parasite based first generation vaccines, second generation vaccines based on antigenic protein or recombinant protein, and third generation vaccines derived from antigen-encoding DNA plasmids including heterologous prime-boost Leishmania vaccine have been examined for control and prevention of visceral leishmaniasis. Vaccines based on recombinant protein and antigen-encoding DNA plasmids have given promising results and few vaccines including Leishmune®, Leishtec, and CaniLeish® have been licensed for canine visceral leishmaniasis. A systematic investigation of these vaccine candidates can lead to development of promising vaccine for human visceral leishmaniasis, most probably in the near future. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Visceral pain hypersensitivity in functional gastrointestinal disorders.

    Science.gov (United States)

    Farmer, A D; Aziz, Q

    2009-01-01

    Functional gastrointestinal disorders (FGIDs) are a highly prevalent group of heterogeneous disorders whose diagnostic criteria are symptom based in the absence of a demonstrable structural or biochemical abnormality. Chronic abdominal pain or discomfort is a defining characteristic of these disorders and a proportion of patients may display heightened pain sensitivity to experimental visceral stimulation, termed visceral pain hypersensitivity (VPH). We examined the most recent literature in order to concisely review the evidence for some of the most important recent advances in the putative mechanisms concerned in the pathophysiology of VPH. VPH may occur due to anomalies at any level of the visceral nociceptive neuraxis. Important peripheral and central mechanisms of sensitization that have been postulated include a wide range of ion channels, neurotransmitter receptors and trophic factors. Data from functional brain imaging studies have also provided evidence for aberrant central pain processing in cortical and subcortical regions. In addition, descending modulation of visceral nociceptive pathways by the autonomic nervous system, hypothalamo-pituitary-adrenal axis and psychological factors have all been implicated in the generation of VPH. Particular areas of controversy have included the development of efficacious treatment of VPH. Therapies have been slow to emerge, mainly due to concerns regarding safety. The burgeoning field of genome wide association studies may provide further evidence for the pleiotropic genetic basis of VPH development. Tangible progress will only be made in the treatment of VPH when we begin to individually characterize patients with FGIDs based on their clinical phenotype, genetics and visceral nociceptive physiology.

  15. Peripheral lidocaine, but not ketamine inhibit capsaicin-induced hyperalgesia in humans

    DEFF Research Database (Denmark)

    Gottrup, Hanne; Bach, Flemming Winther; Arendt-Nielsen, Lars

    2000-01-01

    We examined the effect of the subcutaneous infiltration of ketamine, lidocaine and saline before injury on capsaicin-induced pain and hyperalgesia. Twelve healthy volunteers participated in two separate, randomized, double-blind, placebo-controlled crossover experiments. In experiment 1, 100...... micrograms capsaicin was injected intradermally in one volar forearm 10 min after the skin had been pretreated with lidocaine 20.0 mg in 2.0 ml or 0.9% saline 2.0 ml at the capsaicin injection site. In experiment 2, a similar capsaicin test was given 10 min after the skin had been pretreated with ketamine 5...... and brush stimuli, and areas of brush-evoked and punctate-evoked hyperalgesia. Lidocaine reduced all measures compared with placebo (P

  16. Opioid-induced hyperalgesia in chronic pain patients and the mitigating effects of gabapentin.

    Science.gov (United States)

    Stoicea, Nicoleta; Russell, Daric; Weidner, Greg; Durda, Michael; Joseph, Nicholas C; Yu, Jeffrey; Bergese, Sergio D

    2015-01-01

    Chronic pain patients receiving opioid drugs are at risk for opioid-induced hyperalgesia (OIH), wherein opioid pain medication leads to a paradoxical pain state. OIH involves central sensitization of primary and secondary afferent neurons in the dorsal horn and dorsal root ganglion, similar to neuropathic pain. Gabapentin, a gamma-aminobutyric acid (GABA) analog anticonvulsant used to treat neuropathic pain, has been shown in animal models to reduce fentanyl hyperalgesia without compromising analgesic effect. Chronic pain patients have also exhibited lower opioid consumption and improved pain response when given gabapentin. However, few human studies investigating gabapentin use in OIH have been performed in recent years. In this review, we discuss the potential mechanisms that underlie OIH and provide a critical overview of interventional therapeutic strategies, especially the clinically-successful drug gabapentin, which may reduce OIH.

  17. Time course of primary and secondary hyperalgesia after heat injury to the skin

    DEFF Research Database (Denmark)

    Møiniche, S; Dahl, J B; Kehlet, H

    1993-01-01

    of the right calf, on two occasions at least 8 days apart. Heat pain detection thresholds (HPDT), heat pain tolerance (HPT), mechanical pain detection threshold (MPDT) and the intensity of burn-injury induced erythema (skin erythema index, SEI) were assessed inside the burn injury. HPT was assessed only in one...... study period. Areas of hyperalgesia to pinprick and brush were determined outside the injury. Assessments were made before and regularly for 72 h after the burn injury. There was a decrease in heat pain and mechanical thresholds, an increase in SEI inside the injury and development of mechanical...... the injury in any volunteer. These findings suggest post-injury development of secondary hyperalgesia to be a dynamic process, closely related in time to a peripheral nociceptive input, with reversal to normal when the peripheral lesion disappears. These observations may be relevant to the concept of "pre...

  18. Codeine-induced hyperalgesia and allodynia: investigating the role of glial activation.

    Science.gov (United States)

    Johnson, J L; Rolan, P E; Johnson, M E; Bobrovskaya, L; Williams, D B; Johnson, K; Tuke, J; Hutchinson, M R

    2014-11-11

    Chronic morphine therapy has been associated with paradoxically increased pain. Codeine is a widely used opioid, which is metabolized to morphine to elicit analgesia. Prolonged morphine exposure exacerbates pain by activating the innate immune toll-like receptor-4 (TLR4) in the central nervous system. In silico docking simulations indicate codeine also docks to MD2, an accessory protein for TLR4, suggesting potential to induce TLR4-dependent pain facilitation. We hypothesized codeine would cause TLR4-dependent hyperalgesia/allodynia that is disparate from its opioid receptor-dependent analgesic rank potency. Hyperalgesia and allodynia were assessed using hotplate and von Frey tests at days 0, 3 and 5 in mice receiving intraperitoneal equimolar codeine (21 mg kg(-1)), morphine (20 mg kg(-1)) or saline, twice daily. This experiment was repeated in animals with prior partial nerve injury and in TLR4 null mutant mice. Interventions with interleukin-1 receptor antagonist (IL-1RA) and glial-attenuating drug ibudilast were assessed. Analyses of glial activation markers (glial fibrillary acid protein and CD11b) in neuronal tissue were conducted at the completion of behavioural testing. Despite providing less acute analgesia (P=0.006), codeine induced similar hotplate hyperalgesia to equimolar morphine vs saline (-9.5 s, Pcodeine does not rely upon conversion to morphine to increase pain sensitivity. This highlights the potential non-opioid receptor-dependent nature of codeine-enhanced pain sensitivity-although the involvement of other codeine metabolites cannot be ruled out. IL-1RA reversed codeine-induced hyperalgesia (Pcodeine-induced changes in pain sensitivity. Glial attenuation with ibudilast reversed codeine-induced allodynia (Pcodeine-induced pain enhancement.

  19. Intraplantar injection of gangliosides produces nociceptive behavior and hyperalgesia via a glutamate signaling mechanism.

    Science.gov (United States)

    Watanabe, Shun; Tan-No, Koichi; Tadano, Takeshi; Higashi, Hideyoshi

    2011-02-01

    Gangliosides are abundant in neural tissue and play important roles in cell-cell adhesion, signal transduction, and cell differentiation. Gangliosides are divided into 4 groups: asialo-, a-, b-, and c-series gangliosides, based on their biosynthetic pathway. St8sia1 knockout mice, which lack b- and c-series gangliosides, exhibit altered nociceptive responses. The mechanism underlying this defect, however, remains unclear. To address this issue, we first investigated the possibility that gangliosides in peripheral nociceptor endings are involved in nociception. Intraplantar injection of the b-series ganglioside GT1b, but not a-series gangliosides such as GM1, produced nociceptive responses and enhanced low-concentration formalin-induced nociception. N-methyl-d-aspartic acid receptor and type I metabotropic glutamate receptor antagonists inhibited GT1b-induced hyperalgesia, suggesting the involvement of glutamate receptors. Furthermore, microdialysis analysis revealed elevated glutamate content in subdermal tissues due to intraplantar injection of GT1b. Co-injection of glutamate dehydrogenase with GT1b attenuated GT1b-induced hyperalgesia. These findings suggested that GT1b induced extracellular glutamate to accumulate in subdermal tissues, thereafter activating glutamate receptors, which in turn resulted in hyperalgesia and nociception. On the other hand, intraplantar injection of sialidase, which cleaves sialyl residues from glycoconjugates such as gangliosides, attenuated the late phase of 2% formalin-induced nociception. Thus, the antinociceptive effects of sialidase and the nociceptive effects of GT1b indicated that endogenous gangliosides are involved in nociceptive responses. These results suggest that gangliosides play important roles in nociceptive responses originating in peripheral nociceptor endings. Ganglioside GT1b induced extracellular glutamate to accumulate in subdermal tissues, thereafter activating glutamate receptors, which in turn resulted in

  20. EphrinB-EphB Signaling Induces Hyperalgesia through ERK5/CREB Pathway in Rats.

    Science.gov (United States)

    Yu, Li-Na; Sun, Li-Hong; Wang, Min; Wang, Lie-Ju; Wu, Ying; Yu, Jing; Wang, Wen-Na; Zhang, Feng-Jiang; Li, Xue; Yan, Min

    2017-05-01

    There are numerous studies implicating that EphB receptors and ephrinB ligands play important roles in modulating the transduction of spinal nociceptive information. EphrinB-EphB signaling may contribute to hyperalgesia via various kinds of downstream molecules, the mechanisms of which have not been completely understood. The aim of the present study was to identify whether ephrinB-EphB signaling could contribute to hyperalgesia through ERK5/CREB pathway. Controlled animal study. University laboratory. This study attempted to detect the changes of pain behaviors and the protein level of p-ERK5 and p-CREB by activating EphB receptors in the spinal cord of rats. To further confirm our hypothesis, we designed LV-siRNA for knockdown of spinal ERK5. When ERK5 was inhibited, we recorded the changes of spinal p-CREB expression and the pain behaviors of rats after activating EphB receptors. We also confirmed this conclusion in rat CCI model. Statistical analyses were performed using GraphPad Prism 5. Intrathecal injection of ephrinB2-Fc in rats evoked thermal hyperalgesia and mechanical allodynia, along with activation of ERK5 and CREB in the spinal cord. Knockdown of ERK5 inhibited ephrinB2-Fc-induced CREB activation and hyperalgesia. Blocking EphB receptors prevented CCI-induced neuropathic pain and spinal ERK5/CREB activation. More underlying mechanisms that underlie the relationship between ephrinB-EphB signaling and ERK5/CREB pathway will need to be explored in future studies. Our study suggests that ERK5/CREB pathway plays important roles in the transduction of nociceptive information associated with ephrinB-EphB signaling. This study provides further understanding of the downstream mechanisms of ephrinB-EphB signaling and helps to explore new targets for treating pathological pain.

  1. Pressure Pain Sensitivity in Patients With Suspected Opioid-Induced Hyperalgesia.

    Science.gov (United States)

    Wasserman, Ronald A; Hassett, Afton L; Harte, Steven E; Goesling, Jenna; Malinoff, Herbert L; Berland, Daniel W; Zollars, Jennifer; Moser, Stephanie E; Brummett, Chad M

    2015-01-01

    This study was designed to test whether a brief quantitative sensory testing assessment could be used to detect hyperalgesia in patients with suspected opioid-induced hyperalgesia (OIH). Twenty patients on long-term opioid therapy with suspected OIH were recruited along with 20 healthy controls. Pressure pain threshold, Pain50, a measure of intermediate suprathreshold pressure pain sensitivity, and tolerance levels were evaluated. As a secondary outcome, changes in pressure pain sensitivity after intravenous administration of placebo (saline) and fentanyl (1.5 μg/kg) were assessed. There were no significant differences in pain measures between healthy controls and patients. However, there was an association between higher doses of opioids and having a lower pain tolerance (r = -0.46, P = 0.041) and lower Pain50 (r = -0.46, P = 0.044), which was consistent with the hypothesis. Patients on more than 100 mg oral morphine equivalents displayed decreased pressure pain tolerance compared with patients taking less than 100 mg oral morphine equivalents (P = 0.042). In addition, male patients showed a hyperalgesic response to fentanyl administration, which was significant for the Pain50 measure (P = 0.002). Whereas there were no differences between patients suspected of having OIH and the healthy controls, the finding that higher doses of opioids were associated with more sensitivity suggests that dose might be an important factor in the development of hyperalgesia. In addition, male patients demonstrated a hyperalgesic response after a bolus of fentanyl. Future studies are needed to develop better diagnostics for detecting hyperalgesia in the clinical setting.

  2. The Area of Secondary Hyperalgesia following Heat Stimulation in Healthy Male Volunteers

    DEFF Research Database (Denmark)

    Hansen, Morten Sejer; Wetterslev, Jørn; Pipper, Christian Bressen

    2016-01-01

    -observer intra-person correlation of 0.85, 95% CI [0.78, 0.90], an intra-observer inter-person correlation of 0.03, 95% CI [0.00, 0.16], and a coefficient of variation of 0.17, 95% CI [0.14, 0.21] was demonstrated. Four percent of the study population had areas of secondary hyperalgesia both below the 1st...

  3. Serotonin modulates insect hemocyte phagocytosis via two different serotonin receptors.

    Science.gov (United States)

    Qi, Yi-Xiang; Huang, Jia; Li, Meng-Qi; Wu, Ya-Su; Xia, Ren-Ying; Ye, Gong-Yin

    2016-03-14

    Serotonin (5-HT) modulates both neural and immune responses in vertebrates, but its role in insect immunity remains uncertain. We report that hemocytes in the caterpillar, Pieris rapae are able to synthesize 5-HT following activation by lipopolysaccharide. The inhibition of a serotonin-generating enzyme with either pharmacological blockade or RNAi knock-down impaired hemocyte phagocytosis. Biochemical and functional experiments showed that naive hemocytes primarily express 5-HT1B and 5-HT2B receptors. The blockade of 5-HT1B significantly reduced phagocytic ability; however, the blockade of 5-HT2B increased hemocyte phagocytosis. The 5-HT1B-null Drosophila melanogaster mutants showed higher mortality than controls when infected with bacteria, due to their decreased phagocytotic ability. Flies expressing 5-HT1B or 5-HT2B RNAi in hemocytes also showed similar sensitivity to infection. Combined, these data demonstrate that 5-HT mediates hemocyte phagocytosis through 5-HT1B and 5-HT2B receptors and serotonergic signaling performs critical modulatory functions in immune systems of animals separated by 500 million years of evolution.

  4. Interaction of hyperalgesia and sensory loss in complex regional pain syndrome type I (CRPS I).

    Science.gov (United States)

    Huge, Volker; Lauchart, Meike; Förderreuther, Stefanie; Kaufhold, Wibke; Valet, Michael; Azad, Shahnaz Christina; Beyer, Antje; Magerl, Walter

    2008-07-23

    Sensory abnormalities are a key feature of Complex Regional Pain Syndrome (CRPS). In order to characterise these changes in patients suffering from acute or chronic CRPS I, we used Quantitative Sensory Testing (QST) in comparison to an age and gender matched control group. 61 patients presenting with CRPS I of the upper extremity and 56 healthy subjects were prospectively assessed using QST. The patients' warm and cold detection thresholds (WDT; CDT), the heat and cold pain thresholds (HPT; CPT) and the occurrence of paradoxical heat sensation (PHS) were observed. In acute CRPS I, patients showed warm and cold hyperalgesia, indicated by significant changes in HPT and CPT. WDT and CDT were significantly increased as well, indicating warm and cold hypoaesthesia. In chronic CRPS, thermal hyperalgesia declined, but CDT as well as WDT further deteriorated. Solely patients with acute CRPS displayed PHS. To a minor degree, all QST changes were also present on the contralateral limb. We propose three pathomechanisms of CRPS I, which follow a distinct time course: Thermal hyperalgesia, observed in acute CRPS, indicates an ongoing aseptic peripheral inflammation. Thermal hypoaesthesia, as detected in acute and chronic CRPS, signals a degeneration of A-delta and C-fibres, which further deteriorates in chronic CRPS. PHS in acute CRPS I indicates that both inflammation and degeneration are present, whilst in chronic CRPS I, the pathomechanism of degeneration dominates, signalled by the absence of PHS. The contralateral changes observed strongly suggest the involvement of the central nervous system.

  5. Interaction of hyperalgesia and sensory loss in complex regional pain syndrome type I (CRPS I.

    Directory of Open Access Journals (Sweden)

    Volker Huge

    Full Text Available BACKGROUND: Sensory abnormalities are a key feature of Complex Regional Pain Syndrome (CRPS. In order to characterise these changes in patients suffering from acute or chronic CRPS I, we used Quantitative Sensory Testing (QST in comparison to an age and gender matched control group. METHODS: 61 patients presenting with CRPS I of the upper extremity and 56 healthy subjects were prospectively assessed using QST. The patients' warm and cold detection thresholds (WDT; CDT, the heat and cold pain thresholds (HPT; CPT and the occurrence of paradoxical heat sensation (PHS were observed. RESULTS: In acute CRPS I, patients showed warm and cold hyperalgesia, indicated by significant changes in HPT and CPT. WDT and CDT were significantly increased as well, indicating warm and cold hypoaesthesia. In chronic CRPS, thermal hyperalgesia declined, but CDT as well as WDT further deteriorated. Solely patients with acute CRPS displayed PHS. To a minor degree, all QST changes were also present on the contralateral limb. CONCLUSIONS: We propose three pathomechanisms of CRPS I, which follow a distinct time course: Thermal hyperalgesia, observed in acute CRPS, indicates an ongoing aseptic peripheral inflammation. Thermal hypoaesthesia, as detected in acute and chronic CRPS, signals a degeneration of A-delta and C-fibres, which further deteriorates in chronic CRPS. PHS in acute CRPS I indicates that both inflammation and degeneration are present, whilst in chronic CRPS I, the pathomechanism of degeneration dominates, signalled by the absence of PHS. The contralateral changes observed strongly suggest the involvement of the central nervous system.

  6. Subjects with Knee Osteoarthritis Exhibit Widespread Hyperalgesia to Pressure and Cold.

    Directory of Open Access Journals (Sweden)

    Penny Moss

    Full Text Available Hyperalgesia to mechanical and thermal stimuli are characteristics of a range of disorders such as tennis elbow, whiplash and fibromyalgia. This study evaluated the presence of local and widespread mechanical and thermal hyperalgesia in individuals with knee osteoarthritis, compared to healthy control subjects. Twenty-three subjects with knee osteoarthritis and 23 healthy controls, matched for age, gender and body mass index, were recruited for the study. Volunteers with any additional chronic pain conditions were excluded. Pain thresholds to pressure, cold and heat were tested at the knee, ipsilateral heel and ipsilateral elbow, in randomized order, using standardised methodology. Significant between-groups differences for pressure pain and cold pain thresholds were found with osteoarthritic subjects demonstrating significantly increased sensitivity to both pressure (p = .018 and cold (p = .003 stimuli, compared with controls. A similar pattern of results extended to the pain-free ipsilateral ankle and elbow indicating widespread pressure and cold hyperalgesia. No significant differences were found between groups for heat pain threshold, although correlations showed that subjects with greater sensitivity to pressure pain were also likely to be more sensitive to both cold pain and heat pain. This study found widespread elevated pain thresholds in subjects with painful knee osteoarthritis, suggesting that altered nociceptive system processing may play a role in ongoing arthritic pain for some patients.

  7. NGF and GDNF differentially regulate TRPV1 expression that contributes to development of inflammatory thermal hyperalgesia.

    Science.gov (United States)

    Amaya, Fumimasa; Shimosato, Goshun; Nagano, Masatoshi; Ueda, Masashi; Hashimoto, Satoru; Tanaka, Yoshifumi; Suzuki, Hidenori; Tanaka, Masaki

    2004-11-01

    The transient receptor potential ion channel, TRPV1 plays an essential role in the development of inflammatory thermal hyperalgesia. We investigated the dependence of inflammatory TRPV1 induction on neurotrophic factor. Rat dorsal root ganglia (DRG) neurons were classified according to immunostaining for trk-A and IB4 and the effects of antibodies against NGF or GDNF on TRPV1 expression within the groups were then analysed by immunohistochemical means. The data were compared with the time course of trophic factor expression and the effects of their antibodies on thermal hyperalgesia against radiant heat after inflammation. Although the levels of both NGF and GDNF were increased by inflammation, NGF rapidly and transiently increased whereas GDNF increased gradually over a period of approximately one week. TRPV1 expression was increased within both trk-A positive and IB4 positive neurons after inflammation. Increased TRPV1 expression within trk-A positive neurons was prevented by anti-NGF but not by anti-GDNF, whereas TRPV1 induction within the IB4 positive group was blocked by anti-GDNF but not by anti-NGF. Both antibodies prevented the short latency of withdrawing an inflamed paw from radiant heat. These results suggest that inflammation differentially increases both NGF and GDNF, which facilitate TRPV1 expression within distinctive neurons to induce thermal hyperalgesia.

  8. An evidence based systematic review of remifentanil associated opioid-induced hyperalgesia.

    Science.gov (United States)

    Rivosecchi, Ryan M; Rice, Mark J; Smithburger, Pamela L; Buckley, Mitchell S; Coons, James C; Kane-Gill, Sandra L

    2014-05-01

    Therapeutic opioid use continues to grow, with greater than a fivefold increase in usage of fentanyl-based products over a 10-year period. Opioids are known for their side-effect profile, including bradycardia and respiratory depression; questions remain, however, regarding lesser known side effects such as opioid-induced hyperalgesia (OIH). A systematic review of published literature addressing remifentanil OIH in the surgical setting was completed. A search was conducted of PubMed, Embase and Ovid from 1946 until June 2013. Inclusion criteria consisted of age ≥ 18 years, humans, full-text articles and English language. A total of 35 unique articles were included. Sixteen articles reported outcomes that supported remifentanil OIH and 6 that refuted and 22 were focused on prevention. There is conflicting evidence regarding the existence of remifentanil OIH. Outcomes evaluating measures of hyperalgesia frequently conclude that remifentanil OIH exists, while those evaluating opioid consumption do not. Therefore, remifentanil does induce a degree of hyperalgesia, but we do not believe that it reaches a level of clinical significance that requires prevention. If a significant concern for the development of remifentanil OIH is suspected, we suggest using the least possible effective dose of remifentanil as the primary prevention strategy.

  9. 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.

  10. Oral administration of stavudine induces hyperalgesia without affecting activity in rats.

    Science.gov (United States)

    Weber, Juliane; Mitchell, Duncan; Kamerman, Peter R

    2007-12-05

    We have investigated whether long-term oral administration of the nucleoside reverse transcriptase inhibitor (NRTI) stavudine affects nociception in Sprague-Dawley rats, and whether any changes of nociception are accompanied by deterioration in activity and appetite. Stavudine (50 mg kg(-1)) was administered to rats orally once daily for six weeks in gelatine cubes. Mechanical hyperalgesia of the tail was assessed using a bar algometer, and thermal hyperalgesia by tail immersion in 49 degrees C water. Withdrawal latencies were compared to those of rats receiving placebo gelatine cubes. Withdrawal latencies to the noxious thermal challenge were not affected by stavudine, but those to the mechanical challenge were significantly decreased in rats receiving stavudine, compared to rats receiving placebo, from week three to week six of drug administration (Prats was assessed by recording daily voluntary wheel running distance and maximum running speed, food intake and body mass. Daily stavudine administration did not adversely affect voluntary running activity, appetite or growth. We have shown that long-term daily oral administration of the NRTI stavudine results in mechanical hyperalgesia in rats within three weeks without affecting appetite, growth and physical activity.

  11. BLOOD CHEMISTRY AND PLATELET SEROTONIN UPTAKE As ...

    African Journals Online (AJOL)

    'AFRICAN JOURNAL OF CLINICAL AND EXPERIMENTAL MICROBIOLOGY MAY 2004 ISSN 1595-689X VOL.5 No.2 ... investigations by means of a questionnaire. .... platelet otomeh'ically. Protein concentration in platelet—rich plasma and in the discharged serotonin was determined serotonin, were determined by the ...

  12. Genetic polymorphism of serotonin transporter 5-HTTLPR ...

    Indian Academy of Sciences (India)

    genetic polymorphism of serotonin transporter in smoking behaviour is reviewed considering the interactive effect of genetic factors. ..... depression. Lancet 347, 731–733. Olausson P., Engel J. A. and Söderpalm B. 2002 Involvement of serotonin in nicotine dependence: processes relevant to positive and negative regulation ...

  13. The serotonin transporter knockout rat : A review

    NARCIS (Netherlands)

    Olivier, Jocelien; Cools, Alexander; Ellenbroek, Bart A.; Cuppen, E.; Homberg, Judith; Kalueff, Allan V.; LaPorte, Justin L.

    2010-01-01

    This chapter dicusses the most recent data on the serotonin transporter knock-out rat, a unique rat model that has been generated by target-selected N-ethyl-N-nitrosourea (ENU) driven mutagenesis. The knock-out rat is the result of a premature stopcodon in the serotonin transporter gene, and the

  14. Serotonin: Modulator of a Drive to Withdraw

    Science.gov (United States)

    Tops, Mattie; Russo, Sascha; Boksem, Maarten A. S.; Tucker, Don M.

    2009-01-01

    Serotonin is a fundamental neuromodulator in both vertebrate and invertebrate nervous systems, with a suspected role in many human mental disorders. Yet, because of the complexity of serotonergic function, researchers have been unable to agree on a general theory. One function suggested for serotonin systems is the avoidance of threat. We propose…

  15. Molecular fMRI of Serotonin Transport.

    Science.gov (United States)

    Hai, Aviad; Cai, Lili X; Lee, Taekwan; Lelyveld, Victor S; Jasanoff, Alan

    2016-11-23

    Reuptake of neurotransmitters from the brain interstitium shapes chemical signaling processes and is disrupted in several pathologies. Serotonin reuptake in particular is important for mood regulation and is inhibited by first-line drugs for treatment of depression. Here we introduce a molecular-level fMRI technique for micron-scale mapping of serotonin transport in live animals. Intracranial injection of an MRI-detectable serotonin sensor complexed with serotonin, together with serial imaging and compartmental analysis, permits neurotransmitter transport to be quantified as serotonin dissociates from the probe. Application of this strategy to much of the striatum and surrounding areas reveals widespread nonsaturating serotonin removal with maximal rates in the lateral septum. The serotonin reuptake inhibitor fluoxetine selectively suppresses serotonin removal in septal subregions, whereas both fluoxetine and a dopamine transporter blocker depress reuptake in striatum. These results highlight promiscuous pharmacological influences on the serotonergic system and demonstrate the utility of molecular fMRI for characterization of neurochemical dynamics. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Immunity and immunosuppression in experimental visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Goto H.

    2004-01-01

    Full Text Available Leishmaniasis is a disease caused by protozoa of the genus Leishmania, and visceral leishmaniasis is a form in which the inner organs are affected. Since knowledge about immunity in experimental visceral leishmaniasis is poor, we present here a review on immunity and immunosuppression in experimental visceral leishmaniasis in mouse and hamster models. We show the complexity of the mechanisms involved and differences when compared with the cutaneous form of leishmaniasis. Resistance in visceral leishmaniasis involves both CD4+ and CD8+ T cells, and interleukin (IL-2, interferon (IFN- gamma, and IL-12, the latter in a mechanism independent of IFN- gamma and linked to transforming growth factor (TGF-ß production. Susceptibility involves IL-10 but not IL-4, and B cells. In immune animals, upon re-infection, the elements involved in resistance are different, i.e., CD8+ T cells and IL-2. Since one of the immunopathological consequences of active visceral leishmaniasis in humans is suppression of T-cell responses, many studies have been conducted using experimental models. Immunosuppression is mainly Leishmania antigen specific, and T cells, Th2 cells and adherent antigen-presenting cells have been shown to be involved. Interactions of the co-stimulatory molecule family B7-CTLA-4 leading to increased level of TGF-ß as well as apoptosis of CD4+ T cells and inhibition of macrophage apoptosis by Leishmania infection are other components participating in immunosuppression. A better understanding of this complex immune response and the mechanisms of immunosuppression in experimental visceral leishmaniasis will contribute to the study of human disease and to vaccine development.

  17. How serotonin shapes moral judgment and behavior

    Science.gov (United States)

    Siegel, Jenifer Z; Crockett, Molly J

    2013-01-01

    Neuroscientists are now discovering how hormones and brain chemicals shape social behavior, opening potential avenues for pharmacological manipulation of ethical values. Here, we review recent studies showing how altering brain chemistry can alter moral judgment and behavior, focusing in particular on the neuromodulator serotonin and its role in shaping values related to harm and fairness. We synthesize previous findings and consider the potential mechanisms through which serotonin could increase the aversion to harming others. We present a process model whereby serotonin influences social behavior by shifting social preferences in the positive direction, enhancing the value people place on others’ outcomes. This model may explain previous findings relating serotonin function to prosocial behavior, and makes new predictions regarding how serotonin may influence the neural computation of value in social contexts. PMID:25627116

  18. Development and application of assays for serotonin

    Energy Technology Data Exchange (ETDEWEB)

    Gow, I.F.

    1987-01-01

    In this thesis, two assays for serotonin were developed, validated, and used to investigate the relationship between platelet aggregation, serotonin levels and sodium status and serotonin levels and platelet function in patients with cardiovascular disease. A radioimmunoassay (RIA) using an (/sup 125/I)-labelled tracer was developed and validated for the measurement of serotonin in human platelet-rich plasma (PRP) and rat serum. Antisera were raised against N-succinamylserotonin conjugated to bovine albumin and, to improve assay sensitivity, the analyte was made chemically similar to the immunogen by conversion to N-acetylserotonin prior to assay, using the specific amino reagent N-acetoxysuccinimide. An assay for serotonin using high-pressure liquid chromatography with electrochemical detection (HPLC-ECD) was developed, and used to validate the RIA. The RIA can be used to assay up to 100 samples/day compared with 10-20/day by the HPLC-ECD assay.

  19. Serotonin, neural markers and memory

    Directory of Open Access Journals (Sweden)

    Alfredo eMeneses

    2015-07-01

    Full Text Available Diverse neuropsychiatric disorders present dysfunctional memory and no effective treatment exits for them; likely as result of the absence of neural markers associated to memory. Neurotransmitter systems and signaling pathways have been implicated in memory and dysfunctional memory; however, their role is poorly understood. Hence, neural markers and cerebral functions and dysfunctions are revised. To our knowledge no previous systematic works have been published addressing these issues. The interactions among behavioral tasks, control groups and molecular changes and/or pharmacological effects are mentioned. Neurotransmitter receptors and signaling pathways, during normal and abnormally functioning memory with an emphasis on the behavioral aspects of memory are revised. With focus on serotonin, since as it is a well characterized neurotransmitter, with multiple pharmacological tools, and well characterized downstream signaling in mammals’ species. 5-HT1A, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 receptors as well as SERT (serotonin transporter seem to be useful neural markers and/or therapeutic targets. Certainly, if the mentioned evidence is replicated, then the translatability from preclinical and clinical studies to neural changes might be confirmed. Hypothesis and theories might provide appropriate limits and perspectives of evidence

  20. Generalized Hyperalgesia in Children and Adults Diagnosed With Hypermobility Syndrome and Ehlers-Danlos Syndrome Hypermobility Type: A Discriminative Analysis.

    Science.gov (United States)

    Scheper, M C; Pacey, V; Rombaut, L; Adams, R D; Tofts, L; Calders, P; Nicholson, L L; Engelbert, R H H

    2017-03-01

    Lowered pressure-pain thresholds have been demonstrated in adults with Ehlers-Danlos syndrome hypermobility type (EDS-HT), but whether these findings are also present in children is unclear. Therefore, the objectives of the study were to determine whether generalized hyperalgesia is present in children with hypermobility syndrome (HMS)/EDS-HT, explore potential differences in pressure-pain thresholds between children and adults with HMS/EDS-HT, and determine the discriminative value of generalized hyperalgesia. Patients were classified in 1 of 3 groups: HMS/EDS-HT, hypermobile (Beighton score ≥4 of 9), and healthy controls. Descriptive data of age, sex, body mass index, Beighton score, skin laxity, and medication usage were collected. Generalized hyperalgesia was quantified by the average pressure-pain thresholds collected from 12 locations. Confounders collected were pain locations/intensity, fatigue, and psychological distress. Comparisons between children with HMS/EDS-HT and normative values, between children and adults with HMS/EDS-HT, and corrected confounders were analyzed with multivariate analysis of covariance. The discriminative value of generalized hyperalgesia employed to differentiate between HMS/EDS-HT, hypermobility, and controls was quantified with logistic regression. Significantly lower pressure-pain thresholds were found in children with HMS/EDS-HT compared to normative values (range -22.0% to -59.0%; P ≤ 0.05). When applying a threshold of 30.8 N/cm 2 for males and 29.0 N/cm 2 for females, the presence of generalized hyperalgesia discriminated between individuals with HMS/EDS-HT, hypermobility, and healthy controls (odds ratio 6.0). Children and adults with HMS/EDS-HT are characterized by hypermobility, chronic pain, and generalized hyperalgesia. The presence of generalized hyperalgesia may indicate involvement of the central nervous system in the development of chronic pain. © 2016, American College of Rheumatology.

  1. Colorectal visceral perception in diverticular disease

    NARCIS (Netherlands)

    Clemens, C. H. M.; Samsom, M.; Roelofs, J.; van Berge Henegouwen, G. P.; Smout, A. J. P. M.

    2004-01-01

    BACKGROUND AND AIMS: The pathogenesis of asymptomatic diverticular disease (ADD) and symptomatic uncomplicated diverticular disease (SUDD) has not been elucidated. The aim of our study was to assess whether altered visceral perception or abnormal compliance of the colorectal wall play a role in

  2. Sympathetic blocks for visceral cancer pain management

    DEFF Research Database (Denmark)

    Mercadante, Sebastiano; Klepstad, Pal; Kurita, Geana Paula

    2015-01-01

    The neurolytic blocks of sympathetic pathways, including celiac plexus block (CPB) and superior hypogastric plexus block (SHPB) , have been used for years. The aim of this review was to assess the evidence to support the performance of sympathetic blocks in cancer patients with abdominal visceral...

  3. Visceral Leishmaniasis in Rural Bihar, India

    Science.gov (United States)

    Singh, Shri Prakash; Malaviya, Paritosh; Picado, Albert; Gidwani, Kamlesh; Singh, Rudra Pratap; Menten, Joris; Boelaert, Marleen; Sundar, Shyam

    2012-01-01

    To identify factors associated with incidence of visceral leishmaniasis (VL), we surveyed 13,416 households in Bihar State, India. VL was associated with socioeconomic status, type of housing, and belonging to the Musahar caste. Annual coverage of indoor residual insecticide spraying was 12%. Increasing such spraying can greatly contribute to VL control. PMID:23017164

  4. Irritable bowel syndrome and visceral hypersensitivity : risk factors and pathophysiological mechanisms.

    Science.gov (United States)

    Deiteren, A; de Wit, A; van der Linden, L; De Man, J G; Pelckmans, P A; De Winter, B Y

    2016-03-01

    Irritable bowel syndrome (IBS) is a common functional gastro-intestinal disorder, characterized by abdominal pain and altered intestinal motility. Visceral hypersensitivity is an important hallmark feature of IBS and is believed to underlie abdominal pain in patients with IBS. The two main risk factors associated with the development of IBS are gastrointestinal inflammation and psychological distress. On a peripheral level, visceral sensitivity seems to be modulated by several mechanisms. Immune cells in the mucosal wall, such as mast cells, and enterochromaffin cells may sensitize afferent nerves by release of their mediators. Furthermore, increased mucosal permeability, altered intestinal microflora and dietary habits may contribute to this feature. On a central level, an increased prevalence of psychiatric comorbidities is demonstrated in IBS patients, alongside alterations in the hormonal brain-gut axis, increased vigilance towards intestinal stimuli and functional and structural changes in the brain. The pathogenesis of IBS is complicated and multifactorial and the treatment remains clinically challenging. Dietary measures and symptomatic control are the cornerstones for IBS treatment and may be sufficient for patients experiencing mild symptoms, alongside education, reassurance and an effective therapeutic physician-patient relationship. New pharmacological therapies are aimed at interfering with mediator release and/or blockade of the relevant receptors within the gut wall, while modulation of the intestinal flora and diet may also be of therapeutic benefit. Tricyclic anti-depressants and serotonin reuptake inhibitors act both on a central and peripheral level by modulating pain signalling pathways. © Acta Gastro-Enterologica Belgica.

  5. Biased Intensity Judgements of Visceral Sensations After Learning to Fear Visceral Stimuli: A Drift Diffusion Approach.

    Science.gov (United States)

    Zaman, Jonas; Madden, Victoria J; Iven, Julie; Wiech, Katja; Weltens, Nathalie; Ly, Huynh Giao; Vlaeyen, Johan W S; Van Oudenhove, Lukas; Van Diest, Ilse

    2017-10-01

    A growing body of research has identified fear of visceral sensations as a potential mechanism in the development and maintenance of visceral pain disorders. However, the extent to which such learned fear affects visceroception remains unclear. To address this question, we used a differential fear conditioning paradigm with nonpainful esophageal balloon distensions of 2 different intensities as conditioning stimuli (CSs). The experiment comprised of preacquisition, acquisition, and postacquisition phases during which participants categorized the CSs with respect to their intensity. The CS+ was always followed by a painful electrical stimulus (unconditioned stimulus) during the acquisition phase and in 60% of the trials during postacquisition. The second stimulus (CS-) was never associated with pain. Analyses of galvanic skin and startle eyeblink responses as physiological markers of successful conditioning showed increased fear responses to the CS+ compared with the CS-, but only in the group with the low-intensity stimulus as CS+. Computational modeling of response times and response accuracies revealed that differential fear learning affected perceptual decision-making about the intensities of visceral sensations such that sensations were more likely to be categorized as more intense. These results suggest that associative learning might indeed contribute to visceral hypersensitivity in functional gastrointestinal disorders. This study shows that associative fear learning biases intensity judgements of visceral sensations toward perceiving such sensations as more intense. Learning-induced alterations in visceroception might therefore contribute to the development or maintenance of visceral pain. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

  6. Pathophysiology of human visceral obesity: an update.

    Science.gov (United States)

    Tchernof, André; Després, Jean-Pierre

    2013-01-01

    Excess intra-abdominal adipose tissue accumulation, often termed visceral obesity, is part of a phenotype including dysfunctional subcutaneous adipose tissue expansion and ectopic triglyceride storage closely related to clustering cardiometabolic risk factors. Hypertriglyceridemia; increased free fatty acid availability; adipose tissue release of proinflammatory cytokines; liver insulin resistance and inflammation; increased liver VLDL synthesis and secretion; reduced clearance of triglyceride-rich lipoproteins; presence of small, dense LDL particles; and reduced HDL cholesterol levels are among the many metabolic alterations closely related to this condition. Age, gender, genetics, and ethnicity are broad etiological factors contributing to variation in visceral adipose tissue accumulation. Specific mechanisms responsible for proportionally increased visceral fat storage when facing positive energy balance and weight gain may involve sex hormones, local cortisol production in abdominal adipose tissues, endocannabinoids, growth hormone, and dietary fructose. Physiological characteristics of abdominal adipose tissues such as adipocyte size and number, lipolytic responsiveness, lipid storage capacity, and inflammatory cytokine production are significant correlates and even possible determinants of the increased cardiometabolic risk associated with visceral obesity. Thiazolidinediones, estrogen replacement in postmenopausal women, and testosterone replacement in androgen-deficient men have been shown to favorably modulate body fat distribution and cardiometabolic risk to various degrees. However, some of these therapies must now be considered in the context of their serious side effects. Lifestyle interventions leading to weight loss generally induce preferential mobilization of visceral fat. In clinical practice, measuring waist circumference in addition to the body mass index could be helpful for the identification and management of a subgroup of overweight or obese

  7. Disruption of Transient Serotonin Accumulation by Non-Serotonin-Producing Neurons Impairs Cortical Map Development

    Directory of Open Access Journals (Sweden)

    Xiaoning Chen

    2015-01-01

    Full Text Available Polymorphisms that alter serotonin transporter SERT expression and functionality increase the risks for autism and psychiatric traits. Here, we investigate how SERT controls serotonin signaling in developing CNS in mice. SERT is transiently expressed in specific sets of glutamatergic neurons and uptakes extrasynaptic serotonin during perinatal CNS development. We show that SERT expression in glutamatergic thalamocortical axons (TCAs dictates sensory map architecture. Knockout of SERT in TCAs causes lasting alterations in TCA patterning, spatial organizations of cortical neurons, and dendritic arborization in sensory cortex. Pharmacological reduction of serotonin synthesis during the first postnatal week rescues sensory maps in SERTGluΔ mice. Furthermore, knockdown of SERT expression in serotonin-producing neurons does not impair barrel maps. We propose that spatiotemporal SERT expression in non-serotonin-producing neurons represents a determinant in early life genetic programming of cortical circuits. Perturbing this SERT function could be involved in the origin of sensory and cognitive deficits associated with neurodevelopmental disorders.

  8. Determinants for the development of visceral leishmaniasis disease.

    Directory of Open Access Journals (Sweden)

    Laura-Isobel McCall

    2013-01-01

    Full Text Available Leishmaniasis is a vector-borne neglected tropical disease associated with a spectrum of clinical manifestations, ranging from self-healing cutaneous lesions to fatal visceral infections. Among the most important questions in Leishmania research is why some species like L. donovani infect visceral organs, whereas other species like L. major remain in the skin. The determinants of visceral leishmaniasis are still poorly understood, although genomic, immunologic, and animal models are beginning to provide important insight into this disease. In this review, we discuss the vector, host, and pathogen factors that mediate the development of visceral leishmaniasis. We examine the progression of the parasite from the initial site of sand fly bite to the visceral organs and its ability to survive there. The identification of visceral disease determinants is required to understand disease evolution, to understand visceral organ survival mechanisms, and potentially to develop better interventions for this largely neglected disease.

  9. Serotonin receptor 3A polymorphism c.-42C > T is associated with severe dyspepsia

    Directory of Open Access Journals (Sweden)

    Grobbee Diederick E

    2011-10-01

    Full Text Available Abstract Background The association between anxiety and depression related traits and dyspepsia may reflect a common genetic predisposition. Furthermore, genetic factors may contribute to the risk of having increased visceral sensitivity, which has been implicated in dyspeptic symptom generation. Serotonin (5-HT modulates visceral sensitivity by its action on 5-HT3 receptors. Interestingly, a functional polymorphism in HTR3A, encoding the 5-HT3 receptor A subunit, has been reported to be associated with depression and anxiety related traits. A functional polymorphism in the serotonin transporter (5-HTT, which terminates serotonergic signalling, was also found associated with these psychiatric comorbidities and increased visceral sensitivity in irritable bowel syndrome, which coexistence is associated with higher dyspeptic symptom severity. We investigated the association between these functional polymorphisms and dyspeptic symptom severity. Methods Data from 592 unrelated, Caucasian, primary care patients with dyspepsia participating in a randomised clinical trial comparing step-up and step-down antacid drug treatment (The DIAMOND trial were analysed. Patients were genotyped for HTR3A c.-42C > T SNP and the 44 bp insertion/deletion polymorphism in the 5-HTT promoter (5-HTTLPR. Intensity of 8 dyspeptic symptoms at baseline was assessed using a validated questionnaire (0 = none; 6 = very severe. Sum score ≥20 was defined severe dyspepsia. Results HTR3A c.-42T allele carriers were more prevalent in patients with severe dyspepsia (OR 1.50, 95% CI 1.06-2.20. This association appeared to be stronger in females (OR 2.05, 95% CI 1.25-3.39 and patients homozygous for the long (L variant of the 5-HTTLPR genotype (OR 2.00, 95% CI 1.01-3.94. Females with 5-HTTLPR LL genotype showed the strongest association (OR = 3.50, 95% CI = 1.37-8.90. Conclusions The HTR3A c.-42T allele is associated with severe dyspeptic symptoms. The stronger association among

  10. Bilateral hand/wrist heat and cold hyperalgesia, but not hypoesthesia, in unilateral carpal tunnel syndrome.

    Science.gov (United States)

    de la Llave-Rincón, Ana Isabel; Fernández-de-las-Peñas, César; Fernández-Carnero, Josué; Padua, Luca; Arendt-Nielsen, Lars; Pareja, Juan A

    2009-10-01

    The aim of the current study was to evaluate bilaterally warm/cold detection and heat/cold pain thresholds over the hand/wrist in patients with carpal tunnel syndrome (CTS). A total of 25 women with strictly unilateral CTS (mean 42 +/- 10 years), and 20 healthy matched women (mean 41 +/- 8 years) were recruited. Warm/cold detection and heat/cold pain thresholds were assessed bilaterally over the carpal tunnel and the thenar eminence in a blinded design. Self-reported measures included both clinical pain history (intensity, location and area) and Boston Carpal Tunnel Questionnaire. No significant differences between groups for both warm and cold detection thresholds in either carpal tunnel or thenar eminence (P > 0.5) were found. Further, significant differences between groups, but not between sides, for both heat and cold pain thresholds in both the carpal tunnel and thenar eminence were found (all P < 0.001). Heat pain thresholds (P < 0.01) were negatively correlated, whereas cold pain thresholds (P < 0.001) were positively correlated with hand pain intensity and duration of symptoms. Our findings revealed bilateral thermal hyperalgesia (lower heat pain and reduced cold pain thresholds) but not hypoesthesia (normal warm/cold detection thresholds) in patients with strictly unilateral CTS when compared to controls. We suggest that bilateral heat and cold hyperalgesia may reflect impairments in central nociceptive processing in patients with unilateral CTS. The bilateral thermal hyperalgesia associated with pain intensity and duration of pain history supports a role of generalized sensitization mechanisms in the initiation, maintenance and spread of pain in CTS.

  11. The effect of the sex of a model on nocebo hyperalgesia induced by social observational learning.

    Science.gov (United States)

    Swider, Karolina; Bąbel, Przemysław

    2013-08-01

    Research shows that placebo analgesia can be induced through social observational learning. Our aim was to replicate and extend this result by studying the effect of the sex of both the model and the subject on the magnitude of placebo analgesia induced by social observational learning. Four experimental (1 through 4) and 2 control (5 and 6) groups were observed: groups 1, 3, and 5 were female; groups 2, 4, and 6 were male. All subjects received pain stimuli of the same intensity preceded by green and red lights. Before receiving pain stimuli, groups 1 and 4 observed a female model and groups 2 and 3 a male model; both models simulated responses to pain stimuli preceded by green lights as less painful than those preceded by red lights. Groups 1 through 4 also rated pain stimuli preceded by green lights as less painful. Further investigation revealed that in fact subjects in experimental groups rated red-associated stimuli as more painful than subjects from control groups who did not observe a model before receiving the same pain stimuli, indicating that nocebo hyperalgesia rather than placebo analgesia was induced. Empathy traits predicted the magnitude of nocebo hyperalgesia. Regardless of the sex of the subject, nocebo hyperalgesia was greater after the male model was observed. The results show that social observational learning is a mechanism that produces placebo effects. They also indicate that the sex of the model plays an important role in this process. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  12. Pharmacokinetic/Pharmacodynamic Relationship of Gabapentin in a CFA-induced Inflammatory Hyperalgesia Rat Model.

    Science.gov (United States)

    Larsen, Malte Selch; Keizer, Ron; Munro, Gordon; Mørk, Arne; Holm, René; Savic, Rada; Kreilgaard, Mads

    2016-05-01

    Gabapentin displays non-linear drug disposition, which complicates dosing for optimal therapeutic effect. Thus, the current study was performed to elucidate the pharmacokinetic/pharmacodynamic (PKPD) relationship of gabapentin's effect on mechanical hypersensitivity in a rat model of CFA-induced inflammatory hyperalgesia. A semi-mechanistic population-based PKPD model was developed using nonlinear mixed-effects modelling, based on gabapentin plasma and brain extracellular fluid (ECF) time-concentration data and measurements of CFA-evoked mechanical hyperalgesia following administration of a range of gabapentin doses (oral and intravenous). The plasma/brain ECF concentration-time profiles of gabapentin were adequately described with a two-compartment plasma model with saturable intestinal absorption rate (K m  = 44.1 mg/kg, V max  = 41.9 mg/h∙kg) and dose-dependent oral bioavailability linked to brain ECF concentration through a transit compartment. Brain ECF concentration was directly linked to a sigmoid E max function describing reversal of hyperalgesia (EC 50, plasma  = 16.7 μg/mL, EC 50, brain  = 3.3 μg/mL). The proposed semi-mechanistic population-based PKPD model provides further knowledge into the understanding of gabapentin's non-linear pharmacokinetics and the link between plasma/brain disposition and anti-hyperalgesic effects. The model suggests that intestinal absorption is the primary source of non-linearity and that the investigated rat model provides reasonable predictions of clinically effective plasma concentrations for gabapentin.

  13. Withania somnifera root extract prolongs analgesia and suppresses hyperalgesia in mice treated with morphine.

    Science.gov (United States)

    Orrù, Alessandro; Marchese, Giorgio; Casu, Gianluca; Casu, Maria Antonietta; Kasture, Sanjay; Cottiglia, Filippo; Acquas, Elio; Mascia, Maria Paola; Anzani, Nicola; Ruiu, Stefania

    2014-04-15

    Previous studies demonstrated that Withania somnifera Dunal (WS), a safe medicinal plant, prevents the development of tolerance to the analgesic effect of morphine. In the present study, we investigated whether WS extract (WSE) (100 mg/kg, i.p.) may also modulate the analgesic effect induced by acute morphine administration (2.5, 5, 10 mg/kg, s.c.) in the tail-flick and in the hot plate tests, and if it may prevent the development of 2.5 mg/kg morphine-induced rebound hyperalgesia in the low intensity tail-flick test. Further, to characterize the receptor(s) involved in these effects, we studied, by receptor-binding assay, the affinity of WSE for opioid (μ, δ, k), cannabinoid (CB1, CB2), glutamatergic (NMDA), GABAergic (GABAA, GABAB), serotoninergic (5HT2A) and adrenergic (α2) receptors. The results demonstrated that (i) WSE alone failed to alter basal nociceptive threshold in both tests, (ii) WSE pre-treatment significantly protracted the antinociceptive effect induced by 5 and 10 mg/kg of morphine only in tail-flick test, (iii) WSE pre-treatment prevented morphine-induced hyperalgesia in the low intensity tail-flick test, and (iv) WSE exhibited a high affinity for the GABAA and moderate affinity for GABAB, NMDA and δ opioid receptors. WSE prolongs morphine-induced analgesia and suppresses the development of morphine-induced rebound hyperalgesia probably through involvement of GABAA, GABAB, NMDA and δ opioid receptors. This study suggests the therapeutic potential of WSE as a valuable adjuvant agent in opioid-sparing therapies. Copyright © 2013 Elsevier GmbH. All rights reserved.

  14. Janus kinase 2 activation participates in prostaglandin E2-induced hyperalgesia.

    Science.gov (United States)

    Vieira, André Schwambach; Araldi, Dionéia; Dias, Elayne Vieira; do Prado, Filipe César; Tambeli, Claudia Herrera; Parada, Carlos Amilcar

    2016-12-01

    Prostaglandin E2 (PGE2) is one of the major signaling molecules involved in hyperalgesia, acting directly on nociceptors and resulting in the activation of PKA and PKC. Once active, these kinases phosphorylate many cellular proteins, resulting in changes on nociceptors sensorial transduction properties. The Janus Kinases (JAKs) are a family of intracellular signaling molecules generally associated with cytokine signaling, and their activity can be increased in nociceptors after peripheral inflammation. However, there are no evidences of JAKs direct involvement in PGE2 mediated sensitization of nociceptors. Therefore, the aim of the present study was to explore a possible role for JAKs in PGE2 mediated sensitization. In cultured dorsal root ganglion (DRG) neurons, we observed that the administration of PGE2 increases capsaicin induced calcium transients, and a pre-incubation of DRG cells with the JAK inhibitor AG490 blocks this PGE2 in vitro effect. Intrathecal administration of AG490 to ten-weeks-old male Wistar rats reduces the hyperalgesia induced by the intraplantar administration of PGE2 or carrageenan in the right hind paw. We also observed that carrageenan administration in the right hind paw induced an increase in membrane associated PKCepsilon in the ipsilateral L5 DRG, and this increase was blocked by intrathecal AG490 administration. In conclusion the present study indicates that the JAKs expressed in the DRG and spinal cord may have a role in the sensitization of nociceptors by a peripheral inflammatory event. Moreover, the inhibition of JAKs may be a possible novel pharmacological target for the control of the inflammatory hyperalgesia. Copyright © 2016. Published by Elsevier Inc.

  15. Metamizole (dipyrone) effects on sevoflurane requirements and postoperative hyperalgesia in rats.

    Science.gov (United States)

    Ruiz-Pérez, Daniel; Benito, Javier; Largo, Carlota; Polo, Gonzalo; Canfrán, Susana; Gómez de Segura, Ignacio Alvarez

    2017-08-01

    Unlike non-steroidal anti-inflammatory drugs (NSAIDs), metamizole has poor anti-inflammatory effects; and is suitable for models where analgesia, but not anti-inflammatory effects, is desirable. Like opioids, these drugs produce perioperative analgesia while reducing anaesthetic requirements, but it remains unclear whether they may develop tolerance or hyperalgesia, and thus decrease in analgesic efficacy. The aim was to determine whether tolerance or hyperalgesia to metamizole occurred in rats, and whether the sevoflurane minimum alveolar concentration (MAC) was affected. In a randomized, prospective, controlled study, male Wistar rats ( n = 8 per group) were administered metamizole (300 mg/kg, day 4). Previously, the following treatments were provided: daily metamizole for four days (0-3), morphine (10 mg/kg; positive control, day 0 only) or saline (negative control). The main outcome measures were mechanical (MNT) and warm thermal (WNT) nociceptive quantitative sensory thresholds. The baseline sevoflurane MAC and the reduction produced by the treatments were also determined. The mean (SD) baseline MAC [2.4(0.2)%vol] was decreased by morphine and metamizole by 45(11)% and 33(7)% ( P = 0.000, both), respectively. Baseline MNT [35.4(4.5) g] and WNT [13.2(2.4) s] were decreased by morphine and metamizole: MNT reduction of 22(6)% ( P = 0.000) and 22(7)% ( P = 0.001), respectively and WNT reduction of 34(14)% ( P = 0.000) and 24(13)% ( P = 0.001). The baseline MAC on day 4 was neither modified by treatments nor the MAC reduction produced by metamizole (days 0 and 4; P > 0.05). In conclusion, repeated metamizole administration may produce hyperalgesia, although it may not modify its anaesthetic sparing effect. The clinical relevance of this effect in painful research models requiring prolonged analgesic therapy warrants further investigation.

  16. How serotonin shapes moral judgment and behavior

    National Research Council Canada - National Science Library

    Siegel, Jenifer Z; Crockett, Molly J

    2013-01-01

    .... Here, we review recent studies showing how altering brain chemistry can alter moral judgment and behavior, focusing in particular on the neuromodulator serotonin and its role in shaping values...

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

    DEFF Research Database (Denmark)

    Pedersen, J L; Kehlet, H

    1998-01-01

    was demonstrated by significantly higher pain thresholds and lower pain responses on the second and third day of the study. The burn model is a sensitive psychophysical model of acute inflammatory pain, when cross-over designs and within-day comparisons are used, and the model is suitable for double-blind, placebo......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...

  18. KCNQ channels in nociceptive cold-sensing trigeminal ganglion neurons as therapeutic targets for treating orofacial cold hyperalgesia.

    Science.gov (United States)

    Abd-Elsayed, Alaa A; Ikeda, Ryo; Jia, Zhanfeng; Ling, Jennifer; Zuo, Xiaozhuo; Li, Min; Gu, Jianguo G

    2015-07-31

    Hyperexcitability of nociceptive afferent fibers is an underlying mechanism of neuropathic pain and ion channels involved in neuronal excitability are potentially therapeutic targets. KCNQ channels, a subfamily of voltage-gated K(+) channels mediating M-currents, play a key role in neuronal excitability. It is unknown whether KCNQ channels are involved in the excitability of nociceptive cold-sensing trigeminal afferent fibers and if so, whether they are therapeutic targets for orofacial cold hyperalgesia, an intractable trigeminal neuropathic pain. Patch-clamp recording technique was used to study M-currents and neuronal excitability of cold-sensing trigeminal ganglion neurons. Orofacial operant behavioral assessment was performed in animals with trigeminal neuropathic pain induced by oxaliplatin or by infraorbital nerve chronic constrictive injury. We showed that KCNQ channels were expressed on and mediated M-currents in rat nociceptive cold-sensing trigeminal ganglion (TG) neurons. The channels were involved in setting both resting membrane potentials and rheobase for firing action potentials in these cold-sensing TG neurons. Inhibition of KCNQ channels by linopirdine significantly decreased resting membrane potentials and the rheobase of these TG neurons. Linopirdine directly induced orofacial cold hyperalgesia when the KCNQ inhibitor was subcutaneously injected into rat orofacial regions. On the other hand, retigabine, a KCNQ channel potentiator, suppressed the excitability of nociceptive cold-sensing TG neurons. We further determined whether KCNQ channel could be a therapeutic target for orofacial cold hyperalgesia. Orofacial cold hyperalgesia was induced in rats either by the administration of oxaliplatin or by infraorbital nerve chronic constrictive injury. Using the orofacial operant test, we showed that retigabine dose-dependently alleviated orofacial cold hyperalgesia in both animal models. Taken together, these findings indicate that KCNQ channel plays a

  19. Acute type B aortic dissection complicated by visceral ischemia.

    Science.gov (United States)

    Jonker, Frederik H W; Patel, Himanshu J; Upchurch, Gilbert R; Williams, David M; Montgomery, Daniel G; Gleason, Thomas G; Braverman, Alan C; Sechtem, Udo; Fattori, Rossella; Di Eusanio, Marco; Evangelista, Arturo; Nienaber, Christoph A; Isselbacher, Eric M; Eagle, Kim A; Trimarchi, Santi

    2015-04-01

    Acute type B aortic dissection (ABAD) can lead to visceral malperfusion, a potentially life-threatening complication. The purpose of this study was to investigate the presentation, management, and outcomes of ABAD patients with visceral ischemia who are enrolled in the International Registry of Acute Aortic Dissection. Patients with ABAD enrolled in the registry between 1996 and 2013 were identified and stratified based on presence of visceral ischemia at admission. Demographics, medical history, imaging results, management, and outcomes were compared for patients with versus without visceral ischemia. A total of 1456 ABAD patients were identified, of which 104 (7.1%) presented with visceral ischemia. Preoperative limb ischemia (28% vs 7%, P < .001) and acute renal failure (41% vs 14%, P < .001) were more common among patients with visceral ischemia. Endovascular treatment and surgery were offered to 49% and 30% of the visceral ischemia cohort, respectively; remaining patients were managed conservatively. The in-hospital mortality was 30.8% for patients with visceral ischemia and 9.1% for those without visceral ischemia (odds ratio [OR] 4.44; 95% confidence interval [CI], 2.8-7.0, P < .0001). Mortality rates were similar after surgical and endovascular management of visceral ischemia (25.8% and 25.5%, respectively, P = not significant). Among the visceral ischemia group, medical management was a predictor of mortality in multivariate analysis (OR, 5.91; 95% CI, 1.2-31.0; P = .036). Patients with ABAD complicated by visceral ischemia have a high risk of mortality. We observed similar outcomes for patients treated by endovascular management versus surgery, whereas medical management was an independent predictor of mortality. Early diagnosis and intervention for visceral ischemia seems to be crucial. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  20. Enterochromaffin cell hyperplasia and decreased serotonin transporter in a mouse model of postinfectious bowel dysfunction.

    Science.gov (United States)

    Wheatcroft, J; Wakelin, D; Smith, A; Mahoney, C R; Mawe, G; Spiller, R

    2005-12-01

    Patients with postinfective irritable bowel syndrome and Trichinella spiralis-infected mice share many features including visceral hypersensitivity and disordered motility. We assessed enterochromaffin (EC) numbers and serotonin transporter (SERT) using National Institute of Health (NIH) female mice studied for up to 56 days post-T. spiralis infection. The effects of steroid treatment and the T-cell dependence of the observed responses were assessed by infection of hydrocortisone-treated or T-cell receptor knock out [TCR (betaxdelta) KO] animals. Enterochromaffin cell density in uninfected animals increased from duodenum 10.0 cells mm-2 (5.9-41.0) to colon 61.8. (46.3-162) cells mm-2 PIBS, and reduces SERT. This may increase mucosal 5HT availability and contribute to the clinical presentation of PI-IBS.

  1. Endemic transmission of visceral leishmaniasis in Bhutan.

    Science.gov (United States)

    Yangzom, Thinley; Cruz, Israel; Bern, Caryn; Argaw, Daniel; den Boer, Margriet; Vélez, Iván Dario; Bhattacharya, Sujit K; Molina, Ricardo; Alvar, Jorge

    2012-12-01

    Visceral leishmaniasis was first reported in Bhutan in 2006. We conducted studies of the parasite, possible vectors and reservoirs, and leishmanin skin test and risk factor surveys in three villages. Nineteen cases were reported from seven districts. Parasite typing yielded two novel microsatellite sequences, both related to Indian L. donovani. In one case village, 40 (18.5%) of 216 participants had positive leishmanin skin test results, compared with 3 (4.2%) of 72 in the other case village and 0 of 108 in the control village. Positive results were strongly associated with the village and increasing age. None of the tested dogs were infected. Eighteen sand flies were collected, 13 Phlebotomus species and 5 Sergentomyia species; polymerase chain reaction for leishmanial DNA was negative. This assessment suggests that endemic visceral leishmaniasis transmission has occurred in diverse locations in Bhutan. Surveillance, case investigations, and further parasite, vector, and reservoir studies are needed. The potential protective impact of bed nets should be evaluated.

  2. The Valjean effect: Visceral states and cheating.

    Science.gov (United States)

    Williams, Elanor F; Pizarro, David; Ariely, Dan; Weinberg, James D

    2016-09-01

    Visceral states like thirst, hunger, and fatigue can alter motivations, predictions, and even memory. Across 3 studies, we demonstrate that such "hot" states can also shift moral standards and increase dishonest behavior. Compared to participants who had just eaten or who had not yet exercised, hungry and thirsty participants were more likely to behave dishonestly to win a prize. Consistent with the specificity of motivation that is characteristic of visceral states, participants were only more likely to cheat for a prize that could alleviate their current deprived state (such as a bottle of water). Interestingly, this increase in dishonest behavior did not seem to be driven by an increase in the perceived monetary value of the prize. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  3. Immunity to visceral leishmaniasis: implications for immunotherapy.

    Science.gov (United States)

    Khadem, Forough; Uzonna, Jude E

    2014-01-01

    Visceral leishmaniasis, caused by Leishmania donovani, L. infantum (syn. Leishmania chagasi), is a globally widespread disease with a burden of about 400,000 new infections reported annually. It is the most dangerous form of human leishmaniasis in terms of mortality and morbidity and is spreading to several nonendemic areas because of migration, global traveling and military conflicts. The emergence of Leishmania-HIV co-infection and increased prevalence of drug-resistant strains have worsened the impact of the disease. The traditional low-cost drugs are often toxic with several adverse effects, highlighting the need for development of new therapeutic and prophylactic strategies. Therefore, a detailed understanding of mechanisms of protective immunity is extremely important in order to develop new therapeutics in the form of vaccines or immunotherapies. This review gives an overview of visceral leishmaniasis, with particular emphasis on the innate and adaptive immune responses, vaccine and vaccination strategies and their potentials for immunotherapy against the disease.

  4. Management of visceral leishmaniasis: Indian perspective

    OpenAIRE

    Agrawal S; Rai M; Sundar S

    2005-01-01

    Diagnosis and treatment of Indian visceral leishmaniasis (VL) is extremely unsatisfactory. For diagnosis, demonstration of parasites in splenic/marrow smears remains the gold standard, though k39 rapid strip test is a useful method in regions where access to parasite demonstration is difficult. pentavalent antimony remains the mainstay for the treatment of all forms of leishmaniasis globally; however, development of large-scale antimony resistance in Bihar has necessitated search for alternat...

  5. Visceral adiposity, insulin resistance and cancer risk

    LENUS (Irish Health Repository)

    Donohoe, Claire L

    2011-06-22

    Abstract Background There is a well established link between obesity and cancer. Emerging research is characterising this relationship further and delineating the specific role of excess visceral adiposity, as opposed to simple obesity, in promoting tumorigenesis. This review summarises the evidence from an epidemiological and pathophysiological perspective. Methods Relevant medical literature was identified from searches of PubMed and references cited in appropriate articles identified. Selection of articles was based on peer review, journal and relevance. Results Numerous epidemiological studies consistently identify increased risk of developing carcinoma in the obese. Adipose tissue, particularly viscerally located fat, is metabolically active and exerts systemic endocrine effects. Putative pathophysiological mechanisms linking obesity and carcinogenesis include the paracrine effects of adipose tissue and systemic alterations associated with obesity. Systemic changes in the obese state include chronic inflammation and alterations in adipokines and sex steroids. Insulin and the insulin-like growth factor axis influence tumorigenesis and also have a complex relationship with adiposity. There is evidence to suggest that insulin and the IGF axis play an important role in mediating obesity associated malignancy. Conclusions There is much evidence to support a role for obesity in cancer progression, however further research is warranted to determine the specific effect of excess visceral adipose tissue on tumorigenesis. Investigation of the potential mechanisms underpinning the association, including the role of insulin and the IGF axis, will improve understanding of the obesity and cancer link and may uncover targets for intervention.

  6. Regulation of immunity during visceral Leishmania infection.

    Science.gov (United States)

    Rodrigues, Vasco; Cordeiro-da-Silva, Anabela; Laforge, Mireille; Silvestre, Ricardo; Estaquier, Jérôme

    2016-03-01

    Unicellular eukaryotes of the genus Leishmania are collectively responsible for a heterogeneous group of diseases known as leishmaniasis. The visceral form of leishmaniasis, caused by L. donovani or L. infantum, is a devastating condition, claiming 20,000 to 40,000 lives annually, with particular incidence in some of the poorest regions of the world. Immunity to Leishmania depends on the development of protective type I immune responses capable of activating infected phagocytes to kill intracellular amastigotes. However, despite the induction of protective responses, disease progresses due to a multitude of factors that impede an optimal response. These include the action of suppressive cytokines, exhaustion of specific T cells, loss of lymphoid tissue architecture and a defective humoral response. We will review how these responses are orchestrated during the course of infection, including both early and chronic stages, focusing on the spleen and the liver, which are the main target organs of visceral Leishmania in the host. A comprehensive understanding of the immune events that occur during visceral Leishmania infection is crucial for the implementation of immunotherapeutic approaches that complement the current anti-Leishmania chemotherapy and the development of effective vaccines to prevent disease.

  7. Visceral Afferent Pathways and Functional Brain Imaging

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    Stuart W.G. Derbyshire

    2003-01-01

    Full Text Available The application of functional imaging to study painful sensations has generated considerable interest regarding insight into brain dysfunction that may be responsible for functional pain such as that suffered in patients with irritable bowel syndrome (IBS. This review provides a brief introduction to the development of brain science as it relates to pain processing and a snapshot of recent functional imaging results with somatic and visceral pain. Particular emphasis is placed on current hypotheses regarding dysfunction of the brain-gut axis in IBS patients. There are clear and interpretable differences in brain activation following somatic as compared with visceral noxious sensation. Noxious visceral distension, particularly of the lower gastrointestinal tract, activates regions associated with unpleasant affect and autonomic responses. Noxious somatic sensation, in contrast, activates regions associated with cognition and skeletomotor responses. Differences between IBS patients and control subjects, however, were far less clear and interpretable. While this is in part due to the newness of this field, it also reflects weaknesses inherent within the current understanding of IBS. Future use of functional imaging to examine IBS and other functional disorders will be more likely to succeed by describing clear theoretical and clinical endpoints.

  8. Do selective serotonin reuptake inhibitors acutely increase frontal cortex levels of serotonin?

    NARCIS (Netherlands)

    Beyer, Chad E.; Cremers, Thomas I. F. H.

    2008-01-01

    Selective serotonin uptake inhibitors (SSRIs) exert their effects by inhibiting serotonin (5-HT) re-uptake. Although blockade occurs almost immediately, the neurochemical effects on 5-HT, as measured by in vivo microdialysis, have been a matter of considerable debate. In particular, literature

  9. Inhibition of Calotropis procera Latex-Induced Inflammatory Hyperalgesia by Oxytocin and Melatonin

    Science.gov (United States)

    Padhy, Biswa M.; Kumar, Vijay L.

    2005-01-01

    The latex of the wild growing plant Calotropis procera produces inflammation of the skin and mucous membranes upon accidental exposure. On local administration it elicits an intense inflammatory response due to the release of histamine and prostaglandins that is associated with hyperalgesia. In the present study we have evaluated the anti-inflammatory and antinociceptive activity of oxytocin and melatonin against rat paw edema induced by dried latex (DL) of C procera and compared it with that against carrageenan-induced paw edema. Aqueous extract of DL of C procera or carrageenan (1%) was injected into the subplantar surface of the rat paw and the paw volume was measured at 0, 1, 2, 3, 4, 6, 10, and 24 hours. The associated hyperalgesic response and functional impairment were also evaluated concomitantly by dorsal flexion pain test, motility test, and stair climbing ability test. The inhibitory effect of oxytocin and melatonin on edema formation and hyperalgesic response was compared with dexamethasone. DL-induced edema formation was maximum at 2 hours and was associated with decreased pain threshold and functional impairment. Treatment with melatonin significantly attenuated the edematous response while both oxytocin and melatonin increased the pain threshold and improved functional parameters. Both oxytocin and melatonin significantly inhibited the hyperalgesia associated with DL-induced paw edema. Oxytocin was found to be as effective as melatonin in ameliorating the hyperalgesic response. However, it was found to be less effective than melatonin in attenuating edema formation. PMID:16489256

  10. Classical conditioning without verbal suggestions elicits placebo analgesia and nocebo hyperalgesia.

    Science.gov (United States)

    Bąbel, Przemysław; Bajcar, Elżbieta A; Adamczyk, Wacław; Kicman, Paweł; Lisińska, Natalia; Świder, Karolina; Colloca, Luana

    2017-01-01

    The aim of this study was to examine the relationships among classical conditioning, expectancy, and fear in placebo analgesia and nocebo hyperalgesia. A total of 42 healthy volunteers were randomly assigned to three groups: placebo, nocebo, and control. They received 96 electrical stimuli, preceded by either orange or blue lights. A hidden conditioning procedure, in which participants were not informed about the meaning of coloured lights, was performed in the placebo and nocebo groups. Light of one colour was paired with pain stimuli of moderate intensity (control stimuli), and light of the other colour was paired with either nonpainful stimuli (in the placebo group) or painful stimuli of high intensity (in the nocebo group). In the control group, both colour lights were followed by control stimuli of moderate intensity without any conditioning procedure. Participants rated pain intensity, expectancy of pain intensity, and fear. In the testing phase, when both of the coloured lights were followed by identical moderate pain stimuli, we found a significant analgesic effect in the placebo group, and a significant hyperalgesic effect in the nocebo group. Neither expectancy nor fear ratings predicted placebo analgesia or nocebo hyperalgesia. It appears that a hidden conditioning procedure, without any explicit verbal suggestions, elicits placebo and nocebo effects, however we found no evidence that these effects are predicted by either expectancy or fear. These results suggest that classical conditioning may be a distinct mechanism for placebo and nocebo effects.

  11. Classical conditioning without verbal suggestions elicits placebo analgesia and nocebo hyperalgesia.

    Directory of Open Access Journals (Sweden)

    Przemysław Bąbel

    Full Text Available The aim of this study was to examine the relationships among classical conditioning, expectancy, and fear in placebo analgesia and nocebo hyperalgesia. A total of 42 healthy volunteers were randomly assigned to three groups: placebo, nocebo, and control. They received 96 electrical stimuli, preceded by either orange or blue lights. A hidden conditioning procedure, in which participants were not informed about the meaning of coloured lights, was performed in the placebo and nocebo groups. Light of one colour was paired with pain stimuli of moderate intensity (control stimuli, and light of the other colour was paired with either nonpainful stimuli (in the placebo group or painful stimuli of high intensity (in the nocebo group. In the control group, both colour lights were followed by control stimuli of moderate intensity without any conditioning procedure. Participants rated pain intensity, expectancy of pain intensity, and fear. In the testing phase, when both of the coloured lights were followed by identical moderate pain stimuli, we found a significant analgesic effect in the placebo group, and a significant hyperalgesic effect in the nocebo group. Neither expectancy nor fear ratings predicted placebo analgesia or nocebo hyperalgesia. It appears that a hidden conditioning procedure, without any explicit verbal suggestions, elicits placebo and nocebo effects, however we found no evidence that these effects are predicted by either expectancy or fear. These results suggest that classical conditioning may be a distinct mechanism for placebo and nocebo effects.

  12. SHANK3 Deficiency Impairs Heat Hyperalgesia and TRPV1 Signaling in Primary Sensory Neurons.

    Science.gov (United States)

    Han, Qingjian; Kim, Yong Ho; Wang, Xiaoming; Liu, Di; Zhang, Zhi-Jun; Bey, Alexandra L; Lay, Mark; Chang, Wonseok; Berta, Temugin; Zhang, Yan; Jiang, Yong-Hui; Ji, Ru-Rong

    2016-12-21

    Abnormal pain sensitivity is commonly associated with autism spectrum disorders (ASDs) and affects the life quality of ASD individuals. SHANK3 deficiency was implicated in ASD and pain dysregulation. Here, we report functional expression of SHANK3 in mouse dorsal root ganglion (DRG) sensory neurons and spinal cord presynaptic terminals. Homozygous and heterozygous Shank3 complete knockout (Δe4-22) results in impaired heat hyperalgesia in inflammatory and neuropathic pain. Specific deletion of Shank3 in Nav1.8-expressing sensory neurons also impairs heat hyperalgesia in homozygous and heterozygous mice. SHANK3 interacts with transient receptor potential subtype V1 (TRPV1) via Proline-rich region and regulates TRPV1 surface expression. Furthermore, capsaicin-induced spontaneous pain, inward currents in DRG neurons, and synaptic currents in spinal cord neurons are all reduced after Shank3 haploinsufficiency. Finally, partial knockdown of SHANK3 expression in human DRG neurons abrogates TRPV1 function. Our findings reveal a peripheral mechanism of SHANK3, which may underlie pain deficits in SHANK3-related ASDs. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Sex differences and estradiol involvement in hyperalgesia and allodynia in an experimental model of fibromyalgia.

    Science.gov (United States)

    Hernandez-Leon, Alberto; De la Luz-Cuellar, Yarim Elideth; Granados-Soto, Vinicio; González-Trujano, María Eva; Fernández-Guasti, Alonso

    2017-11-08

    Fibromyalgia (FM) is a musculoskeletal chronic pain syndrome. Its prevalence in women is higher than in men possibly by hormonal factors given that symptoms are aggravated during sex hormone-related events, such as the premenstrual period, pregnancy, postpartum or menopause. The aim of the present study was to investigate whether hyperalgesia and allodynia, in reserpine-induced experimental FM, depend on sex, estrous cycle, ovariectomy and replacement with 17β-estradiol. To fulfill this objective, we compared males, intact females with known estrous cycle phases and ovariectomized (OVX) rats treated with 17β-estradiol. Data demonstrated that reserpine administration disrupted the normal estrous cycle and produced that all females entered metestrus/diestrus. In addition, this treatment leads to muscle hyperalgesia and tactile allodynia in a similar manner in male and intact female rats. However, the absence of ovarian hormones (in OVX rats) increased muscle nociception. 17β-estradiol (2.5-10μg/rat) produced antihyperalgesic and antiallodynic effects 24h, but not 8h, after its administration, suggesting a genomic mechanism. The present results support the validity of the reserpine-induced FM model for searching alternatives of treatment, particularly during endocrine phases when pain is exacerbated such as menopause, and that 17β-estradiol replacement might be useful. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Detection of cold pain, cold allodynia and cold hyperalgesia in freely behaving rats

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    Woolf Clifford J

    2005-12-01

    Full Text Available Abstract Background Pain is elicited by cold, and a major feature of many neuropathic pain states is that normally innocuous cool stimuli begin to produce pain (cold allodynia. To expand our understanding of cold induced pain states we have studied cold pain behaviors over a range of temperatures in several animal models of chronic pain. Results We demonstrate that a Peltier-cooled cold plate with ± 1°C sensitivity enables quantitative measurement of a detection withdrawal response to cold stimuli in unrestrained rats. In naïve rats the threshold for eliciting cold pain behavior is 5°C. The withdrawal threshold for cold allodynia is 15°C in both the spared nerve injury and spinal nerve ligation models of neuropathic pain. Cold hyperalgesia is present in the spared nerve injury model animals, manifesting as a reduced latency of withdrawal response threshold at temperatures that elicit cold pain in naïve rats. We also show that following the peripheral inflammation produced by intraplantar injection of complete Freund's adjuvant, a hypersensitivity to cold occurs. Conclusion The peltier-cooled provides an effective means of assaying cold sensitivity in unrestrained rats. Behavioral testing of cold allodynia, hyperalgesia and pain will greatly facilitate the study of the neurobiological mechanisms involved in cold/cool sensations and enable measurement of the efficacy of pharmacological treatments to reduce these symptoms.

  15. Immunomodulatory Effects Mediated by Serotonin

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    Rodrigo Arreola

    2015-01-01

    Full Text Available Serotonin (5-HT induces concentration-dependent metabolic effects in diverse cell types, including neurons, entherochromaffin cells, adipocytes, pancreatic beta-cells, fibroblasts, smooth muscle cells, epithelial cells, and leukocytes. Three classes of genes regulating 5-HT function are constitutively expressed or induced in these cells: (a membrane proteins that regulate the response to 5-HT, such as SERT, 5HTR-GPCR, and the 5HT3-ion channels; (b downstream signaling transduction proteins; and (c enzymes controlling 5-HT metabolism, such as IDO and MAO, which can generate biologically active catabolites, including melatonin, kynurenines, and kynurenamines. This review covers the clinical and experimental mechanisms involved in 5-HT-induced immunomodulation. These mechanisms are cell-specific and depend on the expression of serotonergic components in immune cells. Consequently, 5-HT can modulate several immunological events, such as chemotaxis, leukocyte activation, proliferation, cytokine secretion, anergy, and apoptosis. The effects of 5-HT on immune cells may be relevant in the clinical outcome of pathologies with an inflammatory component. Major depression, fibromyalgia, Alzheimer disease, psoriasis, arthritis, allergies, and asthma are all associated with changes in the serotonergic system associated with leukocytes. Thus, pharmacological regulation of the serotonergic system may modulate immune function and provide therapeutic alternatives for these diseases.

  16. Immunomodulatory Effects Mediated by Serotonin

    Science.gov (United States)

    Arreola, Rodrigo; Becerril-Villanueva, Enrique; Cruz-Fuentes, Carlos; Velasco-Velázquez, Marco Antonio; Garcés-Alvarez, María Eugenia; Hurtado-Alvarado, Gabriela; Quintero-Fabian, Saray; Pavón, Lenin

    2015-01-01

    Serotonin (5-HT) induces concentration-dependent metabolic effects in diverse cell types, including neurons, entherochromaffin cells, adipocytes, pancreatic beta-cells, fibroblasts, smooth muscle cells, epithelial cells, and leukocytes. Three classes of genes regulating 5-HT function are constitutively expressed or induced in these cells: (a) membrane proteins that regulate the response to 5-HT, such as SERT, 5HTR-GPCR, and the 5HT3-ion channels; (b) downstream signaling transduction proteins; and (c) enzymes controlling 5-HT metabolism, such as IDO and MAO, which can generate biologically active catabolites, including melatonin, kynurenines, and kynurenamines. This review covers the clinical and experimental mechanisms involved in 5-HT-induced immunomodulation. These mechanisms are cell-specific and depend on the expression of serotonergic components in immune cells. Consequently, 5-HT can modulate several immunological events, such as chemotaxis, leukocyte activation, proliferation, cytokine secretion, anergy, and apoptosis. The effects of 5-HT on immune cells may be relevant in the clinical outcome of pathologies with an inflammatory component. Major depression, fibromyalgia, Alzheimer disease, psoriasis, arthritis, allergies, and asthma are all associated with changes in the serotonergic system associated with leukocytes. Thus, pharmacological regulation of the serotonergic system may modulate immune function and provide therapeutic alternatives for these diseases. PMID:25961058

  17. Sarcopenia and Visceral Obesity in Esophageal and Gastric Cancer

    Science.gov (United States)

    2017-02-17

    Esophageal Cancer; Gastric Cancer; Sarcopenia; Sarcopenic Obesity; Obesity; Visceral Obesity; Quality of Life; Surgery; Complication of Treatment; Chemotherapeutic Toxicity; Physical Activity; Oncology

  18. Heat pain detection threshold is associated with the area of secondary hyperalgesia following brief thermal sensitization: a study of healthy male volunteers

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    Hansen MS

    2017-01-01

    Full Text Available Morten Sejer Hansen,1 Jørn Wetterslev,2 Christian Bressen Pipper,3 Mohammad Sohail Asghar,1 Jørgen Berg Dahl4 1Department of Anesthesiology, 4231, Centre of Head and Orthopedics, Rigshospitalet, 2Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, 3Section of Biostatistics, Faculty of Health, Copenhagen University, Copenhagen, 4Department of Anesthesiology, Department Z, Bispebjerg Hospital, Copenhagen, Denmark Introduction: The area of secondary hyperalgesia following brief thermal sensitization (BTS of the skin and heat pain detection thresholds (HPDT may both have predictive abilities in regards to pain sensitivity and clinical pain states. The association between HPDT and secondary hyperalgesia, however, remains unsettled, and the dissimilarities in physiologic properties suggest that they may represent 2 distinctively different pain entities. The aim of this study was to investigate the association between HPDT and BTS-induced secondary hyperalgesia. Methods: A sample of 121 healthy male participants was included and tested on 2 separate study days with BTS (45°C, 3 minutes, HPDT, and pain during thermal stimulation (45°C, 1 minute. Areas of secondary hyperalgesia were quantified after monofilament pinprick stimulation. The pain catastrophizing scale (PCS and hospital anxiety and depression scale (HADS were also applied. Results: A significant association between HPDT and the size of the area of secondary hyperalgesia (p<0.0001 was found. The expected change in area of secondary hyperalgesia due to a 1-degree increase in HPDT was estimated to be −27.38 cm2, 95% confidence interval (CI of −37.77 to −16.98 cm2, with an R2 of 0.19. Likewise, a significant association between HADS-depression subscore and area of secondary hyperalgesia (p=0.046 was found, with an estimated expected change in secondary hyperalgesia to a 1-point increase in HADS-depression subscore of 11 cm2, 95% CI (0.19–21.82, and with

  19. Toll-like receptor 4 mutant and null mice retain morphine-induced tolerance, hyperalgesia, and physical dependence.

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    Theresa Alexandra Mattioli

    Full Text Available The innate immune system modulates opioid-induced effects within the central nervous system and one target that has received considerable attention is the toll-like receptor 4 (TLR4. Here, we examined the contribution of TLR4 in the development of morphine tolerance, hyperalgesia, and physical dependence in two inbred mouse strains: C3H/HeJ mice which have a dominant negative point mutation in the Tlr4 gene rendering the receptor non-functional, and B10ScNJ mice which are TLR4 null mutants. We found that neither acute antinociceptive response to a single dose of morphine, nor the development of analgesic tolerance to repeated morphine treatment, was affected by TLR4 genotype. Likewise, opioid induced hyperalgesia and opioid physical dependence (assessed by naloxone precipitated withdrawal were not altered in TLR4 mutant or null mice. We also examined the behavioural consequence of two stereoisomers of naloxone: (- naloxone, an opioid receptor antagonist, and (+ naloxone, a purported antagonist of TLR4. Both stereoisomers of naloxone suppressed opioid induced hyperalgesia in wild-type control, TLR4 mutant, and TLR4 null mice. Collectively, our data suggest that TLR4 is not required for opioid-induced analgesic tolerance, hyperalgesia, or physical dependence.

  20. Behavioral and molecular processing of visceral pain in the brain of mice: impact of colitis and psychological stress

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    Piyush eJain

    2015-07-01

    Full Text Available Gastrointestinal disorders with abdominal pain are associated with central sensitization and psychopathologies that are often exacerbated by stress. Here we investigated the impact of colitis induced by dextran sulfate sodium (DSS and repeated water avoidance stress (WAS on spontaneous and nociception-related behavior and molecular signaling in the mouse brain. DSS increased the mechanical pain sensitivity of the abdominal skin while both WAS and DSS enhanced the mechanical and thermal pain sensitivity of the plantar skin. These manifestations of central sensitization were associated with augmented c-Fos expression in spinal cord, thalamus, hypothalamus, amygdala and prefrontal cortex. While WAS stimulated phosphorylation of mitogen-activated protein kinase (MAPK p42/44, DSS activated another signaling pathway, both of which converged on c-Fos. The DSS- and WAS-induced hyperalgesia in the abdominal and plantar skin and c-Fos expression in the brain disappeared when the mice were subjected to WAS+DSS treatment. Intrarectal allyl isothiocyanate (AITC evoked aversive behavior (freezing, reduction of locomotion and exploration in association with p42/44 MAPK and c-Fos activation in spinal cord and brain. These effects were inhibited by morphine, which attests to their relationship with nociception. DSS and WAS exerted opposite effects on AITC-evoked p42/44 MAPK and c-Fos activation, which indicates that these transduction pathways subserve different aspects of visceral pain processing in the brain. In summary, behavioral perturbations caused by colitis and psychological stress are associated with distinct alterations in cerebral signaling. These findings provide novel perspectives on central sensitization and the sensory and emotional processing of visceral pain stimuli in the brain.

  1. alpha 1-Adrenoceptors modulate citalopram-induced serotonin release

    NARCIS (Netherlands)

    Rea, Kieran; Folgering, Joost; Westerink, Ben H. C.; Cremers, Thomas I. F. H.

    Previous studies suggest that noradrenaline may regulate serotonergic (5-HT) neurotransmission at the serotonin cell body and noradrenaline nerve terminal. Using microdialysis coupled to HPLC, we investigated the effects of alpha 1-adrenoceptor manipulation on extracellular serotonin levels in the

  2. Temperament, character and serotonin activity in the human brain

    DEFF Research Database (Denmark)

    Tuominen, L; Salo, J; Hirvonen, J

    2013-01-01

    The psychobiological model of personality by Cloninger and colleagues originally hypothesized that interindividual variability in the temperament dimension 'harm avoidance' (HA) is explained by differences in the activity of the brain serotonin system. We assessed brain serotonin transporter (5-HTT...

  3. Assessment of incising ethology in the absence and presence of jaw muscle hyperalgesia in a mouse home cage environment.

    Science.gov (United States)

    Widmer, C G; Morris-Wiman, J

    2015-10-01

    Assessment of oral motor behavior in a mouse is challenging due to the lack of currently available techniques that are non-invasive and allow long-term assessment in a home cage environment. The purpose of this study was to evaluate incising behavior using mouse chow attached to a three-dimensional force transducer that was mounted on the existing home cage. In addition, a persistent hyperalgesia condition was introduced to evaluate the sensitivity of the technique to identify incising behavioral changes. Incising activity of CD-1 male and female mice (n=48) was evaluated over a 24 hour recording session during four baseline and six longitudinal hyperalgesia assessment sessions using custom written software. A pre-clinical persistent pain model was used to induce hyperalgesia in the masseter muscle by repetitive acidic saline injections. Sex and age differences were evaluated for multiple incising variables during both light and dark cycles during baseline and hyperalgesia conditions. Significant sex differences were found for multiple incising variables but not for age. Discrete incising frequencies were identified in the range of 4.6-10.4 Hz and were reproducibly found in both female and male mice. A significant shift to lower incising frequencies was observed after repetitive acidic saline injections compared to neutral saline injections. This shift to lower frequencies of incising returned to baseline levels after approximately four weeks but was statistically longer in female compared to male mice. Significant differences were also found for chow intake (reduced) and weight change during the hyperalgesia condition. No significant differences were found for total number of incisions or number of incising episodes per day or incising force. The findings from this study support the use of recording three dimensional incising forces as a sensitive measure of incising behavior. This novel technique allowed the identification of specific incising variables that were

  4. Repeated local administration of noradrenaline or saline inhibits thermal hyperalgesia in pain-sensitized human skin

    Science.gov (United States)

    Drummond, Peter D; Lipnicki, Darren M

    2001-01-01

    Aims Noradrenaline increases thermal hyperalgesia in skin sensitized to heat by the topical application of capsaicin. The aim of this study was to determine whether desensitization to the hyperalgesic effects of noradrenaline would develop after repeated local administrations of noradrenaline in the skin of the forearm. Methods Noradrenaline and saline were administered to the forearm by iontophoresis (200 µA, 2 min, over a surface area of 3.1 cm2) two times per day for 4–10 days in 19 healthy subjects. The adequacy of the desensitization procedure was evaluated by measuring noradrenaline-induced vasoconstriction with laser Doppler fluxmetry. Thresholds and pain ratings to heat were then investigated at treated and control sites before and after the topical application of capsaicin, and after the iontophoresis of noradrenaline. Results At previously untreated sites blood flow was 49 ± 14% (± 95% confidence intervals) lower than flow at reference sites after the iontophoresis of noradrenaline. Vascular signs of adrenergic desensitization developed after 4–5 days of repeated local administration of noradrenaline in the majority of subjects. In those whose vessels constricted after the acute administration of noradrenaline, the adrenergic response averaged 23 ± 15% at the desensitized site compared with 61 ± 9% at previously untreated sites (P noradrenaline and saline treatments inhibited thermal hyperalgesia after the topical application of capsaicin. Heat-pain thresholds averaged 43.2 ± 2.5 °C and 43.0 ± 2.3 °C at the noradrenaline and saline pretreated sites compared with 41.4 ± 2.7 °C at the control site (P noradrenaline and saline pretreated sites compared with 5.3 ± 1.6 at the control site (P noradrenaline heat-pain ratings increased 1.6 ± 1.4 at the site pretreated with saline (P noradrenaline (not significant), consistent with local adrenergic desensitization. Conclusions We conclude that repeated iontophoreses of noradrenaline or saline

  5. Pregabalin reduces opioid consumption and hyperalgesia but not pain intensity after laparoscopic donor nephrectomy.

    Science.gov (United States)

    Myhre, M; Romundstad, L; Stubhaug, A

    2017-11-01

    Gabapentinoids are increasingly used to reduce acute postoperative pain, opioid consumption and opioid-related adverse effects. We explored the opioid-sparing, analgesic and anti-hyperalgesic effect of perioperative administered pregabalin in laparoscopic living donor nephrectomy. In this randomized controlled trial, 80 patients were recruited and randomized to receive pregabalin 150 mg twice daily or placebo on the day of surgery and the first postoperative day as part of a multimodal analgesic regimen. Primary outcome was opioid consumption 0-48 h after surgery. Secondary outcomes were pain intensity at rest and with movement 0-48 h after surgery using the 0-10 Numeric Rating Scale and incisional hyperalgesia measured 24 h post-surgery and at hospital discharge. Further secondary outcomes were adverse effects. Persistent post-surgical pain was registered 6 weeks, 6 and 12 months after surgery. Pregabalin significantly reduced opioid consumption compared with placebo 0-48 h after surgery (median mg [25th, 75th percentile]); 29.0 (22.0-45.5) vs. 41.8 (25.8-63.6) (P = 0.04). Pain intensity 0-48 h after surgery calculated as area under the pain (NRS) vs. time curve was not statistically different between groups at rest (P = 0.12) or with movement (P = 0.21). Pregabalin decreased incisional hyperalgesia 24 h after surgery (median cm [25th, 75th percentile] 8.5 (1.0-18.5) vs. 15.5 (9.5-24.0) (P = 0.02). Nausea (P ≤ 0.01), use of antiemetics (P ≤ 0.01) and pain-related sleep interference (P = 0.02) were reduced with pregabalin. Perioperative pregabalin added to a multimodal analgesic regimen was opioid-sparing, but made no difference to pain intensity score 0-48 h after surgery. Pregabalin may reduce incisional hyperalgesia on the first day after surgery. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  6. Apical constriction in distal visceral endoderm cells initiates global, collective cell rearrangement in embryonic visceral endoderm to form anterior visceral endoderm.

    Science.gov (United States)

    Shioi, Go; Hoshino, Hideharu; Abe, Takaya; Kiyonari, Hiroshi; Nakao, Kazuki; Meng, Wenxiang; Furuta, Yasuhide; Fujimori, Toshihiko; Aizawa, Shinichi

    2017-09-01

    The behavior of visceral endoderm cells was examined as the anterior visceral endoderm (AVE) formed from the distal visceral endoderm (DVE) using the mouse lines R26-H2B-EGFP and R26-PHA7-EGFP to visualize cell nuclei and adherens junction, respectively. The analysis using R26-H2B-EGFP demonstrated global cell rearrangement that was not specific to the DVE cells in the monolayer embryonic visceral endoderm sheet; each population of the endoderm cells moved collectively in a swirling movement as a whole. Most of the AVE cells at E6.5 were not E5.5 DVE cells but were E5.5 cells that were located caudally behind them, as previously reported (Hoshino et al., 2015; Takaoka et al., 2011). In the rearrangement, the posterior embryonic visceral endoderm cells did not move, as extraembryonic visceral endoderm cells did not, and they constituted a distinct population during the process of anterior-posterior axis formation. The analysis using R26-PHA7-EGFP suggested that constriction of the apical surfaces of the cells in prospective anterior portion of the DVE initiated the global cellular movement of the embryonic visceral endoderm to drive AVE formation. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. The serotonin transporter in psychiatric disorders

    DEFF Research Database (Denmark)

    Spies, Marie; Knudsen, Karen Birgitte Moos; Lanzenberger, Rupert

    2015-01-01

    of various psychiatric disorders and their treatment. We review studies that use PET to measure cerebral serotonin transporter activity in psychiatric disorders, focusing on major depressive disorder and antidepressant treatment. We also discuss opportunities and limitations in the application...... of this neuroimaging method in clinical practice. Although results from individual studies diverge, meta-analysis indicates a trend towards reduced serotonin transporter availability in patients with major depressive disorder. Inconsistencies in results might suggest symptom heterogeneity in major depressive disorder...... and might therefore be relevant for stratification of patients into clinical subsets. PET has enabled the elucidation of mechanisms of response to selective serotonin reuptake inhibitors (SSRIs) and hence provides a basis for rational pharmacological treatment of major depressive disorder. Such imaging...

  8. Larva migrans visceral: relato de caso Visceral larva migrans: case report

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    Alexandre Bortoli Machado

    2003-04-01

    Full Text Available Larva migrans visceral é doença infecciosa, adquirida por ingestão de ovos provenientes dos vermes Toxocara canis e/ou Toxocara cati que infestam cães e gatos; as larvas penetram a parede intestinal e migram através dos tecidos levando a alterações diversas, conseqüentes a uma resposta inflamatória imune.¹ Os autores descrevem um caso clínico de larva migrans visceral com apresentação clínica atípica.Visceral larva migrans is an infectious human disease that occurs following ingestion of eggs from the environment originating from roundworms which commonly infect dogs and cats, Toxocara canis and Toxocara cati. The larvae penetrate the gut wall and migrate through the tissues causing disorders consequent to an inflammatory immune response¹. The authors describe a clinical case of visceral larva migrans with an unusual clinical presentation and also its clinical aspects, diagnosis and treatment are reviewed.

  9. Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

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    Beverley Greenwood-Van Meerveld

    2017-11-01

    Full Text Available Visceral pain is generally poorly localized and characterized by hypersensitivity to a stimulus such as organ distension. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. Evidence suggests that long term stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders such as irritable bowel syndrome (IBS. Early life stress (ELS is a risk-factor for the development of IBS, however the mechanisms responsible for the persistent effects of ELS on visceral perception in adulthood remain incompletely understood. In rodent models, stress in adult animals induced by restraint and water avoidance has been employed to investigate the mechanisms of stress-induce pain. ELS models such as maternal separation, limited nesting, or odor-shock conditioning, which attempt to model early childhood experiences such as neglect, poverty, or an abusive caregiver, can produce chronic, sexually dimorphic increases in visceral sensitivity in adulthood. Chronic visceral pain is a classic example of gene × environment interaction which results from maladaptive changes in neuronal circuitry leading to neuroplasticity and aberrant neuronal activity-induced signaling. One potential mechanism underlying the persistent effects of stress on visceral sensitivity could be epigenetic modulation of gene expression. While there are relatively few studies examining epigenetically mediated mechanisms involved in visceral nociception, stress-induced visceral pain has been linked to alterations in DNA methylation and histone acetylation patterns within the brain, leading to increased expression of pro-nociceptive neurotransmitters. This review will discuss the potential neuronal pathways and mechanisms responsible for

  10. Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

    Science.gov (United States)

    Greenwood-Van Meerveld, Beverley; Johnson, Anthony C.

    2017-01-01

    Visceral pain is generally poorly localized and characterized by hypersensitivity to a stimulus such as organ distension. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. Evidence suggests that long term stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders such as irritable bowel syndrome (IBS). Early life stress (ELS) is a risk-factor for the development of IBS, however the mechanisms responsible for the persistent effects of ELS on visceral perception in adulthood remain incompletely understood. In rodent models, stress in adult animals induced by restraint and water avoidance has been employed to investigate the mechanisms of stress-induce pain. ELS models such as maternal separation, limited nesting, or odor-shock conditioning, which attempt to model early childhood experiences such as neglect, poverty, or an abusive caregiver, can produce chronic, sexually dimorphic increases in visceral sensitivity in adulthood. Chronic visceral pain is a classic example of gene × environment interaction which results from maladaptive changes in neuronal circuitry leading to neuroplasticity and aberrant neuronal activity-induced signaling. One potential mechanism underlying the persistent effects of stress on visceral sensitivity could be epigenetic modulation of gene expression. While there are relatively few studies examining epigenetically mediated mechanisms involved in visceral nociception, stress-induced visceral pain has been linked to alterations in DNA methylation and histone acetylation patterns within the brain, leading to increased expression of pro-nociceptive neurotransmitters. This review will discuss the potential neuronal pathways and mechanisms responsible for stress

  11. Designing Visceral, Behavioural and Reflective Products

    Science.gov (United States)

    Aftab, Mersha; Rusli, Helen Agustin

    2017-09-01

    Designers and manufacturers often see consumption as the primary objective of a product - with implications such as discarded products, obsolete wastes, and ecological degradation. The paper aims to find the answer to the question, how emotional design can adapt the discarded and undesirable products into something valuable in a long term? This paper presents a framework combining Chapman's theory and Norman's theory on three levels of emotional design to highlight what long lasting connection with products entails. A design approach is presented combing the Wabi Sabi philosophy that promotes the celebration of decay and damage. This is used as one of the design principles for the experiments conducted on discarded products. Through constant user interaction before, during and after the experiments the evaluation of design as an agent of transformation is done. The user conducted the evaluation based on the Kansei elements of looks, sound, smell, and feel of the product. The experiments confirmed that a long-term value is only achieved through redesigning and reconstructing the perception of people towards products on a reflective level, rather than the visceral and behavioural elements of the product. The research found attachment to the visceral and behavioural elements of a product instead of an emotional one was causing users to discard products faster than required. The research indicated that many people, including designers and manufacturers, are unconsciously focusing on usability (behavioural level) and physical look (visceral level) of a product that are easily replaced, than on a meaningful way (reflective level) to create and maintain long-lasting emotions. The research concluded with a proposition towards digitization of products which could perhaps be an all round solution to make products more appropriate to human emotions. Digitization could give products the ability to capture, store and then communicate the stories, journey and memories back, in

  12. Hyperalgesia induced by low-dose opioid treatment before orthopaedic surgery: An observational case-control study.

    Science.gov (United States)

    Hina, Nabil; Fletcher, Dominique; Poindessous-Jazat, Frédérique; Martinez, Valéria

    2015-04-01

    Chronic pain and opioid consumption may trigger diffuse hyperalgesia, but their relative contributions to pain vulnerability remain unclear. To assess preoperative opioid-induced hyperalgesia and its postoperative clinical consequences in patients with chronic pain scheduled for orthopaedic surgery. A prospective observational study. Raymond Poincare teaching hospital. Adults with or without long-term opioid treatment, scheduled for orthopaedic surgery. Preoperative hyperalgesia was assessed with eight quantitative sensory tests, in a pain-free zone. Postoperative morphine consumption and pain intensity were evaluated using a numerical rating scale (NRS) in the recovery room and during the first 72 h. We analysed results from 68 patients (28 opioid-treated patients and 40 controls). Mean daily opioid consumption was 42 ± 25 mg of morphine equivalent. The opioid-treated group displayed significantly higher levels of preoperative hyperalgesia in three tests: heat tolerance threshold (47.1°C vs. 48.4°C; P = 0.045), duration of tolerance to a 47°C stimulus (40.2 vs. 51.1 s; P = 0.03) and mechanical temporal summation [1.79 vs. 1.02 (ΔNRS10-1); P = 0.036]. Patients in the opioid-treated group consumed more morphine (19.1 vs. 9.38 mg; P = 0.001), had a higher pain intensity (7.6 vs. 5.5; P = 0.001) in the recovery room and a higher cumulative morphine dose at 72 h (39.8 vs. 25.6 mg; P = 0.02). Chronic pain patients treated with low doses of opioid had hyperalgesia before surgery. These results highlight the need to personalise the management of patients treated with opioids before surgery. ID-RCB 2011-A00304-37.

  13. The major brain endocannabinoid 2-AG controls neuropathic pain and mechanical hyperalgesia in patients with neuromyelitis optica.

    Directory of Open Access Journals (Sweden)

    Hannah L Pellkofer

    Full Text Available Recurrent myelitis is one of the predominant characteristics in patients with neuromyelitis optica (NMO. While paresis, visual loss, sensory deficits, and bladder dysfunction are well known symptoms in NMO patients, pain has been recognized only recently as another key symptom of the disease. Although spinal cord inflammation is a defining aspect of neuromyelitis, there is an almost complete lack of data on altered somatosensory function, including pain. Therefore, eleven consecutive patients with NMO were investigated regarding the presence and clinical characteristics of pain. All patients were examined clinically as well as by Quantitative Sensory Testing (QST following the protocol of the German Research Network on Neuropathic Pain (DFNS. Additionally, plasma endocannabinoid levels and signs of chronic stress and depression were determined. Almost all patients (10/11 suffered from NMO-associated neuropathic pain for the last three months, and 8 out of 11 patients indicated relevant pain at the time of examination. Symptoms of neuropathic pain were reported in the vast majority of patients with NMO. Psychological testing revealed signs of marked depression. Compared to age and gender-matched healthy controls, QST revealed pronounced mechanical and thermal sensory loss, strongly correlated to ongoing pain suggesting the presence of deafferentation-induced neuropathic pain. Thermal hyperalgesia correlated to MRI-verified signs of spinal cord lesion. Heat hyperalgesia was highly correlated to the time since last relapse of NMO. Patients with NMO exhibited significant mechanical and thermal dysesthesia, namely dynamic mechanical allodynia and paradoxical heat sensation. Moreover, they presented frequently with either abnormal mechanical hypoalgesia or hyperalgesia, which depended significantly on plasma levels of the endogenous cannabinoid 2-arachidonoylglycerole (2-AG. These data emphasize the high prevalence of neuropathic pain and hyperalgesia

  14. Fatigue-enhanced hyperalgesia in response to muscle insult: induction and development occur in a sex-dependent manner

    Science.gov (United States)

    Gregory, N. S.; Gibson-Corley, K.; Frey-Law, L.; Sluka, K. A.

    2014-01-01

    Chronic muscle pain affects 20–50% of the population, is more common in women than men, and is associated with increased pain during physical activity and exercise. Muscle fatigue is common in people with chronic muscle pain, occurs in response to exercise and is associated with release of fatigue metabolites. Fatigue metabolites can sensitize muscle nociceptors which could enhance pain with exercise. Using a mouse model we tested whether fatigue of a single muscle, induced by electrical stimulation, resulted in enhanced muscle hyperalgesia and if the enhanced hyperalgesia was more pronounced in female mice. Muscle fatigue was induced in combination with a sub-threshold muscle insult (2 injections of pH 5.0 saline) in male and female mice. We show that male and female mice, fatigued immediately prior to muscle insult in the same muscle, develop similar muscle hyperalgesia 24h later. However, female mice also develop hyperalgesia when muscle fatigue and muscle insult occur in different muscles, and when muscle insult is administered 24 hours after fatigue in the same muscle. Further, hyperalgesia lasts significantly longer in females. Finally, muscle insult with or without muscle fatigue results in minimal inflammatory changes in the muscle itself, and sex differences are not related to estradiol (ovariectomy) or changes in brainstem activity (pNR1). Thus, the current model mimics muscle fatigue-induced enhancement of pain observed in chronic muscle pain conditions in the human population. Interactions between fatigue and muscle insult may underlie the development of chronic widespread pain with an associated female predominance observed in human subjects. PMID:23906552

  15. Flow measurements in the major visceral arteries

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, J.; Gerhardt, P.; Terwey, B.; Krastel, A.

    1982-02-01

    Arterial flow was measured by the spill-over technique in 202 coeliac arteries and 158 superior mesenteric arteries during the course of visceral angiography in 250 patients. In the coeliac artery a mean value of 15.8 +- 4.3 ml/sec was obtained, flow in the super mesenteric artery was significantly less at 12.1 +- 3.4 ml/sec. The wide variation from 4 to 26 ml/sec in the coeliac artery was remarkable, as well as flows from six to 20 ml/sec in the superior mesenteric artery.

  16. Immune Regulation during Chronic Visceral Leishmaniasis

    Science.gov (United States)

    Faleiro, Rebecca J.; Kumar, Rajiv; Hafner, Louise M.; Engwerda, Christian R.

    2014-01-01

    Visceral leishmaniasis is a chronic parasitic disease associated with severe immune dysfunction. Treatment options are limited to relatively toxic drugs, and there is no vaccine for humans available. Hence, there is an urgent need to better understand immune responses following infection with Leishmania species by studying animal models of disease and clinical samples from patients. Here, we review recent discoveries in these areas and highlight shortcomings in our knowledge that need to be addressed if better treatment options are to be developed and effective vaccines designed. PMID:25010815

  17. The serotonin transporter plays an important role in male sexual behavior: a study in serotonin transporter knockout rats

    NARCIS (Netherlands)

    Chan, J.Y.; Snoeren, E.; Cuppen, E.; Waldinger, M.; Olivier, B.; Oosting, R.

    2011-01-01

    INTRODUCTION: Serotonin (5-HT) is an important neurotransmitter for sexual behaviors. Heterozygous (+/-) serotonin transporter (SERT) rats and SERT knockout rats (-/-) have serotonergic disturbances with significant elevations of basal extracellular 5-HT levels. AIM: To investigate the putative role

  18. [Serotonin and its receptors in the cardiovascular system].

    Science.gov (United States)

    Nadeev, A D; Zharkikh, I L; Avdonin, P V; Goncharov, N V

    2014-01-01

    Serotonin in cardiovascular system plays an important role in blood coagulation, allergy, and inflammation, as well as in blood vessel tone regulation. In this review, the mechanisms of serotonin effects upon the cells of blood vessels are considered and the list of main agonists and antagonists is presented. The signaling pathways activated by serotonin and their interaction in normal and pathological states are described.

  19. Serotonin-Labeled CdSe Nanocrystals: Applications for Neuroscience

    Science.gov (United States)

    Kippeny, Tadd; Adkins, Erika; Adams, Scott; Thomlinson, Ian; Schroeter, Sally; Defelice, Louis; Blakely, Randy; Rosenthal, Sandra

    2000-03-01

    Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter which has been linked to the regulation of critical behaviors including sleep, appetite, and mood. The serotonin transporter (SERT) is a 12-transmembrane domain protein responsible for clearance of serotonin from extracellular spaces following release. In order to assess the potential for use of ligand-conjugated nanocrystals to target cell surface receptors, ion channels, and transporters we have measured the ability of serotonin-labeled CdSe nanocrystals (SNACs) to block the uptake of tritiated serotonin by the human and Drosophila serotonin transporters (hSERT and dSERT). Estimated Ki values, the SNAC concentration at which half of the serotonin transport activity is blocked, were determined by nonlinear regression to be Ki (hSERT ) = 74uM and Ki (dSERT ) = 29uM. These values and our inability to detect free serotonin indicate that SNACs selectively interact with the serotonin recognition site of the transporter. We have also exposed the SNACs to cells containing ionotropic serotonin receptors and have measured the electrical response of the cell using a two microelectrode voltage clamp. We find that serotonin receptors do respond to the SNACs and we measure currents similar to the free serotonin response. These results indicate that ligand-conjugated nanocrystals can be used to label both receptor and transporter proteins. Initial fluorescence labeling experiments will be discussed.

  20. Role of serotonin in seasonal affective disorder.

    Science.gov (United States)

    Gupta, A; Sharma, P K; Garg, V K; Singh, A K; Mondal, S C

    2013-01-01

    This review was prepared with an aim to show role of serotonin in seasonal affective disorder. Seasonal affective disorder, which is also called as winter depression or winter blues, is mood disorder in which persons with normal mental health throughout most of the year will show depressive symptoms in the winter or, less commonly, in the summer. Serotonin is an important endogenous neurotransmitter which also acts as neuromodulator. The least invasive, natural, and researched treatment of seasonal affective disorder is natural or otherwise is light therapy. Negative air ionization, which acts by liberating charged particles on the sleep environment, has also become effective in treatment of seasonal affective disorder.  

  1. Topical application of disodium isostearyl 2-O-L-ascorbyl phosphate, an amphiphilic ascorbic acid derivative, reduces neuropathic hyperalgesia in rats.

    Science.gov (United States)

    Okubo, Kazumasa; Nakanishi, Hiroki; Matsunami, Maho; Shibayama, Hiroharu; Kawabata, Atsufumi

    2012-06-01

    Ca(v) 3.2 T-type calcium channels, targeted by H(2) S, are involved in neuropathic hyperalgesia in rats and ascorbic acid inhibits Ca(v) 3.2 channels. Therefore, we evaluated the effects of intraplantar (i.pl.) administration of ascorbic acid or topical application of disodium isostearyl 2-O-L-ascorbyl phosphate (DI-VCP), a skin-permeable ascorbate derivative on hyperalgesia induced by NaHS, an H(2) S donor, and on neuropathic hyperalgesia. In rats mechanical hyperalgesia was evoked by i.pl. NaHS, and neuropathic hyperalgesia was induced by L5 spinal nerve cutting (L5SNC) or by repeated administration of paclitaxel, an anti-cancer drug. Dermal ascorbic acid levels were determined colorimetrically. The NaHS-evoked Ca(v) 3.2 channel-dependent hyperalgesia was inhibited by co-administered ascorbic acid. Topical application of DI-VCP, but not ascorbic acid, prevented the NaHS-evoked hyperalgesia, and also increased dermal ascorbic acid levels. Neuropathic hyperalgesia induced by L5SNC or paclitaxel was reversed by i.pl. NNC 55-0396, a selective T-type calcium channel blocker, ascorbic acid or DI-VCP, and by topical DI-VCP, but not by topical ascorbic acid. The effects of i.pl. ascorbic acid and topical DI-VCP in the paclitaxel-treated rats were characterized by the faster onset and greater magnitude, compared with their effects in the L5SNC rats. Dermal ascorbic acid levels in the hindpaw significantly decreased after paclitaxel treatment, but not L5SNC, which was reversed by topical DI-VCP. Ascorbic acid, known to inhibit Ca(v) 3.2 channels, suppressed neuropathic hyperalgesia. DI-VCP ointment for topical application may be of benefit in the treatment of neuropathic pain. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  2. Activation of ERK signalling by Src family kinases (SFKs) in DRG neurons contributes to hydrogen peroxide (H2O2)-induced thermal hyperalgesia.

    Science.gov (United States)

    Singh, Ajeet Kumar; Vinayak, Manjula

    2017-10-01

    Concomitant generation of reactive oxygen species during tissue inflammation has been recognised as a major factor for the development and the maintenance of hyperalgesia, out of which H2O2 is the major player. However, molecular mechanism of H2O2 induced hyperalgesia is still obscure. The aim of present study is to analyse the mechanism of H2O2-induced hyperalgesia in rats. Intraplantar injection of H2O2 (5, 10 and 20 µmoles/paw) induced a significant thermal hyperalgesia in the hind paw, confirmed by increased c-Fos activity in dorsal horn of spinal cord. Onset of hyperalgesia was prior to development of oxidative stress and inflammation. Rapid increase in phosphorylation of extracellular signal regulated kinase (ERK) was observed in neurons of dorsal root ganglia after 20 min of H2O2 (10 µmoles/paw) administration, which gradually returned towards normal level within 24 h, following the pattern of thermal hyperalgesia. The expression of TNFR1 followed the same pattern and colocalised with pERK. ERK phosphorylation was observed in NF-200-positive and -negative neurons, indicating the involvement of ERK in C-fibres as well as in A-fibres. Intrathecal preadministration of Src family kinases (SFKs) inhibitor (PP1) and MEK inhibitor (PD98059) prevented H2O2 induced augmentation of ERK phosphorylation and thermal hyperalgesia. Pretreatment of protein tyrosine phosphatases (PTPs) inhibitor (sodium orthovanadate) also diminished hyperalgesia, although it further increased ERK phosphorylation. Combination of orthovanadate with PP1 or PD98059 did not exhibit synergistic antihyperalgesic effect. The results demonstrate SFKs-mediated ERK activation and increased TNFR1 expression in nociceptive neurons during H2O2 induced hyperalgesia. However, the role of PTPs in hyperalgesic behaviour needs further molecular analysis.

  3. Topical application of disodium isostearyl 2-O-L-ascorbyl phosphate, an amphiphilic ascorbic acid derivative, reduces neuropathic hyperalgesia in rats

    Science.gov (United States)

    Okubo, Kazumasa; Nakanishi, Hiroki; Matsunami, Maho; Shibayama, Hiroharu; Kawabata, Atsufumi

    2012-01-01

    BACKGROUND AND PURPOSE Cav3.2 T-type calcium channels, targeted by H2S, are involved in neuropathic hyperalgesia in rats and ascorbic acid inhibits Cav3.2 channels. Therefore, we evaluated the effects of intraplantar (i.pl.) administration of ascorbic acid or topical application of disodium isostearyl 2-O-L-ascorbyl phosphate (DI-VCP), a skin-permeable ascorbate derivative on hyperalgesia induced by NaHS, an H2S donor, and on neuropathic hyperalgesia. EXPERIMENTAL APPROACH In rats mechanical hyperalgesia was evoked by i.pl. NaHS, and neuropathic hyperalgesia was induced by L5 spinal nerve cutting (L5SNC) or by repeated administration of paclitaxel, an anti-cancer drug. Dermal ascorbic acid levels were determined colorimetrically. KEY RESULTS The NaHS-evoked Cav3.2 channel-dependent hyperalgesia was inhibited by co-administered ascorbic acid. Topical application of DI-VCP, but not ascorbic acid, prevented the NaHS-evoked hyperalgesia, and also increased dermal ascorbic acid levels. Neuropathic hyperalgesia induced by L5SNC or paclitaxel was reversed by i.pl. NNC 55–0396, a selective T-type calcium channel blocker, ascorbic acid or DI-VCP, and by topical DI-VCP, but not by topical ascorbic acid. The effects of i.pl. ascorbic acid and topical DI-VCP in the paclitaxel-treated rats were characterized by the faster onset and greater magnitude, compared with their effects in the L5SNC rats. Dermal ascorbic acid levels in the hindpaw significantly decreased after paclitaxel treatment, but not L5SNC, which was reversed by topical DI-VCP. CONCLUSIONS AND IMPLICATIONS Ascorbic acid, known to inhibit Cav3.2 channels, suppressed neuropathic hyperalgesia. DI-VCP ointment for topical application may be of benefit in the treatment of neuropathic pain. PMID:22229645

  4. Optokinetic stimulation increases limb pain and forehead hyperalgesia in complex regional pain syndrome

    DEFF Research Database (Denmark)

    Knudsen, Lone F.; Drummond, Peter D.

    2015-01-01

    BACKGROUND: Ambiguous visual stimuli increase limb pain in patients with complex regional pain syndrome (CRPS), possibly due to afferent sensory feedback conflicts. Conflicting sensory stimuli can also generate unpleasant sensations in healthy people such as during motion sickness. We wanted...... to investigate the mechanisms underlying the link between sensory conflicts and pain in CRPS using optokinetic stimulation (OKS) - a method known to induce motion sickness. METHODS: Twenty-one CRPS patients underwent OKS and rated symptoms of motion sickness. Patients also rated limb pain and pain....... In a subgroup of nauseated patients who withdrew early from OKS, hyperalgesia to pressure in the ipsilateral forehead persisted longer than in the remaining participants. Sharpness sensations remained constant at all sites. CONCLUSIONS: Sensory conflicts may facilitate pain in CRPS by activating the mechanisms...

  5. Increased capsaicin-induced secondary hyperalgesia in patients with multiple chemical sensitivity

    DEFF Research Database (Denmark)

    Holst, Helle; Arendt-Nielsen, Lars; Mosbech, Holger

    2011-01-01

    the underlying cause of pathophysiological mechanisms triggering multiple chemical sensitivity (MCS) remains disputed.Recently, alterations in the central nervous system, for example,central sensitization, similar to various chronic pain disorders, have been suggested. Capsaicin is used in experi......the underlying cause of pathophysiological mechanisms triggering multiple chemical sensitivity (MCS) remains disputed.Recently, alterations in the central nervous system, for example,central sensitization, similar to various chronic pain disorders, have been suggested. Capsaicin is used...... in experimental pain models to provoke peripheral and central sensitization. In patients with symptoms elicited by odorous chemicals capsaicin-induced secondary hyperalgesia and temporal summation were assessed as markers for abnormal central nociceptive processing together with neurogenic inflammation (flare)....

  6. Lowering barometric pressure aggravates mechanical allodynia and hyperalgesia in a rat model of neuropathic pain.

    Science.gov (United States)

    Sato, J; Morimae, H; Seino, Y; Kobayashi, T; Suzuki, N; Mizumura, K

    1999-04-30

    To examine the effects of meteorological change on the pain-related behaviors of neuropathic rats, animals with a chronic constriction injury (CCI) to the sciatic nerve were exposed to low barometric pressure (LP), 20 mmHg below the natural atmospheric pressure in a climate-controlled room. CCI caused a decreased hindpaw withdrawal threshold to von Frey hair (VFH) stimulation (mechanical allodynia) and prolonged duration of hindpaw withdrawal in response to pinprick stimulation (mechanical hyperalgesia). When the CCI rats were exposed to LP, both these pain-related behaviors were aggravated, whereas no change was seen in a group of controls. In the CCI rats sympathectomy inhibited this LP-induced augmentation of pain-related behaviors. These results show that LP intensifies the abnormalities in the pain-related behaviors of neuropathic rats, and that sympathetic activity contributes to the LP effect.

  7. Is mechanism and symptom-based analgesia an answer to opioid-Induced hyperalgesia?

    Directory of Open Access Journals (Sweden)

    Mayank Gupta

    2015-01-01

    Full Text Available "Cancer Pain" and "Pain in cancer patient" are not synonymous. Opioid-induced Hyperalgesia (OIH is a paradoxical state of nociceptive sensitization caused by exposure to opioids. Neuropathic pain is only partially responsive to opioids; injudicious increase in dose of opioids in neuropathic pain may not only result in inadequate pain relief but also OIH. Majority of literature on OIH is in non-cancer pain with systemic use of opioids. We describe the development and successful treatment of OIH in a 55-year-old male patient with Small cell Carcinoma Lung. Opioid tapering, rotation, systemic desensitization helps in combatting OIH. The use of anti-neuropathic adjuvant analgesics helps not only in preventing and treating OIH but also in understanding putative mechanisms underlying neuropathic pain and OIH.

  8. Local cooling does not prevent hyperalgesia following burn injury in humans

    DEFF Research Database (Denmark)

    Werner, Mads U; Lassen, Birgit Vibeke; Pedersen, Juri L

    2002-01-01

    One of the oldest methods of pain relief following a burn injury is local application of ice or cold water. Experimental data indicate that cooling may also reduce the severity of tissue injury and promote wound healing, but there are no controlled studies in humans evaluating the anti......-inflammatory or anti-hyperalgesic potential of early cooling after thermal injury. Twenty-four healthy volunteers participated in this randomized, single-blinded study. Following baseline measurements, which included inflammatory variables (skin temperature, erythema index) and sensory variables (thermal...... and mechanical detection thresholds, thermal and mechanical pain responses, area of secondary hyperalgesia), first degree burn injuries were induced on both calves by contact thermodes (12.5 cm(2), 47 degrees C for 7 min). Eight minutes after the burn injury, contact thermodes (12.5 cm(2)) were again applied...

  9. Effect of painless diabetic neuropathy on pressure pain hypersensitivity (hyperalgesia after acute foot trauma

    Directory of Open Access Journals (Sweden)

    Tobias Wienemann

    2014-11-01

    Full Text Available Introduction and objective: Acute injury transiently lowers local mechanical pain thresholds at a limb. To elucidate the impact of painless (diabetic neuropathy on this post-traumatic hyperalgesia, pressure pain perception thresholds after a skeletal foot trauma were studied in consecutive persons without and with neuropathy (i.e. history of foot ulcer or Charcot arthropathy. Design and methods: A case–control study was done on 25 unselected clinical routine patients with acute unilateral foot trauma (cases: elective bone surgery; controls: sprain, toe fracture. Cases were 12 patients (11 diabetic subjects with severe painless neuropathy and chronic foot pathology. Controls were 13 non-neuropathic persons. Over 1 week after the trauma, cutaneous pressure pain perception threshold (CPPPT and deep pressure pain perception threshold (DPPPT were measured repeatedly, adjacent to the injury and at the opposite foot (pinprick stimulators, Algometer II®. Results: In the control group, post-traumatic DPPPT (but not CPPPT at the injured foot was reduced by about 15–25%. In the case group, pre- and post-operative CPPPT and DPPPT were supranormal. Although DPPPT fell post-operatively by about 15–20%, it remained always higher than the post-traumatic DPPPT in the control group: over musculus abductor hallucis 615 kPa (kilopascal versus 422 kPa, and over metatarsophalangeal joint 518 kPa versus 375 kPa (medians; case vs. control group; CPPPT did not decrease post-operatively. Conclusion: Physiological nociception and post-traumatic hyperalgesia to pressure are diminished at the foot with severe painless (diabetic neuropathy. A degree of post-traumatic hypersensitivity required to ‘pull away’ from any one, even innocuous, mechanical impact in order to avoid additional damage is, therefore, lacking.

  10. Calotropis procera latex-induced inflammatory hyperalgesia - effect of bradyzide and morphine.

    Science.gov (United States)

    Kumar, Vijay L; Sehgal, Raman

    2007-07-01

    1 The milky white latex of the plant Calotropis procera induces inflammatory response upon accidental exposure and on local administration that could be effectively ameliorated by antihistaminic and standard anti-inflammatory drugs. 2 The aim of the present study was to evaluate the anti-oedematogenic and analgesic effect of the bradykinin antagonist, bradyzide (BDZ) and the opioidergic analgesic, morphine (Mor) against inflammatory hyperalgesia induced by the dried latex (DL) of C. procera in the rat paw oedema model. 3 An aqueous solution of DL (0.1 ml of 1% solution) was injected into the sub-plantar surface of the rat paw and the paw volume was measured at different time intervals. The inhibitory effect of bradyzide and morphine on oedema formation and hyperalgesic response was compared with that of cyproheptadine (CPH), a potent inhibitor of DL-induced oedema formation. 4 The hyperalgesic response was evaluated by the dorsal flexion pain test, compression test and by observing motility, stair-climbing ability, and the grooming behaviour of the rats. 5 The effect of these drugs was also evaluated against DL-induced writhings in the mouse model. 6 Both bradyzide and morphine inhibited DL-induced oedema formation by 30-40% and CPH was more effective in this regard (81% inhibition). The antihyperalgesic effect of both the drugs was more pronounced than that of CPH. Both bradyzide and morphine markedly inhibited the grooming behaviour and the effect of morphine could be reversed by pretreatment with naloxone. 7 Thus, our study shows that DL-induced oedema formation is effectively inhibited by antihistaminic/antiserotonergic drug and associated hyperalgesia by analgesic drugs.

  11. Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice.

    Science.gov (United States)

    Chen, Yong; Boettger, Michael K; Reif, Andreas; Schmitt, Angelika; Uçeyler, Nurcan; Sommer, Claudia

    2010-03-02

    Although it has been largely demonstrated that nitric oxide synthase (NOS), a key enzyme for nitric oxide (NO) production, modulates inflammatory pain, the molecular mechanisms underlying these effects remain to be clarified. Here we asked whether cytokines, which have well-described roles in inflammatory pain, are downstream targets of NO in inflammatory pain and which of the isoforms of NOS are involved in this process. Intraperitoneal (i.p.) pretreatment with 7-nitroindazole sodium salt (7-NINA, a selective neuronal NOS inhibitor), aminoguanidine hydrochloride (AG, a selective inducible NOS inhibitor), L-N(G)-nitroarginine methyl ester (L-NAME, a non-selective NOS inhibitor), but not L-N(5)-(1-iminoethyl)-ornithine (L-NIO, a selective endothelial NOS inhibitor), significantly attenuated thermal hyperalgesia induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA). Real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed a significant increase of nNOS, iNOS, and eNOS gene expression, as well as tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1beta), and interleukin-10 (IL-10) gene expression in plantar skin, following CFA. Pretreatment with the NOS inhibitors prevented the CFA-induced increase of the pro-inflammatory cytokines TNF and IL-1beta. The increase of the anti-inflammatory cytokine IL-10 was augmented in mice pretreated with 7-NINA or L-NAME, but reduced in mice receiving AG or L-NIO. NNOS-, iNOS- or eNOS-knockout (KO) mice had lower gene expression of TNF, IL-1beta, and IL-10 following CFA, overall corroborating the inhibitor data. These findings lead us to propose that inhibition of NOS modulates inflammatory thermal hyperalgesia by regulating cytokine expression.

  12. Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis.

    Science.gov (United States)

    Fletcher, D; Martinez, V

    2014-06-01

    Opioids can increase sensitivity to noxious stimuli and cause opioid-induced hyperalgesia. We performed a systematic review to evaluate the clinical consequences of intra-operative doses of opioid. We identified randomized controlled trials which compared intra-operative opioid to lower doses or placebo in adult patients undergoing surgery from MEDLINE, EMBASE, LILAC, Cochrane, and hand searches of trial registries. We pooled data of postoperative pain intensity, morphine consumption, incidence of opioid-related side-effects, primary and secondary hyperalgesia. For dichotomous outcomes relative risks [95% confidence intervals (CIs)] and for continuous outcomes mean differences (MDs) or standardized mean difference (SMD; 95% CI) were calculated. Twenty-seven studies involving 1494 patients were included in the analysis. Patients treated with high intra-operative doses of opioid reported higher postoperative pain intensity than the reference groups (MD: 9.4 cm; 95% CI: 4.4, 14.5) at 1 h, (MD: 7.1 cm; 95% CI: 2.8, 11.3) at 4 h, and (MD: 3 cm; 95% CI: 0.4, 5.6) at 24 h on a 100 cm visual analogue scale. They also showed higher postoperative morphine use after 24 h (SMD: 0.7; 95% CI: 0.37, 1.02). There was no difference in the incidences of nausea, vomiting, and drowsiness. These results were mainly associated with the use of remifentanil. The impact of other opioids is less clear because of limited data. This review suggests that high intra-operative doses of remifentanil are associated with small but significant increases in acute pain after surgery. © The Author [2014]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Intraoperative Use of Remifentanil and Opioid Induced Hyperalgesia/Acute Opioid Tolerance - Systematic review

    Directory of Open Access Journals (Sweden)

    Sang Hun eKim

    2014-05-01

    Full Text Available IntroductionThe use of opioids has been increasing in operating room and intensive care unit to provide perioperative analgesia as well as stable hemodynamics. However, many authors have suggested that the use of opioids is associated with the expression of acute opioid tolerance (AOT and opioid-induced hyperalgesia (OIH in experimental studies and clinical observations in dose and/or time dependent exposure even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management during anesthesia as well as in the intensive care units because of its rapid onset and offset. ObjectivesSearch of the available literature to assess remifentanil AOT and OIH based on available published data.MethodsWe reviewed articles analyzing remifentanil AOT and OIH, and focused our literature search on evidence based information. Experimental and clinical studies were identified using electronic searches of Medline (PubMed, Ovid, Springer, and Elsevier, ClinicalKey. ResultsOur results showed that the development of remifentanil AOT and OIH is a clinically significant phenomenon requiring further research.Discussions and ConclusionsAOT - defined as an increase in the required opioid dose to maintain adequate analgesia, and OIH - defined as decreased pain threshold, should be suspected with any unexplained pain report unassociated with the disease progression.The clinical significance of these findings was evaluated taking into account multiple methodological issues including the dose and duration of opioids administration, the different infusion mode, the co-administrated anesthetic drug’s effect, method assessing pain sensitivity, and the repetitive and potentially tissue damaging nature of the stimuli used to determine the threshold during opioid infusion.Future studies need to investigate the contribution of remifentanil induced hyperalgesia to chronic pain and the role of pharmacological modulation to reverse this process.

  14. Diffuse traumatic brain injury induces prolonged immune dysregulation and potentiates hyperalgesia following a peripheral immune challenge.

    Science.gov (United States)

    Rowe, Rachel K; Ellis, Gavin I; Harrison, Jordan L; Bachstetter, Adam D; Corder, Gregory F; Van Eldik, Linda J; Taylor, Bradley K; Marti, Francesc; Lifshitz, Jonathan

    2016-01-01

    Nociceptive and neuropathic pain occurs as part of the disease process after traumatic brain injury (TBI) in humans. Central and peripheral inflammation, a major secondary injury process initiated by the traumatic brain injury event, has been implicated in the potentiation of peripheral nociceptive pain. We hypothesized that the inflammatory response to diffuse traumatic brain injury potentiates persistent pain through prolonged immune dysregulation. To test this, adult, male C57BL/6 mice were subjected to midline fluid percussion brain injury or to sham procedure. One cohort of mice was analyzed for inflammation-related cytokine levels in cortical biopsies and serum along an acute time course. In a second cohort, peripheral inflammation was induced seven days after surgery/injury with an intraplantar injection of carrageenan. This was followed by measurement of mechanical hyperalgesia, glial fibrillary acidic protein and Iba1 immunohistochemical analysis of neuroinflammation in the brain, and flow cytometric analysis of T-cell differentiation in mucosal lymph. Traumatic brain injury increased interleukin-6 and chemokine ligand 1 levels in the cortex and serum that peaked within 1-9 h and then resolved. Intraplantar carrageenan produced mechanical hyperalgesia that was potentiated by traumatic brain injury. Further, mucosal T cells from brain-injured mice showed a distinct deficiency in the ability to differentiate into inflammation-suppressing regulatory T cells (Tregs). We conclude that traumatic brain injury increased the inflammatory pain associated with cutaneous inflammation by contributing to systemic immune dysregulation. Regulatory T cells are immune suppressors and failure of T cells to differentiate into regulatory T cells leads to unregulated cytokine production which may contribute to the potentiation of peripheral pain through the excitation of peripheral sensory neurons. In addition, regulatory T cells are identified as a potential target for

  15. Transient Receptor Potential Vanilloid 1 is essential for cisplatin-induced heat hyperalgesia in mice

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    Carlton Susan M

    2010-03-01

    Full Text Available Abstract Background Cisplatin is primarily used for treatment of ovarian and testicular cancer. Oxaliplatin is the only effective treatment for metastatic colorectal cancer. Both are known to cause dose related, cumulative toxic effects on the peripheral nervous system and thirty to forty percent of cancer patients receiving these agents experience painful peripheral neuropathy. The mechanisms underlying painful platinum-induced neuropathy remain poorly understood. Previous studies have demonstrated important roles for TRPV1, TRPM8, and TRPA1 in inflammation and nerve injury induced pain. Results In this study, using real-time, reverse transcriptase, polymerase chain reaction (RT-PCR, we analyzed the expression of TRPV1, TRPM8, and TRPA1 induced by cisplatin or oxaliplatin in vitro and in vivo. For in vitro studies, cultured E15 rat dorsal root ganglion (DRG neurons were treated for up to 48 hours with cisplatin or oxaliplatin. For in vivo studies, trigeminal ganglia (TG were isolated from mice treated with platinum drugs for three weeks. We show that cisplatin and oxaliplatin-treated DRG neurons had significantly increased in TRPV1, TRPA1, and TRPM8 mRNA expression. TG neurons from cisplatin treated mice had significant increases in TRPV1 and TRPA1 mRNA expression while oxaliplatin strongly induced only TRPA1. Furthermore, compared to the cisplatin-treated wild-type mice, cisplatin-treated TRPV1-null mice developed mechanical allodynia but did not exhibit enhancement of noxious heat- evoked pain responses. Immunohistochemistry studies showed that cisplatin-treated mice had no change in the proportion of the TRPV1 immunopositive TG neurons. Conclusion These results indicate that TRPV1 and TRPA1 could contribute to the development of thermal hyperalgesia and mechanical allodynia following cisplatin-induced painful neuropathy but that TRPV1 has a crucial role in cisplatin-induced thermal hyperalgesia in vivo.

  16. Intrathecal tramadol versus intrathecal fentanyl for visceral pain ...

    African Journals Online (AJOL)

    2013-10-29

    Oct 29, 2013 ... local anesthetic agents during management of visceral pain of appendicectomy in Africa in general and in Nigeria in particular. Intrathecal tramadol versus intrathecal fentanyl for visceral pain control during bupivacaine subarachnoid block for open appendicectomy. JM Afolayan, TO Olajumoke1, ...

  17. Autochthonous Outbreak and Expansion of Canine Visceral Leishmaniasis, Uruguay

    Science.gov (United States)

    Satragno, Dinora; Faral-Tello, Paula; Canneva, Bruno; Verger, Lorenzo; Lozano, Alejandra; Vitale, Edgardo; Greif, Gonzalo; Soto, Carlos

    2017-01-01

    We report an outbreak of canine visceral leishmaniasis in Uruguay. Blood specimens from 11/45 dogs tested positive for Leishmania spp. Specimens of Lutzomyia longipalpis sand flies were captured; typing revealed Leishmania infantum. Our findings document an expansion of visceral leishmaniasis to southern South America and risk for vectorborne transmission to humans. PMID:28221113

  18. Genetically modified organisms and visceral leishmaniasis.

    Science.gov (United States)

    Chhajer, Rudra; Ali, Nahid

    2014-01-01

    Vaccination is the most effective method of preventing infectious diseases. Since the eradication of small pox in 1976, many other potentially life compromising if not threatening diseases have been dealt with subsequently. This event was a major leap not only in the scientific world already burdened with many diseases but also in the mindset of the common man who became more receptive to novel treatment options. Among the many protozoan diseases, the leishmaniases have emerged as one of the largest parasite killers of the world, second only to malaria. There are three types of leishmaniasis namely cutaneous (CL), mucocutaneous (ML), and visceral (VL), caused by a group of more than 20 species of Leishmania parasites. Visceral leishmaniasis, also known as kala-azar is the most severe form and almost fatal if untreated. Since the first attempts at leishmanization, we have killed parasite vaccines, subunit protein, or DNA vaccines, and now we have live recombinant carrier vaccines and live attenuated parasite vaccines under various stages of development. Although some research has shown promising results, many more potential genes need to be evaluated as live attenuated vaccine candidates. This mini-review attempts to summarize the success and failures of genetically modified organisms used in vaccination against some of major parasitic diseases for their application in leishmaniasis.

  19. Genetically Modified Organisms and Visceral Leishmaniasis

    Directory of Open Access Journals (Sweden)

    NAHID eALI

    2014-05-01

    Full Text Available Vaccination is the most effective method of preventing infectious diseases. Since the eradication of small pox in 1976, many other potentially life compromising if not threatening diseases have been dealt with subsequently. This event was a major leap not only in the scientific world already burdened with many diseases but also in the mindset of the common man who became more receptive to novel treatment options. Among the many protozoan diseases, the leishmaniases have emerged as one of the largest parasite killers of the world, second only to malaria. There are three types of leishmaniases namely cutaneous (CL, mucocutaneous (ML and visceral (VL, caused by a group of more than 20 species of Leishmania parasites. Visceral leishmaniasis, also known as kala-azar is the most severe form and almost fatal if untreated. Since the first attempts at leishmanization, we have killed parasite vaccines, subunit protein or DNA vaccines, and now we have live recombinant carrier vaccines and live attenuated parasite vaccines under various stages of development. Although some research has shown promising results, many more potential genes need to be evaluated as live attenuated vaccine candidates. This mini-review attempts to summarize the success and failures of genetically modified organisms used in vaccination against some of major parasitic diseases for their application in leishmaniasis.

  20. American visceral Leishmaniasis: a case report

    Directory of Open Access Journals (Sweden)

    H. Langoni

    2005-09-01

    Full Text Available Visceral leishmaniasis is a zoonotic disease caused by parasites of the Leishmania genus. Dog is the major source of infection to man, especially in urban areas. The authors report a case of visceral leishmaniasis in a pit bull female dog from Bocaina, São Paulo, Brazil. The animal presented clinical signs compatible with leishmaniasis, including skin lesions in the body and partial damage of the external ears. The indirect fluorescent antibody test (IFAT demonstrated a titer of 1280, and promastigote forms of Leishmania sp were isolated by the culture of bone marrow puncture. Cytological analysis of the lymph node and smear of the bone marrow puncture revealed macrophages containing amastigote forms of Leishmania sp in their inner region. The test of Polymerase Chain Reaction (PCR utilized the primers LINR4 and LIN19, which amplify 720 base pairs, specific for Leishmania sp. The authors discuss the importance of techniques for a quick and precise diagnosis to this serious zoonosis with great impact in animal and public health.

  1. Measuring the serotonin uptake site using (/sup 3/H)paroxetine--a new serotonin uptake inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Gleiter, C.H.; Nutt, D.J.

    1988-01-01

    Serotonin is an important neurotransmitter that may be involved in ethanol preference and dependence. It is possible to label the serotonin uptake site in brain using the tricyclic antidepressant imipramine, but this also binds to other sites. We have used the new high-affinity uptake blocker paroxetine to define binding to this site and report it to have advantages over imipramine as a ligand.

  2. Perspectives on genetic animal models of serotonin toxicity.

    Science.gov (United States)

    Kalueff, Allan V; LaPorte, Justin L; Murphy, Dennis L

    2008-01-01

    Serotonin syndrome, or serotonin toxicity, is a serious disorder attributable to exaggerated serotonergic function in the brain, most commonly after antidepressant overdose or after combining several psychotropic medications. Similar condition (serotonin syndrome-like behavior) can be evoked in animals experimentally, following administration of serotonergic drugs. In addition to pharmacological stimulation, some genetic and other factors may contribute to serotonin toxicity, prompting the need for new experimental genetic models relevant to this disorder. Here we discuss current problems and perspectives regarding genetic animal models of serotonin-related syndromes, and outline the potential utility of these models in experimental neurochemistry and clinical research.

  3. Clinical chemistry of serotonin and metabolites

    NARCIS (Netherlands)

    Kema, IP; de Vries, EGE; Muskiet, FAJ

    2000-01-01

    Analyses of serotonin and other 5-hydroxyindoles, such as its precursor 5-hydroxytryptophan and major metabolite 5-hydroxyindoleacetic acid (5-HIAA), are indispensable for the elucidation of their (patho)physiological roles. In clinical chemistry attention is mainly focused on the diagnosis and

  4. Central serotonin metabolism and frequency of depression

    NARCIS (Netherlands)

    Praag, H.M. van; Haan, S. de

    1979-01-01

    Central serotonin (5-hydroxytryptamine; 5-HT) metabolism can be disturbed in a subgroup of patients with vital (endogenous, primary) depression. Presumably these disturbances do not result from the depression and have a predisposing rather than a causative relationship to it. This latter statement

  5. Genetic polymorphism of serotonin transporter 5-HTTLPR ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 90; Issue 1. Genetic polymorphism of serotonin transporter 5-HTTLPR: involvement in smoking behaviour. Maria Angelica Ehara Watanabe Sandra Odebrechet Vargas Nunes Marla Karine Amarante Roberta Losi Guembarovski Julie Massayo Maeda Oda Kalil William Alves De ...

  6. Infrared Spectra of Protonated Neurotransmitters: Serotonin

    NARCIS (Netherlands)

    Lagutschenkov, A.; Langer, J.; G. Berden,; Oomens, J.; Dopfer, O.

    2010-01-01

    The gas-phase IR spectrum of the protonated neurotransmitter serotonin (5-hydroxytryptamine) was measured in the fingerprint range by means of IR multiple photon dissociation (IRMPD) spectroscopy. The IRMPD spectrum was recorded in a Fourier transform ion cyclotron resonance mass spectrometer

  7. Infrared spectra of protonated neurotransmitters: serotonin

    NARCIS (Netherlands)

    Lagutschenkov, A.; Langer, J.; Berden, G.; Oomens, J.; Dopfer, O.

    2010-01-01

    The gas-phase IR spectrum of the protonated neurotransmitter serotonin (5-hydroxytryptamine) was measured in the fingerprint range by means of IR multiple photon dissociation (IRMPD) spectroscopy. The IRMPD spectrum was recorded in a Fourier transform ion cyclotron resonance mass spectrometer

  8. Serotonin syndrome caused by olanzapine and clomipramine.

    Science.gov (United States)

    Verre, M; Bossio, F; Mammone, A; Piccirillo, M; Tancioni, F; Tortorella, V; Varano, M

    2008-01-01

    We describe a case of severe serotonin syndrome. The patient was simultaneously taking the atypical antidepressant olanzapine and a tricyclical antidepressant, clomipramine. Symptoms included altered mental state resulting in coma, myoclonus, hyperreflexia, diaphoresis, diarrhoea, disorientation and fever. After suspension of antidepressant drugs, intensive symptomatic treatment and administration of biperiden and cyproheptadine, the patient's condition improved.

  9. Modulation of defensive reflex conditioning in snails by serotonin

    Science.gov (United States)

    Andrianov, Vyatcheslav V.; Bogodvid, Tatiana K.; Deryabina, Irina B.; Golovchenko, Aleksandra N.; Muranova, Lyudmila N.; Tagirova, Roza R.; Vinarskaya, Aliya K.; Gainutdinov, Khalil L.

    2015-01-01

    Highlights Daily injection of serotonin before a training session accelerated defensive reflex conditioning in snails.Daily injection of 5-hydroxytryptophan before a training session in snails with a deficiency of serotonin induced by the “neurotoxic” analog of serotonin 5,7-dihydroxytryptamine, restored the ability of snails to learn.After injection of the “neurotoxic” analogs of serotonin 5,6- and 5,7-dihydroxytryptamine as well as serotonin, depolarization of the membrane and decrease of the threshold potential of premotor interneurons was observed. We studied the role of serotonin in the mechanisms of learning in terrestrial snails. To produce a serotonin deficit, the “neurotoxic” analogs of serotonin, 5,6- or 5,7-dihydroxytryptamine (5,6/5,7-DHT) were used. Injection of 5,6/5,7-DHT was found to disrupt defensive reflex conditioning. Within 2 weeks of neurotoxin application, the ability to learn had recovered. Daily injection of serotonin before a training session accelerated defensive reflex conditioning and daily injections of 5-HTP in snails with a deficiency of serotonin induced by 5,7-DHT restored the snail's ability to learn. We discovered that injections of the neurotoxins 5,6/5,7-DHT as well as serotonin, caused a decrease in the resting and threshold potentials of the premotor interneurons LPa3 and RPa3. PMID:26557063

  10. Tramadol, Pharmacology, Side Effects, and Serotonin Syndrome: A Review.

    Science.gov (United States)

    Beakley, Burton D; Kaye, Adam M; Kaye, Alan D

    2015-01-01

    Serotonin syndrome is a mild to potentially life-threatening syndrome associated with excessive serotonergic activity within the central nervous system. Serotonin syndrome is associated with medication use, drug interactions, and overdose. While serotonin syndrome is often associated with the use of selective serotonin inhibitors (SSRI), an increasing number of reports are being presented involving the use of tramadol. This review article contains an overview of serotonin syndrome while specifically looking at tramadol's pharmacology and risk factors for serotonin syndrome. With tramadol's increasing popularity, the goal of this article is to make physicians more alert and aware of this potential side effect associated with tramadol. In conclusion, with the increasing incidence of serotonin syndrome, prescribing physicians should be aware of and educate their patients on the potential side effects of tramadol. It is important that the prescribing physician reviews patient medications for concurrent serotonergic drugs and monitors for potential abuse.

  11. Perturbation of Serotonin Homeostasis during Adulthood Affects Serotonergic Neuronal Circuitry.

    Science.gov (United States)

    Pratelli, Marta; Migliarini, Sara; Pelosi, Barbara; Napolitano, Francesco; Usiello, Alessandro; Pasqualetti, Massimo

    2017-01-01

    Growing evidence shows that the neurotransmitter serotonin (5-HT) modulates the fine-tuning of neuron development and the establishment of wiring patterns in the brain. However, whether serotonin is involved in the maintenance of neuronal circuitry in the adult brain remains elusive. Here, we use a Tph2(fl)°(x) conditional knockout (cKO) mouse line to assess the impact of serotonin depletion during adulthood on serotonergic system organization. Data show that the density of serotonergic fibers is increased in the hippocampus and decreased in the thalamic paraventricular nucleus (PVN) as a consequence of brain serotonin depletion. Strikingly, these defects are rescued following reestablishment of brain 5-HT signaling via administration of the serotonin precursor 5-hydroxytryptophan (5-HTP). Finally, 3D reconstruction of serotonergic fibers reveals that changes in serotonin homeostasis affect axonal branching complexity. These data demonstrate that maintaining proper serotonin homeostasis in the adult brain is crucial to preserve the correct serotonergic axonal wiring.

  12. Time course of copeptin during a model of experimental pain and hyperalgesia: A randomised volunteer crossover trial.

    Science.gov (United States)

    Mauermann, Eckhard; Blum, Claudine A; Lurati Buse, Giovanna; Bandschapp, Oliver; Ruppen, Wilhelm

    2017-05-01

    A reliable biomarker for quantifying pain or hyperalgesia has yet to be found. A surrogate marker of arginine vasopressin, copeptin, is elevated in a number of states of physiological and psychological stress and may have a role in quantifying pain and/or hyperalgesia. To evaluate copeptin as a biomarker for pain or hyperalgesia developing after 120 min of sustained electrical stimulation. Secondary analysis of a randomised, double-blinded, crossover trial. Single, tertiary university hospital from September 2014 to January 2015. A total of 16 healthy, opioid-naïve white men with no confounding medication or history of pain. Copeptin and cortisol were measured five times during an established model of transdermal electrical stimulation designed to assess pain and hyperalgesia. The primary outcome was the change in copeptin concentration after 120 min of sustained electrical stimulation. Secondary outcomes were copeptin and cortisol concentrations after a subsequent period of rest and analyses of copeptin and cortisol concentrations were made in high-dose and low-dose fentanyl groups separately. Total copeptin concentrations were not significantly elevated after 120 min [9.15 pmol l (interquartile ranges (IQR), 3.45 to 35.45 pmol l); P = 0.150] compared with baseline [6.15 pmol l (IQR, 3.60 to 10.62 pmol l)]. In the high-dose fentanyl group, there was a significant increase in copeptin within individuals [P = 0.001; median, 37.9 pmol l (IQR, 8.1 to 62 pmol l)] after 120 min, and in the low-dose fentanyl group a significant decrease in copeptin concentrations within individuals [P = 0.006; median, 4.7 pmol l (IQR, 3.13 to 9.35 pmol l)]. No correlation between copeptin concentration and either the area under the pain curve or area under the hyperalgesia curve could be found, indicating that the observed differences may be due to other fentanyl-mediated effects. Copeptin concentrations do not appear to be associated

  13. Patologias genitais associadas à leishmaniose visceral canina Genital pathologies associated with canine visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Vinícius Vasconcelos Gomes de Oliveira

    2012-09-01

    Full Text Available A leishmaniose visceral canina (LVC é uma doença parasitária crônica causada por protozoários pertencentes ao gênero Leishmania. No Brasil, a transmissão se dá, principalmente, pela ação hematófaga de insetos vetores pertencentes à subfamília Phlebotominae, particularmente, a espécie Lutzomyia longipalpis. Todavia, a trasmissão vertical e venérea da LVC está presente. Os principais sinais clínicos observados nos animais acometidos pela LVC são linfoadenomegalia, dermatopatias, hepatoesplenomegalia, onicogrifose e oftalmopatias, contudo quadros atípicos podem ser observados, inclusive com o envolvimento do sistema genital. Dessa forma, o objetivo deste artigo é realizar revisão sobre as principais patologias genitais em cães machos e fêmeas com leishmaniose visceral (LV.The canine visceral leishmaniasis (CanL is a chronic parasitic disease caused by protozoa belonging to the genus Leishmania. In Brazil, the transmission occurs mainly by the action of blood-sucking insects belonging to the subfamily Phlebotominae, particularly the Lutzomyia longipalpis species. However, the venereal and vertical transmission of the CanL is present. The main clinical signs observed in animals affected by the CanL are lymphadenopathy, skin diseases, hepatosplenomegaly, onychogryphosis and ophthalmopathy, however atypical manifestations can be observed, including the involvement of the genital system. Thus, the aim of this paper is to review on the major pathologies in genital male and female dogs with visceral leishmaniasis (VL.

  14. Injection of corticotropin-releasing hormone into the amygdala aggravates visceral nociception and induces noradrenaline release in rats.

    Science.gov (United States)

    Su, J; Tanaka, Y; Muratsubaki, T; Kano, M; Kanazawa, M; Fukudo, S

    2015-01-01

    Corticotropin-releasing hormone (CRH) and its receptor 1 (CRH-R1) play an important role in the colonic response to stress. The central nucleus of the amygdala (CeA) is a major extrahypothalamic site that contains a large number of neurons expressing both CRH and CRH-R1. Here, we verified the hypothesis that CRH in the CeA sensitizes visceral nociception via CRH-R1 with release of noradrenaline, dopamine, and serotonin (5-HT) in the CeA. In male Wistar rats, visceral sensitivity was quantified by recording the visceromotor response to colorectal distension (CRD) with administration of vehicle, CRH, or the CRH-R1 antagonist CP-154526+ CRH or CRH-R1 antagonist CP-154526 alone into the CeA. Simultaneously, extracellular levels of noradrenaline, dopamine, and 5-HT were measured in the CeA using microdialysis. All data were obtained under restraint conditions. Administration of CRH into the CeA significantly increased the number of abdominal muscle contractions in response to CRD. CP-154526 significantly blocked the number of abdominal muscle contractions in response to CRD with the administration of CRH into the CeA. Noradrenaline in the CeA was increased by CRD, further increased by CRH, and inhibited by CRH-R1 antagonist. Dopamine in the CeA was also exaggerated by CRH but was not inhibited by CRH-R1 antagonist. 5-HT in the CeA was unchanged. These results suggest that CRH in the CeA sensitizes visceral nociception via CRH-R1 with release of noradrenaline. © 2014 John Wiley & Sons Ltd.

  15. Visceral leishmaniasis in zoo and wildlife.

    Science.gov (United States)

    Souza, Tayse Domingues; Turchetti, Andréia Pereira; Fujiwara, Ricardo Toshio; Paixão, Tatiane Alves; Santos, Renato Lima

    2014-03-01

    Visceral leishmaniasis (VL) is an emerging zoonosis caused by Leishmania (Leishmania) infantum. Although the domestic dog is the main vertebrate host, many zoo and wild mammal species have been diagnosed with L. infantum infection, especially in endemic areas. There are many available diagnostic approaches, including serological, parasitological and molecular tests. Among wild animals, carnivores and primates are more often clinically affected, with some species, such as the bush dog (Speothos venaticus) being especially susceptible to development of clinical signs. There are also reports and research articles of VL in felids, rodents, and marsupials. This work aims to review the occurrence of VL in zoo and wildlife and raise awareness of its importance in the field of conservational veterinary medicine. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Disseminated visceral coccidiosis in sandhill cranes

    Science.gov (United States)

    Carpenter, J.W.; Novilla, M.N.; Fayer, R.; Iverson, G.C.

    1984-01-01

    Disseminated visceral coccidiosis (DVC) caused by Eimeria spp was first recognized as a disease entity in captive sandhill cranes (Grus canadensis) and whooping cranes (G americana) at the Patuxent Wildlife Research Center. Because cranes produced at the Center are reintroduced to the wild to augment wild populations, studies involving both experimentally induced and natural infections were initiated to determine the potential or actual occurrence of DVC in wild Gruidae. Nine sandhill cranes dosed orally with eimerian oocysts of wild origin developed lesions characteristic of DVC. Extraintestinal granulomas associated with developing schizonts were found in 6 birds. Similar lesions were observed in wild sandhill cranes throughout parts of midwestern United States, Alaska, and Saskatchewan. These studies revealed the wide geographic distribution and the high frequency of occurrence of DVC in wild cranes.

  17. [Cutaneous and visceral loxoscelism: a systematic review].

    Science.gov (United States)

    Manríquez, Juan J; Silva, Sergio

    2009-10-01

    Loxoscelism represents a major public health problem for which there are no standard therapeutic interventions. To review available scientific evidence on management of Loxoscelism Systematic review of clinical studies. The search included multiple databases (Medline, Lilacs, Embase, Web of Sciences, Cinahl, Pre-Cinahl, Paperfirst, Proceedingsfirst, Dissertations and Theses, Toxline, Cochrane Library), handsearch of references, and contact with experts. Three clinical trials of poor methodological quality were identified from 5,207 references found. One trial (n = 31), concluded that the use of dapsone was associated with fewer local complications than surgical treatment. A second study (n = 46), concluded that the use of dapsone was superior to clorfenamine for skin lesions. A third study (n = 95) concluded that there was no differences between the use of oral dapsone, antivenom against anti-Loxosceles reclusa or a combination of both. There is insufficient evidence based on good quality studies to recommend treatment guidelines for individuals with skin or visceral loxoscelism.

  18. [Dislipidemia and steatohepatitis with visceral fat].

    Science.gov (United States)

    Yasuda, Daijiro; Maeda, Tomomi; Teramoto, Tamio

    2009-02-01

    The prevalence of metabolic syndrome has been increased recently because of westernized dietary habits and low physical activity in Japan. Metabolic syndrome is diagnosed by the accumulation of dislipidemia, glucose intolerance and/or high blood pressure caused by visceral obesity. The dislipidemia in metabolic syndrome is characterized by the presence of high plasma triglyceride and low HDL-cholesterol, which are associated with increase in small dense LDL and remnant lipoproteins, highly atherogenic lipoproteins. Metabolic syndrome is also often associated with fatty liver, which may be led to non-alcoholic steatohepatitis (NASH). Reduction of body weight and increase in physical activities are highly recommended in overweight patients to inhibit the development of metabolic syndrome, the dislipidemia and NASH.

  19. Spironolactone increases permeability of visceral sheep peritoneum.

    Science.gov (United States)

    Karioti, Aggeliki; Hatzoglou, Chrissi; Zarogiannis, Sotirios; Deligiorgi, Triantafyllia; Kourti, Panagiota; Giannopoulou, Myrto; Arampatzis, Spyros; Liakopoulos, Vassilios; Gourgoulianis, Konstantinos; Molyvdas, Paschalis-Adam; Stefanidis, Ioannis

    2009-01-01

    Aldosterone is a key component of the renin-angiotensin-aldosterone system, and spironolactone, an aldosterone receptor blocker, shows beneficial effects in patients with end-stage renal disease and heart failure. The aim of the present study was to investigate by means of Ussing chamber technique the effect of spironolactone on the transmesothelial permeability of visceral sheep peritoneum in vitro. Peritoneal samples from the omentum of adult sheep were collected immediately after slaughter in a cooled and oxygenated Krebs-Ringer bicarbonate (KRB) solution. Isolated intact sheets of peritoneum were mounted in an Ussing-type chamber. Spironolactone (10(-5) mol/L) was added apically and basolaterally to the KRB solution. The transmesothelial resistance (R) was measured before and serially for 30 minutes after the addition of the substances. Data present the mean +/- standard error of 6 experiments in each case. The control R was 19.8 +/- 0.36 omega x cm2. The addition of spironolactone resulted in a reduction in the R, which became significant on both sides of the membrane within 10 minutes and remained significantly different thereafter. The maximum reduction of R (deltaR%) reached 24.8% +/- 2.3% (p < 0.01) apically and 26.3% +/- 3.2% (p < 0.01) basolaterally. Our data clearly show that spironolactone increases the permeability of visceral sheep peritoneum in a lasting manner. Increased peritoneal permeability could result in increased sodium removal, which has acknowledged beneficial effects both in patients undergoing peritoneal dialysis and in patients with heart failure. Further clinical studies investigating the effect of spironolactone on sodium removal in peritoneal dialysis are justified.

  20. Ancient origin of somatic and visceral neurons

    Science.gov (United States)

    2013-01-01

    Background A key to understanding the evolution of the nervous system on a large phylogenetic scale is the identification of homologous neuronal types. Here, we focus this search on the sensory and motor neurons of bilaterians, exploiting their well-defined molecular signatures in vertebrates. Sensorimotor circuits in vertebrates are of two types: somatic (that sense the environment and respond by shaping bodily motions) and visceral (that sense the interior milieu and respond by regulating vital functions). These circuits differ by a small set of largely dedicated transcriptional determinants: Brn3 is expressed in many somatic sensory neurons, first and second order (among which mechanoreceptors are uniquely marked by the Brn3+/Islet1+/Drgx+ signature), somatic motoneurons uniquely co-express Lhx3/4 and Mnx1, while the vast majority of neurons, sensory and motor, involved in respiration, blood circulation or digestion are molecularly defined by their expression and dependence on the pan-visceral determinant Phox2b. Results We explore the status of the sensorimotor transcriptional code of vertebrates in mollusks, a lophotrochozoa clade that provides a rich repertoire of physiologically identified neurons. In the gastropods Lymnaea stagnalis and Aplysia californica, we show that homologues of Brn3, Drgx, Islet1, Mnx1, Lhx3/4 and Phox2b differentially mark neurons with mechanoreceptive, locomotory and cardiorespiratory functions. Moreover, in the cephalopod Sepia officinalis, we show that Phox2 marks the stellate ganglion (in line with the respiratory — that is, visceral— ancestral role of the mantle, its target organ), while the anterior pedal ganglion, which controls the prehensile and locomotory arms, expresses Mnx. Conclusions Despite considerable divergence in overall neural architecture, a molecular underpinning for the functional allocation of neurons to interactions with the environment or to homeostasis was inherited from the urbilaterian ancestor by

  1. Eugenol derived immunomodulatory molecules against visceral leishmaniasis.

    Science.gov (United States)

    Charan Raja, Mamilla R; Velappan, Anand Babu; Chellappan, Davidraj; Debnath, Joy; Kar Mahapatra, Santanu

    2017-10-20

    Visceral leishmaniasis (VL) is a life threatening infectious disease caused by Leishmania donovani. It leads to the severe immune suppression in the host defense system. Higher cytotoxicity, rigorous side effects and lower therapeutic indexes (TI) of current antileishmanial drugs have created a necessity to develop new molecules with better antileishmanial activity and high TI value. In this study, we have synthesized 36 derivatives of eugenol and screened them for their activity against promastigote and amastigote forms of L. donovani. Among the synthesized derivatives, comp.35 showed better antileishmanial activity against extra cellular promastigotes (IC50- 20.13 ± 0.91 μM) and intracellular amastigotes (EC50-4.25 ± 0.26 μM). The TI value (82.24 ± 3.77) was found to improve by 10-13 fold compared to Amphotericin B and Miltefosine respectively. Treatment with comp.35 (5 μg/ml) enhanced the nitric oxide (NO) generation, iNOS2 mRNA expression (∼8 folds increase) and decreased the arginase-1 activity (∼4 folds) in L. donovani infected peritoneal macrophages. Comp.35 had also increased the IL-12 (∼6 folds) and decreased the IL-10 (∼3 folds) mRNA expression and release in vitro. Results of in vivo studies revealed that comp.35 treatment at 25 mg/kg body weight efficiently cleared the hepatic and splenic parasite burden with enhanced Th1 response in L. donovani infected BALB/c mice. Hence, this study clearly represents comp.35, as an immunomodulatory molecule, can induce host protective immune response against visceral leishmaniasis through enhanced NO generation and Th1 response, which are essentials against this deadly disease. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Self-reported recovery is associated with improvement in localized hyperalgesia among adolescent females with patellofemoral pain

    DEFF Research Database (Denmark)

    Rathleff, Michael Skovdal; Roos, Ewa Maria; Olesen, Jens Lykkegaard

    2016-01-01

    : This is an ancillary analysis of a cluster randomized controlled trial investigating the effect of patient education with or without exercise therapy on self-reported recovery in 121 adolescents with PFP. PPTs were measured at four sites around the knee and on tibialis anterior in a random subsample of 57 female...... adolescents. Changes in localised and distal hyperalgesia from baseline to follow-up were compared to self-reported recovery. Adolescents were categorized as recovered if they rated themselves as "completely recovered" or "strongly recovered" (category 1 or 2) on a 7-point Likert scale. RESULTS: 39......OBJECTIVES: Adolescent females with PFP have localised (around the knee) and distal (tibialis anterior muscle) hyperalgesia assessed by decreased Pressure Pain Thresholds (PPT). This may have implications for treating PFP as both localised and central pain mechanisms may contribute...

  3. Causes of pediatric visceral leishmaniasis in southeastern iran.

    Directory of Open Access Journals (Sweden)

    Ali Hosseininasab

    2014-12-01

    Full Text Available Leishmania infantum is the most frequent cause of visceral leishmaniasis and L. tropica has been rarely linked to the disease in Iran. In this study, bone marrow aspirates were collected from 10 child patients, suspected with visceral leishmaniasis referred to the Pediatric Wards of Kerman Medical Hospitals, Kerman, Iran during 2002-2011. Leishmania species were identified by using nested PCR in all slides. The PCR samples from nine patients indicated L. infantum as principal causative agent of visceral leishmaniasis and one L.tropica as a minor species.

  4. Transcutaneous Electrical Nerve Stimulation (TENS) reduces pain, fatigue, and hyperalgesia while restoring central inhibition in primary fibromyalgia

    OpenAIRE

    Dailey, Dana L.; Rakel, Barbara A.; Vance, Carol GT; Liebano, Richard E.; Anand, Amrit S; Bush, Heather M.; Lee, Kyoung S; Lee, Jennifer E.; Sluka, Kathleen A.

    2013-01-01

    Because TENS works by reducing central excitability and activating central inhibition pathways, we tested the hypothesis that TENS would reduce pain and fatigue and improve function and hyperalgesia in people with fibromyalgia who have enhanced central excitability and reduced inhibition. The current study used a double-blinded randomized, placebo controlled cross-over design to test effects of a single treatment of TENS in people with fibromyalgia. Three treatments were assessed in random or...

  5. A Rat Model of Full Thickness Thermal Injury Characterized by Thermal Hyperalgesia, Mechanical Allodynia, Pronociceptive Peptide Release and Tramadol Analgesia

    Science.gov (United States)

    2014-01-01

    4 weeks (n 2 per time point) post injury to visualize burn pathology . A board certified veterinary pathol ogist characterized the degree of burn...an animal model of thermal hyperalgesia and mechanical allodynia evoked by full thickness thermal injury that shares pathological characteristics with...sections were rinsed in potassium phosphate buffered saline (KPBS) and incubated in primary antibody solution rabbit anti CGRP (1:10,000; Immunostar; Hudson

  6. Test order of quantitative sensory testing facilitates mechanical hyperalgesia in healthy volunteers.

    Science.gov (United States)

    Gröne, Eva; Crispin, Alexander; Fleckenstein, Johannes; Irnich, Dominik; Treede, Rolf-Detlef; Lang, Philip M

    2012-01-01

    Quantitative sensory testing (QST) has become a widely used method to evaluate different submodalities of the somatic sensory system (predominantly) in patients with neuropathic pain. QST consists of 7 tests measuring 13 parameters in order to assess and quantify the perception of temperature, touch, pain, pressure, and vibration. The German Research Network on Neuropathic Pain implemented a standardized QST protocol including a defined testing order of the measurements. Accordingly, subjects tested with QST undergo thermal before mechanical testing. In the present study, we investigated the effect of testing order on the results of QST. Twenty healthy subjects were tested twice, 1 week apart with 2 different QST testing orders: the standardized testing order according to the German Research Network on Neuropathic Pain and a modified testing order in which mechanical stimuli were applied before thermal stimuli. For the test protocol that began with thermal testing, subjects exhibited signs of an increased mechanical perception: The mechanical pain sensitivity was significantly increased (P = .001, Wilcoxon test) for each pinprick stimulator and the mechanical pain threshold was lowered by a factor of 2 when compared with the modified testing order in which mechanical parameters were tested at the beginning of the session without prior thermal stimulation. Thermal parameters were the same for both test-order paradigms. These data indicate that preceding mild thermal stimulation might lead to a sensitization to mechanical stimuli and thus to mechanical hyperalgesia. Alternative habituation mechanisms in the modified testing order resulting from repeated pinprick stimulation at the beginning should also be debated. QST is a helpful diagnostic tool but interpretation should be done with consideration of interaction between test parameters. Reference data are only valid in the testing order from which they are obtained. Present data showed that mechanical hyperalgesia

  7. Nocebo hyperalgesia: contributions of social observation and body-related cognitive styles

    Directory of Open Access Journals (Sweden)

    Vögtle E

    2016-04-01

    Full Text Available Elisabeth Vögtle,1 Birgit Kröner-Herwig,1 Antonia Barke21Department of Clinical Psychology and Psychotherapy, Georg-Elias-Müller-Institute for Psychology, University of Göttingen, Göttingen, 2Department of Psychology, Division of Clinical Psychology and Psychotherapy, Philipps University Marburg, Marburg, Germany Purpose: Recently, it has been shown that nocebo hyperalgesia can be acquired through observational learning. The aim of this study was to investigate socially induced nocebo hyperalgesia and its relationship with pain catastrophizing, somatic complaints, hypochondriacal concerns, and empathy. Participants and methods: Ninety-seven women (43.1±15.5 years were randomly assigned to one of the two conditions. Participants in the nocebo condition (NC watched a video in which a female model displayed more pain when an ointment was applied and less pain when no ointment was applied. In the control condition (CC, the model demonstrated low pain with and without the ointment. Subsequently, all participants received three pressure pain stimuli (60 seconds on each hand. On one hand, the ointment was applied prior to the stimulation. The order of the stimulation of the fingers (middle, index, or ring finger, the side of ointment application (left or right hand, and the side with which the stimulation began were randomized within each group and balanced across the groups. Depending on the randomization, the pressure pain application started with or without ointment and on the left or right hand. Pain ratings on a numerical rating scale (0–10 were collected. In addition, the participants completed questionnaires regarding body-related cognitive styles and empathy. Results: There was a significant difference in the pain ratings between the CC and the NC. The effect of ointment application was also significant, but no interaction between condition and ointment application was found. Only in the CC did the nocebo response correlate with

  8. Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities

    Science.gov (United States)

    Elhabazi, Khadija; Ayachi, Safia; Ilien, Brigitte; Simonin, Frédéric

    2014-01-01

    Opioid-induced hyperalgesia and tolerance severely impact the clinical efficacy of opiates as pain relievers in animals and humans. The molecular mechanisms underlying both phenomena are not well understood and their elucidation should benefit from the study of animal models and from the design of appropriate experimental protocols. We describe here a methodological approach for inducing, recording and quantifying morphine-induced hyperalgesia as well as for evidencing analgesic tolerance, using the tail-immersion and tail pressure tests in wild-type mice. As shown in the video, the protocol is divided into five sequential steps. Handling and habituation phases allow a safe determination of the basal nociceptive response of the animals. Chronic morphine administration induces significant hyperalgesia as shown by an increase in both thermal and mechanical sensitivity, whereas the comparison of analgesia time-courses after acute or repeated morphine treatment clearly indicates the development of tolerance manifested by a decline in analgesic response amplitude. This protocol may be similarly adapted to genetically modified mice in order to evaluate the role of individual genes in the modulation of nociception and morphine analgesia. It also provides a model system to investigate the effectiveness of potential therapeutic agents to improve opiate analgesic efficacy. PMID:25145878

  9. Repeated intramuscular injections of nerve growth factor induced progressive muscle hyperalgesia, facilitated temporal summation, and expanded pain areas.

    Science.gov (United States)

    Hayashi, Koei; Shiozawa, Shinichiro; Ozaki, Noriyuki; Mizumura, Kazue; Graven-Nielsen, Thomas

    2013-11-01

    Intramuscular injection of nerve growth factor (NGF) is known to induce deep-tissue mechanical hyperalgesia. In this study it was hypothesised that daily intramuscular injections of NGF produce a progressive manifestation of soreness, mechanical hyperalgesia, and temporal summation of pain. In a double-blind placebo-controlled design, 12 healthy subjects were injected on 3 days with NGF into the tibialis anterior muscle and with isotonic saline on the contralateral side. Assessments were performed before and after the injections on days 0, 1, and 2, and repeated on days 3, 6, and 10. The self-perceived muscle soreness was assessed on a Likert scale. Computer-controlled pressure algometry was used to assess the pressure pain thresholds (PPTs). Temporal summation of pain after repeated pressure stimulations was assessed by computer-controlled pressure algometry. The pain distribution following painful pressure stimulation was also recorded. Compared with baseline and isotonic saline, the NGF injections caused (Ppain at days 1 to 10; and (4) enlarged pressure-induced pain area after the injection on day 1 to day 6. The daily injections of NGF produced a progressive manifestation of muscle soreness, mechanical hyperalgesia, temporal summation of pressure pain, and pressure-induced pain distribution. These data illustrate that the prolonged NGF application affects peripheral and central mechanisms and may reflect process in musculoskeletal pain conditions. Copyright © 2013. Published by Elsevier B.V.

  10. Serotonin Syndrome: Clinical Findings, Diagnosis, Management

    Directory of Open Access Journals (Sweden)

    Pedro Cintra

    2014-06-01

    Full Text Available The serotonin syndrome is a relatively infrequent clinical entity, but can have potentially lethal consequences. The spectrum of manifestations is highly variable, ranging from mild diarrhea to tremor and mental status changes, autonomic hyperactivity, hyperthermia and clonic contractions. Eighty-five percent of physicians are not familiar with the characteristics of the syndrome. We propose to briefly review its epidemiology, pathophysiology, clinical manifestations, diagnostic criteria and therapeutic, emphasizing practical aspects of clinical performance.

  11. Visceral metabolism and efficiency of energy use by ruminants

    National Research Council Canada - National Science Library

    Gilberto Vilmar Kozloski; João Batista Teixeira da Rocha; Maria de Lourdes Santorio Ciocca

    2001-01-01

    ... absorbed at the intestinal lumen. Probably, the major source of variation in the efficiency of utilization of metabolizable energy among feeds is associated mainly with visceral metabolism and it is unlikely that the ratio ketogenic...

  12. [Visceral leishmaniasis without splenomegaly. A pediatric case report].

    Science.gov (United States)

    Leblanc, C; Nouar, D; Izri, A; Brun, S; Marty, P; Gaudelus, J; De Pontual, L

    2016-04-01

    Pediatric visceral leishmaniasis is caused by Leishmania infantum, a dog parasite transmitted to humans by the bite of the female phlebotomine sand fly. The well-known clinical triad is fever, pallor, and splenomegaly. A secondary macrophage activation syndrome (MAS) can complicate this infection, which is lethal when not treated. When MAS is observed without any explanation, a visceral leishmaniasis is highly recommended. We report a case of visceral leishmaniasis in a 21-month-old child complicated by a macrophage activation syndrome without splenomegaly. No immunodeficiency was diagnosed that could explain this unusual clinical condition. To our knowledge, this is the first case of visceral leishmaniasis without splenomegaly reported to date. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  13. Trigger Points, Pressure Pain Hyperalgesia, and Mechanosensitivity of Neural Tissue in Women with Chronic Pelvic Pain.

    Science.gov (United States)

    Fuentes-Márquez, Pedro; Valenza, Marie Carmen; Cabrera-Martos, Irene; Ríos-Sánchez, Ana; Ocón-Hernández, Olga

    2017-08-25

    This study aims to evaluate the presence of myofascial trigger points (TrPs), widespread pressure pain sensitivity, and mechanosensitivity of neural tissue in women with chronic pelvic pain. Case-control study. Faculty of Health Sciences. Forty women with chronic pelvic pain between age 18 and 60 years and 40 matched healthy controls were included in the study. TrPs were bilaterally explored in gluteus maximus, gluteus medius, gluteus minimus, quadratus lumborum, and adductor magnus muscles. The referred pain reproduced lumbopelvic symptoms. Pressure pain thresholds (PPTs) were also bilaterally assessed over the Pfannenstiel incision point on the abdominal, C5-C6 zygapophyseal joint, second metacarpal, and tibialis anterior muscle. Mechanosensitivity of neural tissue was assessed with the neurodynamics tests of slump and the straight-leg raising. Significant between-group differences were found in TrP presence in patients with chronic pelvic pain (P Neurodynamics show a significantly decreased value in women with CPP. Patients with chronic pelvic pain presented a high percentage of TrPs that reproduce their symptoms. Patients also showed a widespread pressure pain hyperalgesia and more mechanosensitive neural tissue due to a decrease on the range of motion related to neurodynamics.

  14. Slick (Kcnt2 Sodium-Activated Potassium Channels Limit Peptidergic Nociceptor Excitability and Hyperalgesia

    Directory of Open Access Journals (Sweden)

    Danielle L Tomasello

    2017-09-01

    Full Text Available The Slick (Kcnt2 sodium-activated potassium (K Na channel is a rapidly gating and weakly voltage-dependent and sodium-dependent potassium channel with no clearly defined physiological function. Within the dorsal root ganglia (DRGs, we show Slick channels are exclusively expressed in small-sized and medium-sized calcitonin gene–related peptide (CGRP-containing DRG neurons, and a pool of channels are localized to large dense-core vesicles (LDCV-containing CGRP. We stimulated DRG neurons for CGRP release and found Slick channels contained within CGRP-positive LDCV translocated to the neuronal membrane. Behavioral studies in Slick knockout (KO mice indicated increased basal heat detection and exacerbated thermal hyperalgesia compared with wild-type littermate controls during neuropathic and chronic inflammatory pain. Electrophysiologic recordings of DRG neurons from Slick KO mice revealed that Slick channels contribute to outward current, propensity to fire action potentials (APs, and to AP properties. Our data suggest that Slick channels restrain the excitability of CGRP-containing neurons, diminishing pain behavior after inflammation and injury.

  15. Slick (Kcnt2) Sodium-Activated Potassium Channels Limit Peptidergic Nociceptor Excitability and Hyperalgesia

    Science.gov (United States)

    Tomasello, Danielle L; Hurley, Edward; Wrabetz, Lawrence; Bhattacharjee, Arin

    2017-01-01

    The Slick (Kcnt2) sodium-activated potassium (KNa) channel is a rapidly gating and weakly voltage-dependent and sodium-dependent potassium channel with no clearly defined physiological function. Within the dorsal root ganglia (DRGs), we show Slick channels are exclusively expressed in small-sized and medium-sized calcitonin gene–related peptide (CGRP)-containing DRG neurons, and a pool of channels are localized to large dense-core vesicles (LDCV)-containing CGRP. We stimulated DRG neurons for CGRP release and found Slick channels contained within CGRP-positive LDCV translocated to the neuronal membrane. Behavioral studies in Slick knockout (KO) mice indicated increased basal heat detection and exacerbated thermal hyperalgesia compared with wild-type littermate controls during neuropathic and chronic inflammatory pain. Electrophysiologic recordings of DRG neurons from Slick KO mice revealed that Slick channels contribute to outward current, propensity to fire action potentials (APs), and to AP properties. Our data suggest that Slick channels restrain the excitability of CGRP-containing neurons, diminishing pain behavior after inflammation and injury. PMID:28943756

  16. The Underestimated Significance of Conditioning in Placebo Hypoalgesia and Nocebo Hyperalgesia

    Directory of Open Access Journals (Sweden)

    Anne-Kathrin Bräscher

    2018-01-01

    Full Text Available Placebo and nocebo effects are intriguing phenomena in pain perception with important implications for clinical research and practice because they can alleviate or increase pain. According to current theoretical accounts, these effects can be shaped by verbal suggestions, social observational learning, and classical conditioning and are necessarily mediated by explicit expectation. In this review, we focus on the contribution of conditioning in the induction of placebo hypoalgesia and nocebo hyperalgesia and present accumulating evidence that conditioning independent from explicit expectation can cause these effects. Especially studies using subliminal stimulus presentation and implicit conditioning (i.e., without contingency awareness that bypass the development of explicit expectation suggest that conditioning without explicit expectation can lead to placebo and nocebo effects in pain perception. Because only few studies have investigated clinical samples, the picture seems less clear when it comes to patient populations with chronic pain. However, conditioning appears to be a promising means to optimize treatment. In order to get a better insight into the mechanisms of placebo and nocebo effects in pain and the possible benefits of conditioning compared to explicit expectation, future studies should carefully distinguish both methods of induction.

  17. Local cooling does not prevent hyperalgesia following burn injury in humans

    DEFF Research Database (Denmark)

    Werner, Mads U; Lassen, Birgit Vibeke; Pedersen, Juri L

    2002-01-01

    One of the oldest methods of pain relief following a burn injury is local application of ice or cold water. Experimental data indicate that cooling may also reduce the severity of tissue injury and promote wound healing, but there are no controlled studies in humans evaluating the anti-inflammato......One of the oldest methods of pain relief following a burn injury is local application of ice or cold water. Experimental data indicate that cooling may also reduce the severity of tissue injury and promote wound healing, but there are no controlled studies in humans evaluating the anti...... and mechanical detection thresholds, thermal and mechanical pain responses, area of secondary hyperalgesia), first degree burn injuries were induced on both calves by contact thermodes (12.5 cm(2), 47 degrees C for 7 min). Eight minutes after the burn injury, contact thermodes (12.5 cm(2)) were again applied...... on the burns. One of the thermodes cooled the burn (8 degrees C for 30 min) whereas the other thermode was a non-active dummy on the control burn. Inflammatory and sensory variables were followed for 160 min after end of the cooling procedure. The burn injury induced significant increases in skin temperature...

  18. Spared nerve injury rats exhibit thermal hyperalgesia on an automated operant dynamic thermal escape Task

    Directory of Open Access Journals (Sweden)

    Chialvo Dante R

    2005-05-01

    Full Text Available Abstract Well-established methods are available to measure thermal and mechanical sensitivity in awake behaving rats. However, they require experimenter manipulations and tend to emphasize reflexive behaviors. Here we introduce a new behavioral test, with which we examine thermal sensitivity of rats with neuropathic injury. We contrast thermal hyperalgesia between spared nerve injury and chronic constriction injury rats. This device is a fully automated thermal sensitivity assessment tool designed to emphasize integrated learned responses to thermal painful and non-painful stimuli that are applied dynamically to a surface on which the animal is standing. It documents escape behavior in awake, unrestrained animals to innocuous and noxious heating of the floor where the animal is located. Animals learn to minimize pain by escaping to the opposite non-heated side; escape latency is recorded. On this device, thermal stimulus-response curves showed > 6°C leftward shift in both groups of neuropathic rats. In contrast, when these animals were tested on hotplate the stimulus-response shift was

  19. Resident Macrophages in Muscle Contribute to Development of Hyperalgesia in a Mouse Model of Noninflammatory Muscle Pain.

    Science.gov (United States)

    Gong, Wei-Yi; Abdelhamid, Ramy E; Carvalho, Carolina S; Sluka, Kathleen A

    2016-10-01

    Macrophages play a role in innate immunity within the body, are located in muscle tissue, and can release inflammatory cytokines that sensitize local nociceptors. In this study we investigate the role of resident macrophages in the noninflammatory muscle pain model induced by 2 pH 4.0 preservative-free sterile saline (pH 4.0) injections 5 days apart in the gastrocnemius muscle. We showed that injecting 2 pH 4.0 injections into the gastrocnemius muscle increased the number of local muscle macrophages, and depleting muscle macrophages with clodronate liposomes before acid injections attenuated the hyperalgesia produced by this model. To further examine the contribution of local macrophages to this hyperalgesia, we injected mice intramuscularly with C34, a toll-like receptor 4 (TLR4) antagonist. When given before the first pH 4.0 injection, C34 attenuated the muscle and tactile hyperalgesia produced by the model. However, when given before the second injection C34 had no effect on the development of hyperalgesia. Then to test whether activation of local macrophages sensitizes nociceptors to normally non-nociceptive stimuli we replaced either the first or second acid injection with the immune cell activator lipopolysaccharide, or the inflammatory cytokine interleukin (IL)-6. Injecting LPS or IL-6 instead of the either the first or second pH 4.0 injection resulted in a dose-dependent increase in paw withdrawal responses and decrease in muscle withdrawal thresholds. The highest doses of LPS and IL-6 resulted in development of hyperalgesia bilaterally. The present study showed that resident macrophages in muscle are key to development of chronic muscle pain. This article presents evidence for the role of macrophages in the development of chronic muscle pain using a mouse model. These data suggest that macrophages could be a potential therapeutic target to prevent transition of acute to chronic muscle pain particularly in tissue acidosis conditions. Copyright © 2016

  20. Peripheral Serotonin: a New Player in Systemic Energy Homeostasis.

    Science.gov (United States)

    Namkung, Jun; Kim, Hail; Park, Sangkyu

    2015-12-01

    Whole body energy balance is achieved through the coordinated regulation of energy intake and energy expenditure in various tissues including liver, muscle and adipose tissues. A positive energy imbalance by excessive energy intake or insufficient energy expenditure results in obesity and related metabolic diseases. Although there have been many obesity treatment trials aimed at the reduction of energy intake, these strategies have achieved only limited success because of their associated adverse effects. An ancient neurotransmitter, serotonin is among those traditional pharmacological targets for anti-obesity treatment because it exhibits strong anorectic effect in the brain. However, recent studies suggest the new functions of peripheral serotonin in energy homeostasis ranging from the endocrine regulation by gut-derived serotonin to the autocrine/paracrine regulation by adipocyte-derived serotonin. Here, we discuss the role of serotonin in the regulation of energy homeostasis and introduce peripheral serotonin as a possible target for anti-obesity treatment.

  1. Serotonin: a regulator of neuronal morphology and circuitry

    Science.gov (United States)

    Daubert, Elizabeth A.; Condron, Barry G.

    2010-01-01

    Serotonin is an important neuromodulator associated with a wide range of physiological effects in the central nervous system. The exact mechanisms for how serotonin influences brain development are not well understood, although studies in invertebrate and vertebrate model organisms are beginning to unravel a regulatory role for serotonin in neuronal morphology and circuit formation. Recent data suggests a developmental window during which altered serotonin levels permanently impact circuitry, however, the temporal constraints and molecular mechanisms responsible are still under investigation. Growing evidence suggests that alterations in early serotonin signaling contribute to a number of neurodevelopmental and neuropsychiatric disorders. Thus, understanding how altered serotonin signaling affects neuronal morphology and plasticity, and ultimately animal physiology and pathophysiology, will be of great significance. PMID:20561690

  2. MODULATION OF DEFENSIVE REFLEX CONDITIONING IN SNAILS BY SEROTONIN

    Directory of Open Access Journals (Sweden)

    Vyatcheslav V Andrianov

    2015-10-01

    Full Text Available We studied the role of serotonin in the mechanisms of learning in terrestrial snails. To produce a serotonin deficit, the neurotoxic analogues of serotonin, 5,6- or 5,7-dihydroxytryptamine (5,6/5,7-DHT were used. Injection of 5,6/5,7-DHT was found to disrupt defensive reflex conditioning. Within two weeks of neurotoxin application, the ability to learn had recovered. Daily injection of serotonin before a training session accelerated defensive reflex conditioning and daily injections of 5-HTP in snails with a deficiency of serotonin induced by 5,7-DHT restored the snail’s ability to learn. We discovered that injections of the neurotoxins 5,6/5,7-DHT as well as serotonin, caused a decrease in the resting and threshold potentials of the premotor interneurons LPa3 and RPa3.

  3. Congenitally transmitted visceral leishmaniasis: report of two brazilian human cases

    Directory of Open Access Journals (Sweden)

    Myrlena Regina Machado Mescouto-Borges

    2013-04-01

    Full Text Available Visceral leishmaniasis is a relevant public health problem worldwide. Most of the reported cases in Latin America are from Brazil. Herein we report two human cases of congenitally transmitted visceral leishmaniasis in two patients who developed symptoms during pregnancy. The diagnosis was made by visual examination of Leishmania parasites in bone marrow aspirates of the mothers and by detecting parasite kDNA in bone marrow samples of the newborn children using polymerase chain reaction.

  4. Role of Principal Ionotropic and Metabotropic Receptors in Visceral Pain

    OpenAIRE

    Kannampalli, Pradeep; Sengupta, Jyoti N.

    2015-01-01

    Visceral pain is the most common form of pain caused by varied diseases and a major reason for patients to seek medical consultation. It also leads to a significant economic burden due to workdays lost and reduced productivity. Further, long-term use of non-specific medications is also associated with side effects affecting the quality of life. Despite years of extensive research and the availability of several therapeutic options, management of patients with chronic visceral pain is often in...

  5. Emergency endovascular repair of ruptured visceral artery aneurysms

    Directory of Open Access Journals (Sweden)

    Tang Tjun

    2007-07-01

    Full Text Available Abstract Background Visceral artery aneurysms although rare, have very high mortality if they rupture. Case presentation An interesting case of a bleeding inferior pancreaticduodenal artery aneurysm is reported in a young patient who presented with hypovolemic shock while being treated in the hospital after undergoing total knee replacement. Endovascular embolization was successfully employed to treat this patient, with early hospital discharge. Conclusion Prompt diagnosis and endovascular management of ruptured visceral aneuryms can decrease the associated mortality and morbidity.

  6. Serotonin-1A receptor polymorphism (rs6295 associated with thermal pain perception.

    Directory of Open Access Journals (Sweden)

    Fredrik Lindstedt

    Full Text Available BACKGROUND: Serotonin (5-HT is highly involved in pain regulation and serotonin-1A (5-HT1A receptors are important in determining central 5-HT tone. Accordingly, variation in the 5-HT1A receptor gene (HTR1A may contribute to inter-individual differences in human pain sensitivity. The minor G-allele of the HTR1A single nucleotide polymorphism (SNP rs6295 attenuates firing of serotonergic neurons and reduces postsynaptic expression of the receptor. Experiments in rodents suggest that 5-HT1A-agonism modulates pain in opposite directions at mild compared to high noxious intensities. Based upon this and several other similar observations, we hypothesized that G-carriers would exhibit a relative hypoalgesia at mild thermal stimuli but tend towards hyperalgesia at higher noxious intensities. METHODS: Fourty-nine healthy individuals were selectively genotyped for rs6295. Heat- and cold-pain thresholds were assessed along with VAS-ratings of a range of suprathreshold noxious heat intensities (45°C-49°C. Nociceptive-flexion reflex (NFR thresholds were also assessed. RESULTS: Volunteers did not deviate significantly from Hardy-Weinberg equilibrium. G-carriers were less sensitive to threshold-level thermal pain. This relative hypoalgesia was abolished at suprathreshold noxious intensities where G-carriers instead increased their ratings of heat-pain significantly more than C-homozygotes. No differences with regard to NFR-thresholds emerged. CONCLUSION/SIGNIFICANCE: To the best of our knowledge this is the first study of human pain perception on the basis of variation in HTR1A. The results illustrate the importance of including a range of stimulus intensities in assessments of pain sensitivity. In speculation, we propose that an attenuated serotonergic tone may be related to a 'hypo- to hyperalgesic' response-pattern. The involved mechanisms could be of clinical interest as variation in pain regulation is known to influence the risk of developing pain

  7. Effects of orlistat on visceral fat after liposuction.

    Science.gov (United States)

    Montoya, Teresa; Monereo, Susana; Olivar, Juana; Iglesias, Paloma; Díaz, Patricia

    2009-03-01

    Liposuction can aggravate metabolic complications associated with obesity. It has been shown that the recovery of weight lost through these interventions is associated with body fat redistribution toward the visceral cavity, increasing metabolic risk factors for coronary heart disease such as insulin resistance and high triglyceride levels. The aim of this study was to evaluate the consequences of liposuction on body mass redistribution and metabolic parameters 6 months after surgery and to evaluate the use of orlistat treatment (tetrahydrolipstatin) in controlling these parameters. A population of 31 women with a mean body mass index of 26.17+/-3.9 kg/m(2) and undergoing liposuction of more than 1,000 cm(3), was studied. Twelve of them were treated postsurgery with 120 mg of orlistat every 8 hours for the following 6 months. Anthropometric, analytical, and radiological (computed tomography) tests were performed to quantify visceral fat area before surgery and 6 months after surgery. Despite weight loss after liposuction, visceral fat was not modified. Patients treated with orlistat showed a greater reduction in visceral fat, although not statistically significant. Orlistat use induced a reduction in low-density lipoprotein cholesterol values of 20.0+/-22.5 mg/dL, compared with an increase of 8.46+/-20.1 mg/dL in controls (p=.07). Visceral fat does not decrease despite weight loss after liposuction. Orlistat use postliposuction might be a useful tool because it shows a tendency to reduce visceral fat and improve blood lipids profile.

  8. Hyponatremia in visceral leishmaniasis Hiponatremia no calazar

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    Frederico A. Lima Verde

    2010-10-01

    Full Text Available There are few reports linking hyponatremia and visceral leishmaniasis (kala-azar. This is a study of 55 consecutive kala-azar patients and 20 normal individuals as a control group. Hyponatremia and serum hypo-osmolality were detected in 100% of kala-azar patients. High first morning urine osmolality (750.0 ± 52.0 vs. 894.5 ± 30.0mOsm/kg H2O, p Existem poucos relatos relacionando hiponatremia com a leshmaniose visceral (calazar. Este é um estudo de 55 pacientes portadores de calazar e um grupo controle de 20 indivíduos normais. Hiponatremia e hipo-osmolalidade sérica foram detectados em 100% dos pacientes portadores de calazar. A presença de alta osmolalidade da primeira urina da manhã (750,0 ± 52,0 vs. 894,5 ± 30 mOsm/Kg H2O, p < 0,05 e da urina de 24h (426,0 ± 167,0 vs. 514,6 ± 132,0 mOsm/Kg H2O, p < 0,05, demonstraram a presença de persistente secreção de hormônio antidiurético. A concentração de sódio urinário foi elevada (82,3 ± 44,2 vs. 110,3 ± 34,7 mEq/L, p < 0,05. Hipouricemia ocorreu em 61,8% dos pacientes e aumento da fração de excreção urinária de ácido úrico foi detectada em 74,5% dos casos. Aumento da velocidade de filtração glomerular estava presente em 25,4% dos pacientes. Não havia evidência clínica de depleção de volume extracelular. Valores normais de ADH plasmático foram observados nos pacientes com calazar. Não foi detectada disfunção renal ou endócrina. É provável, que a maioria dos pacientes com calazar apresente uma síndrome de secreção inapropriada de hormônio antidiurético.

  9. Significantly increased visceral adiposity index in prehypertension.

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    Yanan Ding

    Full Text Available The prevalence of prehypertension has increased in China, and prehypertension frequently progress to hypertension over a short time period; both have become public health problems. Therefore, this study was conducted to determine the relationship between the Visceral Adiposity Index (VAI and blood pressure (BP in China.A cross-sectional epidemiological survey was conducted in China using a stratified random cluster sampling method. Sex-specific VAI quartile cut-off points were used as follows: 0.88, 1.41, 2.45 in males and 0.85, 1.33, 2.22 in females. Prehypertension and hypertension were each defined according to The Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7 guidelines. A multivariate logistic analysis was conducted to analyze the relationship among VAI, prehypertension and hypertension.The ORs for prehypertension and hypertension in the upper quartiles of the VAI were 1.514 (1.074-2.133, P=0.018 and 1.660 (1.084-2.542, P=0.020, in males, after adjusting for age, education, smoking habits, alcohol consumption, physical activity, serum creatinine, fasting glucose, and plasma insulin. Following further adjustments for the above confounders, chronic kidney disease, and diabetes, the ORs for prehypertension and hypertension in the upper quartile of the VAI were 1.660 1.533 (1.086-2.165, P=0.015, and 1.743 (1.133-2.680, P=0.011, in males. The ORs for prehypertension and hypertension in the upper quartile of the VAI were 1.691 (1.223-2.338, P=0.001, and 1.682 (1.162-2.435, P=0.006, in females, after adjusting for age, education, smoking habits, alcohol consumption, physical activity, serum creatinine, fasting glucose, and plasma insulin. Following further adjustments for the above confounders, chronic kidney disease, and diabetes, the ORs for prehypertension and hypertension in the upper quartile of the VAI were 1.688 (1.220-2.334, P=0.002, and 1.657 (1

  10. Serotonin control of thermotaxis memory behavior in nematode Caenorhabditis elegans.

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    Yinxia Li

    Full Text Available Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans.

  11. Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency

    Science.gov (United States)

    Weng, Rui; Shen, Sensen; Tian, Yonglu; Burton, Casey; Xu, Xinyuan; Liu, Yi; Chang, Cuilan; Bai, Yu; Liu, Huwei

    2015-07-01

    Serotonin is an important neurotransmitter that broadly participates in various biological processes. While serotonin deficiency has been associated with multiple pathological conditions such as depression, schizophrenia, Alzheimer’s disease and Parkinson’s disease, the serotonin-dependent mechanisms remain poorly understood. This study therefore aimed to identify novel biomarkers and metabolic pathways perturbed by serotonin deficiency using metabolomics approach in order to gain new metabolic insights into the serotonin deficiency-related molecular mechanisms. Serotonin deficiency was achieved through pharmacological inhibition of tryptophan hydroxylase (Tph) using p-chlorophenylalanine (pCPA) or genetic knockout of the neuronal specific Tph2 isoform. This dual approach improved specificity for the serotonin deficiency-associated biomarkers while minimizing nonspecific effects of pCPA treatment or Tph2 knockout (Tph2-/-). Non-targeted metabolic profiling and a targeted pCPA dose-response study identified 21 biomarkers in the pCPA-treated mice while 17 metabolites in the Tph2-/- mice were found to be significantly altered compared with the control mice. These newly identified biomarkers were associated with amino acid, energy, purine, lipid and gut microflora metabolisms. Oxidative stress was also found to be significantly increased in the serotonin deficient mice. These new biomarkers and the overall metabolic pathways may provide new understanding for the serotonin deficiency-associated mechanisms under multiple pathological states.

  12. Plasma serotonin in horses undergoing surgery for small intestinal colic

    Science.gov (United States)

    Torfs, Sara C.; Maes, An A.; Delesalle, Catherine J.; Pardon, Bart; Croubels, Siska M.; Deprez, Piet

    2015-01-01

    This study compared serotonin concentrations in platelet poor plasma (PPP) from healthy horses and horses with surgical small intestinal (SI) colic, and evaluated their association with postoperative ileus, strangulation and non-survival. Plasma samples (with EDTA) from 33 horses with surgical SI colic were collected at several pre- and post-operative time points. Serotonin concentrations were determined using liquid-chromatography tandem mass spectrometry. Results were compared with those for 24 healthy control animals. The serotonin concentrations in PPP were significantly lower (P serotonin was not a suitable prognostic factor in horses with SI surgical colic. PMID:25694668

  13. Molecular imaging of serotonin degeneration in mild cognitive impairment.

    Science.gov (United States)

    Smith, Gwenn S; Barrett, Frederick S; Joo, Jin Hui; Nassery, Najlla; Savonenko, Alena; Sodums, Devin J; Marano, Christopher M; Munro, Cynthia A; Brandt, Jason; Kraut, Michael A; Zhou, Yun; Wong, Dean F; Workman, Clifford I

    2017-09-01

    Neuropathological and neuroimaging studies have consistently demonstrated degeneration of monoamine systems, especially the serotonin system, in normal aging and Alzheimer's disease. The evidence for degeneration of the serotonin system in mild cognitive impairment is limited. Thus, the goal of the present study was to measure the serotonin transporter in vivo in mild cognitive impairment and healthy controls. The serotonin transporter is a selective marker of serotonin terminals and of the integrity of serotonin projections to cortical, subcortical and limbic regions and is found in high concentrations in the serotonergic cell bodies of origin of these projections (raphe nuclei). Twenty-eight participants with mild cognitive impairment (age 66.6±6.9, 16 males) and 28 healthy, cognitively normal, demographically matched controls (age 66.2±7.1, 15 males) underwent magnetic resonance imaging for measurement of grey matter volumes and high-resolution positron emission tomography with well-established radiotracers for the serotonin transporter and regional cerebral blood flow. Beta-amyloid imaging was performed to evaluate, in combination with the neuropsychological testing, the likelihood of subsequent cognitive decline in the participants with mild cognitive impairment. The following hypotheses were tested: 1) the serotonin transporter would be lower in mild cognitive impairment compared to controls in cortical and limbic regions, 2) in mild cognitive impairment relative to controls, the serotonin transporter would be lower to a greater extent and observed in a more widespread pattern than lower grey matter volumes or lower regional cerebral blood flow and 3) lower cortical and limbic serotonin transporters would be correlated with greater deficits in auditory-verbal and visual-spatial memory in mild cognitive impairment, not in controls. Reduced serotonin transporter availability was observed in mild cognitive impairment compared to controls in cortical and limbic

  14. Stimulation of aortic smooth muscle cell mitogenesis by serotonin

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    Nemecek, G.M.; Coughlin, S.R.; Handley, D.A.; Moskowitz, M.A.

    1986-02-01

    Bovine aortic smooth muscle cells in vitro responded to 1 nM to 10 ..mu..M serotonin with increased incorporation of (/sup 3/H)thymidine into DNA. The mitogenic effect of serotonin was half-maximal at 80 nM and maximal above 1 ..mu..M. At a concentration of 1 ..mu..M, serotonin stimulated smooth muscle cell mitogenesis to the same extent as human platelet-derived growth factor (PDGF) at 12 ng/ml. Tryptamine was approx. = 1/10th as potent as serotonin as a mitogen for smooth muscle cells. Other indoles that are structurally related to serotonin (D- and L-tryptophan, 5-hydroxy-L-tryptophan, N-acetyl-5-hydroxytryptamine, melatonin, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophol) and quipazine were inactive. The stimulatory effect of serotonin on smooth muscle cell DNA synthesis required prolonged (20-24 hr) exposure to the agonist and was attenuated in the presence of serotonin D receptor antagonists. When smooth muscle cells were incubated with submaximal concentrations of serotonin and PDGF, synergistic rather than additive mitogenic responses were observed. These data indicate that serotonin has a significant mitogenic effect on smooth muscle cells in vitro, which appears to be mediated by specific plasma membrane receptors.

  15. Effect of serotonin on small intestinal contractility in healthy volunteers

    DEFF Research Database (Denmark)

    Hansen, M.B.; Arif, F.; Gregersen, H.

    2008-01-01

    -duodeno-jejunal contractility in healthy human volunteers. Manometric recordings were obtained and the effects of either a standard meal, continuous intravenous infusion of serotonin (20 nmol/kg/min) or intraluminal bolus infusions of graded doses of serotonin (2.5, 25 or 250 nmol) were compared. In addition, platelet......-lived adverse effects following intraluminal serotonin stimulations. We conclude that exogenous serotonin in the lumen of the upper part of the small intestine does not seem to change antro-duodeno-jejunal contractility significantly in healthy adult volunteers Udgivelsesdato: 2008...

  16. Obesity Takes Its Toll on Visceral Pain: High-Fat Diet Induces Toll-Like Receptor 4-Dependent Visceral Hypersensitivity.

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    Mónica Tramullas

    Full Text Available Exposure to high-fat diet induces both, peripheral and central alterations in TLR4 expression. Moreover, functional TLR4 is required for the development of high-fat diet-induced obesity. Recently, central alterations in TLR4 expression have been associated with the modulation of visceral pain. However, it remains unknown whether there is a functional interaction between the role of TLR4 in diet-induced obesity and in visceral pain. In the present study we investigated the impact of long-term exposure to high-fat diet on visceral pain perception and on the levels of TLR4 and Cd11b (a microglial cell marker protein expression in the prefrontal cortex (PFC and hippocampus. Peripheral alterations in TLR4 were assessed following the stimulation of spleenocytes with the TLR4-agonist LPS. Finally, we evaluated the effect of blocking TLR4 on visceral nociception, by administering TAK-242, a selective TLR4-antagonist. Our results demonstrated that exposure to high-fat diet induced visceral hypersensitivity. In parallel, enhanced TLR4 expression and microglia activation were found in brain areas related to visceral pain, the PFC and the hippocampus. Likewise, peripheral TLR4 activity was increased following long-term exposure to high-fat diet, resulting in an increased level of pro-inflammatory cytokines. Finally, TLR4 blockage counteracted the hyperalgesic phenotype present in mice fed on high-fat diet. Our data reveal a role for TLR4 in visceral pain modulation in a model of diet-induced obesity, and point to TLR4 as a potential therapeutic target for the development of drugs to treat visceral hypersensitivity present in pathologies associated to fat diet consumption.

  17. Visceral leishmaniasis in adults with nephropathy

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    H Kaaroud El Jeri

    2017-01-01

    Full Text Available The aim of this study is to evaluate the features of visceral leishmaniasis (VL in adults with nephropathy, who were not infected with the human immunodeficiency virus. This is a retrospective study of 14 adults hospitalized between 2000 and 2014, with VL and renal involvement. Clinical, biological, and therapeutic data were collected from the patients′ medical files. Eleven women and three men, most of whom were from the North of the country, with a mean age of 40.5 years were studied. Lupus was present in five cases, the Sicca syndrome in three cases, diabetes in one case, renal failure on dialysis in two cases, and there were three renal transplant recipients. Major clinical symptoms were fever and weakness in all cases. Enlargement of the spleen was present in eight cases and hepatomegaly in six cases. Biologic inflammatory syndrome and anemia were present in all cases, and pancytopenia was present in seven cases. Renal insufficiency was noted in all cases. Diagnosis of VL was confirmed by bone marrow examination or serology. Treatment consisted of antimoniate in 10 cases and amphotericin B in four cases. Seven deaths were recorded. Clinical symptoms of VL are atypical in patients with nephropathy and therefore, the diagnosis should be suspected in such patients because VL is still endemic in our country.

  18. Management of visceral leishmaniasis: Indian perspective.

    Science.gov (United States)

    Agrawal, S; Rai, M; Sundar, S

    2005-01-01

    Diagnosis and treatment of Indian visceral leishmaniasis (VL) is extremely unsatisfactory. For diagnosis, demonstration of parasites in splenic/marrow smears remains the gold standard, though k39 rapid strip test is a useful method in regions where access to parasite demonstration is difficult. pentavalent antimony remains the mainstay for the treatment of all forms of leishmaniasis globally; however, development of large-scale antimony resistance in Bihar has necessitated search for alternative drugs. Amphotericin B is the most effective, though toxic, drug for patients with refractory VL. Lipid formulations of amphotericin B, though safe and effective, are too expensive to be useful for poor patients of this region. These hold advantage as large quantity of the drug can safely be given over a short period of time, thus leading to a decrease in the hospital stay to a few days instead of several weeks. Oral miltefosine, an alkyl phospholipid, has recently been approved and marketed in India for the treatment of VL. Miltefosine cures 94% patients with VL if given in a daily dose of 50-100 mg for 28 days. Most common adverse events are mild vomiting and diarrhea. Paromomycin, an amino glycoside, is undergoing a pivotal phase-III clinical trial, and is likely to be approved and available to patients with VL at an affordable cost. To protect the already scarce inventory of antileishmanial drugs, it is time that combination chemotherapy is introduced for the treatment of VL in India.

  19. Management of visceral leishmaniasis: Indian perspective

    Directory of Open Access Journals (Sweden)

    Agrawal S

    2005-01-01

    Full Text Available Diagnosis and treatment of Indian visceral leishmaniasis (VL is extremely unsatisfactory. For diagnosis, demonstration of parasites in splenic/marrow smears remains the gold standard, though k39 rapid strip test is a useful method in regions where access to parasite demonstration is difficult. pentavalent antimony remains the mainstay for the treatment of all forms of leishmaniasis globally; however, development of large-scale antimony resistance in Bihar has necessitated search for alternative drugs. Amphotericin B is the most effective, though toxic, drug for patients with refractory VL. Lipid formulations of amphotericin B, though safe and effective, are too expensive to be useful for poor patients of this region. These hold advantage as large quantity of the drug can safely be given over a short period of time, thus leading to a decrease in the hospital stay to a few days instead of several weeks. Oral miltefosine, an alkyl phospholipid, has recently been approved and marketed in India for the treatment of VL. Miltefosine cures 94% patients with VL if given in a daily dose of 50-100 mg for 28 days. Most common adverse events are mild vomiting and diarrhea. Paromomycin, an amino glycoside, is undergoing a pivotal phase-III clinical trial, and is likely to be approved and available to patients with VL at an affordable cost. To protect the already scarce inventory of antileishmanial drugs, it is time that combination chemotherapy is introduced for the treatment of VL in India.

  20. Colorectal visceral perception in diverticular disease.

    Science.gov (United States)

    Clemens, C H M; Samsom, M; Roelofs, J; van Berge Henegouwen, G P; Smout, A J P M

    2004-05-01

    The pathogenesis of asymptomatic diverticular disease (ADD) and symptomatic uncomplicated diverticular disease (SUDD) has not been elucidated. The aim of our study was to assess whether altered visceral perception or abnormal compliance of the colorectal wall play a role in these clinical entities. Ten ADD patients, 11 SUDD patients, and nine healthy controls were studied. Using a dual barostat device, sensations were scored and compliance curves obtained using stepwise intermittent isobaric distensions of the rectum and sigmoid, before and after a liquid meal. In addition, the colonic response to eating was assessed by monitoring the volumes of both barostat bags at operating pressure before and after the meal. In the rectum, perception was increased in the SUDD group compared with controls (p = 0.010) and the ADD group (p = 0.030). Rectal compliance curves were not different between the groups. In the sigmoid colon, perception in the pre- and postprandial periods was increased in SUDD compared with controls (p = 0.018) but not when compared with ADD. Sigmoid volume-pressure curves had comparable slopes (compliance) in all groups but were shifted downwards in SUDD compared with ADD in the preprandial period (p = 0.026). The colonic response to eating (decrease in intrabag volume) was similar in all three groups, both in the rectum and sigmoid. Symptomatic but not asymptomatic uncomplicated diverticular disease is associated with heightened perception of distension, not only in the diverticula bearing sigmoid, but also in the unaffected rectum. This hyperperception is not due to altered wall compliance.

  1. Nanomedicines for Therapy of Visceral Leishmaniasis.

    Science.gov (United States)

    Want, Muzamil Yaqub; Yadav, Priya; Afrin, Farhat

    2016-03-01

    Visceral leishmaniasis (VL) or kala-azar is a vector borne infectious disease caused by the protozoan parasites of the genus Leishmania. VL is endemic in more than 85 countries with an estimated 0.2-0.5 million people at risk, causing high morbidity and mortality across the globe. In the absence of effective vaccines, treatment solely relies on chemotherapy and can be 100% fatal within two years, if left untreated. However, the present chemotherapeutics is limited by toxicity, non-compliance, location of parasites within the lysosomal vacuoles of macrophages, impairing the accession of many potential antileishmanial drugs, prolonged and cumbersome regimen that is unaffordable by rural population with alarming increase in unresponsiveness, complications of post kala-azar dermal leishmaniasis (PKDL) and HIV co-infections. Nanotechnology offers promising approach in the treatment of VL as it reduces toxicity, improves the therapeutic index of drugs, and can selectively deliver the antileishmanial cargos to the intracellular pathogens. In addition, nanoparticles can interact with the host immune system, modulating the immune response in a way that may favor the elimination of the Leishmania parasites. In this review, we give an overview of the strategies and delivery systems employed for the antileishmanial drugs towards the riddance of deadly VL.

  2. Maternal 25-hydroxyvitamin D is inversely correlated with foetal serotonin.

    Science.gov (United States)

    Murthi, Padma; Davies-Tuck, Miranda; Lappas, Martha; Singh, Harmeet; Mockler, Joanne; Rahman, Rahana; Lim, Rebecca; Leaw, Bryan; Doery, James; Wallace, Euan M; Ebeling, Peter R

    2017-03-01

    Maternal vitamin D deficiency during pregnancy has been linked to impaired neurocognitive development in childhood. The mechanism by which vitamin D affects childhood neurocognition is unclear but may be via interactions with serotonin, a neurotransmitter involved in foetal brain development. In this study, we aimed to explore associations between maternal and foetal vitamin D concentrations, and foetal serotonin concentrations at term. Serum 25-hydroxyvitamin D (25(OH)D, nmol/l) and serotonin (5-HT, nmol/l) concentrations were measured in maternal and umbilical cord blood from mother-infant pairs (n = 64). Association between maternal 25(OH)D, cord 25(OH)D and cord serotonin was explored using linear regression, before and after adjusting for maternal serotonin levels. We also assessed the effects of siRNA knockdown of the vitamin D receptor (VDR) and administration of 10 nm 1,25-dihydroxyvitamin D3 on serotonin secretion in human umbilical vein endothelial cells (HUVECs) in vitro. We observed an inverse relationship between both maternal and cord 25(OH)D concentrations with cord serotonin concentrations. The treatment of HUVECs with 1,25-dihydroxyvitamin D3 in vitro decreased the release of serotonin (193·9 ±14·8 nmol/l vs 458·9 ± 317·5 nmol/l, control, P serotonin release in cultured HUVECs. These observations provide the first evidence of an inverse relationship between maternal 25(OH)D and foetal serotonin concentrations. We propose that maternal vitamin D deficiency increases foetal serotonin concentrations and thereby contributes to longer-term neurocognitive impairment in infants and children. © 2016 John Wiley & Sons Ltd.

  3. Excessive visceral fat accumulation in advanced chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Furutate R

    2011-08-01

    Full Text Available Ryuko Furutate1, Takeo Ishii1,2, Ritsuko Wakabayashi1, Takashi Motegi1,2, Kouichi Yamada1,2, Akihiko Gemma2, Kozui Kida1,21Respiratory Care Clinic, Nippon Medical School, Kudan-Minami, Chiyoda-ku, Tokyo, Japan; 2Department of Internal Medicine, Division of Pulmonary Medicine, Infectious Diseases and Oncology, Nippon Medical School, Sendagi, Bunkyo-ku, Tokyo, JapanBackground: Previous studies have suggested links between chronic obstructive pulmonary disease (COPD, cardiovascular disease, and abdominal obesity. Although abdominal visceral fat is thought to be associated with cardiovascular risk factors, the degree of visceral fat accumulation in patients with COPD has not been directly studied. The aim of this study was to investigate the abdominal visceral fat accumulation and the association between visceral fat and the severity and changes in emphysema in COPD patients.Methods: We performed clinical and laboratory tests, including pulmonary function, dyspnea score, and the six-minute walking test in COPD patients (n = 101 and control, which included subjects with a smoking history but without airflow obstruction (n = 62. We used computed tomography to evaluate the abdominal visceral fat area (VFA, subcutaneous fat area (SFA, and the extent of emphysema.Results: The COPD group had a larger VFA than the control group. The prevalence of non-obese subjects with an increased VFA was greater in the Global Initiative for Chronic Obstructive Lung Disease Stages III and IV than in the other stages of COPD. The extent of emphysema was inversely correlated with waist circumference and SFA. However, VFA did not decrease with the severity of emphysema. VFA was positively correlated with the degree of dyspnea.Conclusion: COPD patients have excessive visceral fat, which is retained in patients with more advanced stages of COPD or severe emphysema despite the absence of obesity.Keywords: abdominal obesity, chronic obstructive pulmonary disease, emphysema

  4. Effect of Intramuscular Protons, Lactate, and ATP on Muscle Hyperalgesia in Rats.

    Science.gov (United States)

    Gregory, Nicholas S; Whitley, Phillip E; Sluka, Kathleen A

    2015-01-01

    Chronic muscle pain is a significant health problem leading to disability[1]. Muscle fatigue can exacerbate muscle pain. Metabolites, including ATP, lactate, and protons, are released during fatiguing exercise and produce pain in humans. These substances directly activate purinergic (P2X) and acid sensing ion channels (ASICs) on muscle nociceptors, and when combined, produce a greater increase in neuron firing than when given alone. Whether the enhanced effect of combining protons, lactate, and ATP is the sum of individual effects (additive) or more than the sum of individual effects (synergistic) is unknown. Using a rat model of muscle nociceptive behavior, we tested each of these compounds individually over a range of physiologic and supra-physiologic concentrations. Further, we combined all three compounds in a series of dilutions and tested their effect on muscle nociceptive behavior. We also tested a non-hydrolyzable form of ATP (α,β-meATP) alone and in combination with lactate and acidic pH. Surprisingly, we found no dose-dependent effect on muscle nociceptive behavior for protons, lactate, or ATP when given alone. We similarly found no effect after application of each two-metabolite combination. Only pH 4 saline and α,β-meATP produced hyperalgesia when given alone. When all 3 substances were combined, however, ATP (2.4μm), lactate (10mM), and acidic pH (pH 6.0) produced an enhanced effect greater than the sum of the effects of the individual components, i.e. synergism. α,β me ATP (3nmol), on the other hand, showed no enhanced effects when combined with lactate (10mM) or acidic pH (pH 6.0), i.e. additive. These data suggest that combining fatigue metabolites in muscle produces a synergistic effect on muscle nociception.

  5. Muscle hyperalgesia is widespread in patients with complex regional pain syndrome.

    Science.gov (United States)

    van Rooijen, Diana E; Marinus, Johan; van Hilten, Jacobus J

    2013-12-01

    Patients with complex regional pain syndrome (CRPS) frequently show prominent sensory abnormalities in their affected limb, which may extend proximally and even to unaffected body regions. This study examines whether sensory dysfunction is observed in unaffected body parts of CRPS patients, and investigates whether the extent of dysfunction is similar for the various sensory modalities. Quantitative sensory testing was performed in the unaffected extremities and cheeks of 48 patients with CRPS of the arm (31 with dystonia), and the results were compared with values obtained among healthy controls. The most prominent abnormality was the pressure pain threshold, which showed a consistent pattern of higher sensitivity in unaffected contralateral arms and unaffected legs, as well as the cheek, and demonstrated the largest effect sizes. The cheeks of CRPS patients showed thermal hypoesthesia and hyperalgesia as well as a loss of vibration detection. Except for a lower vibration threshold in the contralateral leg of CRPS patients with dystonia, no differences in sensory modalities were found between CRPS patients with and without dystonia. These results point to a general disturbance in central pain processing in patients with CRPS, which may be attributed to impaired endogenous pain control. Since pressure pain is the most deviant sensory abnormality in both unaffected and affected body regions of CRPS patients, this test may serve as an important outcome parameter in future studies and may be used as a tool to monitor the course of the disease. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  6. Synthesis of lipid mediators during UVB-induced inflammatory hyperalgesia in rats and mice.

    Directory of Open Access Journals (Sweden)

    Marco Sisignano

    Full Text Available Peripheral sensitization during inflammatory pain is mediated by a variety of endogenous proalgesic mediators including a number of oxidized lipids, some of which serve endogenous modulators of sensory TRP-channels. These lipids are eicosanoids of the arachidonic acid and linoleic acid pathway, as well as lysophophatidic acids (LPAs. However, their regulation pattern during inflammatory pain and their contribution to peripheral sensitization is still unclear. Here, we used the UVB-model for inflammatory pain to investigate alterations of lipid concentrations at the site of inflammation, the dorsal root ganglia (DRGs as well as the spinal dorsal horn and quantified 21 lipid species from five different lipid families at the peak of inflammation 48 hours post irradiation. We found that known proinflammatory lipids as well as lipids with unknown roles in inflammatory pain to be strongly increased in the skin, whereas surprisingly little changes of lipid levels were seen in DRGs or the dorsal horn. Importantly, although there are profound differences between the number of cytochrome (CYP genes between mice and rats, CYP-derived lipids were regulated similarly in both species. Since TRPV1 agonists such as LPA 18∶1, 9- and 13-HODE, 5- and 12-HETE were elevated in the skin, they may contribute to thermal hyperalgesia and mechanical allodynia during UVB-induced inflammatory pain. These results may explain why some studies show relatively weak analgesic effects of cyclooxygenase inhibitors in UVB-induced skin inflammation, as they do not inhibit synthesis of other proalgesic lipids such as LPA 18∶1, 9-and 13-HODE and HETEs.

  7. Effect of Intramuscular Protons, Lactate, and ATP on Muscle Hyperalgesia in Rats.

    Directory of Open Access Journals (Sweden)

    Nicholas S Gregory

    Full Text Available Chronic muscle pain is a significant health problem leading to disability[1]. Muscle fatigue can exacerbate muscle pain. Metabolites, including ATP, lactate, and protons, are released during fatiguing exercise and produce pain in humans. These substances directly activate purinergic (P2X and acid sensing ion channels (ASICs on muscle nociceptors, and when combined, produce a greater increase in neuron firing than when given alone. Whether the enhanced effect of combining protons, lactate, and ATP is the sum of individual effects (additive or more than the sum of individual effects (synergistic is unknown. Using a rat model of muscle nociceptive behavior, we tested each of these compounds individually over a range of physiologic and supra-physiologic concentrations. Further, we combined all three compounds in a series of dilutions and tested their effect on muscle nociceptive behavior. We also tested a non-hydrolyzable form of ATP (α,β-meATP alone and in combination with lactate and acidic pH. Surprisingly, we found no dose-dependent effect on muscle nociceptive behavior for protons, lactate, or ATP when given alone. We similarly found no effect after application of each two-metabolite combination. Only pH 4 saline and α,β-meATP produced hyperalgesia when given alone. When all 3 substances were combined, however, ATP (2.4μm, lactate (10mM, and acidic pH (pH 6.0 produced an enhanced effect greater than the sum of the effects of the individual components, i.e. synergism. α,β me ATP (3nmol, on the other hand, showed no enhanced effects when combined with lactate (10mM or acidic pH (pH 6.0, i.e. additive. These data suggest that combining fatigue metabolites in muscle produces a synergistic effect on muscle nociception.

  8. Opioid-induced hyperalgesia in community-dwelling adults with chronic pain.

    Science.gov (United States)

    Hooten, W Michael; Lamer, Tim J; Twyner, Channing

    2015-06-01

    The hyperalgesic effects of long-term opioid use in community-dwelling adults with chronic pain have not been widely reported. Therefore, the primary aim of this study was to determine the associations between opioid use and heat pain (HP) perception in a sample of community-dwelling adults with chronic pain. The study cohort involved 187 adults (85 opioid and 102 nonopioid) with chronic pain consecutively admitted to an outpatient interdisciplinary pain treatment program. Heat pain perception was assessed using a validated quantitative sensory test method of levels. An effect of opioid use was observed for nonstandardized (P = 0.004) and standardized (P = 0.005) values of HP 5-0.5 in which values of the opioid group were lower (more hyperalgesic) compared with those of the nonopioid group. HP 5-0.5 is a measure of the slope of the line connecting HP 0.5 (HP threshold) and HP 5 (intermediate measure of HP tolerance). In univariable (P = 0.019) and multiple variable (P = 0.003) linear regression analyses (adjusted for age, sex, body mass index, work status, pain diagnosis, pain severity, depression, and pain catastrophizing), opioid use was associated with lower (more hyperalgesic) nonstandardized values of HP 5-0.5. Similarly, in univariable (P = 0.004) and multiple variable (P = 0.011) linear regression analyses (adjusted for work status, pain diagnosis, pain severity, depression, and pain catastrophizing), opioid use was associated with lower standardized values of HP 5-0.5. In this sample of community-dwelling adults, these observations suggest that long-term opioid use was associated with hyperalgesia independent of other clinical factors known to influence HP perception.

  9. Mutational scanning of the human serotonin transporter reveals fast translocating serotonin transporter mutants

    DEFF Research Database (Denmark)

    Kristensen, Anders S; Larsen, Mads B; Johnsen, Laust B

    2004-01-01

    The serotonin transporter (SERT) belongs to a family of sodium-chloride-dependent transporters responsible for uptake of amino acids and biogenic amines from the extracellular space. SERT represents a major pharmacological target in the treatment of several clinical conditions, including depression...

  10. No link of serotonin 2C receptor editing to serotonin transporter genotype

    NARCIS (Netherlands)

    Lyddon, R.; Cuppen, E.; Haroutunian, V.; Siever, L.J.; Dracheva, S.

    2010-01-01

    RNA editing is a post-transcriptional process, which has the potential to alter the function of encoded proteins. In particular, serotonin 2C receptor (5-HT2cR) mRNA editing can produce 24 protein isoforms of varying functionality. Rodent studies have shown that 5-HT2cR editing is dynamically

  11. Thermal hyperalgesia and mechanical allodynia produced by intrathecal administration of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein, gp120.

    Science.gov (United States)

    Milligan, E D; Mehmert, K K; Hinde, J L; Harvey, L O; Martin, D; Tracey, K J; Maier, S F; Watkins, L R

    2000-04-07

    Astrocytes and microglia in the spinal cord have recently been reported to contribute to the development of peripheral inflammation-induced exaggerated pain states. Both lowering of thermal pain threshold (thermal hyperalgesia) and lowering of response threshold to light tactile stimuli (mechanical allodynia) have been reported. The notion that spinal cord glia are potential mediators of such effects is based on the disruption of these exaggerated pain states by drugs thought to preferentially affect glial function. Activation of astrocytes and microglia can release many of the same substances that are known to mediate thermal hyperalgesia and mechanical allodynia. The aim of the present series of studies was to determine whether exaggerated pain states could also be created in rats by direct, intraspinal immune activation of astrocytes and microglia. The immune stimulus used was peri-spinal (intrathecal, i.t.) application of the Human Immunodeficiency Virus type 1 (HIV-1) envelope glycoprotein, gp120. This portion of HIV-1 is known to bind to and activate microglia and astrocytes. Robust thermal hyperalgesia (tail-flick, TF, and Hargreaves tests) and mechanical allodynia (von Frey and touch-evoked agitation tests) were observed in response to i.t. gp120. Heat denaturing of the complex protein structure of gp120 blocked gp120-induced thermal hyperalgesia. Lastly, both thermal hyperalgesia and mechanical allodynia to i.t. gp120 were blocked by spinal pretreatment with drugs (fluorocitrate and CNI-1493) thought to preferentially disrupt glial function.

  12. A Visible-Light-Sensitive Caged Serotonin

    OpenAIRE

    Cabrera, R.; Filevich, O; Garcia-Acosta, B; Athilingam, J; Bender, KJ; Poskanzer, KE; R. Etchenique

    2017-01-01

    Serotonin, or 5-hydroxytryptamine (5HT), is an important neurotransmitter in the nervous system of both vertebrates and invertebrates. Deficits in 5HT signaling are responsible for many disabling psychiatric conditions, and its molecular machinery is the target of many pharmaceuticals. We present a new 5HT phototrigger, the compound [Ru(bpy)2(PMe3)(5HT)]2+, where PMe3 is trimethylphosphine. As with other ruthenium-bipyridyl based caged compounds, [Ru(bpy)2(PMe3)(5HT)]2+ presents activity in t...

  13. Serotonin Immunoreactive Cells and Nerve Fibers in the Mucosa of ...

    African Journals Online (AJOL)

    They appeared not to be in contact with the immunopositive endocrine and mast cells. The current study shows that serotonin may be released by the immunoreactive elements in the stomach and that future work is needed to characterize the ultrastructural features of serotonin positive nerve fibers in the pyloric mucosa.

  14. Serotonin: is it a marker for the diagnosis of hepatocellular ...

    African Journals Online (AJOL)

    Hoda Aly Abd El Moety

    2013-04-19

    Apr 19, 2013 ... Abstract Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer mortality among men worldwide. Serotonin is a biogenic amine, ligand of a family of 5-HT receptors that reflect the diversity of serotonergic actions. Majority of serotonin in body (90%) is synthesized by enterochromaffin ...

  15. Context-dependent modulation of auditory processing by serotonin

    Science.gov (United States)

    Hurley, L.M.; Hall, I.C.

    2011-01-01

    Context-dependent plasticity in auditory processing is achieved in part by physiological mechanisms that link behavioral state to neural responses to sound. The neuromodulator serotonin has many characteristics suitable for such a role. Serotonergic neurons are extrinsic to the auditory system but send projections to most auditory regions. These projections release serotonin during particular behavioral contexts. Heightened levels of behavioral arousal and specific extrinsic events, including stressful or social events, increase serotonin availability in the auditory system. Although the release of serotonin is likely to be relatively diffuse, highly specific effects of serotonin on auditory neural circuitry are achieved through the localization of serotonergic projections, and through a large array of receptor types that are expressed by specific subsets of auditory neurons. Through this array, serotonin enacts plasticity in auditory processing in multiple ways. Serotonin changes the responses of auditory neurons to input through the alteration of intrinsic and synaptic properties, and alters both short- and long-term forms of plasticity. The infrastructure of the serotonergic system itself is also plastic, responding to age and cochlear trauma. These diverse findings support a view of serotonin as a widespread mechanism for behaviorally relevant plasticity in the regulation of auditory processing. This view also accommodates models of how the same regulatory mechanism can have pathological consequences for auditory processing. PMID:21187135

  16. Serotonin synthesis rate and the tryptophan hydroxylase-2

    DEFF Research Database (Denmark)

    Furmark, Tomas; Marteinsdottir, Ina; Frick, Andreas

    2016-01-01

    It is disputed whether anxiety disorders, like social anxiety disorder, are characterized by serotonin over- or underactivity. Here, we evaluated whether our recent finding of elevated neural serotonin synthesis rate in patients with social anxiety disorder could be reproduced in a separate cohor...

  17. Serotonin: Is it a marker for the diagnosis of hepatocellular ...

    African Journals Online (AJOL)

    Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer mortality among men worldwide. Serotonin is a biogenic amine, ligand of a family of 5-HT receptors that reflect the diversity of serotonergic actions. Majority of serotonin in body (90%) is synthesized by enterochromaffin cells of the gastrointestinal ...

  18. Looking on the bright side of serotonin transporter gene variation.

    NARCIS (Netherlands)

    Homberg, J.R.; Lesch, K.P.

    2011-01-01

    Converging evidence indicates an association of the short (s), low-expressing variant of the repeat length polymorphism, serotonin transporter-linked polymorphic region (5-HTTLPR), in the human serotonin transporter gene (5-HTT, SERT, SLC6A4) with anxiety-related traits and increased risk for

  19. Dopamine and serotonin regulate tumor behavior by affecting angiogenesis

    NARCIS (Netherlands)

    Peters, Marloes; Walenkamp, Annemiek M. E.; Kema, Ido P.; Meijer, Coby; de Vries, Elisabeth G. E.; Oosting, Sjoukje F.

    2014-01-01

    The biogenic amines dopamine and serotonin are neurotransmitters and hormones, which are mainly produced in the central nervous system and in the gastro-intestinal tract. They execute local and systemic functions such as intestinal motility and tissue repair. Dopamine and serotonin are primarily

  20. Cost of visceral leishmaniasis care in Brazil.

    Science.gov (United States)

    de Carvalho, Isis Polianna Silva Ferreira; Peixoto, Henry Maia; Romero, Gustavo Adolfo Sierra; de Oliveira, Maria Regina Fernandes

    2017-12-01

    To estimate the Brazilian direct and indirect costs of human visceral leishmaniasis (VL) in 2014. Cost-of-illness study on the Brazilian public health system and societal perspective. VL cases registered in the Notifiable Diseases Information System in the year of 2014 were considered. Direct medical costs regarding diagnostic, treatment and care provided to patients with VL were estimated through the top-down approach. The indirect costs related to productivity loss due to premature mortality and morbidity were estimated by means of the human-capital method. In 2014, 9895 suspected cases of VL were reported in the Notifiable Diseases Information System, and 3453 were later confirmed. There were 234 patients with Leishmania-HIV coinfection underwent a secondary prophylaxis. The total cost of VL in Brazil was US$ 14 190 701.50 (US$ 14 189 150.10 to 14 199 940.53) that varied according to the sensitivity analysis. The total of direct medical costs corresponded to US$ 1 873 681.96 (US$1 872 130.55 to 1 882 920.99), and the majority of costs was associated with hospitalisation (40%), followed by treatment (22%), and secondary prophylaxis (18%). Productivity loss corresponded to US$ 11 421 683.37 for premature mortality and US$ 895 336.18 for work absence due to hospitalisation by the illness. VL represents an expensive health problem for the Brazilian public health system and society, mainly because of its productivity loss due to premature mortality. Interventions to reduce VL lethality could have a great impact on decreasing the cost of illness. © 2017 John Wiley & Sons Ltd.

  1. Human visceral leishmaniasis: a picture from Italy.

    Science.gov (United States)

    Abdalmaula, Giuma Harun; Barbadoro, Pamela; Marigliano, Anna; Illuminati, Diego; Di Stanislao, Francesco; D'Errico, Marcello Mario; Prospero, Emilia

    2013-12-01

    The aim of our study was to describe the distribution of Visceral Leishmaniasis (VL) in Italy, focusing on HIV-infected patients, to estimate the burden of the disease and the public health actions that should be undertaken. A review of official notifications and hospitalization data has been performed. From 2006 to 2008, a total of 289 cases of VL were notified; the overall notification rate was 1.63/1,000,000 (95% CI 1.45-1.83). In total, 1192 VL-associated hospitalizations were detected, with a hospitalization rate of 6.71/1,000,000 (95% CI 6.34-7.10). For the age group "≤ 24 years", a statistically significant increase was detected (p<0.05). A total of 68.9% (n = 821) of hospitalizations were detected in HIV-positive patients. The geographic distribution of rates revealed a significant increase in the north-eastern area of the country. Our study confirms that the epidemiological pattern of VL is changing and that, in Italy, control measures and preventive strategies should be based on not only the official notification system but also hospital data. This would lead to the identification of areas of parasite spread and to the creation of awareness campaigns geared toward general practitioners in the affected areas. Easy case detection would allow for timely public health actions and strategies for the implementation of more effective interventions for reservoir control. Copyright © 2013 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  2. Making Climate Change Visceral Through the Arts

    Science.gov (United States)

    Bilodeau, C.

    2016-12-01

    Through their affective power, the arts offer a more visceral understanding of our global crisis and have a greater potential to inspire people to take action than scientific data alone. In this talk, I will look at three projects that use art to translate scientific data into sensory experiences, galvanize communities around visions of a positive future, and make climate change relevant to our lives. Jill Pelto's work makes science visible. A recent graduate from the University of Maine, Pelto practices what she calls glaciogenic art. As an artist and scientist, she uses her creative skills to communicate information about extreme environmental issues. Pelto's watercolors merge scientific data commonly found on graphs with the interpretation of that data in the form of illustrations. The result is an immediate understanding of the science and its implications. The Land Art Generator Initiative provides a platform for artists, architects, landscape architects, and other creatives working with engineers and scientists to bring forward human-centered solutions for sustainable energy infrastructures that enhance the city as works of public art while cleanly powering thousands of homes. Land Art Generator works are optimistic reminders that there is still time to make positive changes. Climate Change Theatre Action was a series of 100 readings and performances of climate change plays, poems and songs, written by writers from all six continents, presented in over 25 countries in support of the United Nations 2015 Paris Climate Conference. Events ranged from informal readings in classrooms to fully-staged performances, and often included presentations and/or panel conversations with scientists. The project reached people from all walks of life (including homeless youth and refugees) and had a powerful impact on audiences.

  3. Involvement of spinal glutamate transporter-1 in the development of mechanical allodynia and hyperalgesia associated with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Shi J

    2016-11-01

    Full Text Available Jinshan Shi,1,* Ke Jiang,2,* Zhaoduan Li,3 1Department of Anesthesiology, Guizhou Provincial People’s Hospital, 2Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, 3Department of Anesthesiology, Tianjin Nankai Hospital, Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: Little is known about the effects of the development of type 2 diabetes on glutamate homeostasis in the spinal cord. Therefore, we quantified the extracellular levels of glutamate in the spinal cord of Zucker diabetic fatty (ZDF rats using in vivo microdialysis. In addition, protein levels of glutamate transporter-1 (GLT-1 in the spinal cord of ZDF rats were measured using Western blot. Finally, the effects of repeated intrathecal injections of ceftriaxone, which was previously shown to enhance GLT-1 expression, on the development of mechanical allodynia and hyperalgesia as well as on basal extracellular level of glutamate and the expression of GLT-1 in the spinal cord of ZDF rats were evaluated. It was found that ZDF rats developed mechanical hyperalgesia and allodynia, which were associated with increased basal extracellular levels of glutamate and attenuated levels of GLT-1 expression in the spinal cord, particularly in the dorsal horn. Furthermore, repeated intrathecal administrations of ceftriaxone dose-dependently prevented the development of mechanical hyperalgesia and allodynia in ZDF rats, which were correlated with enhanced GLT-1 expression without altering the basal glutamate levels in the spinal cord of ZDF rats. Overall, the results suggested that impaired glutamate reuptake in the spinal cord may contribute to the development of neuropathic pains in type 2 diabetes. Keywords: diabetes, peripheral neuropathy, spinal cord, Zucker diabetic fatty rats, glutamate, glutamate transporter-1

  4. Galanin-Mediated Behavioural Hyperalgesia from the Dorsomedial Nucleus of the Hypothalamus Involves Two Independent Descending Pronociceptive Pathways.

    Directory of Open Access Journals (Sweden)

    Diana Amorim

    Full Text Available Activation of the dorsomedial nucleus of the hypothalamus (DMH by galanin (GAL induces behavioural hyperalgesia. Since DMH neurones do not project directly to the spinal cord, we hypothesized that the medullary dorsal reticular nucleus (DRt, a pronociceptive region projecting to the spinal dorsal horn (SDH and/or the serotoninergic raphe-spinal pathway acting on the spinal 5-HT3 receptor (5HT3R could relay descending nociceptive facilitation induced by GAL in the DMH. Heat-evoked paw-withdrawal latency (PWL and activity of SDH neurones were assessed in monoarthritic (ARTH and control (SHAM animals after pharmacological manipulations of the DMH, DRt and spinal cord. The results showed that GAL in the DMH and glutamate in the DRt lead to behavioural hyperalgesia in both SHAM and ARTH animals, which is accompanied particularly by an increase in heat-evoked responses of wide-dynamic range neurons, a group of nociceptive SDH neurones. Facilitation of pain behaviour induced by GAL in the DMH was reversed by lidocaine in the DRt and by ondansetron, a 5HT3R antagonist, in the spinal cord. However, the hyperalgesia induced by glutamate in the DRt was not blocked by spinal ondansetron. In addition, in ARTH but not SHAM animals PWL was increased after lidocaine in the DRt and ondansetron in the spinal cord. Our data demonstrate that GAL in the DMH activates two independent descending facilitatory pathways: (i one relays in the DRt and (ii the other one involves 5-HT neurones acting on spinal 5HT3Rs. In experimental ARTH, the tonic pain-facilitatory action is increased in both of these descending pathways.

  5. Chronic administration of modafinil induces hyperalgesia in mice: reversal by L-NG-nitro-arginine methyl ester and 7-nitroindazole.

    Science.gov (United States)

    Gupta, Rachna; Gupta, Lalit Kumar; Bhattacharya, Swapan K

    2014-08-05

    Modafinil [2-((diphenylmethyl) sulfinyl) acetamide] is a central nervous system stimulant. It has received considerable attention as a potential psychotropic agent in several psychiatric disorders. The current study was carried out to investigate the effect of modafinil after acute administration on animal models of pain in mice. Also, this study evaluated the effect of L-NG-nitroarginine methyl ester (L-NAME), 7-nitroindazole (7-NI) and naloxone following chronic administration of modafinil. Modafinil was administered in the doses of 50, 100 or 200 mg/kg once in acute study and it showed significantly increased tail-flick latency (tfl) and paw-licking latency. In formalin test modafinil (100 mg/kg) significantly reduced licking/biting time in both early and late phases in comparison to control. In chronic study, modafinil 100 mg/kg administered for 10 days, produced a progressive decrease in the reaction time (i.e., tfl/paw-licking latency) in comparison to day 1 values which started building up from day 4 and fully established at day 6, indicating hyperalgesic response. Prior administration of 7-NI (on day 7) and L-NAME (on day 10) prevented the hyperalgesic response while naloxone on day 10 did not have a significant effect on modafinil-induced hyperalgesia. These results demonstrate that modafinil has a potential role in pain as it exhibited antinociceptive effect after acute administration in a dose-dependent manner and on chronic administration it caused hyperalgesia. This hyperalgesia is reversed by nitric oxide synthase inhibitors, suggesting the possibility of involvement of nitric oxide pathway. Further studies are required to evaluate the role of modafinil in clinical pain. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Elective visceral hybrid repair of type III thoracoabdominal aortic aneurysm

    Directory of Open Access Journals (Sweden)

    Marjanović Ivan

    2012-01-01

    Full Text Available Introduction. According to the classification given by Crawford et al. type III thoracoabdominal aortic aneurysm (TAAA is dilatation of the aorta from the level of the rib 6 to the separation of the aorta below the renal arteries, capturing all the visceral branch of aorta. Visceral hybrid reconstruction of TAAA is a procedure developed in recent years in the world, which involves a combination of conventional, open and endovascular aortic reconstruction surgery at the level of separation of the left subclavian artery to the level of visceral branches of aorta. Case report. We presented a 75-years-old man, with elective visceral hybrid reconstruction of type III TAAA. Computerized scanning (CT angiography of the patient showed type III TAAA with the maximum transverse diameter of aneurysm of 92 mm. Aneurysm started at the level of the sixth rib, and the end of the aneurysm was 1 cm distal to the level of renal arteries. Aneurysm compressed the esophagus, causing the patient difficulty in swallowing act, especially solid food, and frequent back pain. From the other comorbidity, the patient had been treated for a long time, due to chronic obstructive pulmonary disease and hypertension. In general endotracheal anesthesia with epidural analgesia, the patient underwent visceral hybrid reconstruction of TAAA, which combines classic, open vascular surgery and endovascular procedures. Classic vascular surgery is visceral reconstruction using by-pass procedure from the distal, normal aorta to all visceral branches: celiac trunk, superior mesenteric artery and both renal arteries, with ligature of all arteries very close to the aorta. After that, by synchronous endovascular technique a complete aneurysmal exclusion of thoracoabdominal aneurysm with thoracic stent-graft was performed. The postoperative course was conducted properly and the patient left the Clinic for Vascular Surgery on postoperative day 21. Control CT, performed 3 months after the surgery

  7. A specific role for serotonin in overcoming effort cost.

    Science.gov (United States)

    Meyniel, Florent; Goodwin, Guy M; Deakin, Jf William; Klinge, Corinna; MacFadyen, Christine; Milligan, Holly; Mullings, Emma; Pessiglione, Mathias; Gaillard, Raphaël

    2016-11-08

    Serotonin is implicated in many aspects of behavioral regulation. Theoretical attempts to unify the multiple roles assigned to serotonin proposed that it regulates the impact of costs, such as delay or punishment, on action selection. Here, we show that serotonin also regulates other types of action costs such as effort. We compared behavioral performance in 58 healthy humans treated during 8 weeks with either placebo or the selective serotonin reuptake inhibitor escitalopram. The task involved trading handgrip force production against monetary benefits. Participants in the escitalopram group produced more effort and thereby achieved a higher payoff. Crucially, our computational analysis showed that this effect was underpinned by a specific reduction of effort cost, and not by any change in the weight of monetary incentives. This specific computational effect sheds new light on the physiological role of serotonin in behavioral regulation and on the clinical effect of drugs for depression. ISRCTN75872983.

  8. Infrared Thermography in Serotonin-Induced Itch Model in Rats

    DEFF Research Database (Denmark)

    Jasemian, Yousef; Gazerani, Parisa; Dagnæs-Hansen, Frederik

    2012-01-01

    The study validated the application of infrared thermography in a serotonin-induced itch model in rats since the only available method in animal models of itch is the count of scratching bouts. Twenty four adult Sprague-Dawley male rats were used in 3 experiments: 1) local vasomotor response...... with no scratching reflex was investigated. Serotonin elicited significant scratching and lowered the local temperature at the site of injection. A negative dose-temperature relationship of serotonin was found by thermography. Vasoregulation at the site of serotonin injection took place in the absence of scratching...... reflexes. Thermography is a reliable, non-invasive, and objective method for assessment in serotonin-induced itch model in rat....

  9. Serotonin enhances solitariness in phase transition of the migratory locust

    Directory of Open Access Journals (Sweden)

    Xiaojiao eGuo

    2013-10-01

    Full Text Available The behavioral plasticity of locusts is a striking trait presented during the reversible phase transition between solitary and gregarious individuals. However, the results of serotonin as a neurotransmitter from the migratory locust Locusta migratoria in phase transition showed an alternative profile compared to the results from the desert locust Schistoserca gregaria. In this study, we investigated the roles of serotonin in the brain during the phase change of the migratory locust. During the isolation of gregarious nymphs, the concentration of serotonin in the brain increased significantly, whereas serotonin receptors (i.e. 5-HT1, 5-HT2 and 5-HT7 we identified here showed invariable expression patterns. Pharmacological intervention showed that serotonin injection in the brain of gregarious nymphs did not induced the behavior change toward solitariness, but injection of this chemical in isolated gregarious nymphs accelerated the behavioral change from gregarious to solitary phase. During the crowding of solitary nymphs, the concentration of serotonin in the brain remained unchanged, whereas 5-HT2 increased after 1 h of crowding and maintained stable expression level thereafter. Activation of serotonin-5-HT2 signaling with a pharmaceutical agonist inhibited the gregariousness of solitary nymphs in crowding treatment. These results indicate that the fluctuations of serotonin content and 5-HT2 expression are results of locust phase change. Overall, this study demonstrates that serotonin enhances the solitariness of the gregarious locusts. Serotonin may regulate the withdrawal-like behavioral pattern displayed during locust phase change and this mechanism is conserved in different locust species.

  10. A Dualistic Conformational Response to Substrate Binding in the Human Serotonin Transporter Reveals a High Affinity State for Serotonin*

    Science.gov (United States)

    Bjerregaard, Henriette; Severinsen, Kasper; Said, Saida; Wiborg, Ove; Sinning, Steffen

    2015-01-01

    Serotonergic neurotransmission is modulated by the membrane-embedded serotonin transporter (SERT). SERT mediates the reuptake of serotonin into the presynaptic neurons. Conformational changes in SERT occur upon binding of ions and substrate and are crucial for translocation of serotonin across the membrane. Our understanding of these conformational changes is mainly based on crystal structures of a bacterial homolog in various conformations, derived homology models of eukaryotic neurotransmitter transporters, and substituted cysteine accessibility method of SERT. However, the dynamic changes that occur in the human SERT upon binding of ions, the translocation of substrate, and the role of cholesterol in this interplay are not fully elucidated. Here we show that serotonin induces a dualistic conformational response in SERT. We exploited the substituted cysteine scanning method under conditions that were sensitized to detect a more outward-facing conformation of SERT. We found a novel high affinity outward-facing conformational state of the human SERT induced by serotonin. The ionic requirements for this new conformational response to serotonin mirror the ionic requirements for translocation. Furthermore, we found that membrane cholesterol plays a role in the dualistic conformational response in SERT induced by serotonin. Our results indicate the existence of a subpopulation of SERT responding differently to serotonin binding than hitherto believed and that membrane cholesterol plays a role in this subpopulation of SERT. PMID:25614630

  11. A dualistic conformational response to substrate binding in the human serotonin transporter reveals a high affinity state for serotonin

    DEFF Research Database (Denmark)

    Bjerregaard, Henriette; Severinsen, Kasper; Said, Saida

    2015-01-01

    that were sensitized to detect a more outward-facing conformation of SERT. We found a novel high affinity outward-facing conformational state of the human SERT induced by serotonin. The ionic requirements for this new conformational response to serotonin mirror the ionic requirements for translocation...

  12. Serotonin in the sudden infant death syndrome.

    Science.gov (United States)

    Waters, Karen

    2010-11-01

    It seems likely that some infants who die from sudden infant death syndrome (SIDS) have a brainstem abnormality of the serotonergic system. Evidence suggests that infants who died from SIDS had defective respiratory and/or autonomic responses that led to death instead of recovery after an acute insult. The serotonergic neuromodulator system has roles in the control of cardiac autonomic and respiratory function, as well as now being identified as abnormal in infants with SIDS. This manuscript reviews the multiple roles of serotonin with reference to the functional aspects of the relevant brain regions. Correlations with pre- or postnatal exposure to stressors, or an underlying genetic process are also reviewed. Together, these studies indicate that perturbed function of the serotonin system will have significant physiological impact during early development. Understanding the functional importance of these systems assists understanding of the pathogenesis of SIDS. In conclusion, whether an infant inherits serotonergic defects and is therefore "inherently vulnerable", or whether postnatal stressors can induce the abnormalities, any functional abnormalities of the serotonergic system that result are likely to be subclinical in the majority of cases and not easily detected with current medical tools. Copyright 2010 Prous Science, S.A.U. or its licensors. All rights reserved.

  13. Acupuncture causes serotonin release by mast cells.

    Science.gov (United States)

    Dimitrov, Nikolay; Atanasova, Dimitrinka; Tomov, Nikola; Sivrev, Dimitar; Lazarov, Nikolai

    2017-01-01

    Mast cells (MCs) are important object in experimental acupuncture due to their putative involvement in local reactions to needling. In the rat, they are shown to contain in their granules, among other tissue mediators, serotonin, also called 5-hydroxytryptamine (5-HT). The aim of this study is to examine the normal distribution of 5-HT-containing MCs in soft tissues of Zusanli (ST36) acupuncture point (acupoint) and their morphological changes caused by experimental acupuncture. We observed 5-HT-immunopositive MCs in the tissues and in the vicinity of the needle tract formed after acupuncture. As a result of acupuncture needling, the tissue integrity is disrupted and certain folds are formed in the direction of the needle tract. Connective tissue in the vicinity of the needle tract gets compressed and displaced, together with the 5-HT-immunoreactive MCs seen there. Some of those 5-HT-immunopositive MCs showed signs of degranulation with numerous discharged granules, some of them found at a considerable distance form the cell. Furthermore, 5-HT-immunopositive MCs are unevenly distributed in soft tissues of ST36 acupoint. Larger numbers of 5-HT-containing MCs were visualized in subcutis and dermis, compared to the observed in striated muscles. Placing the acupuncture needle into the rat skin caused a formation of an apparent needle tract, tissue displacement and degranulation of 5-HT-immunopositive MCs. The demonstrated serotonin release by means of MC degranulation might be involved in the local tissue response to acupuncture.

  14. The Visceral Novel Reader and Novelized Medicine in Georgian Britain.

    Science.gov (United States)

    Class, Monika

    The article introduces "the visceral novel reader" as a diachronic, context-sensitive mode of novelistic reception, in which fact and fiction overlap cognitively: the mental rehearsal of the activity of seeing, hearing, smelling, tasting, and touching while reading novels and, vice versa, the mental rehearsal of novels in the act of perceiving the real world. Located at the intersection of literature, medicine and science, "the visceral novel reader" enhances our understanding of the role that novels played in the dialectic construction of erudition in English. In Georgian Britain, reading practices became a testing ground for the professionalization of physicians, natural philosophers, and men of letters. While it was in the professionals' common interest to implement protocols that taught readers to separate body from mind, and fact from fiction, novels came to stand for "debased" (visceral) reading. Novels inverted these notions by means of medicalization (regimentation, somatization, and individuation) and contributed to the professional stratification of medicine and literature.

  15. VISCERAL ABDOMINAL PAIN AND OPPORTUNITIES OF SPASMOLYTIC TREATMENT

    Directory of Open Access Journals (Sweden)

    E.A. Kornienko

    2008-01-01

    Full Text Available Results of treatment of 30 children with visceral abdominal pain caused by different etiological factors with neurotropic selective m9cholinergic antagonist hyoscine butilbromide (buscopan are presented in this article. Two groups of children were treated with hyoscine butilbromide and drotaverine accordingly. Administration of hyoscine butilbromide allows to stop pain in 93% of patients; mean duration of abdominal pain was 3,4 ± 1,2 days (4,2 ± 1,4 days in children treated with drotaverine, р < 0,05. Activity of dyspeptic disorders was decreased at the time of treatment. a tolerance to hyoscine butilbromide was satisfactory, and no adverse events were registered. hyoscine butilbromide is effective in treatment of visceral abdominal pain in children, allowing shortening its duration more actively then drotaverine.Key words: children, visceral abdominal pain, hyoscine butilbromide.

  16. Tuberous sclerosis with visceral leishmaniasis: a case report

    Directory of Open Access Journals (Sweden)

    Pandey Krishna

    2009-09-01

    Full Text Available Abstract Introduction Visceral leishmaniasis, a tropical infectious disease, is a major public health problem in India. Tuberous sclerosis, a congenital neuro-ectodermosis, is an uncommon disease which requires life long treatment. Case presentation A 15-year-old Indian patient, presented to the outpatient department of our institute with a high-grade fever for two months, splenomegaly and a history of generalized tonic-clonic convulsions since childhood. The clinical and laboratory findings suggested visceral leishmaniasis with tuberous sclerosis. The patient was treated with miltefosine and antiepileptics. Conclusion The patient responded well and in a follow up six months after presentation, she was found free of visceral leishmaniasis and seizures. Diagnosis and treatment of this rare combination of diseases is difficult.

  17. Visceral metabolism and efficiency of energy use by ruminants

    Directory of Open Access Journals (Sweden)

    Kozloski Gilberto Vilmar

    2001-01-01

    Full Text Available The visceral system (liver and portal-drained viscera represents an interface between diet and the animal, and it acts as the main site of regulation of nutrients that are used for maintenance, growth, lactation, reproduction, and physical activities of animals. However the functions carried out by visceral organs have, however, a significant energetic cost and are influenced by a variety of factors, such as the level of feed intake and diet composition, among others. As a result, variable quantities of substances are metabolized by them and, thus, the pattern and the quantity of nutrients available to the peripheral tissues can be quite different from those absorbed at the intestinal lumen. Probably, the major source of variation in the efficiency of utilization of metabolizable energy among feeds is associated mainly with visceral metabolism and it is unlikely that the ratio ketogenic/glucogenic of absorbed substances has determinant effect under physiological conditions.

  18. Plasma anti-serotonin and serotonin anti-idiotypic antibodies are elevated in panic disorder.

    Science.gov (United States)

    Coplan, J D; Tamir, H; Calaprice, D; DeJesus, M; de la Nuez, M; Pine, D; Papp, L A; Klein, D F; Gorman, J M

    1999-04-01

    The psychoneuroimmunology of panic disorder is relatively unexplored. Alterations within brain stress systems that secondarily influence the immune system have been documented. A recent report indicated elevations of serotonin (5-HT) and ganglioside antibodies in patients with primary fibromyalgia, a condition with documented associations with panic disorder. In line with our interest in dysregulated 5-HT systems in panic disorder (PD), we wished to assess if antibodies directed at the 5-HT system were elevated in patients with PD in comparison to healthy volunteers. Sixty-three patients with panic disorder and 26 healthy volunteers were diagnosed by the SCID. Employing ELISA, we measured anti-5-HT and 5-HT anti-idiotypic antibodies (which are directed at 5-HT receptors). To include all subjects in one experiment, three different batches were run during the ELISA. Plasma serotonin anti-idiotypic antibodies: there was a significant group effect [patients > controls (p = .007)] and batch effect but no interaction. The mean effect size for the three batches was .76. Following Z-score transformation of each separate batch and then combining all scores, patients demonstrated significantly elevated levels of plasma serotonin anti-idiotypic antibodies. Neither sex nor age as covariates affected the significance of the results. There was a strong correlation between anti-serotonin antibody and serotonin anti-idiotypic antibody measures. Plasma anti-serotonin antibodies: there was a significant diagnosis effect [patients > controls (p = .037)]. Mean effect size for the three batches was .52. Upon Z-score transformation, there was a diagnosis effect with antibody elevations in patients. Covaried for sex and age, the result falls below significance to trend levels. The data raise the possibility that psychoimmune dysfunction, specifically related to the 5-HT system, may be present in PD. Potential interruption of 5-HT neurotransmission through autoimmune mechanisms may be of

  19. Increased Hyperalgesia and Proinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion After Surgery and/or Fentanyl Administration in Rats.

    Science.gov (United States)

    Chang, Lu; Ye, Fang; Luo, Quehua; Tao, Yuanxiang; Shu, Haihua

    2018-01-01

    Perioperative fentanyl has been reported to induce hyperalgesia and increase postoperative pain. In this study, we tried to investigate behavioral hyperalgesia, the expression of proinflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the activation of microglia in the spinal cord and dorsal root ganglion (DRG) in a rat model of surgical plantar incision with or without perioperative fentanyl. Four groups of rats (n = 32 for each group) were subcutaneously injected with fentanyl at 60 μg/kg or normal saline for 4 times with 15-minute intervals. Plantar incisions were made to rats in 2 groups after the second drug injection. Mechanical and thermal nociceptive thresholds were assessed by the tail pressure test and paw withdrawal test on the day before, at 1, 2, 3, 4 hours, and on the days 1-7 after drug injection. The lumbar spinal cord, bilateral DRG, and cerebrospinal fluid of 4 rats in each group were collected to measure IL-1β, IL-6, and TNF-α on the day before, at the fourth hour, and on the days 1, 3, 5, and 7 after drug injection. The lumbar spinal cord and bilateral DRG were removed to detect the ionized calcium-binding adapter molecule 1 on the day before and on the days 1 and 7 after drug injection. Rats injected with normal saline only demonstrated no significant mechanical or thermal hyperalgesia or any increases of IL-1β, IL-6, and TNF-α in the spinal cord or DRG. However, injection of fentanyl induced analgesia within as early as 4 hours and a significant delayed tail mechanical and bilateral plantar thermal hyperalgesia after injections lasting for 2 days, while surgical plantar incision induced a significant mechanical and thermal hyperalgesia lasting for 1-4 days. The combination of fentanyl and incision further aggravated the hyperalgesia and prolonged the duration of hyperalgesia. The fentanyl or surgical incision upregulated the expression of IL-1β, IL-6, and TNF-α in the

  20. Epidemiology of visceral leishmaniasis in Georgia.

    Directory of Open Access Journals (Sweden)

    Giorgi Babuadze

    2014-03-01

    Full Text Available This study investigated the transmission and prevalence of Leishmania parasite infection of humans in two foci of Visceral Leishmaniasis (VL in Georgia, the well known focus in Tbilisi in the East, and in Kutaisi, a new focus in the West of the country. The seroprevalence of canine leishmaniasis was investigated in order to understand the zoonotic transmission. Blood samples of 1575 dogs (stray and pet and 77 wild canids were tested for VL by Kalazar Detect rK39 rapid diagnostic tests. Three districts were investigated in Tbilisi and one in Kutaisi. The highest proportions of seropositive pet dogs were present in District #2 (28.1%, 82/292 and District #1 (26.9%, 24/89 in Tbilisi, compared to 17.3% (26/150 of pet dogs in Kutaisi. The percentage of seropositive stray dogs was also twice as high in Tbilisi (16.1%, n = 670 than in Kutaisi (8%, n = 50; only 2/58 wild animals screened were seropositive (2. 6%. A total of 873 Phlebotomine sand flies were collected, with 5 different species identified in Tbilisi and 3 species in Kutaisi; 2.3% of the females were positive for Leishmania parasites. The Leishmanin Skin Test (LST was performed on 981 human subjects in VL foci in urban areas in Tbilisi and Kutaisi. A particularly high prevalence of LST positives was observed in Tbilisi District #1 (22.2%, 37.5% and 19.5% for ages 5-9, 15-24 and 25-59, respectively; lower prevalence was observed in Kutaisi (0%, 3.2% and 5.2%, respectively; P<0.05. This study shows that Tbilisi is an active focus for leishmaniasis and that the infection prevalence is very high in dogs and in humans. Although exposure is as yet not as high in Kutaisi, this is a new VL focus. The overall situation in the country is alarming and new control measures are urgently needed.

  1. Management of visceral leishmaniasis with therapeutic vaccines

    Directory of Open Access Journals (Sweden)

    Rawat K

    2016-09-01

    Full Text Available Keerti Rawat,1 Narendra K Yadav,1 Sumit Joshi,1 Sneha Ratnapriya,1 Amogh A Sahasrabuddhe,2 Anuradha Dube1 1Division of Parasitology, 2Division of Molecular and Structural Biology, Council of Scientific and Industrial Research-Central Drug Research Institute, Lucknow, India Abstract: Visceral leishmaniasis (VL, a phlebotomine-borne neglected tropical disease, is caused by parasites of the Leishmania donovani complex. While L. donovani infection is restricted to the Indian subcontinent and East Africa, where transmission is anthroponotic, Leishmania infantum occurs in Europe, North Africa, and parts of Latin America, where it is zoonotic in nature with dogs as reservoir hosts. Though the incidence of VL caused by L. infantum has been on the decline, L. donovani continues to cause epidemics periodically. By and large, a small proportion of L. donovani infection manifests as clinical disease but majority of the infected individuals remain asymptomatic and contribute to the perpetuation of the VL transmission cycle via the sand fly vector. This is one of the major stumbling blocks to World Health Organization initiatives to eliminate this deadly disease by 2020. These parasites reside within the host macrophages and impair the immune system of the infected individual, which ultimately results in marked immunosuppression. In the absence of any safe and effective vector control measure, attempts have been made to design therapeutic vaccine(s that can exclusively target infected macrophages. So far, two vaccines – a glycoprotein complex from L. donovani promastigote, fucose–mannose ligand with saponin, commercialized as Leishmune®, as well as a polyprotein vaccine formulation, Leish-111f + monophosphoryl lipid A plus squalene emulsion in combination with glucantime, have been successfully evaluated for their immunotherapeutic potential against canine VL. However, encouraging results obtained from several experimental trials so far against human VL

  2. Visceral schistosomiasis among domestic ruminants slaughtered in Wayanad, South India.

    Science.gov (United States)

    Ravindran, R; Lakshmanan, B; Ravishankar, C; Subramanian, H

    2007-11-01

    This short communication reports the prevalence of visceral schistosomiasis by worm counts from the mesentery of domestic ruminants of the hilly district of Wayanad, located in Kerala, one of the states in South India. We found 57.3, 50, and 4.7% of cattle, buffaloes and goats, respectively, had visceral schistosomiasis upon slaughter at a municipal slaughter house in Kalpetta. Our findings show that the prevalence of Schistosoma spindale infection is very high in Wayanad in comparison to previous reports from this and neighboring countries.

  3. [Visceral leishmaniasis, pemphigus and immunosuppressive treatment: case report from Morocco].

    Science.gov (United States)

    Maleb, A; Messaoudi, N; Chbouki, O; Daoudi, N; Oumghar, K; Lahmadi, K; Elmoussaoui, D; Ezzahraoui, K; Ngoh, Akwa E; Benomar, F; Abi, R; Jeaidi, A; Nazih, M; Belmekki, A; Chakour, M

    2011-02-01

    Atypical forms of visceral leishmaniasis associated with immunosuppressive treatment are difficult to diagnose and cause high mortality. The purpose of this report is to describe a case involving a 42-year-old patient living in a leishmaniasis-endemic area, who was undergoing immunosuppressive treatment using corticosteroids and methotrexate for pemphigus. Despite clinical and laboratory findings consistent with visceral leishmaniasis, detection of Leishmania bodies was a coincidental finding of cytological examination of bone marrow during workup for pancytopenia and associated clinical signs. This case argues in favor of systematic screening for this opportunistic parasitic disease before undertaking immunosuppressive treatment in patients presenting risk factors and consistent clinical/laboratory findings.

  4. Visceral leishmaniasis diagnosed in a patient with MALT lymphoma

    DEFF Research Database (Denmark)

    Kaae, Jeanette; Nørgaard, Peter; Himmelstrup, B

    2007-01-01

    We report a case of visceral leishmaniasis in a 66-year-old female with a history of MALT lymphoma in the gastrointestinal tract. The patient presented with major hemorrhage per rectum and perforation of the small intestine. Due to unexplained decreasing platelets, lymphoma bone marrow involvement...... was suspected and bone marrow examination was performed. Surprisingly, Leishman-Donovan bodies were detected. The low platelet count, caused by the combination of MALT lymphoma and visceral leishmaniasis, appears to have aggravated the symptoms of the intestinal lymphoma. Leishmaniasis should be suspected even...... among asymptomatic patients with immune compromising illnesses and a travel history to areas where leishmaniasis is endemic....

  5. Cutaneous and visceral leishmaniasis during anti-TNFα therapy.

    Science.gov (United States)

    Guarneri, Claudio; Bevelacqua, Valentina; Patterson, James W; Tchernev, Georgi

    2017-03-01

    The long-term use of novel antipsoriatic systemic biotechnological drugs may increase susceptibility to opportunistic infections. Several cases of visceral leishmaniasis have been reported in immunosuppressed individuals, including those who have been treated with tumour necrosis factor alpha (TNFα) blocking agents. Simultaneous occurrence of cutaneous and visceral involvement has been more rarely recorded in the medical literature. Herein, we describe a case of mucosal leishmaniasis occurring in a farmer living in an endemic region, who was treated with golimumab because of psoriatic arthritis. This highlights the importance of recognizing cutaneous lesions as a first indicator of possible underlying kala-azar disease.

  6. Functional dyspepsia: the role of visceral hypersensitivity in its pathogenesis.

    LENUS (Irish Health Repository)

    Keohane, John

    2012-02-03

    Functional, or non-ulcer, dyspepsia (FD) is one of the most common reasons for referral to gastroenterologists. It is associated with significant morbidity and impaired quality of life. Many authorities believe that functional dyspepsia and irritable bowel syndrome represent part of the spectrum of the same disease process. The pathophysiology of FD remains unclear but several theories have been proposed including visceral hypersensitivity, gastric motor dysfunction, Helicobacter pylori infection and psychosocial factors. In this review, we look at the evidence, to date, for the role of visceral hypersensitivity in the aetiology of FD.

  7. Presentation of AIDS with Disseminated Cutaneous and Visceral Leishmaniasis in Iran

    Directory of Open Access Journals (Sweden)

    Mohammadali Davarpanah

    2015-01-01

    Full Text Available Leishmaniasis is an infectious disease in form of visceral (VL, cutaneous (CL, and mucocutaneous (MCL leishmaniasis. Immunocompromised patients have increased risk of Leishmania infection, especially in endemic areas for visceral leishmaniasis, where in the world HIV/VL coinfection has become endemic. The case here suffers from both AIDS and visceral-cutaneous leishmaniasis. We report an Iranian woman with disseminated cutaneous and visceral leishmaniasis who became positive for HIV test.

  8. Secondary hyperalgesia in the rat first degree burn model is independent of spinal cyclooxygenase and nitric oxide synthase

    Science.gov (United States)

    Sorkin, Linda S.; Doom, Carmen M.; Maruyama, Karly P.; Nanigian, Danielle B.

    2009-01-01

    Various animal models of pain are dependent on activation of different glutamate receptor subtypes. First-degree burn of the paw elicits a secondary hyperalgesia that is dependent on Ca2++ permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), but not N-methyl-D-aspartate (NMDA) receptors. The present study takes advantage of that specificity by examining the effects of spinal pretreatments of agents on this secondary hyperalgesia. Rats with indwelling intrathecal catheters were pretreated with agents prior to paw injury. Mechanical withdrawal thresholds were measured before, and for three h after the injury. Spinal pretreatment with cyclooxygenase (10 and 30 μg (S)-(+)-ibuprofen; and 3 and 30 μg ketorolac) and nitric oxide synthase (33 and 100 μg NG Nitro-L-arginine methyl ester hydrochloride (L-NAME) and 10 μg thiocitrulline) inhibitors resulted in no specific anti-allodynia. In contrast, ziconotide (0.3, 1.0 and 3 μg), the N-type voltage gated calcium channel antagonist was very effective in blocking burn-induced sensitivity at all doses used. L-type (Diltiazam 230 μg) and P-type (Agatoxin IVA 0.3 μg) calcium channel blockers produced intermediate effects. Thus, cyclooxygenase and nitric oxide synthase are assumed not to be downstream of Ca2++ permeable AMPA receptors. Voltage gated calcium channels blockers could exert their effects either pre- or post-synaptically. PMID:18440503

  9. Transplantation of bone marrow-derived mononuclear cells improves mechanical hyperalgesia, cold allodynia and nerve function in diabetic neuropathy.

    Directory of Open Access Journals (Sweden)

    Keiko Naruse

    Full Text Available Relief from painful diabetic neuropathy is an important clinical issue. We have previously shown that the transplantation of cultured endothelial progenitor cells or mesenchymal stem cells ameliorated diabetic neuropathy in rats. In this study, we investigated whether transplantation of freshly isolated bone marrow-derived mononuclear cells (BM-MNCs alleviates neuropathic pain in the early stage of streptozotocin-induced diabetic rats. Two weeks after STZ injection, BM-MNCs or vehicle saline were injected into the unilateral hind limb muscles. Mechanical hyperalgesia and cold allodynia in SD rats were measured as the number of foot withdrawals to von Frey hair stimulation and acetone application, respectively. Two weeks after the BM-MNC transplantation, sciatic motor nerve conduction velocity (MNCV, sensory nerve conduction velocity (SNCV, sciatic nerve blood flow (SNBF, mRNA expressions and histology were assessed. The BM-MNC transplantation significantly ameliorated mechanical hyperalgesia and cold allodynia in the BM-MNC-injected side. Furthermore, the slowed MNCV/SNCV and decreased SNBF in diabetic rats were improved in the BM-MNC-injected side. BM-MNC transplantation improved the decreased mRNA expression of NT-3 and number of microvessels in the hind limb muscles. There was no distinct effect of BM-MNC transplantation on the intraepidermal nerve fiber density. These results suggest that autologous transplantation of BM-MNCs could be a novel strategy for the treatment of painful diabetic neuropathy.

  10. Intradermal administration of magnesium sulphate and magnesium chloride produces hypesthesia to mechanical but hyperalgesia to heat stimuli in humans

    Directory of Open Access Journals (Sweden)

    Ikemoto Tatsunori

    2009-08-01

    Full Text Available Abstract Background Although magnesium ions (Mg2+ are known to display many similar features to other 2+ charged cations, they seem to have quite an important and unique role in biological settings, such as NMDA blocking effect. However, the role of Mg2+ in the neural transmission system has not been studied as sufficiently as calcium ions (Ca2+. To clarify the sensory effects of Mg2+ in peripheral nervous systems, sensory changes after intradermal injection of Mg2+ were studied in humans. Methods Magnesium sulphate, magnesium chloride and saline were injected into the skin of the anterior region of forearms in healthy volunteers and injection-induced irritating pain ("irritating pain", for short, tactile sensation, tactile pressure thresholds, pinch-pain changes and intolerable heat pain thresholds of the lesion were monitored. Results Flare formation was observed immediately after magnesium sulphate or magnesium chloride injection. We found that intradermal injections of magnesium sulphate and magnesium chloride transiently caused irritating pain, hypesthesia to noxious and innocuous mechanical stimulations, whereas secondary hyperalgesia due to mechanical stimuli was not observed. In contrast to mechanical stimuli, intolerable heat pain-evoking temperature was significantly decreased at the injection site. In addition to these results, spontaneous pain was immediately attenuated by local cooling. Conclusion Membrane-stabilizing effect and peripheral NMDA-blocking effect possibly produced magnesium-induced mechanical hypesthesia, and extracellular cation-induced sensitization of TRPV1 channels was thought to be the primary mechanism of magnesium-induced heat hyperalgesia.

  11. Serotonin 2c receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis

    Science.gov (United States)

    Energy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor a...

  12. Serotonin and the regulation of mammalian energy balance.

    Science.gov (United States)

    Donovan, Michael H; Tecott, Laurence H

    2013-01-01

    Maintenance of energy balance requires regulation of the amount and timing of food intake. Decades of experiments utilizing pharmacological and later genetic manipulations have demonstrated the importance of serotonin signaling in this regulation. Much progress has been made in recent years in understanding how central nervous system (CNS) serotonin systems acting through a diverse array of serotonin receptors impact feeding behavior and metabolism. Particular attention has been paid to mechanisms through which serotonin impacts energy balance pathways within the hypothalamus. How upstream factors relevant to energy balance regulate the release of hypothalamic serotonin is less clear, but work addressing this issue is underway. Generally, investigation into the central serotonergic regulation of energy balance has had a predominantly "hypothalamocentric" focus, yet non-hypothalamic structures that have been implicated in energy balance regulation also receive serotonergic innervation and express multiple subtypes of serotonin receptors. Moreover, there is a growing appreciation of the diverse mechanisms through which peripheral serotonin impacts energy balance regulation. Clearly, the serotonergic regulation of energy balance is a field characterized by both rapid advances and by an extensive and diverse set of central and peripheral mechanisms yet to be delineated.

  13. Association between salivary serotonin and the social sharing of happiness

    Science.gov (United States)

    Ishii, Keiko; Ohtsubo, Yohsuke; Noguchi, Yasuki; Ochi, Misaki; Yamasue, Hidenori

    2017-01-01

    Although human saliva contains the monoamine serotonin, which plays a key role in the modulation of emotional states, the association between salivary serotonin and empathic ability remains unclear. In order to elucidate the associations between salivary serotonin levels, trait empathy, and the sharing effect of emotions (i.e., sharing emotional experiences with others), we performed a vignette-based study. Participants were asked to evaluate their happiness when they experience several hypothetical life events, whereby we manipulated the valence of the imagined event (positive, neutral, or negative), as well as the presence of a friend (absent, positive, or negative). Results indicated that the presence of a happy friend significantly enhanced participants’ happiness. Correlation analysis demonstrated that salivary serotonin levels were negatively correlated with happiness when both the self and friend conditions were positive. Correlation analysis also indicated a negative relationship between salivary serotonin levels and trait empathy (particularly in perspective taking), which was measured by the Interpersonal Reactivity Index. Furthermore, an exploratory multiple regression analysis suggested that mothers’ attention during childhood predicted salivary serotonin levels. Our findings indicate that empathic abilities and the social sharing of happiness decreases as a function of salivary serotonin levels. PMID:28683075

  14. Association between salivary serotonin and the social sharing of happiness.

    Science.gov (United States)

    Matsunaga, Masahiro; Ishii, Keiko; Ohtsubo, Yohsuke; Noguchi, Yasuki; Ochi, Misaki; Yamasue, Hidenori

    2017-01-01

    Although human saliva contains the monoamine serotonin, which plays a key role in the modulation of emotional states, the association between salivary serotonin and empathic ability remains unclear. In order to elucidate the associations between salivary serotonin levels, trait empathy, and the sharing effect of emotions (i.e., sharing emotional experiences with others), we performed a vignette-based study. Participants were asked to evaluate their happiness when they experience several hypothetical life events, whereby we manipulated the valence of the imagined event (positive, neutral, or negative), as well as the presence of a friend (absent, positive, or negative). Results indicated that the presence of a happy friend significantly enhanced participants' happiness. Correlation analysis demonstrated that salivary serotonin levels were negatively correlated with happiness when both the self and friend conditions were positive. Correlation analysis also indicated a negative relationship between salivary serotonin levels and trait empathy (particularly in perspective taking), which was measured by the Interpersonal Reactivity Index. Furthermore, an exploratory multiple regression analysis suggested that mothers' attention during childhood predicted salivary serotonin levels. Our findings indicate that empathic abilities and the social sharing of happiness decreases as a function of salivary serotonin levels.

  15. Selective serotonin reuptake inhibitors and risk for gastrointestinal bleeding

    Directory of Open Access Journals (Sweden)

    Batić-Mujanović Olivera

    2014-01-01

    Full Text Available The most of the known effects of selective serotonin reuptake inhibitors, beneficial or harmful, are associated with the inhibitory action of the serotonin reuptake transporter. This mechanism is present not only in neurons, but also in other cells such as platelets. Serotoninergic mechanism seems to have an important role in hemostasis, which has long been underestimated. Abnormal activation may lead to a prothrombotic state in patients treated with selective serotonin reuptake inhibitors. On one hand there may be an increased risk of bleeding, and on the other hand reduction in thrombotic risk may be possible. Serotonin is critical to maintain a platelet haemostatic function, such as platelet aggregation. Evidences from the studies support the hypothesis that antidepressants with a relevant blockade of action of serotonin reuptake mechanism may increase the risk of bleeding, which can occur anywhere in the body. Epidemiological evidences are, however, the most robust for upper gastrointestinal bleeding. It is estimated that this bleeding can occur in 1 in 100 to 1 in 1.000 patient-years of exposure to the high-affinity selective serotonin reuptake inhibitors, with very old patients at the highest risk. The increased risk may be of particular relevance when selective serotonin reuptake inhibitors are taken simultaneously with nonsteroidal anti-inflammatory drugs, low dose of aspirin or warfarin.

  16. Association between salivary serotonin and the social sharing of happiness.

    Directory of Open Access Journals (Sweden)

    Masahiro Matsunaga

    Full Text Available Although human saliva contains the monoamine serotonin, which plays a key role in the modulation of emotional states, the association between salivary serotonin and empathic ability remains unclear. In order to elucidate the associations between salivary serotonin levels, trait empathy, and the sharing effect of emotions (i.e., sharing emotional experiences with others, we performed a vignette-based study. Participants were asked to evaluate their happiness when they experience several hypothetical life events, whereby we manipulated the valence of the imagined event (positive, neutral, or negative, as well as the presence of a friend (absent, positive, or negative. Results indicated that the presence of a happy friend significantly enhanced participants' happiness. Correlation analysis demonstrated that salivary serotonin levels were negatively correlated with happiness when both the self and friend conditions were positive. Correlation analysis also indicated a negative relationship between salivary serotonin levels and trait empathy (particularly in perspective taking, which was measured by the Interpersonal Reactivity Index. Furthermore, an exploratory multiple regression analysis suggested that mothers' attention during childhood predicted salivary serotonin levels. Our findings indicate that empathic abilities and the social sharing of happiness decreases as a function of salivary serotonin levels.

  17. Probable Tapentadol-Associated Serotonin Syndrome After Overdose.

    Science.gov (United States)

    Walczyk, Heather; Liu, Cheuk H Michael; Alafris, Antonia; Cohen, Henry

    2016-04-01

    Drug-induced serotonin syndrome is a potentially life-threatening condition. An Ovid MEDLINE, and PubMed search from 1950 to October 2015 revealed one published case report of suspected tapentadol-induced serotonin syndrome. We report a probable case of tapentadol-induced serotonin syndrome after overdose. A 48-year-old male was found unresponsive after a witnessed overdose of medications including tapentadol. After administration of naloxone by emergency medical services, the patient became combative and presented with altered mental status. He was managed with physical and pharmacologic restraints in the emergency department. Other medications that could be implicated in the patient's presentation include duloxetine and amitriptyline. It was suspected that the opioid properties of tapentadol were masking the patient's signs and symptoms of serotonin syndrome. The patient was admitted to the medical intensive care unit, remained stable, and was discharged 2 days later. Currently, there is one published case report of suspected tapentadol-induced serotonin syndrome after an overdose. The manufacturer of tapentadol reported no cases of serotonin syndrome during clinical trials, but there have been postmarketing cases reported with co-administration of other serotonergic drugs. We report a probable case of tapentadol-induced serotonin syndrome after overdose. Further research is needed to better understand the pharmacology and incidence behind this adverse event.

  18. Serotonin syndrome following methylene blue administration during cardiothoracic surgery.

    Science.gov (United States)

    Smith, Christina J; Wang, Dorothy; Sgambelluri, Anna; Kramer, Robert S; Gagnon, David J

    2015-04-01

    Despite its favorable safety profile, there have been reports of methylene blue-induced encephalopathy and serotonin syndrome in patients undergoing parathyroidectomy. We report a case of serotonin syndrome following methylene blue administration in a cardiothoracic surgery patient. A 59-year-old woman taking preoperative venlafaxine and trazodone was given a single dose of 2 mg/kg methylene blue (167 mg) during a planned coronary artery bypass and mitral valve repair. Postoperatively, she was febrile to 38.7°C and developed full-body tremors, rhythmic twitching of the perioral muscles, slow conjugate roving eye movements, and spontaneous movements of the upper extremities. Electroencephalography revealed generalized diffuse slowing consistent with toxic encephalopathy, and a computed tomography scan showed no acute process. The patient's symptoms were most consistent with a methylene blue-induced serotonin syndrome. Her motor symptoms resolved within 48 hours and she was eventually discharged home. Only 2 cases of methylene blue-induced serotonin syndrome during cardiothoracic surgery have been described in the literature, with this report representing the third case. Methylene blue and its metabolite, azure B, are potent, reversible inhibitors of monoamine oxidase A which is responsible for serotonin metabolism. Concomitant administration of methylene blue with serotonin-modulating agents may precipitate serotonin syndrome. © The Author(s) 2015.

  19. Abdominal diameters as indicators of visceral fat : comparison between magnetic resonance imaging and anthropometry

    NARCIS (Netherlands)

    van der Kooy, K; Leenen, R; Seidell, J C; Deurenberg, P.; Visser, M

    The aim of the present study was to investigate the usefulness of abdominal diameters to indicate visceral fat, their relationship with serum lipids and their capability of detecting changes in visceral fat. Before and after weight loss, visceral and subcutaneous fat, and the sagittal and transverse

  20. Serotonin Mechanisms in Heart Valve Disease I

    Science.gov (United States)

    Jian, Bo; Xu, Jie; Connolly, Jeanne; Savani, Rashmin C.; Narula, Navneet; Liang, Bruce; Levy, Robert J.

    2002-01-01

    Clinical disorders associated with increased serotonin [5-hydroxytryptamine (5-HT)] levels, such as carcinoid syndrome, and the use of serotonin agonists, such as fenfluoramine have been associated with a valvulopathy characterized by hyperplastic valvular and endocardial lesions with increased extracellular matrix. Furthermore, 5-HT has been demonstrated to up-regulate transforming growth factor (TGF)-β in mesangial cells via G-protein signal transduction. We investigated the hypothesis that increased exposure of heart valve interstitial cells to 5-HT may result in increased TGF-β1 expression and activity because of serotonin receptor-mediated signal transduction with activation of Gαq, and subsequently up-regulation of phospholipase C. Thus, in the present study we performed a clinical-pathological investigation of retrieved carcinoid and normal valve cusps using immunohistochemical techniques to detect the presence of TGF-β1 and other proteins associated with TGF-β expression, including TGF-β receptors I and II, latent TGF-β-associated peptide (LAP), and α-smooth muscle actin. Carcinoid valve cusps demonstrated the unusual finding of widespread smooth muscle actin involving the interstitial cells in the periphery of carcinoid nodules; these same cells were also positive for LAP. Normal valve cusps were only focally positive for smooth muscle actin and LAP. In sheep aortic valve interstitial cell cultures 5-HT induced TGF-β1 mRNA production and increased TGF-β1 activity. 5-HT also increased collagen biosynthesis at the dosages studied. Furthermore, TGF-β1 added to SAVIC cultures increased the production of sulfated glycan and hyaluronic acid. In addition, overexpression of Gαq using an adenoviral expression vector for a constitutively active Gαq mutant (Q209L-Gαq) resulted in increased phospholipase C activity as well as up-regulation of TGF-β expression and activity. These results strongly support the view that G-protein-related signal

  1. Serotonin syndrome:case report and current concepts.

    LENUS (Irish Health Repository)

    Fennell, J

    2005-05-01

    Selective serotonin reuptake inhibitors (SSRI\\'s) are increasingly being used as the first line therapeutic agent for the depression. It is therefore not unusual to see a case of overdose with these agents. More commonly an adverse drug reaction may be seen among the older patients who are particularly vulnerable to the serotonin syndrome due to multiple co-morbidity and polypharmacy. The clinical picture of serotonin syndrome (SS) is non-specific and there is no confirmatory test. SS may go unrecognized because it is often mistaken for a viral illness, anxiety, neurological disorder or worsening psychiatric condition.

  2. Serotonin as a Biomarker: Stress Resilience among Battlefield Airmen Trainees

    Science.gov (United States)

    2016-05-21

    Depression -Dejection 0.310 0.358 Fatigue 0.929 0.384 Friendliness 0.295 0.046 Serotonin 0.281 0.489 Tension-Anxiety 0.789 0.912 Total Distress...Discriminant analysis showed that subjects with increased serotonin levels were more likely to SIE. Confusion-bewilderment, depression -dejection, and...and that NPY may be a protective factor during acute stress [10]. Studies have established that low levels of serotonin are associated with depression

  3. Hippocampal volume and serotonin transporter polymorphism in major depressive disorder

    DEFF Research Database (Denmark)

    Ahdidan, Jamila; Foldager, Leslie; Rosenberg, Raben

    2013-01-01

    Objective: The main aim of the present study was to replicate a previous finding in major depressive disorder (MDD) of association between reduced hippocampal volume and the long variant of the di- and triallelic serotonin transporter polymorphism in SLC6A4 on chromosome 17q11.2. Secondarily, we...... that we aimed to replicate, and no significant associations with the serotonin transporter polymorphism were found. Conclusions: The present quantitative and morphometric MRI study was not able to replicate the previous finding of association between reduced hippocampal volume in depressed patients...... and the serotonin transporter polymorphism....

  4. Serotonin syndrome associated with MDPV use: a case report.

    Science.gov (United States)

    Mugele, Josh; Nañagas, Kristine A; Tormoehlen, Laura M

    2012-07-01

    Serotonin syndrome is associated with use of certain street drugs, including methamphetamine, cocaine, and ecstasy. We describe a case of a woman who developed clinical findings consistent with serotonin syndrome after insufflation of 3,4-methylenedioxypyrovalerone (MDPV), a synthetic amphetamine. MDPV belongs to a group of substances called phenylethylamines, which are β-ketone analogs of other drugs of abuse, such as amphetamines and 3,4-methylenedioxymethamphetamine. She also received fentanyl initially during her hospitalization, which has also been associated with serotonin syndrome. In addition to benzodiazepines and supportive care, she was treated with cyproheptadine for 8 days, with slow resolution of her symptoms. Copyright © 2011. Published by Mosby, Inc.

  5. The Role of Serotonin beyond the Central Nervous System during Embryogenesis

    OpenAIRE

    Lv, Junhua; Liu, Feng

    2017-01-01

    Serotonin, or 5-hydroxytryptamine (5-HT), is a well-known neurotransmitter that plays vital roles in neural activities and social behaviors. Clinically, deficiency of serotonin is linked with many psychiatric disorders. Interestingly, a large proportion of serotonin is also produced outside the central nervous system (CNS). There is increasing evidence demonstrating important roles of serotonin in the peripheral tissues. Here, we will describe the multiple biological functions of serotonin in...

  6. Effect of a weight cycle on visceral fat accumulation

    NARCIS (Netherlands)

    van der Kooy, K; Leenen, R; Seidell, J C; Deurenberg, P.; Hautvast, J.G.A.J.

    1993-01-01

    Magnetic resonance imaging was used to study the effect of a single weight cycle on three fat depots: the visceral and subcutaneous abdominal depots and the subcutaneous depot at the trochanter level. Obese subjects (17 men, 15 women) were examined before and after weight-loss intervention and 67 wk

  7. Antimony to Cure Visceral Leishmaniasis Unresponsive to Liposomal Amphotericin B

    Science.gov (United States)

    Morizot, Gloria; Jouffroy, Romain; Faye, Albert; Chabert, Paul; Belhouari, Katia; Calin, Ruxandra; Charlier, Caroline; Miailhes, Patrick; Siriez, Jean-Yves; Mouri, Oussama; Yera, Hélène; Gilquin, Jacques; Tubiana, Roland; Lanternier, Fanny; Mamzer, Marie-France; Legendre, Christophe; Peyramond, Dominique; Caumes, Eric; Lortholary, Olivier; Buffet, Pierre

    2016-01-01

    We report on 4 patients (1 immunocompetent, 3 immunosuppressed) in whom visceral leishmaniasis had become unresponsive to (or had relapsed after) treatment with appropriate doses of liposomal amphotericin B. Under close follow-up, full courses of pentavalent antimony were administered without life-threatening adverse events and resulted in rapid and sustained clinical and parasitological cure. PMID:26735920

  8. visceral leishmaniasis with concomittant post kala-azar dermal ...

    African Journals Online (AJOL)

    hi-tech

    2003-08-08

    Aug 8, 2003 ... province, Kenya. INTRODUCTION. Visceral Leishmaniasis or kala-azar is caused by species of Leishmania donovani complex. These are Leishmania donovani donovani in East Africa and Asia, Leishmania donovani infantum in the Mediterranean Basin and. Leishmania donovani chagasi in Latin America ...

  9. [Uncommon cutaneous presentation of visceral Leishmaniasis associated with HIV].

    Science.gov (United States)

    Cossart, C; Le Moal, G; Garcia, M; Frouin, E; Hainaut-Wierzbicka, E; Roblot, F

    2016-12-01

    Visceral leishmaniasis is not normally expressed in skin. Herein, we describe the case of an HIV-positive patient who developed two unusual skin manifestations during an episode of visceral leishmaniasis. A 48-year-old female patient consulted initially for infiltrated purpura of all four limbs. Skin biopsy revealed leukocytoclastic vasculitis with Leishman-Donovan bodies. Laboratory tests showed medullary, splenic, gastric and colic involvement, suggesting systemic disease, and enabling visceral leishmaniasis to be diagnosed. Two years later, despite prolonged treatment, the patient presented maculopapular exanthema, and histology revealed persistent Leishman-Donovan bodies. We report herein an association of two rare skin manifestations in an HIV-positive patient with visceral leishmaniasis: infiltrated purpura and maculopapular exanthema. However, the underlying mechanisms remain hypothetical. The initial leukocytoclastic exanthema could be secondary to either polyclonal hypergammaglobulinaemia or to IgA deposits, or possibly to mechanical impairment of blood vessels by the actual parasite. The maculopapular exanthema occurring later raised the possibility of post-Kala-Azar leishmaniasis due to blood-borne dissemination in an anergic subject or perhaps even immune reconstitution inflammatory syndrome. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. Development and application of 'simple' diagnostic tools for visceral leishmaniasis

    NARCIS (Netherlands)

    Schallig, H. D.; Schoone, G. J.; Kroon, C. C.; Hailu, A.; Chappuis, F.; Veeken, H.

    2001-01-01

    The diagnosis of visceral leishmaniasis is difficult. Due to the limitations of direct methods to detect parasites, indirect immunological methods are widely employed. The simple affordable and sensitive/specific direct agglutination test (DAT) is perhaps the most important diagnostic tool under

  11. Magnetic resonance imaging of atherosclerosis : studies in visceral obesity

    NARCIS (Netherlands)

    Alizadeh Dehnavi, Reza

    2009-01-01

    The aim of this thesis was to explore the relation between visceral obesity and the accompanying metabolic disturbances, systemic inflammation and the atherosclerotic process. A newly developed magnetic resonance vessel wall imaging technique was implemented in phenotyping patients and as a

  12. Quantification of visceral adipose tissue in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Frøssing, Signe; Nylander, Malin Chatarina; Chabanova, Elizaveta

    2018-01-01

    Background Polycystic ovary syndrome (PCOS) is associated with frequent overweight and abdominal obesity. Quantifying visceral adipose tissue (VAT) in PCOS patients can be a tool to assess metabolic risk and monitor effects of treatment. The latest dual-energy X-ray absorptiometry (DXA) technology...

  13. Imaging the Visceral Soma: A Corporeal Feminist Interpretation

    African Journals Online (AJOL)

    denise

    The Indo-Pacific Journal of Phenomenology (IPJP) can be found at www.ipjp.org. Imaging the Visceral Soma: A Corporeal Feminist Interpretation by Ingrid Richardson and Carly Harper. Abstract. Feminist philosophers of technoscience have long argued that it is vital that we question biomedical and scientific claims to an ...

  14. Association between visceral fat, IL-8 and endometrial cancer.

    Science.gov (United States)

    Ciortea, Razvan; Mihu, Dan; Mihu, Carmen Mihaela

    2014-01-01

    In endometrial cancer, visceral obesity, as a risk factor, is associated with a chronic inflammatory process, confirmed by the elevation of serum inflammatory markers in obese patients. The aim of the present study was to evaluate the correlation between visceral fat, assessed by ultrasonography, and the systemic levels of interleukin (IL)-8 in patients with endometrial cancer. This study also evaluated the usefulness of abdominal ultrasonography in assessing the visceral fat correlated with systemic inflammatory status, as an alternative method to identify patients at risk of endometrial cancer. The study was a case-control analysis including two groups of patients: Group I: 44 patients diagnosed with endometrial cancer; group II: 44 patients with no gynecological pathology. The diagnosis of endometrial cancer was performed following histopathological examination that evaluated the tissue material obtained through endometrial biopsy. These patients underwent ultrasound examination by which intraperitoneal fat was determined. IL-8 levels were determined for each patient. The Student's t-test was used for the comparison of the means and the Mann-Whitney test for rank comparison of two independent samples. In patients diagnosed with endometrial cancer, the visceral fat area evaluated by ultrasound was significantly larger (pendometrial cancer group were significantly elevated (pendometrial cancer.

  15. Blood pressure rhythmicity and visceral fat in children with hypertension.

    Science.gov (United States)

    Niemirska, Anna; Litwin, Mieczysław; Feber, Janusz; Jurkiewicz, Elżbieta

    2013-10-01

    Primary hypertension is associated with disturbed activity of the sympathetic nervous system and altered blood pressure rhythmicity. We analyzed changes in cardiovascular rhythmicity and its relation with target organ damage during 12 months of antihypertensive treatment in 50 boys with hypertension (median, 15.0 years). The following parameters were obtained before and after 12 months of antihypertensive treatment: 24-hour ambulatory blood pressure, left ventricular mass, carotid intima-media thickness, and MRI for visceral and subcutaneous adipose tissue. Amplitudes and acrophases of mean arterial pressure and heart rate rhythms were obtained for 24-, 12-, and 8-hour periods. After 1 year of treatment, 68% of patients were normotensive, and left ventricular mass and carotid intima-media thickness decreased in 60% and 62% of patients, respectively. Blood pressure and heart rate rhythmicity patterns did not change. Changes in blood pressure amplitude correlated with the decrease of waist circumference (P=0.035). Moreover, the decrease of visceral fat correlated with the decrease of 24-hour mean arterial pressure and heart rate acrophases (both Pblood pressure and heart rate rhythms between patients who achieved or did not achieve normotension and regression of left ventricular mass and carotid intima-media thickness. It was concluded that abnormal cardiovascular rhythmicity persists in children with primary hypertension despite effective antihypertensive treatment, which suggests that it may be the primary abnormality. The correlation between changes in cardiovascular rhythmicity and visceral obesity may indicate that the visceral fat plays an important role in the sympathetic activity of adolescents with hypertension.

  16. visceral leishmaniasis with concomittant post kala-azar dermal ...

    African Journals Online (AJOL)

    hi-tech

    East African Medical Journal Vol. 80 No. 8 August 2003. VISCERAL LEISHMANIASIS WITH CONCOMITTANT POST KALA-AZAR DERMAL LEISHMANIASIS RESPONDS TO ORAL SITAMAQUINE: CASE. REPORT. J. Mbui, MBChB, MMed, MSc,Senior Research Officer, R. Rashid, MBChB, MMed, Principal Research Officer, ...

  17. Visceral leishmaniasis in Northern Ethiopia | Haile | East African ...

    African Journals Online (AJOL)

    Background: Visceral leishmaniasis (VL) has been well documented by the Medecins sans Frontieres (MSF) VL treatment programmeme in the Tigray region of Ethiopia, but reports are limited from other facilities in this region where this disease continues to cause substantial morbidity and mortality. Objective: To describe ...

  18. Visceral Pedagogies: Pornography, Affect, and Safety in the University Classroom

    Science.gov (United States)

    Paasonen, Susanna

    2016-01-01

    This article addresses the pedagogical choices and the visceral reverberations involved in teaching porn in the university classroom. The author discusses different aims and goals for teaching pornography, as well as the some key pedagogical considerations and options involved in this, drawing on her own experiences teaching porn in Finnish gender…

  19. Agonist-directed signaling of serotonin 5-HT2C receptors: differences between serotonin and lysergic acid diethylamide (LSD).

    Science.gov (United States)

    Backstrom, J R; Chang, M S; Chu, H; Niswender, C M; Sanders-Bush, E

    1999-08-01

    For more than 40 years the hallucinogen lysergic acid diethylamide (LSD) has been known to modify serotonin neurotransmission. With the advent of molecular and cellular techniques, we are beginning to understand the complexity of LSD's actions at the serotonin 5-HT2 family of receptors. Here, we discuss evidence that signaling of LSD at 5-HT2C receptors differs from the endogenous agonist serotonin. In addition, RNA editing of the 5-HT2C receptor dramatically alters the ability of LSD to stimulate phosphatidylinositol signaling. These findings provide a unique opportunity to understand the mechanism(s) of partial agonism.

  20. Serotonin-Sensitive Adenylate Cyclase in Neural Tissue and Its Similarity to the Serotonin Receptor: A Possible Site of Action of Lysergic Acid Diethylamide

    Science.gov (United States)

    Nathanson, James A.; Greengard, Paul

    1974-01-01

    An adenylate cyclase (EC 4.6.1.1) that is activated specifically by low concentrations of serotonin has been identified in homogenates of the thoracic ganglia of an insect nervous system. The activation of this enzyme by serotonin was selectively inhibited by extremely low concentrations of D-lysergic acid diethylamide (LSD), 2-bromo-LSD, and cyproheptadine, agents which are known to block certain serotonin receptors in vivo. The inhibition was competitive with respect to serotonin, and the calculated inhibitory constant of LSD for this serotonin-sensitive adenylate cyclase was 5 nM. The data are consistent with a model in which the serotonin receptor of neural tissue is intimately associated with a serotonin-sensitive adenylate cyclase which mediates serotonergic neurotransmission. The results are also compatible with the possibility that some of the physiological effects of LSD may be mediated through interaction with serotonin-sensitive adenylate cyclase. PMID:4595572

  1. Rat Model of Lumbar Facet Joint Osteoarthritis Associated With Facet-mediated Mechanical Hyperalgesia Induced by Intra-articular Injection of Monosodium Iodoacetate

    Directory of Open Access Journals (Sweden)

    Kai Gong

    2011-03-01

    Conclusion: An experimental LFJ OA model associated with facet-mediated mechanical hyperalgesia can be established by intra-articular injection of MIA. This model might provide a useful tool for further study to ascertain the complex mechanism of facet joint pain.

  2. Effects of TAK-480, a novel tachykinin NK(2)-receptor antagonist, on visceral hypersensitivity in rabbits and ricinoleic acid-induced defecation in guinea pigs.

    Science.gov (United States)

    Tanaka, Takahiro; Tanaka, Akiko; Nakamura, Akihiro; Matsushita, Kozo; Imanishi, Akio; Matsumoto-Okano, Shiho; Inatomi, Nobuhiro; Miura, Kasei; Toyoda, Masao; Mizojiri, Gaku; Tsukimi, Yasuhiro

    2012-01-01

    TAK-480, 4-(difluoromethoxy)-N-((1R,2S)-2-(((3aR,4R,9bR)-4-(methoxymethyl)-2, 3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl)carbonyl)cyclohexyl)benzamide, is a novel tachykinin NK(2)-receptor antagonist. In this study, we investigated its antagonistic activity and efficacy in animal models of visceral hypersensitivity and stimulated bowel function which have been implicated to underlie the symptoms in irritable bowel syndrome (IBS). TAK-480 showed potent binding affinity for human NK(2) receptors with a marked species difference and a 10,000-fold selectivity versus NK(1) and NK(3) receptors. TAK-480 dose-dependently antagonized colonic contractions induced by administration of the NK(2) receptor-selective agonist beta-Ala(8)-NKA(4-10) (βA-NKA) in anesthetized rabbits. In a rabbit model of intracolonic zymosan-induced visceral hypersensitivity, TAK-480 markedly inhibited the visceromotor response to colorectal distension, in contrast to the moderate inhibition by the serotonin 5-HT(3)-receptor antagonist alosetron. In addition, TAK-480 suppressed ricinoleic acid-induced defecation without affecting spontaneous defecation in guinea pigs, whereas alosetron suppressed both. Furthermore, TAK-480 inhibited smooth muscle contractions produced by natural tachykinins (substance P, neurokinin A, and neurokinin B) as well as βA-NKA in an isolated human colon. In conclusion, the novel NK(2)-receptor antagonist TAK-480 improved visceral hypersensitivity and accelerated defecation without causing constipation in experimental animals. Furthermore, the potent functional blockade of NK(2) receptors in human colon might suggest the potential effectiveness of TAK-480 in IBS patients.

  3. An autism-associated serotonin transporter variant disrupts multisensory processing

    National Research Council Canada - National Science Library

    J K Siemann; C L Muller; C G Forsberg; R D Blakely; J Veenstra-vanderweele; M T Wallace

    2017-01-01

    ... (that is, multisensory function). The serotonin system has an important role in sensory development and function, and alterations of serotonergic signaling have been suggested to have a role in ASD...

  4. Serotonin blockade delays learning performance in a cooperative fish.

    Science.gov (United States)

    Soares, Marta C; Paula, José R; Bshary, Redouan

    2016-09-01

    Animals use learning and memorizing to gather information that will help them to make ecologically relevant decisions. Neuro-modulatory adjustments enable them to make associations between stimuli and appropriate behavior. A key candidate for the modulation of cooperative behavior is serotonin. Previous research has shown that modulation of the serotonergic system spontaneously affects the behavior of the cleaner wrasse Labroides dimidiatus during interactions with so-called 'client' reef fish. Here, we asked whether shifts in serotonin function affect the cleaners' associative learning abilities when faced with the task to distinguish two artificial clients that differ in their value as a food source. We found that the administration of serotonin 1A receptor antagonist significantly slowed learning speed in comparison with saline treated fish. As reduced serotonergic signaling typically enhances fear, we discuss the possibility that serotonin may affect how cleaners appraise, acquire information and respond to client-derived stimuli via manipulation of the perception of danger.

  5. Differential involvement of trigeminal transition zone and laminated subnucleus caudalis in orofacial deep and cutaneous hyperalgesia: the effects of interleukin-10 and glial inhibitors

    Directory of Open Access Journals (Sweden)

    LaGraize Stacey C

    2009-12-01

    Full Text Available Abstract Background In addition to caudal subnucleus caudalis (Vc of the spinal trigeminal complex, recent studies indicate that the subnuclei interpolaris/caudalis (Vi/Vc transition zone plays a unique role in processing deep orofacial nociceptive input. Studies also suggest that glia and inflammatory cytokines contribute to the development of persistent pain. By systematically comparing the effects of microinjection of the antiinflammatory cytokine interleukin (IL-10 and two glial inhibitors, fluorocitrate and minocycline, we tested the hypothesis that there was a differential involvement of Vi/Vc and caudal Vc structures in deep and cutaneous orofacial pain. Results Deep or cutaneous inflammatory hyperalgesia, assessed with von Frey filaments, was induced in rats by injecting complete Freund's adjuvant (CFA into the masseter muscle or skin overlying the masseter, respectively. A unilateral injection of CFA into the masseter or skin induced ipsilateral hyperalgesia that started at 30 min, peaked at 1 d and lasted for 1-2 weeks. Secondary hyperalgesia on the contralateral site also developed in masseter-, but not skin-inflamed rats. Focal microinjection of IL-10 (0.006-1 ng, fluorocitrate (1 μg, and minocycline (0.1-1 μg into the ventral Vi/Vc significantly attenuated masseter hyperalgesia bilaterally but without an effect on hyperalgesia after cutaneous inflammation. Injection of the same doses of these agents into the caudal Vc attenuated ipsilateral hyperalgesia after masseter and skin inflammation, but had no effect on contralateral hyperalgesia after masseter inflammation. Injection of CFA into the masseter produced significant increases in N-methyl-D-aspartate (NMDA receptor NR1 serine 896 phosphorylation and glial fibrillary acidic protein (GFAP levels, a marker of reactive astrocytes, in Vi/Vc and caudal Vc. In contrast, cutaneous inflammation only produced similar increases in the Vc. Conclusion These results support the hypothesis

  6. Variable transcriptional responsiveness of the P2 × 3 receptor gene during CFA-induced inflammatory hyperalgesia.

    Science.gov (United States)

    Nuñez-Badinez, Paulina; Sepúlveda, Hugo; Diaz, Emilio; Greffrath, Wolfgang; Treede, Rolf-Detlef; Stehberg, Jimmy; Montecino, Martin; van Zundert, Brigitte

    2017-12-08

    The purinergic receptor P2 × 3 (P2 × 3-R) plays important roles in molecular pathways of pain, and reduction of its activity or expression effectively reduces chronic inflammatory and neuropathic pain sensation. Inflammation, nerve injury, and cancer-induced pain can increase P2 × 3-R mRNA and/or protein levels in dorsal root ganglia (DRG). However, P2 × 3-R expression is unaltered or even reduced in other pain studies. The reasons for these discrepancies are unknown and might depend on the applied traumatic intervention or on intrinsic factors such as age, gender, genetic background and/or epigenetics. In this study, we sought to get insights into the molecular mechanisms responsible for inflammatory hyperalgesia by determining P2 × 3-R expression in DRG neurons of juvenile male rats that received a Complete Freund's Adjuvant (CFA) bilateral paw injection. We demonstrate that all CFA-treated rats showed inflammatory hyperalgesia, however, only a fraction (14-20%) displayed increased P2 × 3-R mRNA levels, reproducible across both sides. Immunostaining assays did not reveal significant increases in the percentage of P2 × 3-positive neurons, indicating that increased P2 × 3-R at DRG somas is not critical for inducing inflammatory hyperalgesia in CFA-treated rats. Chromatin immunoprecipitation (ChIP) assays showed a correlated (R2 = 0.671) enrichment of the transcription factor Runx1 and the epigenetic active mark histone H3 acetylation (H3Ac) at the P2 × 3-R gene promoter in a fraction of the CFA-treated rats. These results suggest that animal-specific increases in P2 × 3-R mRNA levels are likely associated with the genetic/epigenetic context of the P2 × 3-R locus that controls P2 × 3-R gene transcription by recruiting Runx1 and epigenetic co-regulators that mediate histone acetylation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. In vivo imaging of cerebral serotonin transporter and serotonin(2A) receptor binding in 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") and hallucinogen users

    DEFF Research Database (Denmark)

    Erritzoe, David; Frøkjær, Vibe; Holst, Klaus K

    2011-01-01

    Both hallucinogens and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") have direct agonistic effects on postsynaptic serotonin(2A) receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin.......Both hallucinogens and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") have direct agonistic effects on postsynaptic serotonin(2A) receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin....

  8. Interest in paromomycin for the treatment of visceral leishmaniasis (kala-azar

    Directory of Open Access Journals (Sweden)

    Wiwanitkit V

    2012-06-01

    Full Text Available Viroj Wiwanitkit1–31Wiwanitkit House, Bang Khae, Bangkok, Thailand; 2Hainan Medical University, Haikou, Hainan, People's Republic of China; 3Joseph Ayo Babalola University, Ikeji-Arakeji, Osun State, NigeriaAbstract: Leishmaniasis is an important vector-borne disease, and it is classified as one of the most important tropical fly-borne infections. This disease can cause two types of clinical manifestations: cutaneous forms and visceral forms. Visceral leishmaniasis, which is also called kala-azar, is a very serious infection that can be fatal. The management of visceral leishmaniasis requires informed diagnostic and therapeutic approaches. Continuous research and development regarding the treatment of visceral leishmaniasis had led to many improvements. Paromomycin is a relatively new antibiotic drug that has been used for the treatment of visceral leishmaniasis for several years. This article reviews and discusses the use of paromomycin for visceral leishmaniasis therapy.Keywords: visceral, leishmaniasis, paromomycin

  9. Divergent Roles of Central Serotonin in Adult Hippocampal Neurogenesis

    OpenAIRE

    Song, Ning-Ning; Huang, Ying; Yu, Xin; Lang, Bing; Ding, Yu-Qiang; Zhang, Lei

    2017-01-01

    The central serotonin (5-HT) system is the main target of selective serotonin reuptake inhibitors (SSRIs), the first-line antidepressants widely used in current general practice. One of the prominent features of chronic SSRI treatment in rodents is the enhanced adult neurogenesis in the hippocampus, which has been proposed to contribute to antidepressant effects. Therefore, tremendous effort has been made to decipher how central 5-HT regulates adult hippocampal neurogenesis. In this paper, we...

  10. Genetics of premenstrual syndrome: investigation of specific serotonin receptor polymorphisms

    OpenAIRE

    Dhingra, Vandana

    2014-01-01

    Premenstrual dysphoric disorder (PMDD) is a distressing and disabling syndrome causing a significant degree of impairment on daily functioning and interpersonal relationships in 3-8% of the women. With the convincing evidence that PMS is inheritable and that serotonin is important in the pathogenesis of PMS, and failure of initial studies to demonstrate significant associations between key genes controlling the synthesis, reuptake and catabolism of serotonin and PMDD, the main aim of this the...

  11. SEP-225289 serotonin and dopamine transporter occupancy: a PET study.

    Science.gov (United States)

    DeLorenzo, Christine; Lichenstein, Sarah; Schaefer, Karen; Dunn, Judith; Marshall, Randall; Organisak, Lisa; Kharidia, Jahnavi; Robertson, Brigitte; Mann, J John; Parsey, Ramin V

    2011-07-01

    SEP-225289 is a novel compound that, based on in vitro potencies for transporter function, potentially inhibits reuptake at dopamine, norepinephrine, and serotonin transporters. An open-label PET study was conducted during the development of SEP-225289 to investigate its dopamine and serotonin transporter occupancy. Different single doses of SEP-225289 were administered to healthy volunteers in 3 cohorts: 8 mg (n = 7), 12 mg (n = 5), and 16 mg (n = 7). PET was performed before and approximately 24 h after oral administration of SEP-225289, to assess occupancy at trough levels. Dopamine and serotonin transporter occupancies were estimated from PET using (11)C-N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane ((11)C-PE2I) and (11)C-N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine ((11)C-DASB), respectively. Plasma concentration of SEP-225289 was assessed before ligand injection, and subjects were monitored for adverse events. Average dopamine and serotonin transporter occupancies increased with increasing doses of SEP-225289. Mean dopamine and serotonin transporter occupancies were 33% ± 11% and 2% ± 13%, respectively, for 8 mg; 44% ± 4% and 9% ± 10%, respectively, for 12 mg; and 49% ± 7% and 14% ± 15%, respectively, for 16 mg. On the basis of the relationship between occupancy and plasma concentration, dopamine transporter IC(50) (the plasma concentration of drug at 50% occupancy) was determined (4.5 ng/mL) and maximum dopamine transporter occupancy was extrapolated (85%); however, low serotonin transporter occupancy prevented similar serotonin transporter calculations. No serious adverse events were reported. At the doses evaluated, occupancy of the dopamine transporter was significantly higher than that of the serotonin transporter, despite similar in vitro potencies, confirming that, in addition to in vitro assays, PET occupancy studies can be instrumental to the drug development process by informing early decisions about

  12. Visceral adipose tissue area measurement at a single level: can it represent visceral adipose tissue volume?

    Science.gov (United States)

    Noumura, Yusuke; Kamishima, Tamotsu; Sutherland, Kenneth; Nishimura, Hideho

    2017-08-01

    Measurement of visceral adipose tissue (VAT) needs to be accurate and sensitive to change for risk monitoring. The purpose of this study is to determine the CT slice location where VAT area can best reflect changes in VAT volume and body weight. 60 plain abdominal CT images from 30 males [mean age (range) 51 (41-68) years, mean body weight (range) 71.1 (101.9-50.9) kg] who underwent workplace screenings twice within a 1-year interval were evaluated. Automatically calculated and manually corrected areas of the VAT of various scan levels using "freeform curve" region of interest on CT were recorded and compared with body weight changes. The strongest correlations of VAT area with VAT volume and body weight changes were shown in a slice 3 cm above the lower margin of L3 with r values of 0.853 and 0.902, respectively. VAT area measurement at a single level 3 cm above the lower margin of the L3 vertebra is feasible and can reflect changes in VAT volume and body weight. Advances in knowledge: As VAT area at a CT slice 3cm above the lower margin of L3 can best reflect interval changes in VAT volume and body weight, VAT area measurement should be selected at this location.

  13. Vitamin B complex attenuated heat hyperalgesia following infraorbital nerve constriction in rats and reduced capsaicin in vivo and in vitro effects.

    Science.gov (United States)

    Kopruszinski, Caroline M; Reis, Renata C; Bressan, Elisangela; Reeh, Peter W; Chichorro, Juliana G

    2015-09-05

    Vitamins of the B complex attenuate some neuropathic pain sensory aspects in various animal models and in patients, but the mechanisms underlying their effects remain to be elucidated. Herein it was investigated if the treatment with a vitamin B complex (VBC) reduces heat hyperalgesia in rats submitted to infraorbital nerve constriction and the possibility that TRPV1 receptors represent a target for B vitamins. In the present study, the VBC refers to a combination of vitamins B1, B6 and B12 at low- (18, 18 and 1.8mg/kg, respectively) or high- (180, 180 and 18mg/kg, respectively) doses. Acute treatment of rats with either the low- or the high-doses combination reduced heat hyperalgesia after nerve injury, but the high-doses combination resulted in a long-lasting effect. Repeated treatment with the low-dose combination reduced heat hyperalgesia on day four after nerve injury and showed a synergist effect with a single injection of carbamazepine (3 or 10mg/kg), which per se failed to modify the heat threshold. In naïve rats, acute treatment with the high-dose of VBC or B1 and B12 vitamins independently reduced heat hyperalgesia evoked by capsaicin (3µg into the upper lip). Moreover, the VBC, as well as, each one of the B vitamins independently reduced the capsaicin-induced calcium responses in HEK 293 cells transiently transfected with the human TRPV1 channels. Altogether, these results indicate that B vitamins can be useful to control heat hyperalgesia associated with trigeminal neuropathic pain and that modulation of TRPV1 receptors may contribute to their anti-hyperalgesic effects. Copyright © 2015. Published by Elsevier B.V.

  14. Increased serum IL-6 level time-dependently regulates hyperalgesia and spinal mu opioid receptor expression during CFA-induced arthritis.

    Science.gov (United States)

    Tekieh, E; Zaringhalam, Jalal; Manaheji, H; Maghsoudi, N; Alani, B; Zardooz, H

    2011-01-01

    Interleukin (IL)-6 is known to cause pro- and anti-inflammatory effects during different stages of inflammation. Recent therapeutic investigations have focused on treatment of various inflammatory disorders with anti-cytokine substances. As a result, the aim of this study was to further elucidate the influence of IL-6 in hyperalgesia and edema during different stages of Complete Freund's Adjuvant (CFA)-induced arthritis (AA) in male Wistar rats. AA was induced by a single subcutaneous injection of CFA into the rats' hindpaw. Anti-IL-6 was administered either daily or weekly during the 21 days of study. Spinal mu opioid receptor (mOR) expression was detected by Western blotting. Daily and weekly treatment with an anti-IL-6 antibody significantly decreased paw edema in the AA group compared to the AA control group. Additionally, daily and weekly anti-IL-6 administration significantly reduced hyperalgesia on day 7 in the AA group compared to the AA control group; however, there were significant increases in hyperalgesia in the antibody-treated group on days 14 and 21 compared to the AA control group. IL-6 antibody-induced increases in hyperalgesia on the 14th and 21st days after CFA injection correlated with a time-dependent, significant reduction in spinal mOR expression during anti-IL-6 treatment. Our study confirmed the important time-dependent relationship between serum IL-6 levels and hyperalgesia during AA. These results suggest that the stages of inflammation in AA must be considered for anti-hyperalgesic and anti-inflammatory interventions via anti-IL-6 antibody treatment.

  15. Multiple cellular responses to serotonin contribute to epithelial homeostasis.

    Directory of Open Access Journals (Sweden)

    Vaibhav P Pai

    Full Text Available Epithelial homeostasis incorporates the paradoxical concept of internal change (epithelial turnover enabling the maintenance of anatomical status quo. Epithelial cell differentiation and cell loss (cell shedding and apoptosis form important components of epithelial turnover. Although the mechanisms of cell loss are being uncovered the crucial triggers that modulate epithelial turnover through regulation of cell loss remain undetermined. Serotonin is emerging as a common autocrine-paracine regulator in epithelia of multiple organs, including the breast. Here we address whether serotonin affects epithelial turnover. Specifically, serotonin's roles in regulating cell shedding, apoptosis and barrier function of the epithelium. Using in vivo studies in mouse and a robust model of differentiated human mammary duct epithelium (MCF10A, we show that serotonin induces mammary epithelial cell shedding and disrupts tight junctions in a reversible manner. However, upon sustained exposure, serotonin induces apoptosis in the replenishing cell population, causing irreversible changes to the epithelial membrane. The staggered nature of these events induced by serotonin slowly shifts the balance in the epithelium from reversible to irreversible. These finding have very important implications towards our ability to control epithelial regeneration and thus address pathologies of aberrant epithelial turnover, which range from degenerative disorders (e.g.; pancreatitis and thyrioditis to proliferative disorders (e.g.; mastitis, ductal ectasia, cholangiopathies and epithelial cancers.

  16. Central serotonin neurons are required for arousal to CO2.

    Science.gov (United States)

    Buchanan, Gordon F; Richerson, George B

    2010-09-14

    There is a long-standing controversy about the role of serotonin in sleep/wake control, with competing theories that it either promotes sleep or causes arousal. Here, we show that there is a marked increase in wakefulness when all serotonin neurons are genetically deleted in mice hemizygous for ePet1-Cre and homozygous for floxed Lmx1b (Lmx1b(f/f/p)). However, this only occurs at cool ambient temperatures and can be explained by a thermoregulatory defect that leads to an increase in motor activity to generate heat. Because some serotonin neurons are stimulated by CO(2), and serotonin activates thalamocortical networks, we hypothesized that serotonin neurons cause arousal in response to hypercapnia. We found that Lmx1b(f/f/p) mice completely lacked any arousal response to inhalation of 10% CO(2) (with 21% O(2) in balance N(2)) but had normal arousal responses to hypoxia, sound, and air puff. We propose that serotonin neurons mediate the potentially life-saving arousal response to hypercapnia. Impairment of this response may contribute to sudden unexpected death in epilepsy, sudden infant death syndrome, and sleep apnea.

  17. Serotonin receptors in depression: from A to B

    Science.gov (United States)

    Nautiyal, Katherine M.; Hen, René

    2017-01-01

    The role of serotonin in major depressive disorder (MDD) is the focus of accumulating clinical and preclinical research. The results of these studies reflect the complexity of serotonin signaling through many receptors, in a large number of brain regions, and throughout the lifespan. The role of the serotonin transporter in MDD has been highlighted in gene by environment association studies as well as its role as a critical player in the mechanism of the most effective antidepressant treatments – selective serotonin reuptake inhibitors. While the majority of the 15 known receptors for serotonin have been implicated in depression or depressive-like behavior, the serotonin 1A (5-HT 1A) and 1B (5-HT 1B) receptors are among the most studied. Human brain imaging and genetic studies point to the involvement of 5-HT 1A and 5-HT 1B receptors in MDD and the response to antidepressant treatment. In rodents, the availability of tissue-specific and inducible knockout mouse lines has made possible the identification of the involvement of 5-HT 1A and 5-HT 1B receptors throughout development and in a cell-type specific manner. This, and other preclinical pharmacology work, shows that autoreceptor and heteroreceptor populations of these receptors have divergent roles in modulating depression-related behavior as well as responses to antidepressants and also have different functions during early postnatal development compared to during adulthood. PMID:28232871

  18. Serotonin Regulates the Feeding and Reproductive Behaviors of Pratylenchus penetrans.

    Science.gov (United States)

    Han, Ziduan; Boas, Stephanie; Schroeder, Nathan E

    2017-07-01

    The success of all plant-parasitic nematodes is dependent on the completion of several complex behaviors. The lesion nematode Pratylenchus penetrans is an economically important parasite of a diverse range of plant hosts. Unlike the cyst and root-knot nematodes, P. penetrans moves both within and outside of the host roots and can feed from both locations. Adult females of P. penetrans require insemination by actively moving males for reproduction and can lay eggs both within and outside of the host roots. We do not have a complete understanding of the molecular basis for these behaviors. One candidate modulator of these behaviors is the neurotransmitter serotonin. Previous research demonstrated an effect of exogenously applied serotonin on the feeding and male mating behaviors of cyst and root-knot nematodes. However, there are no data on the role of exogenous serotonin on lesion nematodes. Similarly, there are no data on the presence and function of endogenous serotonin in any plant-parasitic nematode. Here, we establish that exogenous serotonin applied to P. penetrans regulates both feeding and sex-specific behaviors. Furthermore, using immunohistochemistry and pharmacological assays, our data suggest that P. penetrans utilizes endogenous serotonin to regulate both feeding and sex-specific behaviors.

  19. Increased hypothalamic serotonin turnover in inflammation-induced anorexia.

    Science.gov (United States)

    Dwarkasing, J T; Witkamp, R F; Boekschoten, M V; Ter Laak, M C; Heins, M S; van Norren, K

    2016-05-20

    Anorexia can occur as a serious complication of disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections between peripheral inflammation, anorexia and hypothalamic serotonin metabolism and signaling pathways. First, we investigated the response of two hypothalamic neuronal cell lines to TNFα, IL-6 and LPS. Next, we studied transcriptomic changes and serotonergic activity in the hypothalamus of mice after intraperitoneal injection with TNFα, IL-6 or a combination of TNFα and IL-6. In vitro, we showed that hypothalamic neurons responded to inflammatory mediators by releasing cytokines. This inflammatory response was associated with an increased serotonin release. Mice injected with TNFα and IL-6 showed decreased food intake, associated with altered expression of inflammation-related genes in the hypothalamus. In addition, hypothalamic serotonin turnover showed to be elevated in treated mice. Overall, our results underline that peripheral inflammation reaches the hypothalamus where it affects hypothalamic serotoninergic metabolism. These hypothalamic changes in serotonin pathways are associated with decreased food intake, providing evidence for a role of serotonin in inflammation-induced anorexia.

  20. Effect of endurance training on hypothalamic serotonin concentration and performance.

    Science.gov (United States)

    Caperuto, E C; dos Santos, R V T; Mello, M T; Costa Rosa, L F B P

    2009-02-01

    1. Serotonin is a neurotransmitter that modulates several functions, such as food intake, energy expenditure, motor activity, mood and sleep. Acute exhaustive endurance exercise increases the synthesis, concentration and metabolism of serotonin in the brain. This phenomenon could be responsible for central fatigue after prolonged and exhaustive exercise. However, the effect of chronic exhaustive training on serotonin is not known. The present study was conducted to examine the effect of exhaustive endurance training on performance and serotonin concentrations in the hypothalamus of trained rats. 2. Rats were divided into three groups: sedentary rats (SED), moderately trained rats (MOD) and exhaustively trained rats (EXT), with an increase of 200% in the load carried during the final week of training. 3. Hypothalamic serotonin concentrations were similar between the SED and MOD groups, but were higher in the EXT group (P MOD group (P < 0.05). 4. Thus, the present study demonstrates that exhaustive training increases serotonin concentrations in the hypothalamus, together with decreased endurance performance after inadequate recovery time. However, the mechanism underlying these changes remains unknown.

  1. Brain serotonin content regulates the manifestation of tramadol-induced seizures in rats: disparity between tramadol-induced seizure and serotonin syndrome.

    Science.gov (United States)

    Fujimoto, Yohei; Funao, Tomoharu; Suehiro, Koichi; Takahashi, Ryota; Mori, Takashi; Nishikawa, Kiyonobu

    2015-01-01

    Tramadol-induced seizures might be pathologically associated with serotonin syndrome. Here, the authors investigated the relationship between serotonin and the seizure-inducing potential of tramadol. Two groups of rats received pretreatment to modulate brain levels of serotonin and one group was treated as a sham control (n = 6 per group). Serotonin modulation groups received either para-chlorophenylalanine or benserazide + 5-hydroxytryptophan. Serotonin, dopamine, and histamine levels in the posterior hypothalamus were then measured by microdialysis, while simultaneously infusing tramadol until seizure onset. In another experiment, seizure threshold with tramadol was investigated in rats intracerebroventricularly administered with either a serotonin receptor antagonist (methysergide) or saline (n = 6). Pretreatment significantly affected seizure threshold and serotonin fluctuations. The threshold was lowered in para-chlorophenylalanine group and raised in benserazide + 5-hydroxytryptophan group (The mean ± SEM amount of tramadol needed to induce seizures; sham: 43.1 ± 4.2 mg/kg, para-chlorophenylalanine: 23.2 ± 2.8 mg/kg, benserazide + 5-hydroxytryptophan: 59.4 ± 16.5 mg/kg). Levels of serotonin at baseline, and their augmentation with tramadol infusion, were less in the para-chlorophenylalanine group and greater in the benserazide + 5-hydroxytryptophan group. Furthermore, seizure thresholds were negatively correlated with serotonin levels (correlation coefficient; 0.71, P seizure threshold (P seizures, and that serotonin concentrations were negatively associated with seizure thresholds. Moreover, serotonin receptor antagonism precipitated seizure manifestation, indicating that tramadol-induced seizures are distinct from serotonin syndrome.

  2. INFLUENCE OF A SEROTONIN-RICH AND DOPAMINE-RICH DIET ON PLATELET SEROTONIN CONTENT AND URINARY-EXCRETION OF BIOGENIC-AMINES AND THEIR METABOLITES

    NARCIS (Netherlands)

    KEMA, IP; SCHELLINGS, AMJ; MEIBORG, G; HOPPENBROUWERS, CJM; MUSKIET, FAJ

    Using high-performance liquid chromatography and gas chromatography, we reevaluated the 24-h influence of a serotonin- and dopamine-rich diet on platelet serotonin and serotonin, 5-hydroxyindoleacetic acid (5-HIAA), and major catecholamine metabolites in the urine of 15 healthy adults. Although

  3. Adipocitos, obesidad visceral, inflamación y enfermedad cardiovascular Adipocytes, visceral obesity, inflammation and cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Fernando Manzur

    2010-09-01

    Full Text Available La obesidad es un importante problema de salud a nivel mundial. Se considera el resultado de la combinación de factores genéticos, alimentación inadecuada y falta de actividad física regular. La ingestión de una dieta de alta densidad energética, es la principal causa de obesidad visceral o central, ya que el exceso de energía se almacena en los adipocitos, que aumentan en tamaño y en número, o ambos, en especial los viscerales, produciendo un incremento en la tasa de lipólisis, que a su vez, estimula la secreción de citoquinas por leucocitos, macrófagos y adipocitos, y conduce a estado proinflamatorio, resistencia a la insulina y disfunción endotelial. Esta última, favorecida por el proceso inflamatorio, puede ser el vínculo de unión entre la obesidad y la enfermedad cardiovascular. Así, la disfunción del tejido adiposo representa el mecanismo etiopatogénico en el desarrollo de enfermedad cardiovascular, iniciado por la obesidad visceral.Worldwide obesity is an important health problem that results from the combination of genetic factors, inadequate food intake and lack of regular physical activity. Intake of a high energy-dense diet is the main cause of visceral and central obesity, since energy excess is stored in adipocytes that increase in size and/or number, especially visceral adipocytes, causing an increment in lipolysis rate that in turn stimulates the cytokines secretion from leucocytes, macrophages and adipocytes, leading to a pro-inflammatory state, insulin resistance and endothelial dysfunction. This endothelial dysfunction favored by the inflammatory process can be the connecting bond between obesity and cardiovascular disease. Thus, adipose tisssue dysfunction constitutes the ethio-pathogenic mechanism in the development of cardiovascular disease, initiated by visceral obesity.

  4. The effect of pre- versus postinjury infiltration with lidocaine on thermal and mechanical hyperalgesia after heat injury to the skin

    DEFF Research Database (Denmark)

    Dahl, J B; Brennum, J; Arendt-Nielsen, L

    1993-01-01

    The aim of the study was to evaluate the effects of pre- and postinjury infiltration with lidocaine on alterations in mechanical and thermal sensitivity after heat injury to the skin. In the first part of the study, burn injuries (15 x 25 mm rectangular thermode, 50 degrees C, 7 min) were produced...... degrees C, 6 min) were produced twice in each subject on the medial side of the left and right calves at least 24 h apart (n = 10). This was preceded by subcutaneous (s.c.) infiltration with 5-6 ml of 1% plain lidocaine (pre-injury block) on one day, and the same block was performed 35 min after injury...... the 2 days of examination. In the second part of the study, it was observed that pre-injury infiltration with lidocaine reduced hyperalgesia to pinprick and brush outside the injury more effectively than postinjury block, but only for the first 70 min after injury, while no significant difference...

  5. Systematic administration of B vitamins attenuates neuropathic hyperalgesia and reduces spinal neuron injury following temporary spinal cord ischaemia in rats.

    Science.gov (United States)

    Yu, C-Z; Liu, Y-P; Liu, S; Yan, M; Hu, S-J; Song, X-J

    2014-01-01

    B vitamins have been demonstrated to be effective in treating chronic pain due to peripheral nerve injury. We investigated whether B vitamins could alleviate neuropathic pain and reduce neuron injury following temporary ischaemia in a rat model of spinal cord ischaemia-reperfusion injury (SCII). SCII was produced by transiently blocking the unilateral lumbar arteries in adult male Sprague-Dawley rats. Behavioural and neurochemical signs of neuropathic pain and spinal neuron injury were analysed with and without B vitamin treatment. SCII caused behavioural thermal hyperalgesia and mechanical allodynia and neurochemical alterations, including increased expression of the vanilloid receptor 1 (VR1) and induction of c-Fos, as well as activation of the astrocytes and microglial cells in the spinal cord. Repetitive systemic administration of vitamin B complex (B1/B6/B12 at 33/33/0.5 mg/kg, i.p., daily, for 7-14 consecutive days) significantly reduced thermal hyperalgesia and the increased expression of VR1 and c-Fos, as well as activation of the astrocytes and microglial cells. SCII caused a dramatic decrease of the expression of the rate-limiting enzyme glutamic acid decarboxylase-65 (GAD65), which synthesizes γ-aminobutyric acid (GABA) in the axonal terminals, and β-III-tubulin, and also caused loss of Nissl bodies in the spinal cord. These alterations were largely prevented and rescued by the B vitamin treatment. These findings support the idea that the B vitamins are capable of neuroprotection and antinociception during spinal cord injury due to temporary ischaemia. Rescuing the loss of inhibitory GABAergic tone may reduce spinal central sensitization and contribute to B vitamin-induced analgesia. © 2013 European Pain Federation - EFIC®

  6. Pressure pain sensitivity topographical maps reveal bilateral hyperalgesia of the hands in patients with unilateral carpal tunnel syndrome.

    Science.gov (United States)

    Fernández-de-Las-Peñas, César; Madeleine, Pascal; Martínez-Perez, Almudena; Arendt-Nielsen, Lars; Jiménez-García, Rodrigo; Pareja, Juan A

    2010-08-01

    To assess topographical pressure pain sensitivity maps of the hand in patients with unilateral carpal tunnel syndrome (CTS) as compared with healthy subjects. A total of 20 women with CTS (ages 32-52 years) and 20 healthy matched women (ages 32-51 years) were recruited. Pressure pain thresholds (PPTs) were measured bilaterally over 30 locations of the palm of each hand by an assessor blinded to the subjects' conditions. Patients showed lower PPTs in both hands in all of the measurement points as compared with controls (P < 0.001 for all). PPTs were lower in those points over the proximal phalanx of the fingers and the thenar eminency as compared with those points located over the distal phalanx of the fingers (P < 0.001). CTS patients showed lower PPT levels in dermatomes C6, C7, and C8 when compared with healthy controls (P < 0.001 for all), but without differences between dermatomes (P = 0.4). PPT was negatively correlated with both hand pain intensity and duration of symptoms (P < 0.001 for all). Our findings revealed bilateral generalized pressure pain hyperalgesia in unilateral CTS because lower PPT levels were found in all of the points. The pressure pain hyperalgesia was not uniformly distributed since PPTs were lower in points over the proximal phalanx of the fingers and the thenar eminency as compared with those points located over the distal phalanx of the fingers. The decrease in PPT levels was associated with the intensity and the duration of the pain symptoms, supporting a role of both peripheral and central sensitization mechanisms in this pain condition.

  7. Spinal interleukin-17 promotes thermal hyperalgesia and NMDA NR1 phosphorylation in an inflammatory pain rat model

    Science.gov (United States)

    Meng, Xianze; Zhang, Yu; Lao, Lixing; Saito, Rikka; Li, Aihui; Bäckman, Cristina M.; Berman, Brian M.; Ren, Ke; Wei, Pin-Kang; Zhang, Rui-Xin

    2013-01-01

    It is known that interleukin-17 (IL-17) is associated with autoimmune disorders and that peripheral IL-17 plays a role in arthritis and neuropathic pain. The present study investigated the possibility of spinal cell expression of IL-17 during inflammatory pain and possible IL-17 involvement in such pain. Hyperalgesia was induced by injecting complete Freund’s adjuvant (CFA, 0.08 ml, 40 μg Mycobacterium tuberculosis) into one hind paw of the rat. Paw withdrawal latency (PWL) was tested before (−48 h) and 2 and 24 h after CFA to assess hyperalgesia. IL-17 antibody (0.2–2 μg/rat) was given intrathecally (i.t.) 24 h before CFA to block the action of basal IL-17 and 2 h prior to each of two PWL tests to block CFA-induced IL-17. I.t. recombinant IL-17 (10–400 ng/rat) was administered to naive rats to determine its effects on PWL and phosphorylated-NR1 (p-NR1). P-NR1 modulates N-methyl-D-aspartate receptor (NMDAR) activity to facilitate pain. Spinal cords were removed for IL-17 immunostaining, double immunostaining of IL-17/cell markers and IL-17 receptor A (IL-17RA)/NR1, for western blot of IL-17, p-NR1, IL-17RA, and GFAP, for in situ IL-17RA hybridization, and for real time PCR of IL-17RA. The data shows that 1) IL-17 is up-regulated in activated and non-activated astrocytes, 2) IL-17RA is localized in NR1-immunoreactive neurons and up-regulated, and 3) IL-17 antibody at 2 μg/rat significantly increased PWL (PIL-17-injected rats. The results suggest that spinal IL-17 is produced by astrocytes and enhances p-NR1 to facilitate pain. PMID:23246025

  8. Heat hyperalgesia and mechanical hypersensitivity induced by calcitonin gene-related peptide in a mouse model of neurofibromatosis.

    Directory of Open Access Journals (Sweden)

    Stephanie White

    Full Text Available This study examined whether mice with a deficiency of neurofibromin, a Ras GTPase activating protein, exhibit a nociceptive phenotype and probed a possible contribution by calcitonin gene-related peptide. In the absence of inflammation, Nf1+/- mice (B6.129S6 Nf1/J and wild type littermates responded comparably to heat or mechanical stimuli, except for a subtle enhanced mechanical sensitivity in female Nf1+/- mice. Nociceptive phenotype was also examined after inflammation induced by capsaicin and formalin, which release endogenous calcitonin gene-related peptide. Intraplantar injection of capsaicin evoked comparable heat hyperalgesia and mechanical hypersensitivity in Nf1+/- and wild type mice of both genders. Formalin injection caused a similar duration of licking in male Nf1+/- and wild type mice. Female Nf1+/- mice licked less than wild type mice, but displayed other nociceptive behaviors. In contrast, intraplantar injection of CGRP caused greater heat hyperalgesia in Nf1+/- mice of both genders compared to wild type mice. Male Nf1+/- mice also exhibited greater mechanical hypersensitivity; however, female Nf1+/- mice exhibited less mechanical hypersensitivity than their wild type littermates. Transcripts for calcitonin gene-related peptide were similar in the dorsal root ganglia of both genotypes and genders. Transcripts for receptor activity-modifying protein-1, which is rate-limiting for the calcitonin gene-related peptide receptor, in the spinal cord were comparable for both genotypes and genders. The increased responsiveness to intraplantar calcitonin gene-related peptide suggests that the peripheral actions of calcitonin gene-related peptide are enhanced as a result of the neurofibromin deficit. The analgesic efficacy of calcitonin gene-related peptide receptor antagonists may therefore merit investigation in neurofibromatosis patients.

  9. Epigallocatechin-3-Gallate Reduces Myometrial Infiltration, Uterine Hyperactivity, and Stress Levels and Alleviates Generalized Hyperalgesia in Mice Induced With Adenomyosis

    Science.gov (United States)

    Chen, Yumei; Zhu, Bo; Zhang, Hongping; Liu, Xishi

    2013-01-01

    In an effort to search for novel therapeutics for adenomyosis, we sought to determine whether treatment with epigallocatechin-3-gallate (EGCG) would suppress the myometrial infiltration, improve pain behavior, lower stress level, and reduce uterine contractility in a mice model of adenomyosis. Adenomyosis was induced in 28 female ICR mice neonatally dosed with tamoxifen, while another 12 (group C) were dosed with solvent only, which served as a blank control. Starting from 4 weeks after birth, hot plate test was administrated to all mice every 4 weeks. At the 16th week, all mice induced with adenomyosis were randomly divided into 3 groups: low-dose EGCG (5 mg/kg), high-dose EGCG (50 mg/kg), and untreated. Group C received no treatment. After 3 weeks of treatment, the hot plate test was administered again, a blood sample was taken to measure the plasma corticosterone level by enzyme-linked immunosorbent assay, and then all mice were sacrificed. The depth of myometrial infiltration and uterine contractility were also evaluated. We found that the induction of adenomyosis resulted in progressive generalized hyperalgesia, along with elevated amplitude and frequency of uterine contractions as well as elevated plasma corticosterone levels. The EGCG treatment dose dependently suppressed myometrial infiltration, improved generalized hyperalgesia, reduced uterine contractility, and lowered plasma corticosterone levels. These results suggest that induced adenomyosis causes pain and elevates stress levels in mice. Uterine hyperactivity may contribute to dysmenorrhea in women with adenomyosis who might also have elevated stress level due to pain. The EGCG appears to be a promising compound for treating adenomyosis. PMID:23703534

  10. Impaired inflammatory pain and thermal hyperalgesia in mice expressing neuron-specific dominant negative mitogen activated protein kinase kinase (MEK

    Directory of Open Access Journals (Sweden)

    Kaplan David

    2006-01-01

    Full Text Available Abstract Background Numerous studies have implicated spinal extracellular signal-regulated kinases (ERKs as mediators of nociceptive plasticity. These studies have utilized pharmacological inhibition of MEK to demonstrate a role for ERK signaling in pain, but this approach cannot distinguish between effects of ERK in neuronal and non-neuronal cells. The present studies were undertaken to test the specific role of neuronal ERK in formalin-induced inflammatory pain. Dominant negative MEK (DN MEK mutant mice in which MEK function is suppressed exclusively in neurons were tested in the formalin model of inflammatory pain. Results Formalin-induced second phase spontaneous pain behaviors as well as thermal hyperalgesia measured 1 – 3 hours post-formalin were significantly reduced in the DN MEK mice when compared to their wild type littermate controls. In addition, spinal ERK phosphorylation following formalin injection was significantly reduced in the DN MEK mice. This was not due to a reduction of the number of unmyelinated fibers in the periphery, since these were almost double the number observed in wild type controls. Further examination of the effects of suppression of MEK function on a downstream target of ERK phosphorylation, the A-type potassium channel, showed that the ERK-dependent modulation of the A-type currents is significantly reduced in neurons from DN MEK mice compared to littermate wild type controls. Conclusion Our results demonstrate that the neuronal MEK-ERK pathway is indeed an important intracellular cascade that is associated with formalin-induced inflammatory pain and thermal hyperalgesia.

  11. Heat hyperalgesia and mechanical hypersensitivity induced by calcitonin gene-related peptide in a mouse model of neurofibromatosis.

    Science.gov (United States)

    White, Stephanie; Marquez de Prado, Blanca; Russo, Andrew F; Hammond, Donna L

    2014-01-01

    This study examined whether mice with a deficiency of neurofibromin, a Ras GTPase activating protein, exhibit a nociceptive phenotype and probed a possible contribution by calcitonin gene-related peptide. In the absence of inflammation, Nf1+/- mice (B6.129S6 Nf1/J) and wild type littermates responded comparably to heat or mechanical stimuli, except for a subtle enhanced mechanical sensitivity in female Nf1+/- mice. Nociceptive phenotype was also examined after inflammation induced by capsaicin and formalin, which release endogenous calcitonin gene-related peptide. Intraplantar injection of capsaicin evoked comparable heat hyperalgesia and mechanical hypersensitivity in Nf1+/- and wild type mice of both genders. Formalin injection caused a similar duration of licking in male Nf1+/- and wild type mice. Female Nf1+/- mice licked less than wild type mice, but displayed other nociceptive behaviors. In contrast, intraplantar injection of CGRP caused greater heat hyperalgesia in Nf1+/- mice of both genders compared to wild type mice. Male Nf1+/- mice also exhibited greater mechanical hypersensitivity; however, female Nf1+/- mice exhibited less mechanical hypersensitivity than their wild type littermates. Transcripts for calcitonin gene-related peptide were similar in the dorsal root ganglia of both genotypes and genders. Transcripts for receptor activity-modifying protein-1, which is rate-limiting for the calcitonin gene-related peptide receptor, in the spinal cord were comparable for both genotypes and genders. The increased responsiveness to intraplantar calcitonin gene-related peptide suggests that the peripheral actions of calcitonin gene-related peptide are enhanced as a result of the neurofibromin deficit. The analgesic efficacy of calcitonin gene-related peptide receptor antagonists may therefore merit investigation in neurofibromatosis patients.

  12. An approach for serotonin depletion in pigs: effects on serotonin receptor binding

    DEFF Research Database (Denmark)

    Ettrup, Anders; Kornum, Birgitte R; Weikop, Pia

    2011-01-01

    Depletion of central serotonin (5-HT) levels and dysfunction in serotonergic transmission are implicated in a variety of human CNS disorders. The mechanisms behind these serotonergic deficits have been widely studied using rodent models, but only to a limited extent in larger animal models. The pig...... concentrations of 5-HT in seven distinct brain structures from one hemisphere: frontal and occipital cortex, striatum, hippocampus, cerebellum, rostral, and caudal brain stem, were determined. The other hemisphere was processed for receptor autoradiography. Treatments with 50 mg/kg and 100 mg/kg pCPA caused...

  13. Gastric pentadecapeptide BPC 157 effective against serotonin syndrome in rats.

    Science.gov (United States)

    Boban Blagaic, Alenka; Blagaic, Vladimir; Mirt, Mirela; Jelovac, Nikola; Dodig, Goran; Rucman, Rudolf; Petek, Marijan; Turkovic, Branko; Anic, Tomislav; Dubovecak, Miroslav; Staresinic, Mario; Seiwerth, Sven; Sikiric, Predrag

    2005-04-11

    Serotonin syndrome commonly follows irreversible monoamine oxidase (MAO)-inhibition and subsequent serotonin (5-HT) substrate (in rats with fore paw treading, hind limbs abduction, wet dog shake, hypothermia followed by hyperthermia). A stable gastric pentadecapeptide BPC 157 with very safe profile (inflammatory bowel disease clinical phase II, PL-10, PLD-116, PL-14736, Pliva) reduced the duration of immobility to a greater extent than imipramine, and, given peripherally, has region specific influence on brain 5-HT synthesis (alpha-[14C]methyl-L-tryptophan autoradiographic measurements) in rats, different from any other serotonergic drug. Thereby, we investigate this peptide (10 microg, 10 ng, 10 pg/kg i.p.) in (i) full serotonin syndrome in rat combining pargyline (irreversible MAO-inhibition; 75 mg/kg i.p.) and subsequent L-tryptophan (5-HT precursor; 100 mg/kg i.p.; BPC 157 as a co-treatment), or (ii, iii) using pargyline or L-tryptophan given separately, as a serotonin-substrate with (ii) pargyline (BPC 157 as a 15-min posttreatment) or as a potential serotonin syndrome inductor with (iii) L-tryptophan (BPC 157 as a 15 min-pretreatment). In all experiments, gastric pentadecapeptide BPC 157 contrasts with serotonin-syndrome either (i) presentation (i.e., particularly counteracted) or (ii) initiation (i.e., neither a serotonin substrate (counteraction of pargyline), nor an inductor for serotonin syndrome (no influence on L-tryptophan challenge)). Indicatively, severe serotonin syndrome in pargyline + L-tryptophan rats is considerably inhibited even by lower pentadecapeptide BPC 157 doses regimens (particularly disturbances such as hyperthermia and wet dog shake thought to be related to stimulation of 5-HT2A receptors), while the highest pentadecapeptide dose counteracts mild disturbances present in pargyline rats (mild hypothermia, feeble hind limbs abduction). Thereby, in severe serotonin syndrome, gastric pentadecapeptide BPC 157 (alone, no behavioral or

  14. Serotonin and migraine: biology and clinical implications.

    Science.gov (United States)

    Hamel, E

    2007-11-01

    Migraine is the most frequent neurological disorder in the adult population worldwide, affecting up to 12% of the general population and more frequent in women ( approximately 25%). It has a high impact on our society due to its disabling nature and, therein, reduced quality of life and increased absenteeism from work. Headache is the primary clinical manifestation and it has been associated with 'a hereditary or predisposed sensitivity of neurovascular reactions to certain stimuli or to cyclic changes in the central nervous system' (1). Amongst the many neurotransmitters in the brain, the serotonergic (serotonin, 5-HT) system from the brainstem raphe nucleus has been most convincingly implicated in migraine pathophysiology. The documented changes in 5-HT metabolism and in the processing of central 5-HT-mediated responses during and in between migraine attacks have led to the suggestion that migraine is a consequence of a central neurochemical imbalance that involves a low serotonergic disposition. Although the exact cascade of events that link abnormal serotonergic neurotransmission to the manifestation of head pain and the accompanying symptoms has yet to be fully understood, recent evidence suggests that a low 5-HT state facilitates activation of the trigeminovascular nociceptive pathway, as induced by cortical spreading depression. In this short review, we present and discuss the original and most recent findings that support a role for altered serotonergic neurotransmission in the manifestation of migraine headache.

  15. 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.

  16. Effects of selective serotonin reuptake inhibition on neural activity related to risky decisions and monetary rewards in healthy males

    DEFF Research Database (Denmark)

    Macoveanu, Julian; Fisher, Patrick M; Haahr, Mette E

    2014-01-01

    Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are commonly prescribed antidepressant drugs targeting the dysfunctional serotonin (5-HT) system, yet little is known about the functional effects of prolonged serotonin reuptake inhibition in healthy individuals. Here we used...

  17. SEROTONIN, CATECHOLAMINES, HISTAMINE, AND THEIR METABOLITES IN URINE, PLATELETS, AND TUMOR-TISSUE OF PATIENTS WITH CARCINOID-TUMORS

    NARCIS (Netherlands)

    KEMA, IP; DEVRIES, EGE; SLOOFF, MJH; BIESMA, B; MUSKIET, FAJ

    We monitored long-term (median 11 months) concentrations of platelet serotonin and urinary serotonin, 5-hydroxyindoleacetic acid, and seven catecholamine metabolites in 44 patients with carcinoid tumors. Tumor serotonin and catecholamine contents (11 patients) and urinary histamine and

  18. KSAC, the first defined polyprotein vaccine candidate for visceral leishmaniasis.

    Science.gov (United States)

    Goto, Yasuyuki; Bhatia, Ajay; Raman, Vanitha S; Liang, Hong; Mohamath, Raodoh; Picone, Alessandro F; Vidal, Silvia E Z; Vedvick, Thomas S; Howard, Randall F; Reed, Steven G

    2011-07-01

    A subunit vaccine using a defined antigen(s) may be one effective solution for controlling leishmaniasis. Because of genetic diversity in target populations, including both dogs and humans, a multiple-antigen vaccine will likely be essential. However, the cost of a vaccine to be used in developing countries must be considered. We describe herein a multiantigen vaccine candidate comprised of antigens known to be protective in animal models, including dogs, and to be recognized by humans immune to visceral leishmaniasis. The polyprotein (KSAC) formulated with monophosphoryl lipid A, a widely used adjuvant in human vaccines, was found to be immunogenic and capable of inducing protection against Leishmania infantum, responsible for human and canine visceral leishmaniasis, and against L. major, responsible for cutaneous leishmaniasis. The results demonstrate the feasibility of producing a practical, cost-effective leishmaniasis vaccine capable of protecting both humans and dogs against multiple Leishmania species.

  19. Visceral Leishmaniasis in Latin America and therapy perspectives

    Directory of Open Access Journals (Sweden)

    Catalina Tovar A

    2017-05-01

    Full Text Available In Latin America, visceral leishmaniasis is caused by Leishmania infantum. In this geographical area, main vectors associated with transmission are Lutzomyia longipalpis and Lutzomyia evansi, with dogs being incriminated as the main reservoir involved in transmission of the disease. This pathology primarily affects children between 0 - 5 years, a highly susceptible population where socio-economic, environmental and nutritional factors affects the pathological outcome and increase the likelihood of vector-human contact. According to the World Health Organization (WHO recommended treatment for Visceral Leishmaniasis is liposomal amphotericin B, a drug with a limited and variable availability between countries depending on market prices, which leaves pentavalent antimonial as the most widely used treatment despite the associated toxic effects. In the Americas, evidence on the efficacy of single-dose (monotherapy and combination therapies as options for treating these parasites is required.

  20. Host resistance to visceral leishmaniasis: prevalence and prevention.

    Science.gov (United States)

    Maran, Naiara; Gomes, Pollyanna Stephanie; Freire-de-Lima, Leonardo; Freitas, Elisangela Oliveira; Freire-de-Lima, Célio Geraldo; Morrot, Alexandre

    2016-01-01

    Visceral leishmaniasis (VL) is a chronic parasitic disease caused by the vector-borne Leishmania donovani and Leishmania (L.) infantum chagasi parasites. The disease affects about 12 million humans in more than 90 countries worldwide. If not treated, the visceral form of Leishmania infection is potentially fatal, yielding about 50000 deaths per year. In the vertebrate host, the Leishmania species causing VL spread systematically to propagate in macrophage reservoirs distributed in the tissues of internal organs, primarily the liver, spleen, bone marrow and the lymph nodes. The infection is associated with evolved mechanisms from the parasite to subvert the host immune system in order to establish a persistent infection. Currently, efforts are being deployed to develop new anti-leishmanial therapies in VL combining immunomodulatory treatment regimens that burst the host immune responses together with leishmanicidal drugs that target the parasite growth. Discoveries in this field are discussed in this article.

  1. Scintigraphy usefulness in the diagnosis of visceral candidiasis

    Energy Technology Data Exchange (ETDEWEB)

    Ythier, H.; Legghe, R.; Foucher, C.

    1987-01-01

    From the features of two cases, the authors stress the usefulness of the scintigraphy as regards to the diagnosis of visceral candidial abscesses. Such fungal localisations are not unfrequent, especially in immunodeficient patients (haematologic malignancies undergoing chemotherapy, lupus, serious visceral illness...). The positive diagnosis is uneasy because of non-specific clinical features and frequent negative blood cultures. Splenic localisation is the most likely. Citrate Gallium scintigraphy together with splenic labelled RBC scan enables us to give a precise view of the splenic involvment and even of the abdominal extension of the fungal abscess. From the literature review and these two cases, the excellent adequacy of the scintigraphy to the follow-up of systemic candidiasis is underlined and is compared to other usual morphological studies such as US scan and CT examination. In both cases, the diagnosis is fully confirmed by mycological examination.

  2. Leishmaniose visceral canina no Rio de Janeiro - Brasil

    OpenAIRE

    Marzochi,Mauro Célio de A.; Sérgio Gomes Coutinho; Paulo Chagastelles Sabroza; Miguel Alves de Souza; Pelágio Parigot Medeiros de de Souza; Luciano Toledo; Rangel Filho,Francisco B.

    1985-01-01

    No recente e mais meridional foco endêmico de leishmaniose visceral do Brasil, associado à presença de Lutzomyia longipalpis e a infecção canina, os autores discutem a importância do cão doméstico como reservatório natural da infecção, assim como sumarizam os achados epidemiológicos, clínicos, parasitológicos e terapêuticos da doença canina observados no Município do Rio de Janeiro, Brasil.Based on the recent and most southernly endemic focus of visceral leishmaniasis in Brazil, associated wi...

  3. Leishmaniose visceral: estudo retrospectivo de fatores associados à letalidade Visceral leishmaniasis: retrospective study on factors associated with lethality

    Directory of Open Access Journals (Sweden)

    Daniel Gomes de Alvarenga

    2010-04-01

    Full Text Available INTRODUÇÃO: A leishmaniose visceral é um problema de saúde pública, com grau de letalidade alcançando 10%. Para o tratamento medicamentoso, é recomendado o antimoniato de metilglucamina. Este estudo tem como objetivo avaliar o uso de medicamento em casos de leishmaniose visceral atendidos no Serviço de Infectologia do Núcleo de Hospital Universitário de Campo Grande Estado do Mato Grosso do Sul. MÉTODOS: Para coleta de dados, foram pesquisados prontuários de 76 pacientes com diagnóstico de leishmaniose visceral atendidos pelo Serviço de Infectologia do Hospital Universitário de Campo Grande. RESULTADOS: Foram analisados prontuários de 76 (28,9% pacientes (56 homens e 20 mulheres apresentavam comorbidades. Como droga de 1ª escolha, 88,2% dos pacientes utilizaram o antimoniato-N-metil glucamina com evolução para óbito de 18,4%. A análise de sobrevida mostrou diferença estatisticamente significativa em pacientes com e sem comorbidades (pINTRODUCTION: Visceral leishmaniasis is a public health problem, with lethality reaching 10%. The recommended drug treatment is methylglucamine antimoniate. This study aimed to evaluate drug use for cases of visceral leishmaniasis treated at the Infectology Clinic of the Campo Grande University Hospital Center, State of Mato Grosso do Sul. METHODS: To collect data, we examined the medical records of 76 patients with a diagnosis of visceral leishmaniasis treated at this Infectology Clinic. RESULTS: The medical files of 76 patients (56 men and 20 women; 28.9% showed comorbidities. The first choice drug for 88.2% of the patients was N-methylglucamine antimoniate, with a fatal outcome for 18.4%. Survival analysis showed a statistically significant difference between patients with and without comorbidities (p <0.0001 and with comorbidities who used Glucantime® (p < 0.0009. The fatality rate of 18.4% indicates the low efficiency of the healthcare measures used. CONCLUSIONS: The results suggest that

  4. Canine Visceral Leishmaniasis, United States and Canada, 2000–2003

    OpenAIRE

    Duprey, Zandra H.; Steurer, Francis J.; Rooney, Jane A.; Kirchhoff, Louis V.; Jackson, Joan E.; Rowton, Edgar D.; Peter M. Schantz

    2006-01-01

    Visceral leishmaniasis, caused by protozoa of the genus Leishmania donovani complex, is a vectorborne zoonotic infection that infects humans, dogs, and other mammals. In 2000, this infection was implicated as causing high rates of illness and death among foxhounds in a kennel in New York. A serosurvey of >12,000 foxhounds and other canids and 185 persons in 35 states and 4 Canadian provinces was performed to determine geographic extent, prevalence, host range, and modes of transmission within...

  5. Gut Chemosensing: Interactions between Gut Endocrine Cells and Visceral Afferents

    OpenAIRE

    Raybould, Helen E.

    2009-01-01

    Chemosensing in the gastrointestinal tract is less well understood than many aspects of gut mechanosensitivity; however, it is important in the overall function of the GI tract and indeed the organism as a whole. Chemosensing in the gut represents a complex interplay between the function of enteroendocrine (EEC) cells and visceral (primarily vagal) afferent neurons. In this brief review, I will concentrate on new data on endocrine cells in chemosensing in the GI tract, in particular on new fi...

  6. Reduced cortical thickness associated with visceral fat and BMI

    OpenAIRE

    Veit, Ralf; Kullmann, Stephanie; Heni, Martin; Machann, Jürgen; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

    2014-01-01

    Structural brain imaging studies have shown that obesity is associated with widespread reductions in gray matter (GM) volume. Although the body mass index (BMI) is an easily accessible anthropometric measure, substantial health problems are more related to specific body fat compartments, like visceral adipose tissue (VAT). We investigated cortical thickness measures in a group of 72 healthy subjects (BMI range 20–35 kg/m2, age range 19–50 years). Multiple regression analyses were performed us...

  7. Visceral leishmaniasis masquerading as tuberculosis in a patient with AIDS

    Science.gov (United States)

    Yaduvanshi, A.; Jain, M.; Jain, S; Jain, S.; Arora, S.

    1999-01-01

    We report a case of visceral leishmaniasis presenting as significant lymphadenopathy in a patient with acquired immune deficiency syndrome. The lymphadenopathy was initially suspected to be tubercular in nature on pathological examination. This report highlights the increasing incidence of acquired immune deficiency syndrome and Leishmania co-infection in India, and the importance of demonstrating tubercle bacilli on culture before suggesting a diagnosis of tuberculosis.


Keywords: leishmaniasis; AIDS; tuberculosis PMID:10567601

  8. Effects of selective serotonin reuptake inhibitors on platelet serotonin parameters in major depressive disorder.

    Science.gov (United States)

    Bakish, D; Cavazzoni, P; Chudzik, J; Ravindran, A; Hrdina, P D

    1997-01-15

    The effects of treatment with serotonin (5-HT) reuptake inhibitors on platelet 5-HT2 receptors, 5-HT reuptake sites an 5-HT uptake were studied in a double-blind trial comparing two selective serotonin reuptake inhibitors (SSRI), paroxetine, and fluoxetine, for the treatment of major depression. Hamilton Depression Rating Scale (HAM-D) scores and platelet 5-HT parameters were determined in 21 depressed patients at baseline, after 4 and 8 weeks of treatment, and were compared to 21 healthy controls. Antidepressant treatment did not significantly alter the density of 5-HT reuptake sites, labelled with [3H]paroxetine, or 5-HT2 receptors, labelled with [3H]LSD. However, a strong correlation was observed between the HAM-D suicidality item and 5-HT2 receptor density at baseline. A marked increase in platelet 5-HT2 receptors at baseline was observed in suicidal depressed patients compared to those with no suicidal ideation and healthy controls. Changes in [3H]paroxetine Bmax and in [3H]5-HT uptake significantly correlated with change in HAM-D score at 4 and 8 weeks respectively. These results confirm previous reports of an association between suicidality and platelet 5-HT2 receptor upregulation. Our data also lends support to the use of platelet 5-HT parameters as indicators of antidepressant efficacy, particularly in suicidal depressed patients.

  9. Serotonin transporter gene polymorphisms: Relation with platelet serotonin level in patients with primary Sjogren's syndrome.

    Science.gov (United States)

    Markeljevic, J; Sarac, H; Bozina, N; Henigsberg, N; Simic, M; Cicin Sain, L

    2015-05-15

    Significantly lower platelet serotonin level (PSL) in patients with primary Sjogren's syndrome (pSS) than in healthy controls has been reported in our prior studies. In the present report, we demonstrated effect of functional polymorphisms in the serotonin transporter gene (5-HTT) on PSL. We describe a group of 61 pSS patients and 100 healthy individuals subjects, who received PSL measurement in our prior study. All subjects were genotyped for the promoter 5-HTTLPR (L/S), rs25531 (A/G) and intronic 5-HTTVNTRin2 (l/s) polymorphisms. Overall, the presence of 5-HTTVNTRin2 ss genotype was associated with significantly lower PSL in pSS patients, not in healthy controls. Reduced PSL in pSS patients is in line with hypothesis of association between chronic immunoinflammation and 5-HT system dysregulation, identifying additional mechanisms such as altered 5-HT transport as potential genetic factor contributing to PSL depletion. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Infecções experimentaes na Leishmaniose visceral americana Experimental infections in american visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Aristides Marques da Cunha

    1938-01-01

    Full Text Available Passando em revista as experiencias de infecção que effectuamos e que acabamos de relatar, vemos que, as culturas isoladas de casos de Leishmaniose visceral americana quer do homem quer do cão, são capazes de infectar hamsters, rhesus e cães de maneira identica ao que acontece com as outras formas de Kala-Azar. Notamos ainda que a evolução da doença e as lesões observadas nos animaes assim infectados, se assemelham ao que tem sido observado nessa enfermidade aproximando-a de maneira singular do Kala-Azar mediterraneo. É sobretudo no cão que a semelhança se torna mais patente. A infecção da pelle e as lesões por ella provocadas que observamos, não differem em nada das que tem sido descriptas na infecção natural do cão e já assignaladas tambem na infecção experimental desse animal, embora de maneira menos completa do que fazemos agora aqui. As lesões oculares com formação de placas de keratite, a infeccção massiça do intestino nos casos fataes de infecção e até mesmo as lesões do figado descriptas por Adler como peculiares á infecção experimental, (infiltração em torno da veia central do lobulo constituem outros tantos caracteres que mostram a completa analogia entre as infecções do cão que obtivemos e as já observadas no Kala-Azar mediterraneo. Além disso, a presença de Leishmanias na pelle, as vezes em grande numero e a constancia dessa localisação parasitaria, vem mostrar que o cão apresenta as condições necessarias para desempenhar o papel de depositario de virus tal como acontece no Kala-Azar mediterraneo, tanto mais que é elle encontrado naturalmente infectado, nas regiões em que grassa a doença. Mas não é só a infecção do cão que mostra essa semelhança; nos outros animaes tambem se verifica o mesmo facto e até pequenos signaes, taes como a tumefacção das patas assignalada nos hamsters infectados com Leishmania infantum, foram tambem observados aqui. Por outro lado, a reacção de

  11. Role of Nampt and Visceral Adiposity in Esophagogastric Junction Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Haijun Li

    2017-01-01

    Full Text Available Nampt including eNampt and iNampt may contribute to mediating obesity-associated cancers. This study investigated the role of Nampt in esophagogastric junction adenocarcinoma (EGA, a cancer strongly correlated with obesity. Visceral adiposity was defined by waist circumference or VFA. eNampt in sera were measured by enzyme-linked immunosorbent assay. iNampt expression in EGA was determined by PCR, western blot, and immunohistochemistry. Sera eNampt were significantly elevated in these overweight and obese patients, especially for viscerally obese patients, and positively correlated with BMI, waist circumference, VFA, and also primary tumor, regional lymph nodes, and TNM stage (P<0.05. iNampt expression in both the mRNA and protein levels was upregulated in EGAs (P<0.05. iNampt staining was found primarily in the cytoplasm and nuclei and significantly associated with tumor, lymph nodes, and TNM stage and also correlated positively with serum eNampt, BMI, total fat area, VFA, superficial fat area, and waist circumference (P<0.05. iNampt, eNampt, tumor, lymph nodes, and TNM stage correlated to the survival of EGAs, and iNampt expression and TNM stage affected the prognosis independently (P<0.05. This study highlighted the association of eNampt/iNampt with visceral obesity and a potential impact on the biology of EGA.

  12. Negative mood affects brain processing of visceral sensation.

    Science.gov (United States)

    Coen, Steven J; Yágüez, Lidia; Aziz, Qasim; Mitterschiffthaler, Martina T; Brammer, Mick; Williams, Steven C R; Gregory, Lloyd J

    2009-07-01

    A link between negative emotional state and abnormal visceral sensation has been frequently reported. However, the influence of negative emotion on brain processing of painful visceral sensations has not been investigated. We used functional magnetic resonance imaging (fMRI) and negative emotional stimuli to investigate the effects of negative emotion on brain processing of esophageal sensation. Twelve healthy male volunteers (age range, 21-32 years) participated in the study. Negative emotion was induced using emotionally valent music. fMRI images were acquired during 2 experimental runs; throughout these, volunteers received randomized nonpainful and painful distentions to the esophagus during neutral and negative emotion. Subjective perception of each stimulus was acquired, as were mood ratings. Sadness ratings increased significantly following negative mood induction (P .05). Following painful stimulation, brain activity increased in the right hemisphere during negative emotion and was localized to the anterior cingulate cortex (ACC; BA24/32), anterior insula, and inferior frontal gyrus. Following nonpainful stimulation during negative emotion, brain activity increased in the right anterior insula and ACC (BA24 and 32). This study provides new information about the influence of negative affect on central processing of visceral pain. Evidence of right hemispheric dominance during negative emotion indicates this hemisphere is predominately associated with sympathetic activity (arousal, negative affect) and that the right insula and right ACC are integral to subjective awareness of emotion through interoception.

  13. Effects of visceral adiposity on glycerol pathways in gluconeogenesis.

    Science.gov (United States)

    Neeland, Ian J; Hughes, Connor; Ayers, Colby R; Malloy, Craig R; Jin, Eunsook S

    2017-02-01

    To determine the feasibility of using oral 13 C labeled glycerol to assess effects of visceral adiposity on gluconeogenic pathways in obese humans. Obese (BMI ≥30kg/m 2 ) participants without type 2 diabetes underwent visceral adipose tissue (VAT) assessment and stratification by median VAT into high VAT-fasting (n=3), low VAT-fasting (n=4), and high VAT-refed (n=2) groups. Participants ingested [U- 13 C 3 ] glycerol and blood samples were subsequently analyzed at multiple time points over 3h by NMR spectroscopy. The fractions of plasma glucose (enrichment) derived from [U- 13 C 3 ] glycerol via hepatic gluconeogenesis, pentose phosphate pathway (PPP), and tricarboxylic acid (TCA) cycle were assessed using 13 C NMR analysis of glucose. Mixed linear models were used to compare 13 C enrichment in glucose between groups. Mean age, BMI, and baseline glucose were 49years, 40.1kg/m 2 , and 98mg/dl, respectively. Up to 20% of glycerol was metabolized in the TCA cycle prior to gluconeogenesis and PPP activity was minor (gluconeogenesis from glycerol in obese humans. Our findings provide preliminary evidence that excess visceral fat disrupts multiple pathways in hepatic gluconeogenesis from glycerol. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Early visceral pain predicts chronic pain after laparoscopic cholecystectomy.

    Science.gov (United States)

    Blichfeldt-Eckhardt, Morten Rune; Ording, Helle; Andersen, Claus; Licht, Peter B; Toft, Palle

    2014-11-01

    Chronic pain after laparoscopic cholecystectomy is related to postoperative pain during the first postoperative week, but it is unknown which components of the early pain response is important. In this prospective study, 100 consecutive patients were examined preoperatively, 1 week postoperatively, and 3, 6, and 12 months postoperatively for pain, psychological factors, and signs of hypersensitivity. Overall pain, incisional pain (somatic pain component), deep abdominal pain (visceral pain component), and shoulder pain (referred pain component) were registered on a 100-mm visual analogue scale during the first postoperative week. Nine patients developed chronic unexplained pain 12 months postoperatively. In a multivariate analysis model, cumulated visceral pain during the first week and number of preoperative biliary pain attacks were identified as independent risk factors for unexplained chronic pain 12 months postoperatively. There were no consistent signs of hypersensitivity in the referred pain area either pre- or postoperatively. There were no significant associations to any other variables examined. The risk of chronic pain after laparoscopic cholecystectomy is relatively low, but significantly related to the visceral pain response during the first postoperative week. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  15. Voltammetric and Mathematical Evidence for Dual Transport Mediation of Serotonin Clearance In Vivo

    Science.gov (United States)

    Wood, Kevin M.; Zeqja, Anisa; Nijhout, H. Frederik; Reed, Michael C.; Best, Janet; Hashemi, Parastoo

    2014-01-01

    The neurotransmitter serotonin underlies many of the brain’s functions. Understanding serotonin neurochemistry is important for improving treatments for neuropsychiatric disorders such as depression. Antidepressants commonly target serotonin clearance via serotonin transporters (SERTs) and have variable clinical effects. Adjunctive therapies, targeting other systems including serotonin autoreceptors, also vary clinically and carry adverse consequences. Fast scan cyclic voltammetry (FSCV) is particularly well suited for studying antidepressant effects on serotonin clearance and autoreceptors by providing real-time chemical information on serotonin kinetics in vivo. However, the complex nature of in vivo serotonin responses makes it difficult to interpret experimental data with established kinetic models. Here, we electrically stimulated the mouse medial forebrain bundle (MFB) to provoke and detect terminal serotonin in the substantia nigra reticulata (SNr). In response to MFB stimulation we found three dynamically distinct serotonin signals. To interpret these signals we developed a computational model that supports two independent serotonin reuptake mechanisms (high affinity, low efficiency reuptake mechanism and low affinity, high efficiency reuptake system) and bolsters an important inhibitory role for the serotonin autoreceptors. Our data and analysis, afforded by the powerful combination of voltammetric and theoretical methods, gives new understanding of the chemical heterogeneity of serotonin dynamics in the brain. This diverse serotonergic matrix likely contributes to clinical variability of antidepressants. PMID:24702305

  16. Updates on the biology of serotonin and tryptophan hydroxylase.

    Science.gov (United States)

    Swami, Tara; Weber, H Christian

    2018-02-01

    To summarize the most recent findings relevant to the biology of serotonin (5-hydroxytryptamine; 5-HT) and the enzyme tryptophan hydroxylase (TPH) in human gastrointestinal disease. Serotonin is synthesized in the central nervous system (CNS) and the gastrointestinal tract where it is secreted from enteroendocrine cells. Its biosynthesis is regulated by two isoforms of the enzyme TPH of which TPH1 is localized predominantly in gastrointestinal enteroendocrine cells. Serotonin activates the peristaltic reflexes, regulates gastrointestinal motility, and has a role in intestinal inflammation. Inhibition of TPH with novel molecules represents a new pharmacological tool in the successful management of carcinoid syndrome in patients with gastrointestinal neuroendocrine tumors (GI-NETs). Certain 5-HT receptor subtype agonists and antagonists are useful in the treatment of functional gastrointestinal disorders. The gastrointestinal tract is the largest storage organ for serotonin where its biosynthesis is regulated by TPH1. It has several important functions in gastrointestinal motility, secretion, and inflammation. Furthermore, TPH represents a target for inhibitory pharmacological therapy of serotonin access states such as the carcinoid syndrome.

  17. Major depressive disorder and diabetes: does serotonin bridge the gap?

    Science.gov (United States)

    De Long, Nicole E; Stepita, Rebecca A; Taylor, Valerie H; Holloway, Alison C

    2015-01-01

    Major depressive disorder (MDD) is one of the most common psychiatric illnesses worldwide, with reported prevalence rates ranging between 10% and 19%. Pharmacotherapy is a first-line option for the management of MDD and, as a result, the use of antidepressants has increased 4 fold in the last 20 years. Serotonin is the most commonly dysregulated neurotransmitter in the etiology of MDD and this system is the primary focus of most medications used in the treatment of illness. Although antidepressant use in adults increases the risk of developing new onset type 2 diabetes, the mechanisms underlying this association are poorly defined. This review will focus on 1) the evidence from human and animal studies suggesting a link between the use of antidepressants that target serotonin signaling (i.e., SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), serotonin antagonist and reuptake inhibitors (SARIs), and noradrenergic and specific serotonergic antidepressants (NaSSAs)) and increased risk of diabetes, and 2) the mechanisms by which alterations in serotonin signalling by antidepressants can affect glucose homeostasis.

  18. Serotonin inhibits low-threshold spike interneurons in the striatum

    Science.gov (United States)

    Cains, Sarah; Blomeley, Craig P; Bracci, Enrico

    2012-01-01

    Low-threshold spike interneurons (LTSIs) are important elements of the striatal architecture and the only known source of nitric oxide in this nucleus, but their rarity has so far prevented systematic studies. Here, we used transgenic mice in which green fluorescent protein is expressed under control of the neuropeptide Y (NPY) promoter and striatal NPY-expressing LTSIs can be easily identified, to investigate the effects of serotonin on these neurons. In sharp contrast with its excitatory action on other striatal interneurons, serotonin (30 μm) strongly inhibited LTSIs, reducing or abolishing their spontaneous firing activity and causing membrane hyperpolarisations. These hyperpolarisations persisted in the presence of tetrodotoxin, were mimicked by 5-HT2C receptor agonists and reversed by 5-HT2C antagonists. Voltage-clamp slow-ramp experiments showed that serotonin caused a strong increase in an outward current activated by depolarisations that was blocked by the specific M current blocker XE 991. In current-clamp experiments, XE 991 per se caused membrane depolarisations in LTSIs and subsequent application of serotonin (in the presence of XE 991) failed to affect these neurons. We concluded that serotonin strongly inhibits striatal LTSIs acting through postsynaptic 5-HT2C receptors and increasing an M type current. PMID:22495583

  19. Serotonin inhibits low-threshold spike interneurons in the striatum.

    Science.gov (United States)

    Cains, Sarah; Blomeley, Craig P; Bracci, Enrico

    2012-05-15

    Low-threshold spike interneurons (LTSIs) are important elements of the striatal architecture and the only known source of nitric oxide in this nucleus, but their rarity has so far prevented systematic studies. Here, we used transgenic mice in which green fluorescent protein is expressed under control of the neuropeptide Y (NPY) promoter and striatal NPY-expressing LTSIs can be easily identified, to investigate the effects of serotonin on these neurons. In sharp contrast with its excitatory action on other striatal interneurons, serotonin (30 μM) strongly inhibited LTSIs, reducing or abolishing their spontaneous firing activity and causing membrane hyperpolarisations.These hyperpolarisations persisted in the presence of tetrodotoxin, were mimicked by 5-HT(2C) receptor agonists and reversed by 5-HT(2C) antagonists. Voltage-clamp slow-ramp experiments showed that serotonin caused a strong increase in an outward current activated by depolarisations that was blocked by the specific M current blocker XE 991. In current-clamp experiments,XE 991 per se caused membrane depolarisations in LTSIs and subsequent application of serotonin (in the presence of XE 991) failed to affect these neurons.We concluded that serotonin strongly inhibits striatal LTSIs acting through postsynaptic 5-HT(2C) receptors and increasing an M type current.

  20. The association of mast cells and serotonin in children with chronic abdominal pain of unknown etiology

    Directory of Open Access Journals (Sweden)

    Shankar Ravi

    2010-10-01

    Full Text Available Abstract Background Abdominal pain of unknown origin affects up to 20% of school-aged children. Evaluation of children is symptom-based without clear guidelines to investigate molecular mechanisms of abdominal pain. Aberrant molecular mechanisms may increase intestinal permeability leading to interactions between the immune and nervous systems, subclinical inflammation, and visceral pain. This study evaluated the association between interleukin-6 (IL-6, mast cell infiltrates, and serotonin (5-HT levels in gastrointestinal (GI biopsies, with perceived abdominal pain in a pediatric cohort. Methods Clinical data and biopsy samples from pediatric patients (n = 48 with chronic abdominal pain, with and without inflammation were included. Formalin-fixed paraffin-embedded GI biopsies were sectioned and immunohistochemistry performed for IL-6 and 5-HT; mast cells were identified with toluidine blue stain. Histological findings were compared to self-reported abdominal pain between groups. Results There was significantly greater IL-6 immunoreactivity in biopsies with confirmed histologic inflammation (p = 0.004. There was a greater number of mast cells per HPF in non-inflammatory biopsies (3.5 ± 2.9 compared to the inflammatory biopsies (2.6 ± 1.8 p = 0.049. The non-inflammatory biopsy group was significantly less likely to respond to standard treatment as evidenced by higher pain reports (p = .018. Mast cells (p = .022 and 5-HT (p = .02 were significantly related to abdominal pain scores. Conclusions A potential association between self-reported abdominal pain, number of mast cells, and 5-HT levels, which may contribute to perceived GI pain in pediatric patients may exist.

  1. Serotonin 2B receptor signaling is required for craniofacial morphogenesis and jaw joint formation in Xenopus.

    Science.gov (United States)

    Reisoli, Elisa; De Lucchini, Stefania; Nardi, Irma; Ori, Michela

    2010-09-01

    Serotonin (5-HT) is a neuromodulator that plays many different roles in adult and embryonic life. Among the 5-HT receptors, 5-HT2B is one of the key mediators of 5-HT functions during development. We used Xenopus laevis as a model system to further investigate the role of 5-HT2B in embryogenesis, focusing on craniofacial development. By means of gene gain- and loss-of-function approaches and tissue transplantation assays, we demonstrated that 5-HT2B modulates, in a cell-autonomous manner, postmigratory skeletogenic cranial neural crest cell (NCC) behavior without altering early steps of cranial NCC development and migration. 5-HT2B overexpression induced the formation of an ectopic visceral skeletal element and altered the dorsoventral patterning of the branchial arches. Loss-of-function experiments revealed that 5-HT2B signaling is necessary for jaw joint formation and for shaping the mandibular arch skeletal elements. In particular, 5-HT2B signaling is required to define and sustain the Xbap expression necessary for jaw joint formation. To shed light on the molecular identity of the transduction pathway acting downstream of 5-HT2B, we analyzed the function of phospholipase C beta 3 (PLC) in Xenopus development and showed that PLC is the effector of 5-HT2B during craniofacial development. Our results unveiled an unsuspected role of 5-HT2B in craniofacial development and contribute to our understanding of the interactive network of patterning signals that is involved in the development and evolution of the vertebrate mandibular arch.

  2. Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women

    DEFF Research Database (Denmark)

    Fox, Caroline S; Liu, Yongmei; White, Charles C

    2012-01-01

    of European ancestry. Subcutaneous and visceral fat were quantified in 5,560 women and 4,997 men from 4 population-based studies. Genome-wide genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of subcutaneous adipose...... tissue (SAT), visceral adipose tissue (VAT), VAT adjusted for body mass index, and VAT/SAT ratio (a metric of the propensity to store fat viscerally as compared to subcutaneously) in the overall sample and in women and men separately. A weighted z-score meta-analysis was conducted. For the VAT/SAT ratio......-specific analyses. Our most significant finding was for VAT in women, rs1659258 near THNSL2 (p = 1.6 × 10-08), but not men (p = 0.75). Validation of this SNP in the GIANT consortium data demonstrated a similar sex-specific pattern, with observed significance in women (p = 0.006) but not men (p = 0.24) for BMI...

  3. Transient Serotonin Toxicity Evoked by Combination of Electroconvulsive Therapy and Fluoxetine

    Directory of Open Access Journals (Sweden)

    René Klysner

    2014-01-01

    Full Text Available The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine.

  4. Organization of Monosynaptic Inputs to the Serotonin and Dopamine Neuromodulatory Systems

    Directory of Open Access Journals (Sweden)

    Sachie K. Ogawa

    2014-08-01

    Full Text Available Serotonin and dopamine are major neuromodulators. Here, we used a modified rabies virus to identify monosynaptic inputs to serotonin neurons in the dorsal and median raphe (DR and MR. We found that inputs to DR and MR serotonin neurons are spatially shifted in the forebrain, and MR serotonin neurons receive inputs from more medial structures. Then, we compared these data with inputs to dopamine neurons in the ventral tegmental area (VTA and substantia nigra pars compacta (SNc. We found that DR serotonin neurons receive inputs from a remarkably similar set of areas as VTA dopamine neurons apart from the striatum, which preferentially targets dopamine neurons. Our results suggest three major input streams: a medial stream regulates MR serotonin neurons, an intermediate stream regulates DR serotonin and VTA dopamine neurons, and a lateral stream regulates SNc dopamine neurons. These results provide fundamental organizational principles of afferent control for serotonin and dopamine.

  5. Systemic arteriosclerosis and eating behavior in Japanese type 2 diabetic patients with visceral fat accumulation.

    Science.gov (United States)

    Fukuda, Shiro; Hirata, Ayumu; Nishizawa, Hitoshi; Nagao, Hirofumi; Kashine, Susumu; Kimura, Takekazu; Inoue, Kana; Fujishima, Yuya; Yamaoka, Masaya; Kozawa, Junji; Kitamura, Tetsuhiro; Yasuda, Tetsuyuki; Maeda, Norikazu; Imagawa, Akihisa; Funahashi, Tohru; Shimomura, Iichiro

    2015-01-16

    Visceral fat accumulation is a major etiological factor in the progression of type 2 diabetes mellitus and atherosclerosis. We described previously visceral fat accumulation and multiple cardiovascular risk factors in a considerable number of Japanese non-obese subjects (BMI arteriosclerosis, serum adiponectin concentration, and eating behavior in type 2 diabetic patients with and without visceral fat accumulation. The study subjects were 75 Japanese type 2 diabetes mellitus (age: 64.8 ± 11.5 years, mean ± SD). Visceral fat accumulation represented an estimated visceral fat area of 100 cm(2) using the bioelectrical impedance analysis method. Subjects were divided into two groups; with (n = 53) and without (n = 22) visceral fat accumulation. Systemic arteriosclerosis was scored for four arteries by ultrasonography. Eating behavior was assessed based on The Guideline for Obesity questionnaire issued by the Japan Society for the Study of Obesity. The visceral fat accumulation (+) group showed significantly higher systemic vascular scores and significantly lower serum adiponectin levels than the visceral fat accumulation (-) group. With respect to the eating behavior questionnaire items, (+) patients showed higher values for the total score and many of the major sub-scores than (-) patients. Type 2 diabetic patients with visceral fat accumulation showed 1) progression of systemic arteriosclerosis, 2) low serum adiponectin levels, and 3) differences in eating behavior, compared to those without visceral fat accumulation. Taken together, the findings highlight the importance of evaluating visceral fat area in type 2 diabetic patients. Furthermore, those with visceral fat accumulation might need to undergo more intensive screening for systemic arteriosclerosis and consider modifying their eating behaviors.

  6. Tratamento farmacológico da hiperalgesia experimentalmente induzida pelo núcleo pulposo Pharmacologic treatment of hyperalgesia experimentally induced by nucleus pulposus

    Directory of Open Access Journals (Sweden)

    André Luiz de Souza Grava

    2010-01-01

    Full Text Available OBJETIVO: Avaliar o efeito de drogas anti-inflamatórias (dexametasona, indometacina, atenolol, indometacina e atenolol e analgésica (morfina sobre a hiperalgesia experimentalmente induzida pelo núcleo pulposo em contato com o gânglio da raiz dorsal de L5. MÉTODOS: Trinta ratos Wistar machos com peso de 220 a 250g foram utilizados no estudo. A indução da hiperalgesia foi realizada por meio do contato de fragmento de núcleo pulposo retirado da região sacrococcígea e colocado sobre o gânglio da raiz dorsal de L5. Os 30 animais foram divididos em grupos experimentais de acordo com a droga utilizada. As drogas foram administradas durante duas semanas a partir da realização do procedimento cirúrgico para a indução da hiperalgesia. A hiperalgesia mecânica e térmica foram avaliadas por meio do teste da pressão constante da pata, von Frey eletrônico e Hargraves por um período de sete semanas. RESULTADOS: A maior redução da hiperalgesia foi observada no grupo de animais tratados pela morfina, seguido pela dexametasona, indometacina e atenolol. A redução da hiperalgesia foi observada após a interrupção da administração das drogas, com exceção do grupo de animais tratados com morfina, nos quais ocorreu aumento da hiperalgesia após a interrupção do tratamento. CONCLUSÕES: A hiperalgesia induzida pelo contato do núcleo pulposo com o gânglio da raiz dorsal pode ser reduzida com a administração de anti-inflamatórios e analgésicos, tendo sido observado a maior redução da hiperalgesia com a administração da morfina e dexametasona.OBJECTIVE: To evaluate the effect of antiinflammatory (dexamethasone, indomethacin, atenolol, indomethacin and atenolol and analgesic drugs (morphine on hyperalgesia experimentally induced by nucleus pulposus (NP contact with the L5- dorsal root ganglion (DRG. METHODS: Thirty male Wistar rats with weights ranging from 220 to 250 g were used in the study. The hyperalgesia was induced by

  7. The α7 nicotinic ACh receptor agonist compound B and positive allosteric modulator PNU-120596 both alleviate inflammatory hyperalgesia and cytokine release in the rat

    DEFF Research Database (Denmark)

    Munro, G; Hansen, Rikke Rie; Erichsen, Hk

    2012-01-01

    ACh receptor agonist compound B with the positive allosteric modulator (PAM) PNU-120596 and the standard non-steroidal anti-inflammatory drug (NSAID), diclofenac, in rats with hind paw inflammation induced by either formalin, carrageenan or complete Freund's adjuvant (CFA). KEY RESULTS: When administered...... before carrageenan, both diclofenac (30 mg·kg(-1) ) and PNU-120596 (30 mg·kg(-1) ) significantly reduced mechanical hyperalgesia and weight-bearing deficits for up to 4 h. Compound B (30 mg·kg(-1) ) also attenuated both measures of pain-like behaviour, albeit less robustly. Whereas compound B and PNU......-120596 attenuated the carrageenan-induced increase in levels of TNF-α and IL-6 within the hind paw oedema, diclofenac only attenuated IL-6 levels. Established mechanical hyperalgesia induced by carrageenan or CFA was also partially reversed by compound B and PNU-120596. However, diclofenac...

  8. Effects of target-controlled infusion of high-dose naloxone on pain and hyperalgesia in a human thermal injury model

    DEFF Research Database (Denmark)

    Springborg, Anders D; Jensen, Elisabeth K; Taylor, Bradley K

    2016-01-01

    injury has demonstrated reinstatement of nociceptive hypersensitivity indicating unmasking of latent sensitization. In a recent human study, pain hypersensitivity assessed as secondary hyperalgesia area (SHA), was reinstated 7 days after a mild thermal injury, in 4 out of 12 subjects after a naloxone...... infusion.The aims of the present study are first, to replicate our previous findings in a larger-sized study; second, to examine if high sensitizers (subjects presenting with large SHA after a thermal injury) develop a higher degree of hypersensitivity after naloxone challenge than low sensitizers...... and secondary hyperalgesia areas (days 1-4).The naloxone-induced unmasking of latent sensitization is an interesting model for exploring the transition from acute to chronic pain. The results from the present study may provide valuable information regarding future research in persistent postsurgical pain states....

  9. Sex Differences in Serotonin 1 Receptor Binding in Rat Brain

    Science.gov (United States)

    Fischette, Christine T.; Biegon, Anat; McEwen, Bruce S.

    1983-10-01

    Male and female rats exhibit sex differences in binding by serotonin 1 receptors in discrete areas of the brain, some of which have been implicated in the control of ovulation and of gonadotropin release. The sex-specific changes in binding, which occur in response to the same hormonal (estrogenic) stimulus, are due to changes in the number of binding sites. Castration alone also affects the number of binding sites in certain areas. The results lead to the conclusion that peripheral hormones modulate binding by serotonin 1 receptors. The status of the serotonin receptor system may affect the reproductive capacity of an organism and may be related to sex-linked emotional disturbances in humans.

  10. Serotonin, ATRX, and DAXX Expression in Pituitary Adenomas

    DEFF Research Database (Denmark)

    Casar-Borota, Olivera; Botling, Johan; Granberg, Dan

    2017-01-01

    Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker...... in the NETs, has not been systematically evaluated in pituitary NETs. Although mutations in ATRX or DAXX have been reported in a significant proportion of pancreatic NETs, the mutational status of ATRX and DAXX and their possible pathogenetic role in pituitary NETs are unknown. Facing a difficult diagnostic...... case of an invasive serotonin and adrenocorticotroph hormone immunoreactive NET in the sellar region, we explored the immunohistochemical expression of serotonin, ATRX, and DAXX in a large series of pituitary endocrine tumors of different types from 246 patients and in 2 corticotroph carcinomas. None...

  11. Protonated serotonin: Geometry, electronic structures and photophysical properties

    Science.gov (United States)

    Omidyan, Reza; Amanollahi, Zohreh; Azimi, Gholamhassan

    2017-07-01

    The geometry and electronic structures of protonated serotonin have been investigated by the aim of MP2 and CC2 methods. The relative stabilities, transition energies and geometry of sixteen different protonated isomers of serotonin have been presented. It has been predicted that protonation does not exhibit essential alteration on the S1 ← S0 electronic transition energy of serotonin. Instead, more complicated photophysical nature in respect to its neutral analogue is suggested for protonated system owing to radiative and non-radiative deactivation pathways. In addition to hydrogen detachment (HD), hydrogen/proton transfer (H/PT) processes from ammonium to indole ring along the NH+⋯ π hydrogen bond have been predicted as the most important photophysical consequences of SERH+ at S1 excited state. The PT processes is suggested to be responsible for fluorescence of SERH+ while the HD driving coordinate is proposed for elucidation of its nonradiative deactivation mechanism.

  12. Effects of ageing on serotonin transporters in healthy females

    Energy Technology Data Exchange (ETDEWEB)

    Kuikka, J.T. [Dept. of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital (Finland); Dept. of Forensic Psychiatry, University of Kuopio and Niuvanniemi Hospital, Kuopio (Finland); Tammela, L.; Karhunen, L.; Uusitupa, M. [Dept. of Clinical Nutrition, University of Kuopio and Kuopio University Hospital, Kuopio (Finland); Bergstroem, K.A. [Dept. of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital (Finland); Tiihonen, J. [Dept. of Forensic Psychiatry, University of Kuopio and Niuvanniemi Hospital, Kuopio (Finland)

    2001-07-01

    The effect of ageing on brain serotonin transporters was evaluated in 19 healthy female volunteers (age range 22-74 years) using single-photon emission tomography and [{sup 123}I] nor-{beta}-CIT. The study subjects were scanned 0.3, 3, 6 and 23 h after injection of 185 MBq of [{sup 123}I] nor-{beta}-CIT. The ratio of the distribution volume for tracer in the midbrain to that in the cerebellum minus 1 was used as an index for serotonin transporter binding. An age-related decline of 2% per decade (r=-0.47; P<0.05) was found in the midbrain. The decline in [{sup 123}I] nor-{beta}-CIT binding in the serotonin transporter-rich area is much less than that in dopamine transporters in the striatum (6% per decade). (orig.)

  13. Mechanism of Paroxetine (Paxil) Inhibition of the Serotonin Transporter.

    Science.gov (United States)

    Davis, Bruce A; Nagarajan, Anu; Forrest, Lucy R; Singh, Satinder K

    2016-04-01

    The serotonin transporter (SERT) is an integral membrane protein that exploits preexisting sodium-, chloride-, and potassium ion gradients to catalyze the thermodynamically unfavorable movement of synaptic serotonin into the presynaptic neuron. SERT has garnered significant clinical attention partly because it is the target of multiple psychoactive agents, including the antidepressant paroxetine (Paxil), the most potent selective serotonin reuptake inhibitor known. However, the binding site and orientation of paroxetine in SERT remain controversial. To provide molecular insight, we constructed SERT homology models based on the Drosophila melanogaster dopamine transporter and docked paroxetine to these models. We tested the predicted binding configurations with a combination of radioligand binding and flux assays on wild-type and mutant SERTs. Our data suggest that the orientation of paroxetine, specifically its fluorophenyl ring, in SERT's substrate binding site directly depends on this pocket's charge distribution, and thereby provide an avenue toward understanding and enhancing high-affinity antidepressant activity.

  14. Estradiol upregulates voltage-gated sodium channel 1.7 in trigeminal ganglion contributing to hyperalgesia of inflamed TMJ

    Science.gov (United States)

    Bi, Rui-Yun; Meng, Zhen; Zhang, Peng; Wang, Xue-Dong

    2017-01-01

    Background Temporomandibular disorders (TMDs) have the highest prevalence in women of reproductive age. The role of estrogen in TMDs and especially in TMDs related pain is not fully elucidated. Voltage-gated sodium channel 1.7 (Nav1.7) plays a prominent role in pain perception and Nav1.7 in trigeminal ganglion (TG) is involved in the hyperalgesia of inflamed Temporomandibular joint (TMJ). Whether estrogen could upregulate trigeminal ganglionic Nav1.7 expression to enhance hyperalgesia of inflamed TMJ remains to be explored. Methods Estrous cycle and plasma levels of 17β-estradiol in female rats were evaluated with vaginal smear and enzyme linked immunosorbent assay, respectively. Female rats were ovariectomized and treated with 17β-estradiol at 0 μg, 20 μg and 80 μg, respectively, for 10 days. TMJ inflammation was induced using complete Freund’s adjuvant. Head withdrawal thresholds and food intake were measured to evaluate the TMJ nociceptive responses. The expression of Nav1.7 in TG was examined using real-time PCR and western blot. The activity of Nav1.7 promoter was examined using luciferase reporter assay. The locations of estrogen receptors (ERα and ERβ), the G protein coupled estrogen receptor (GPR30), and Nav1.7 in TG were examined using immunohistofluorescence. Results Upregulation of Nav1.7 in TG and decrease in head withdrawal threshold were observed with the highest plasma 17β-estradiol in the proestrus of female rats. Ovariectomized rats treated with 80 μg 17β-estradiol showed upregulation of Nav1.7 in TG and decrease in head withdrawal threshold as compared with that of the control or ovariectomized rats treated with 0 μg or 20 μg. Moreover, 17β-estradiol dose-dependently potentiated TMJ inflammation-induced upregulation of Nav1.7 in TG and also enhanced TMJ inflammation-induced decrease of head withdrawal threshold in ovariectomized rats. In addition, the estrogen receptor antagonist, ICI 182,780, partially blocked the 17

  15. The Relation between Visceral and Subcutaneous Fat to Bone Mass among Egyptian Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Sahar A. El-Masry

    2014-12-01

    CONCLUSIONS: Visceral and subcutaneous fat had significant positive association with bone mass in children; males and females respectively. On the contrary such association disappeared during adolescence.

  16. Visceral and subcutaneous fat have different origins and evidence supports a mesothelial source.

    Science.gov (United States)

    Chau, You-Ying; Bandiera, Roberto; Serrels, Alan; Martínez-Estrada, Ofelia M; Qing, Wei; Lee, Martin; Slight, Joan; Thornburn, Anna; Berry, Rachel; McHaffie, Sophie; Stimson, Roland H; Walker, Brian R; Chapuli, Ramon Muñoz; Schedl, Andreas; Hastie, Nick

    2014-04-01

    Fuelled by the obesity epidemic, there is considerable interest in the developmental origins of white adipose tissue (WAT) and the stem and progenitor cells from which it arises. Whereas increased visceral fat mass is associated with metabolic dysfunction, increased subcutaneous WAT is protective. There are six visceral fat depots: perirenal, gonadal, epicardial, retroperitoneal, omental and mesenteric, and it is a subject of much debate whether these have a common developmental origin and whether this differs from that for subcutaneous WAT. Here we show that all six visceral WAT depots receive a significant contribution from cells expressing Wt1 late in gestation. Conversely, no subcutaneous WAT or brown adipose tissue arises from Wt1-expressing cells. Postnatally, a subset of visceral WAT continues to arise from Wt1-expressing cells, consistent with the finding that Wt1 marks a proportion of cell populations enriched in WAT progenitors. We show that all visceral fat depots have a mesothelial layer like the visceral organs with which they are associated, and provide several lines of evidence that Wt1-expressing mesothelium can produce adipocytes. These results reveal a major ontogenetic difference between visceral and subcutaneous WAT, and pinpoint the lateral plate mesoderm as a major source of visceral WAT. They also support the notion that visceral WAT progenitors are heterogeneous, and suggest that mesothelium is a source of adipocytes.

  17. Altered Insula Activity during Visceral Interoception in Weight-Restored Patients with Anorexia Nervosa

    National Research Council Canada - National Science Library

    Kerr, Kara L; Moseman, Scott E; Avery, Jason A; Bodurka, Jerzy; Zucker, Nancy L; Simmons, W Kyle

    2016-01-01

    .... Aberrant visceral interoceptive processing within the insula has been hypothesized to be an important mechanism in AN's pathophysiology due to the theoretical link between interoception and emotional experience...

  18. Transient Serotonin Toxicity Evoked by Combination of Electroconvulsive Therapy and Fluoxetine

    DEFF Research Database (Denmark)

    Klysner, René; Bjerg Bendsen, Birgitte; Hansen, Maja Soon

    2014-01-01

    The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine.......The serotonin syndrome has been described only in rare instances for electroconvulsive therapy combined with an antidepressant medication. We describe a case of serotonin toxicity induced by electroconvulsive therapy in combination with fluoxetine....

  19. Age-related effect of serotonin transporter genotype on amygdala and prefrontal cortex function in adolescence

    OpenAIRE

    Wiggins, Jillian Lee; Bedoyan, Jirair K.; Carrasco, Melisa; Swartz, Johnna R.; Martin, Donna M.; Monk, Christopher S.

    2012-01-01

    The S and LG alleles of the serotonin transporter-linked polymorphic region (5-HTTLPR) lower serotonin transporter expression. These low expressing alleles are linked to increased risk for depression and brain activation patterns found in depression (increased amygdala activation and decreased amygdala-prefrontal cortex connectivity). Paradoxically, serotonin transporter blockade relieves depression symptoms. Rodent models suggest that decreased serotonin transporter in early life produces de...

  20. [Serotonin dysfunctions in the background of the seven deadly sins].

    Science.gov (United States)

    Janka, Zoltán

    2003-11-20

    The symbolic characters of the Seven Deadly Sins can be traced from time to time in the cultural history of human mankind, being directly specified in certain artistic products. Such are, among others, the painting entitled "The Seven Deadly Sins and the Four Lost Things" by Hieronymus Bosch and the poems Divina Commedia and The Foerie Queene by Dante Alighieri and Edmund Spenser, respectively. However, there are several paragraphs referring to these behaviours of the Seven Deadly Sins in the Bible and in the dramas of William Shakespeare. The objective of the present review is to propose that dysfunctions in the central serotonergic system might be involved in the neurobiology of these 'sinful' behaviour patterns. Evidences indicate that behaviour traits such as Accidia (Sloth), Luxuria (Lust, Lechery), Superbia (Pride), Ira (Wrath, Anger), Invidia (Envy), Avaritia (Greed, Avarice), and Gula (Gluttony) can relate to the functional alterations of serotonin in the brain. Results of biochemical and molecular genetic (polymorphism) studies on the human serotonergic system (receptor, transporter, enzyme), findings of functional imaging techniques, effects of depletion (or supplementation) of the serotonin precursor tryptophan, data of challenge probe investigations directed to testing central serotonergic functions, alterations in the peripheral serotonin measures (platelet), and the changes in the CSF 5-hydroxy-indoleacetic acid content indicate such serotonergic involvement. Furthermore, results of animal experiments on behaviour change (aggressive, dominant or submissive, appetite, alcohol preference) attributed to serotonin status modification and the clinically evidenced therapeutic efficacy of pharmacological interventions, based on the modulation and perturbation of the serotonergic system (e.g. selective serotonin reuptake inhibitors), in treating the 'sinful' behaviour forms and analogous pathological states reaching the severity of psychiatric disorders

  1. The dorsomedial hypothalamus mediates stress-induced hyperalgesia and is the source of the pronociceptive peptide cholecystokinin in the rostral ventromedial medulla.

    Science.gov (United States)

    Wagner, K M; Roeder, Z; Desrochers, K; Buhler, A V; Heinricher, M M; Cleary, D R

    2013-05-15

    While intense or highly arousing stressors have long been known to suppress pain, relatively mild or chronic stress can enhance pain. The mechanisms underlying stress-induced hyperalgesia (SIH) are only now being defined. The physiological and neuroendocrine effects of mild stress are mediated by the dorsomedial hypothalamus (DMH), which has documented connections with the rostral ventromedial medulla (RVM), a brainstem region capable of facilitating nociception. We hypothesized that stress engages both the DMH and the RVM to produce hyperalgesia. Direct pharmacological activation of the DMH increased sensitivity to mechanical stimulation in awake animals, confirming that the DMH can mediate behavioral hyperalgesia. A behavioral model of mild stress also produced mechanical hyperalgesia, which was blocked by inactivation of either the DMH or the RVM. The neuropeptide cholecystokinin (CCK) acts in the RVM to enhance nociception and is abundant in the DMH. Using a retrograde tracer and immunohistochemical labeling, we determined that CCK-expressing neurons in the DMH are the only significant supraspinal source of CCK in the RVM. However, not all neurons projecting from the DMH to the RVM contained CCK, and microinjection of the CCK2 receptor antagonist YM022 in the RVM did not interfere with SIH, suggesting that transmitters in addition to CCK play a significant role in this connection during acute stress. While the RVM has a well-established role in facilitation of nociception, the DMH, with its well-documented role in stress, may also be engaged in a number of chronic or abnormal pain states. Taken as a whole, these findings establish an anatomical and functional connection between the DMH and RVM by which stress can facilitate pain. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Repeated forced swim stress enhances CFA-evoked thermal hyperalgesia and affects the expressions of pCREB and c-Fos in the insular cortex.

    Science.gov (United States)

    Imbe, H; Kimura, A; Donishi, T; Kaneoke, Y

    2014-02-14

    Stress affects brain activity and promotes long-term changes in multiple neural systems. Exposure to stressors causes substantial effects on the perception and response to pain. In several animal models, chronic stress produces lasting hyperalgesia. The insular (IC) and anterior cingulate cortices (ACC) are the regions exhibiting most reliable pain-related activity. And the IC and ACC play an important role in pain modulation via the descending pain modulatory system. In the present study we examined the expression of phospho-cAMP response element-binding protein (pCREB) and c-Fos in the IC and ACC after forced swim stress (FS) and complete Freund's adjuvant (CFA) injection to clarify changes in the cerebral cortices that affect the activity of the descending pain modulatory system in the rats with stress-induced hyperalgesia. FS (day 1, 10min; days 2-3, 20min) induced an increase in the expression of pCREB and c-Fos in the anterior IC (AIC). CFA injection into the hindpaw after the FS shows significantly enhanced thermal hyperalgesia and induced a decrease in the expression of c-Fos in the AIC and the posterior IC (PIC). Quantitative image analysis showed that the numbers of c-Fos-immunoreactive neurons in the left AIC and PIC were significantly lower in the FS+CFA group (L AIC, 95.9±6.8; L PIC, 181.9±23.1) than those in the naive group (L AIC, 151.1±19.3, pCFA-induced thermal hyperalgesia through dysfunction of the descending pain modulatory system. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Co-induction of cyclooxyenase-2 and early growth response gene (Egr-1 in spinal cord in a clinical model of persistent inflammation and hyperalgesia

    Directory of Open Access Journals (Sweden)

    Dolan Sharron

    2011-11-01

    Full Text Available Abstract Background This study characterised the effects of persistent peripheral inflammation of the foot on pain and spinal cord expression of cyclooxygenase-1 and -2 (COX-1 and COX-2 and early growth response gene 1 (Egr-1, known markers of neuronal plasticity, in a clinical model of naturally-occurring inflammatory disease and hyperalgesia in sheep ('footrot', before and after routine treatment (parenteral treatment with antibiotics and antiseptic footbathing. The temporal pattern of expression of COX-1, COX-2 and Egr-1 mRNA and protein were analysed using real-time PCR and Western blotting. Results Animals affected with persistent peripheral inflammation displayed significant hyperalgesia and lameness (a proxy indicator of spontaneous pain restricted to the inflamed limb. Hyperalgesia and lameness were significantly attenuated 1 day after treatment, and resolved further by day 7 and day 3, respectively. COX-2 but not COX-1, protein expression was up-regulated in spinal cord from lame animals on day 0, before treatment. Following treatment and attenuation of pain behaviours, levels of COX-2 returned to control levels. Significant induction of Egr-1 mRNA and protein were observed in spinal cord from lame animals. Three days after treatment, levels of Egr-1 mRNA returned to control levels, however, Egr-1 protein remained elevated. Conclusion Elevated levels of spinal COX-2 and Egr-1 protein correlate with the presence of pain and hyperalgesia, and may underlie persistent pain, although a direct causal link has still to be established. Understanding the temporal pattern of expression of key mediators in clinical pain states may lead to better strategies to manage pain.

  4. Contralateral Hyperalgesia from Injection of Endothelin-1 into the Ipsilateral Paw Requires Efferent Conduction into the Contralateral Paw.

    Science.gov (United States)

    Strichartz, Gary R; Khodorova, Alla; Wang, Jeffrey Chi-Fei; Chen, Yu-Wen; Huang, Chuan-Chin

    2015-10-01

    Contralateral hyperalgesia, occurring after unilateral injury, is usually explained by central sensitization in spinal cord and brain. We previously reported that injection of endothelin-1 (ET-1) into one rat hindpaw induces prolonged mechanical and chemical sensitization of the contralateral hindpaw. Here, we examined the role of contralateral efferent activity in this process. ET-1 (2 nmol, 10 μL) was injected subcutaneously into the plantar surface of right (ipsilateral) hindpaw (ILP), and the thermal response latency and mechanical threshold for nocifensive withdrawal were determined by the use of, respectively, plantar radiant heating and von Frey filaments, for both ILP and contralateral hindpaws (CLP). Either paw was anesthetized for 60 minutes by direct injection of bupivacaine (0.25%, 40 μL), 30 minutes before ET-1. Alternatively, the contralateral sciatic nerve was blocked for 6 to 12 hours by percutaneous injection of bupivacaine-releasing microspheres 30 minutes before injection of ET-1. Systemic actions of these bupivacaine formulations were simulated by subcutaneous injection at the nuchal midline. After the injection of ET-1, the mechanical threshold of both ILP and CLP decreased by 2 hours, appeared to be lowest around 24 hours, and recovered through 48 hours to preinjection baseline at 72 hours. These hypersensitive responses were suppressed by bupivacaine injected into the ipsilateral paw before ET-1. Injection of the CLP by bupivacaine also suppressed the hypersensitivity of the CLP at all test times, and that of the ILP, except at 2 hours when it increased the sensitivity. This same pattern of change occurred when the contralateral sciatic nerve was blocked by bupivacaine-releasing microspheres. The systemic actions of these bupivacaine formulations were much smaller and only reached significance at 24 hours post-ET-1. Thermal hypersensitivity after ET-1 injection also occurred in both ILP and CLP and showed the same pattern in response to the

  5. Both synthesis and reuptake are critical for replenishing the releasable serotonin pool in Drosophila

    Science.gov (United States)

    Borue, Xenia; Condron, Barry; Venton, B. Jill

    2010-01-01

    The two main sources of serotonin available for release are expected to be newly synthesized serotonin and serotonin recycled after reuptake by the serotonin transporter (SERT). However, their relative importance for maintaining release and the time course of regulation are unknown. We studied serotonin signaling in the ventral nerve cord of the larval Drosophila central nervous system. Fast-scan cyclic voltammetry at implanted microelectrodes was used to detect serotonin elicited by channelrhodopsin2-mediated depolarization. The effects of reuptake were probed by incubating in cocaine, which is selective for the serotonin transporter in Drosophila. p-chlorophenylalanine (PCPA), an inhibitor of tryptophan hydroxylase2, was used to investigate the effects of synthesis. Stimulations were repeated at various intervals to assess the time course of recovery of the releasable pool. Reuptake is important for the rapid replenishment of the releasable pool, on the 1 minute time scale. Synthesis is critical to the longer-term replenishment (10 min) of the releasable pool, especially when reuptake is also inhibited. Concurrent synthesis and reuptake inhibition decreased both serotonin tissue content measured by immunohistochemistry (by 50%) and the initial amount of evoked serotonin (by 65%). Decreases in evoked serotonin are rescued by inhibiting action potential propagation with tetrodotoxin, implicating endogenous activity in the depletion. These results show synthesis is necessary to replenish part of the releasable serotonin pool that is depleted after reuptake inhibition, suggesting that regulation of synthesis may modulate the effects of serotonin reuptake inhibitors. PMID:20070864

  6. Coaction of Stress and Serotonin Transporter Genotype in Predicting Aggression at the Transition to Adulthood

    Science.gov (United States)

    Conway, Christopher C.; Keenan-Miller, Danielle; Hammen, Constance; Lind, Penelope A.; Najman, Jake M.; Brennan, Patricia A.

    2012-01-01

    Despite consistent evidence that serotonin functioning affects stress reactivity and vulnerability to aggression, research on serotonin gene-stress interactions (G x E) in the development of aggression remains limited. The present study investigated variation in the promoter region of the serotonin transporter gene (5-HTTLPR) as a moderator of the…

  7. Serum serotonin concentration associated with bone mineral density in Chinese postmenopausal women.

    Science.gov (United States)

    Wei, Qiu-Shi; Chen, Zhen-Qiu; Tan, Xin; Kang, Lu-Chen; Jiang, Xiao-Bing; Liang, Jiang; He, Wei; Deng, Wei-Min

    2017-02-01

    Recent studies have shown that circulating serotonin plays a potential role in bone metabolism. However, conflicting results have been reported for the relationship between serum serotonin concentrations and bone mineral density (BMD). We investigated whether the serum serotonin concentrations related to BMD in Chinese postmenopausal women. Serum serotonin and bone turnover concentrations of 117 premenopausal women and 262 asymptomatic postmenopausal women were analyzed by enzyme-linked immunosorbent assay. BMD at the lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry. The relationship between serotonin and BMD was investigated. The postmenopausal women had lower mean serum serotonin concentrations compared to the premenopausal women. Serotonin concentrations were negatively associated with age, weight, BMI, fat mass, and β-CTX concentrations in postmenopausal women. No significant correlations were found between serotonin and these parameters in premenopausal women. In postmenopausal women, age- and BMI-adjusted serotonin concentrations were positively correlated with BMD of the lumbar spine and femoral neck. Multiple regression analyses showed serum serotonin and β-CTX were the predictors for lumbar spine BMD. Only serum serotonin was the determinant for femoral neck BMD. In conclusion, lower serum serotonin concentrations are linked to low lumbar spine and femoral neck BMD in postmenopausal women.

  8. 21 CFR 862.1390 - 5-Hydroxyindole acetic acid/serotonin test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false 5-Hydroxyindole acetic acid/serotonin test system... Test Systems § 862.1390 5-Hydroxyindole acetic acid/serotonin test system. (a) Identification. A 5-hydroxyindole acetic acid/serotonin test system is a device intended to measure 5-hydroxyindole acetic acid...

  9. Interaction of antidepressants with the serotonin and norepinephrine transporters

    DEFF Research Database (Denmark)

    Sørensen, Lena; Andersen, Jacob; Thomsen, Mette

    2012-01-01

    The serotonin transporter (SERT) and the norepinephrine transporter (NET) are sodium-dependent neurotransmitter transporters responsible for reuptake of released serotonin and norepinephrine, respectively, into nerve terminals in the brain. A wide range of inhibitors of SERT and NET are used...... as treatment of depression and anxiety disorders or as psychostimulant drugs of abuse. Despite their clinical importance, the molecular mechanisms by which various types of antidepressant drugs bind and inhibit SERT and NET are still elusive for the majority of the inhibitors, including the molecular basis...

  10. Functional characterization of serotonin receptor subtypes in human duodenal secretion

    DEFF Research Database (Denmark)

    Engelmann, Bodil Elisabeth; Bindslev, Niels; Poulsen, Steen Seier

    2006-01-01

    Serotonin (5-HT) stimulates ion secretion in the gastrointestinal tract and the sensitivity for 5-HT might be altered in dyspeptic patients infected with Helicobacter pylori. The purpose of the present study was to characterize the 5-HT-induced electrogenic ion transport in the duodenum of dyspep......Serotonin (5-HT) stimulates ion secretion in the gastrointestinal tract and the sensitivity for 5-HT might be altered in dyspeptic patients infected with Helicobacter pylori. The purpose of the present study was to characterize the 5-HT-induced electrogenic ion transport in the duodenum...

  11. Serotonin transporter evolution and impact of polymorphic transcriptional regulation

    DEFF Research Database (Denmark)

    Søeby, Karen; Larsen, Svend Ask; Olsen, Line

    2005-01-01

    The serotonin transporter (SERT) is the primary drug target in the current antidepressant therapy. A functional polymorphism in the 2nd intron of the 5HTT gene encoding the SERT has been identified and associated with susceptibility to affective disorders and treatment response to antidepressants...... in the VNTRs of all mammalian SERT genes. The number of these putative binding sites varies proportionally to the length of the VNTR. We propose that the intronic VNTR have been selectively targeted through mammalian evolution to finetune transcriptional regulation of the serotonin expression....

  12. L-Arginine supplementation prevents allodynia and hyperalgesia in painful diabetic neuropathic rats by normalizing plasma nitric oxide concentration and increasing plasma agmatine concentration.

    Science.gov (United States)

    Rondón, Lusliany J; Farges, M C; Davin, N; Sion, B; Privat, A M; Vasson, M P; Eschalier, A; Courteix, C

    2017-07-19

    Neuropathic pain is a common diabetic complication. It is characterized by symptoms of spontaneous and stimulus-evoked pain including hyperalgesia and allodynia. L-Arginine is a common precursor of many metabolites of biological interest, in particular, nitric oxide (NO), ornithine, and hence polyamines. In central nervous system, NO, glutamate, and polyamines share an N-methyl-D-aspartate (NMDA) receptor-mediated effect. We hypothesized that a variation in arginine metabolism caused by diabetes may contribute to development and maintenance of neuropathic pain and to the worsening of clinical and biological signs of diabetes. We examined whether oral L-arginine supplementation (2.58 ± 0.13 g/l in drinking water for 3 weeks) could improve the development of neuropathic pain and the clinical, biological, and metabolic complications of diabetes in streptozocin (STZ)-induced diabetic (D) rats. STZ administration induced classical symptoms of type 1 diabetes. Diabetic rats also displayed mechanical hypersensitivity, tactile, and thermal allodynia. Plasma citrulline and NO levels were increased in diabetic hyperalgesic/allodynic rats. L-Arginine supplementation failed to reduce hyperglycaemia, polyphagia, and weight loss. Moreover, it abolished hyperalgesia and allodynia by normalizing NO plasma concentration and increasing plasma agmatine concentration. L-Arginine supplementation prevented the development of mechanical hyperalgesia, tactile, and thermal allodynia in painful diabetic neuropathy with concomitant reduction of NO and increased agmatine production, offering new therapeutic opportunities for the management of diabetic neuropathic pain.

  13. Mutations in the Caenorhabditis elegans serotonin reuptake transporter MOD-5 reveal serotonin-dependent and -independent activities of fluoxetine.

    Science.gov (United States)

    Ranganathan, R; Sawin, E R; Trent, C; Horvitz, H R

    2001-08-15

    We isolated two mutants defective in the uptake of exogenous serotonin (5-HT) into the neurosecretory motor neurons of Caenorhabditis elegans. These mutants were hypersensitive to exogenous 5-HT and hyper-responsive in the experience-dependent enhanced slowing response to food modulated by 5-HT. The two allelic mutations defined the gene mod-5 (modulation of locomotion defective), which encodes the only serotonin reuptake transporter (SERT) in C. elegans. The selective serotonin reuptake inhibitor fluoxetine (Prozac) potentiated the enhanced slowing response, and this potentiation required mod-5 function, establishing a 5-HT- and SERT-dependent behavioral effect of fluoxetine in C. elegans. By contrast, other responses of C. elegans to fluoxetine were independent of MOD-5 SERT and 5-HT. Further analysis of the MOD-5-independent behavioral effects of fluoxetine could lead to the identification of novel targets of fluoxetine and could facilitate the development of more specific human pharmaceuticals.

  14. Serotonin, Amygdala and Fear: Assembling the Puzzle.

    Science.gov (United States)

    Bocchio, Marco; McHugh, Stephen B; Bannerman, David M; Sharp, Trevor; Capogna, Marco

    2016-01-01

    The fear circuitry orchestrates defense mechanisms in response to environmental threats. This circuitry is evolutionarily crucial for survival, but its dysregulation is thought to play a major role in the pathophysiology of psychiatric conditions in humans. The amygdala is a key player in the processing of fear. This brain area is prominently modulated by the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). The 5-HT input to the amygdala has drawn particular interest because genetic and pharmacological alterations of the 5-HT transporter (5-HTT) affect amygdala activation in response to emotional stimuli. Nonetheless, the impact of 5-HT on fear processing remains poorly understood.The aim of this review is to elucidate the physiological role of 5-HT in fear learning via its action on the neuronal circuits of the amygdala. Since 5-HT release increases in the basolateral amygdala (BLA) during both fear memory acquisition and expression, we examine whether and how 5-HT neurons encode aversive stimuli and aversive cues. Next, we describe pharmacological and genetic alterations of 5-HT neurotransmission that, in both rodents and humans, lead to altered fear learning. To explore the mechanisms through which 5-HT could modulate conditioned fear, we focus on the rodent BLA. We propose that a circuit-based approach taking into account the localization of specific 5-HT receptors on neurochemically-defined neurons in the BLA may be essential to decipher the role of 5-HT in emotional behavior. In keeping with a 5-HT control of fear learning, we review electrophysiological data suggesting that 5-HT regulates synaptic plasticity, spike synchrony and theta oscillations in the BLA via actions on different subcellular compartments of principal neurons and distinct GABAergic interneuron populations. Finally, we discuss how recently developed optogenetic tools combined with electrophysiological recordings and behavior could progress the knowledge of the mechanisms underlying 5

  15. Serotonin hypothesis and pulmonary artery hypertension

    Directory of Open Access Journals (Sweden)

    Monika Kloza

    2014-06-01

    Full Text Available Tętnicze nadciśnienie płucne jest postępującą chorobą, prowadzącą do niewydolności prawej komory serca i przedwczesnej śmierci. Charakteryzuje się podwyższonym ciśnieniem w tętnicy płucnej, zwiększeniem oporu naczyniowego, przebudową naczyń płucnych oraz dysfunkcją śródbłonka. Patomechanizm tej choroby jest wciąż nieznany. Sugeruje się, że dysfunkcja śródbłonka zaburza równowagę między czynnikami wazodylatacyjnymi a wazokonstrykcyjnymi, w tym np. serotoniną (5-HT. Pierwotnie teorię serotoninową tętniczego nadciśnienia płucnego powiązano z przyjmowaniem leków anoreksygennych, pochodnych fenfluraminy, hamujących wychwyt zwrotny 5-HT. Obecnie potwierdzono zaangażowanie wszystkich składowych układu serotoninergicznego w krążeniu płucnym w tym patomechanizm. W komórkach śródbłonka tętnicy płucnej, hydroksylaza tryptofanu 1 katalizuje reakcję syntezy serotoniny z tryptofanu. 5-HT kurczy naczynia płucne przez pobudzenie receptorów serotoninowych, głównie 5-HT1B i 5-HT2A, a także jest transportowana przez transporter serotoniny (SERT do wnętrza komórki mięśni gładkich tętnicy płucnej, a następnie działając przez kinazę Rho (ROCK lub reaktywne formy tlenu powoduje skurcz naczyń i/lub wzrost aktywacji czynników transkrypcyjnych i proliferację. Potwierdzono interakcję między receptorem 5-HT1B i SERT w modulowaniu skurczu naczyń płucnych i ich proliferacji. W pracy omówiono dowody wpływu 5-HT na rozwój tętniczego nadciśnienia płucnego i możliwe cele terapeutyczne w obrębie układu serotoninergicznego.

  16. Challenging the current paradigm of melanoma progression: brain metastasis as isolated first visceral site

    Science.gov (United States)

    Ma, Michelle W.; Qian, Meng; Lackaye, Daniel J.; Berman, Russell S.; Shapiro, Richard L.; Pavlick, Anna C.; Golfinos, John G.; Parker, Erik C.; Darvishian, Farbod; Hernando, Eva; Shao, Yongzhao; Osman, Iman

    2012-01-01

    Melanoma brain metastasis that develops as the isolated first visceral site challenges the current paradigm of tumor progression in which brain metastasis is regarded as the final stage. Here we test the hypothesis that melanoma patients who develop brain metastasis as the isolated first visceral site have distinct clinicopathological features at the time of primary melanoma diagnosis. Cutaneous melanoma patients enrolled in 2 prospectively collected databases were studied (Cohort 1: 1972–1982, Cohort 2: 2002–2009). Patients who developed brain metastasis as isolated first visceral site were compared with (1) all other patients, (2) patients who developed visceral metastasis: extracranial only or extracranial and brain, and (3) patients who progressed to other isolated visceral sites first. Two hundred seven of 2280 (9.1%) patients developed brain metastasis (median follow–up, 5.2 y). Seventy–four of 207 (35.7%) brain metastasis patients progressed to brain metastasis as the isolated first visceral site. These patients presented with primaries that were thinner and had no mitosis compared with all other visceral metastasis patients (Fisher's combined P = .02, .05, respectively), and there was a significant difference in American Joint Committee on Cancer stage distribution at initial melanoma diagnosis (combined P = .02). Post–visceral metastasis survival, however, was shorter in patients with brain metastasis as isolated first visceral site than in patients with visceral metastasis: extracranial and brain (combined P = .03). Brain metastasis as isolated first visceral site is a distinct clinicopathological entity. Studies are needed to better understand the biological factors driving this phenotype at the time of primary melanoma diagnosis and to determine its clinical implications. PMID:22561799

  17. Development and evaluation of agents for targeting visceral amyloid.

    Science.gov (United States)

    Wall, Jonathan S; Solomon, Alan; Kennel, Stephen J

    2011-12-01

    Wall, JS, Solomon A, Kennel, SJ. Development and evaluation of agents for targeting visceral amyloid. Visceral amyloidosis is a rare disease characterized by the deposition in organs and tissues of protein fibrils, heparan sulfate proteoglycan as well as serum amyloid P component and other serum proteins. Imaging these pathologic deposits aids in the clinical management of patients with amyloidosis. Whole body scintigraphic imaging of amyloid load as well as organ specific anatomic imaging provides information that can inform prognosis and can be used to monitor disease progression or response to therapy. These capabilities are limited in the USA, which has led to our development and evaluation of two new reagents that specifically target amyloid in vivo and have been used to image visceral deposits in mice and patients with AL amyloidosis. The fibril-reactive mAb 11-1F4, when labeled with iodine-124 was shown to bind AL amyloid in patients by using PET/CT imaging. These studies were performed to support the evaluation of this reagent as a novel immunotherapy for AL patients. In addition, we have identified a heparin-binding peptide that co-localizes with murine AA amyloid in vivo and can be used to image the deposits. The interaction of this peptide, designated p5, with amyloid is dependent on the net positive charge and truncated forms that would be more desirable as clinical imaging agents were found to be significantly less efficient for amyloid imaging. The development and positive preclinical validation of these two reagents offers potential new therapeutic and diagnostic tools for patients with these devastating diseases.

  18. Blood pressure and renal injury in dogs with visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Marlos G. Sousa

    Full Text Available Abstract: Systemic hypertension is known to be a common consequence of chronic renal disease, which is frequently diagnosed in dogs with visceral leishmaniasis. Although many veterinary investigations have looked at the renal injury caused by Leishmania spp., the role played by this complication in the development of arterial hypertension documented in some animals with visceral leishmaniasis is not completely understood. In this study, 18 adult dogs with naturally-occurring visceral leishmaniasis and varying clinical signs underwent an indirect blood pressure measurement. Also, sera and spot urine were used for laboratory tests. The median systolic blood pressure was 135.2mmHg (95% confidence interval: 128.5-147.7, median mean arterial pressure was 105.8mmHg (98.3-110.4, and median diastolic arterial pressure was 88.5mmHg (77.8-92.5. No differences existed between asymptomatic and symptomatic animals regarding arterial pressure, and no correlations were documented between blood pressure and serum creatinine, blood urea, urine protein-to-creatinine ratio, urine specific gravity, and the fractional excretion of sodium and potassium. Although an association between hypertension and the identification of inflammation on histopathology could not be demonstrated in hypertensive animals, the assessment of kidney samples from 12 dogs indicated mild inflammation with a lymphoplasmacytic infiltrate (6/12, moderate inflammation with multifocal lymphoplasmacytic and histiocytic infiltrates (3/12, and multifocal degeneration and protein casts (2/12. Anti-Leishmania spp. immunohistochemistry assays stained the renal epithelium in 2/12 of the animals. Even though mild systemic hypertension was documented in a small subset of animals, no relationship between the severity of clinical signs and hypertension could be anticipated.

  19. Visceral Malperfusion in Aortic Dissection: The Michigan Experience.

    Science.gov (United States)

    Kamman, Arnoud V; Yang, Bo; Kim, Karen M; Williams, David M; Michael Deeb, George; Patel, Himanshu J

    2017-01-01

    One of the most dreaded complications of acute aortic dissection is end-organ malperfusion. We summarize current evidence and describe our treatment paradigm in the setting of malperfusion in aortic dissection. Given the difficulty with identifying isolated visceral malperfusion in aortic dissection, both in the literature as well as in our practice, we have broadened the discussion to include data examining the presentation complex of malperfusion, particularly if mesenteric ischemia is identified. The approach to treating malperfusion syndrome is different depending on whether the patient presents with type A dissection vs type B dissection with malperfusion. Although thoracic endovascular aortic repair has emerged as the dominant strategy for resolving malperfusion for complicated type B dissection, fenestration may still have a role in its treatment. In contrast, for type A aortic dissection presenting with visceral malperfusion, the concept of operative repair after restoration of end-organ perfusion has been proposed with increasing frequency in recent reports. At the University of Michigan, we apply a patient-specific algorithm, based on the presence of malperfusion with end-organ dysfunction. In those patients presenting with visceral malperfusion, we prefer to first fenestrate, await resolution of the malperfusion syndrome and then perform central aortic repair. We recognize that other groups have implemented similar algorithms to reduce the dismal results of operative procedures in this cohort. However, the most appropriate period of delay remains unknown and there is a persistent risk of rupture before repair is performed. Future studies should be performed to determine whether these various treatment paradigms have merit. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible?

    Directory of Open Access Journals (Sweden)

    Leslie Shanks

    Full Text Available Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals.Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367 in the VL group compared to 7.9% (200/2526 in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively.The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study.

  1. Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible?

    Science.gov (United States)

    Shanks, Leslie; Ritmeijer, Koert; Piriou, Erwan; Siddiqui, M Ruby; Kliescikova, Jarmila; Pearce, Neil; Ariti, Cono; Muluneh, Libsework; Masiga, Johnson; Abebe, Almaz

    2015-01-01

    Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL) infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals. Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs) was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367) in the VL group compared to 7.9% (200/2526) in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively). The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study.

  2. Serotonin modifies corticotropin-releasing factor-induced behaviors of chicks.

    Science.gov (United States)

    Zhang, Rong; Tachibana, Tetsuya; Takagi, Tomo; Koutoku, Tomoyuki; Denbow, D Michael; Furuse, Mitsuhiro

    2004-05-05

    Glucagon-like peptide-1 (GLP-1) decreased corticotropin-releasing factor (CRF)-induced behaviors in neonatal chicks, and serotonin is one of the possible mechanisms through which GLP-1 affects CRF-induced behaviors. The present experiments were conducted to confirm the effect of serotonin on CRF-induced behaviors. In Experiment 1, chicks were intracerebroventricularly injected with either saline, 0.1 microg of CRF, 5.0 microg of serotonin, or 0.1 microg of CRF plus 5.0 microg of serotonin. Injection of CRF caused excitation as evidenced by increased spontaneous activities and distress vocalizations (DVs) compared to the control group. The effect of CRF was attenuated by serotonin since chicks became quiet after given CRF with serotonin. Sleep-like behaviors were observed in the serotonin group. The number of defecations was increased by CRF and decreased by serotonin. Both CRF and serotonin increased plasma corticosterone, and the effect was synergistic. Serotonin dose-dependently decreased locomotor activities of chicks after central administration of 0.1 microg of CRF, 0.1 microg of CRF plus 2.5, 5.0, or 10.0 microg of serotonin in Experiment 2. CRF-induced DVs were modified by serotonin. Instead of DVs, tender and low-pitched vocalizations were observed in chicks treated with CRF plus serotonin, the voice frequencies of which were less than 10 kHz. In conclusion, serotonin attenuated the CRF-induced behaviors while stimulating corticosterone release. These results indicate that the role of serotonin is dependent on the behaviors being measured. Copyright 2003 Elsevier B.V.

  3. Electroacupuncture Inhibition of Hyperalgesia in Rats with Adjuvant Arthritis: Involvement of Cannabinoid Receptor 1 and Dopamine Receptor Subtypes in Striatum

    Directory of Open Access Journals (Sweden)

    Yin Shou

    2013-01-01

    Full Text Available Electroacupuncture (EA has been regarded as an alternative treatment for inflammatory pain for several decades. However, the molecular mechanisms underlying the antinociceptive effect of EA have not been thoroughly clarified. Previous studies have shown that cannabinoid CB1 receptors are related to pain relief. Accumulating evidence has shown that the CB1 and dopamine systems sometimes interact and may operate synergistically in rat striatum. To our knowledge, dopamine D1/D2 receptors are involved in EA analgesia. In this study, we found that repeated EA at Zusanli (ST36 and Kunlun (BL60 acupoints resulted in marked improvements in thermal hyperalgesia. Both western blot assays and FQ-PCR analysis results showed that the levels of CB1 expression in the repeated-EA group were much higher than those in any other group (P=0.001. The CB1-selective antagonist AM251 inhibited the effects of repeated EA by attenuating the increases in CB1 expression. The two kinds of dopamine receptors imparted different actions on the EA-induced CB1 upregulation in AA rat model. These results suggested that the strong activation of the CB1 receptor after repeated EA resulted in the concomitant phenomenon of the upregulation of D1 and D2 levels of gene expression.

  4. Reactive Oxygen Species Donors Increase the Responsiveness of Dorsal Horn Neurons and Induce Mechanical Hyperalgesia in Rats

    Directory of Open Access Journals (Sweden)

    Hee Young Kim

    2015-01-01

    Full Text Available Our previous studies suggest that reactive oxygen species (ROS scavengers have analgesic effect on neuropathic pain through spinal mechanisms in the rat. The studies suggest that superoxide in spinal cord is one of important mediators of persistent pain. To test the hypothesis that increase of superoxide-derived intermediates leads to central sensitization and pain, the effects of an intrathecal injection of chemical ROS donors releasing either OH∙, OCl-, or H2O2 were examined on pain behaviors. Following treatment with t-BOOH (OH∙ donor, dorsal horn neuron responses to mechanical stimuli in normal rats and the changes of neuronal excitability were explored on substantia gelatinosa (SG neurons using whole-cell patch clamping recordings. Intrathecal administration of t-BOOH or NaOCl (OCl- donor, but not H2O2, significantly decreased mechanical thresholds of hind paws. The responses of wide dynamic range neurons to mechanical stimuli increased after a local application of t-BOOH. The t-BOOH increased the frequency and the amplitude of excitatory postsynaptic potentials, depolarized membrane potential in SG neurons, and increased the frequency of action potentials evoked by depolarizing current pulses. These results suggest that elevated ROS, especially OH∙, in the spinal cord sensitized dorsal horn neurons and produced hyperalgesia in normal rats.

  5. Transcutaneous Electrical Nerve Stimulation (TENS) reduces pain, fatigue, and hyperalgesia while restoring central inhibition in primary fibromyalgia

    Science.gov (United States)

    Dailey, Dana L; Rakel, Barbara A; Vance, Carol GT; Liebano, Richard E; Anand, Amrit S; Bush, Heather M; Lee, Kyoung S; Lee, Jennifer E; Sluka, Kathleen A

    2014-01-01

    Because TENS works by reducing central excitability and activating central inhibition pathways, we tested the hypothesis that TENS would reduce pain and fatigue and improve function and hyperalgesia in people with fibromyalgia who have enhanced central excitability and reduced inhibition. The current study used a double-blinded randomized, placebo controlled cross-over design to test effects of a single treatment of TENS in people with fibromyalgia. Three treatments were assessed in random order: active TENS, placebo TENS, no TENS. The following measures were assessed before and after each TENS treatment: pain and fatigue at rest and movement, pressure pain thresholds (PPTs), 6 minute walk test (6MWT), range of motion (ROM), five time sit to stand test (FTSTS), and single leg stance (SLS). Conditioned pain modulation (CPM) was completed at end of testing. There was a significant decrease in pain and fatigue with movement for active TENS compared to placebo and no TENS. PPTs increased at site of TENS (spine) and outside site of TENS (leg) when compared to placebo TENS or no TENS. During Active TENS CPM was significantly stronger compared to placebo TENS and no TENS. No changes in functional tasks were observed with TENS. Thus, the current study suggests TENS has short-term efficacy in relieving symptoms of fibromyalgia while the stimulator is active. Future clinical trials should examine the effects of repeated daily delivery of TENS, similar to how TENS is used clinically, on pain, fatigue, function and quality of life in individuals with fibromyalgia. PMID:23900134

  6. Alloxan-induced diabetic thermal hyperalgesia, prophylaxis and phytotherapeutic effects of Rheum ribes L. in mouse model.

    Science.gov (United States)

    Raafat, Karim; Aboul-Ela, Maha; El-Lakany, Abdalla

    2014-03-26

    Rheum ribes L., known as Syrian rhubarb, is used in traditional Lebanese folk medicine for the treatment of diabetes. The present study aims to investigate the activities of R. ribes aqueous extract for glucose homeostasis, in vivo antioxidant and diabetic neuropathy protection in mice. The acute and the subacute effects of various doses of R. ribes on blood glucose and in vivo antioxidant activity utilizing serum catalase level (CAT) were studied in alloxan-diabetic mice. The high doses significantly lowered glucose level and increased serum CAT in alloxan-diabetic mice. Pretreatment with the extract prior to alloxination, protected the mice from acquiring diabetes and diabetic neuropathy. Treatment with the extract for 8 weeks alleviated hyperalgesia in diabetic mice. Our findings provide clinicians with promising drugs intended for the management of the symptoms of diabetic complications. The protective activity of R. ribes against acquiring diabetes and diabetic neuropathy might pave the way for preparing a prophylactic treatment for diabetes risk groups.

  7. Visceral leishmaniasis and leishmaniasis-HIV coinfection: comparative study

    Directory of Open Access Journals (Sweden)

    João Victor Soares Coriolano Coutinho

    Full Text Available Abstract INTRODUCTION: This study aimed to draw clinical and epidemiological comparisons between visceral leishmaniasis (VL and VL associated with human immunodeficiency virus (HIV infection. METHOD: Retrospective study. RESULTS: Of 473 cases of VL, 5.5% were coinfected with HIV. The highest proportion of cases of both VL and VL/HIV were found among men. A higher proportion of VL cases was seen in children aged 0-10 years, whereas coinfection was more common in those aged 18-50 years. CONCLUSIONS: VL/HIV coinfected patients presented slightly differently to and had a higher mortality rate than those with VL only.

  8. Visceral leishmaniasis: immunology and prospects for a vaccine.

    Science.gov (United States)

    Kaye, P M; Aebischer, T

    2011-10-01

    Human visceral leishmaniasis (HVL) is the most severe clinical form of a spectrum of neglected tropical diseases caused by protozoan parasites of the genus Leishmania. Caused mainly by L. donovani and L. infantum/chagasi, HVL accounts for more than 50 000 deaths every year. Drug therapy is available but costly, and resistance against several drug classes has evolved. Here, we review our current understanding of the immunology of HVL and approaches to and the status of vaccine development against this disease. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

  9. Trace elements in sera from patients with visceral leishmaniasis

    Energy Technology Data Exchange (ETDEWEB)

    Mukhopadhyay, R.; Bhattacharya, A. [Department of Zoology, Calcutta University, Calcutta (India); Chakraborty, A.; Sudarshan, M.; Jal, P.K.; Chintalapudi, S.N. [Inter University Consortium for DAE Facilities, Calcutta Centre 3/LB-8, Bidhan Nagar, Calcutta (India); Dutta, R.K. [Schonland Research Centre for Nuclear Sciences, University of Witwatersrand, Johannesburg (South Africa)

    2000-07-01

    Trace elements are known to have pivotal role in human health and disease. Present investigation employed PIXE analysis to probe into the elemental profile of patients suffering from visceral Leishmaniasis. Remarkable alternations were observed in concentration of elements like Cl, K, Ca, Mn, Fe, Cu, Zn. The pattern of enhancement of elemental concentration corresponds to the progression of the disease. Additionally, our present data reflect probable correlation between alteration in trace elemental status and other pathological syndromes associated with Leishmaniasis. The possibility of considering trace elements as a diagnostic marker for a better understanding of the disease is discussed. (author)

  10. Longitudinal variance of visceral fat thickness in pregnant adolescents.

    Science.gov (United States)

    Dutra, Luciana P; Cisneiros, Rosangela M; Souza, Alex S; Diniz, Carolina P; Moura, Laís A; Figueiroa, Jose N; Alves, João G B

    2014-02-01

    This study aims to investigate the longitudinal change in visceral fat thickness (VFT) during normal pregnancy. A prospective cohort study with 75 primiparous adolescents was carried out in Petrolina, Brazil. VFT was evaluated by ultrasound between 12-20 weeks gestation and immediately after delivery. We noted a statistically significant increase in VFT; 1.3 cm ± 1.0. No correlation was found between VFT and maternal anthropometric variables. VFT increases about 30% from the first to the second half of pregnancy in primiparous adolescents. © 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  11. CXCL13 regulates the trafficking of GluN2B-containing NMDA receptor via IL-17 in the development of remifentanil-induced hyperalgesia in rats.

    Science.gov (United States)

    Zhu, M; Yuan, S T; Yu, W L; Jia, L L; Sun, Y

    2017-05-01

    This study aimed to investigate whether CXCL13 modulated the trafficking of NMDA receptor via interleukin (IL)-17 in a rat model of remifentanil-induced hyperalgesia (RIH).Although chemokines are crucial regulators of neuroinflammation, spinal N-methyl-d-aspartate (NMDA) receptor activation, and development of hypernociceptive process, little is known about specific pathogenesis and effective treatment. Inflammatory mediators are required for excitatory synaptic transmission in pathologic pain. A neutralizing antibody against CXCL13 (anti-CXCL13), antiserum against IL-17 (anti-IL-17), and recombinant CXCL13 and IL-17 were administered intrathecally to explore the roles of CXCL13, IL-17, and NMDA receptor, as well as the prevention of hyperalgesia. Paw withdrawal threshold and paw withdrawal latency were employed to record mechanical allodynia and thermal hyperalgesia. Reverse transcriptase quantitative polymerase chain reaction was used to evaluate the levels of CXCL13/CXCR5 and IL-17/IL-17RA in the spinal dorsal horn. The trafficking of spinal GluN2B-containing NMDA receptor was assessed by Western blot after nociceptive testing. This study found mechanical allodynia and thermal hyperalgesia with a remarkable increase in the expression of spinal CXCL13/CXCR5 and IL-17/IL-17RA and trafficking of GluN2B-containing NMDA receptor after remifentanil exposure. Behavioral RIH and elevated GluN2B trafficking were dampened by intrathecal anti-CXCL13 and anti-IL-17, respectively. The delivery of exogenous CXCL13 dose-dependently generated a rapid nociceptive hypersensitivity in naïve rats, which was prevented by coadministering anti-IL-17. CXCL13-induced IL-17RA overproduction and GluN2B trafficking were reversed by anti-IL-17 treatment. GluN2B antagonist also blocked CXCL13, and IL-17 directly induced hyperalgesia. This study highlighted the contribution of IL-17 pathway in the trafficking of CXCL13-induced GluN2B-containing NMDA receptor in the pathogenesis of RIH

  12. Bromodomain-containing Protein 4 Activates Voltage-gated Sodium Channel 1.7 Transcription in Dorsal Root Ganglia Neurons to Mediate Thermal Hyperalgesia in Rats.

    Science.gov (United States)

    Hsieh, Ming-Chun; Ho, Yu-Cheng; Lai, Cheng-Yuan; Wang, Hsueh-Hsiao; Lee, An-Sheng; Cheng, Jen-Kun; Chau, Yat-Pang; Peng, Hsien-Yu

    2017-11-01

    Bromodomain-containing protein 4 binds acetylated promoter histones and promotes transcription; however, the role of bromodomain-containing protein 4 in inflammatory hyperalgesia remains unclear. Male Sprague-Dawley rats received hind paw injections of complete Freund's adjuvant to induce hyperalgesia. The dorsal root ganglia were examined to detect changes in bromodomain-containing protein 4 expression and the activation of genes involved in the expression of voltage-gated sodium channel 1.7, which is a key pain-related ion channel. The intraplantar complete Freund's adjuvant injections resulted in thermal hyperalgesia (4.0 ± 1.5 s; n = 7). The immunohistochemistry and immunoblotting results demonstrated an increase in the bromodomain-containing protein 4-expressing dorsal root ganglia neurons (3.78 ± 0.38 fold; n = 7) and bromodomain-containing protein 4 protein levels (2.62 ± 0.39 fold; n = 6). After the complete Freund's adjuvant injection, histone H3 protein acetylation was enhanced in the voltage-gated sodium channel 1.7 promoter, and cyclin-dependent kinase 9 and phosphorylation of RNA polymerase II were recruited to this area. Furthermore, the voltage-gated sodium channel 1.7-mediated currents were enhanced in neurons of the complete Freund's adjuvant rats (55 ± 11 vs. 19 ± 9 pA/pF; n = 4 to 6 neurons). Using bromodomain-containing protein 4-targeted antisense small interfering RNA to the complete Freund's adjuvant-treated rats, the authors demonstrated a reduction in the expression of bromodomain-containing protein 4 (0.68 ± 0.16 fold; n = 7), a reduction in thermal hyperalgesia (7.5 ± 1.5 s; n = 7), and a reduction in the increased voltage-gated sodium channel 1.7 currents (21 ± 4 pA/pF; n = 4 to 6 neurons). Complete Freund's adjuvant triggers enhanced bromodomain-containing protein 4 expression, ultimately leading to the enhanced excitability of nociceptive neurons and thermal hyperalgesia. This effect is

  13. Effects of Postnatal Serotonin Agonism on Fear Response and Memory

    Science.gov (United States)

    The neurotransmitter serotonin (5-HT) also acts as a neurogenic compound in the developing brain. Early administration of a 5-HT agonist could alter the development of the serotonergic circuitry, altering behaviors mediated by 5-HT signaling, such as memory, fear and aggression. White leghorn chicks...

  14. Perinatal vs genetic programming of serotonin states associated with anxiety.

    Science.gov (United States)

    Altieri, Stefanie C; Yang, Hongyan; O'Brien, Hannah J; Redwine, Hannah M; Senturk, Damla; Hensler, Julie G; Andrews, Anne M

    2015-05-01

    Large numbers of women undergo antidepressant treatment during pregnancy; however, long-term consequences for their offspring remain largely unknown. Rodents exposed to serotonin transporter (SERT)-inhibiting antidepressants during development show changes in adult emotion-like behavior. These changes have been equated with behavioral alterations arising from genetic reductions in SERT. Both models are highly relevant to humans yet they vary in their time frames of SERT disruption. We find that anxiety-related behavior and, importantly, underlying serotonin neurotransmission diverge between the two models. In mice, constitutive loss of SERT causes life-long increases in anxiety-related behavior and hyperserotonemia. Conversely, early exposure to the antidepressant escitalopram (ESC; Lexapro) results in decreased anxiety-related behavior beginning in adolescence, which is associated with adult serotonin system hypofunction in the ventral hippocampus. Adult behavioral changes resulting from early fluoxetine (Prozac) exposure were different from those of ESC and, although somewhat similar to SERT deficiency, were not associated with changes in hippocampal serotonin transmission in late adulthood. These findings reveal dissimilarities in adult behavior and neurotransmission arising from developmental exposure to different widely prescribed antidepressants that are not recapitulated by genetic SERT insufficiency. Moreover, they support a pivotal role for serotonergic modulation of anxiety-related behavior.

  15. The genetics of the serotonin transporter and irritable bowel syndrome.

    Science.gov (United States)

    Colucci, Rocchina; Blandizzi, Corrado; Bellini, Massimo; Ghisu, Narcisa; Tonini, Marcello; Del Tacca, Mario

    2008-07-01

    Serotonin transporter (SERT) mediates the intracellular reuptake of released serotonin, thus regulating its biological functions. Abnormalities in serotonin reuptake can alter enteric serotonergic signalling, leading to sensory, motor and secretory gut dysfunctions, which contribute to the pathophysiology of irritable bowel syndrome (IBS). This relationship has fostered the use of selective serotonin reuptake inhibitors (SSRIs) in the treatment of IBS. Current data on the efficacy of SSRIs in IBS, association of the SERT gene promoter polymorphism 5-HTTLPR with IBS and the expression pattern of SERT in the intestinal mucosa of IBS patients are conflicting. Recent molecular studies have raised critical questions about multiple SERT mRNA transcripts in the human gut, the role of polymorphic SERT promoter in the regulation of enteric SERT expression and the ability of 5-HTTLPR to affect human SERT gene transcription. The present review highlights recent advances in SERT genetics, discusses their implications for potential therapeutic applications of SSRIs in IBS and presents original suggestions for future investigations.

  16. Serotonin Transporter Gene, Depressive Symptoms, and Interleukin-6

    NARCIS (Netherlands)

    Su, Shaoyong; Zhao, Jinying; Bremner, J. Douglas; Miller, Andrew H.; Tang, Weining; Bouzyk, Mark; Snieder, Harold; Novik, Olga; Afzal, Nadeem; Goldberg, Jack; Vaccarino, Viola

    2009-01-01

    Background-We explored the relationship of genetic variants of the serotonin transporter gene SLC6A4, a key regulator of the serotonergic neurotransmission, with both depressive symptoms and plasma interleukin-6 (IL-6) levels. Methods and Results-We genotyped 20 polymorphisms in 360 male twins (mean

  17. Selective serotonin reuptake inhibitors for depression in pregnancy.

    Science.gov (United States)

    Susser, Leah C; Sansone, Stephanie A; Hermann, Alison D

    2016-12-01

    Perinatal depression is associated with a high risk of morbidity and mortality and may have long-term consequences on child development. The US Preventive Services Task Force has recently recognized the importance of identifying and treating women with depression in the perinatal period. However, screening and accessing appropriate treatment come with logistical challenges. In many areas, there may not be sufficient access to psychiatric care, and, until these resources develop, the burden may inadvertently fall on obstetricians. As a result, understanding the risks of perinatal depression in comparison with the risks of treatment is important. Many studies of selective serotonin reuptake inhibitors in pregnancy fail to control for underlying depressive illness, which can lead to misinterpretation of selective serotonin reuptake inhibitor risk by clinicians. This review discusses the risks and benefits of selective serotonin reuptake inhibitor treatment in pregnancy within the context of perinatal depression. Whereas selective serotonin reuptake inhibitors may be associated with certain risks, the absolute risks are low and may be outweighed by the risks of untreated depression for many women and their offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Buspirone is an effective augmenting agent of serotonin selective re ...

    African Journals Online (AJOL)

    Background. Buspirone has previously been reported to be effective in the augmentation of the antidepressant effect of serotonin selective re-uptake inhibitors (SSRls) in depressed outpatients. We report on buspirone augmentation of SSRls in severe treatment-refractory depression in inpatients. Methods. A retrospective ...

  19. Serotonin receptors: Subtypes, functional responses and therapeutic relevance

    NARCIS (Netherlands)

    P.R. Saxena (Pramod Ranjan)

    1995-01-01

    textabstractRecent, rapid progress in the molecular biology of serotonin (5-HT) receptors requires conceptual re-thinking with respect to receptor classification. Thus, based on operational criteria (agonist and antagonist rank order), as well as transduction mechanisms involved and the structure of

  20. Serotonin 2A receptor antagonists for treatment of schizophrenia

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn Hylsebeck; Rasmussen, Hans; Arnt, Jørn

    2011-01-01

    : Preclinical, clinical and post-mortem studies of the serotonin 5-HT2A system in schizophrenia are reviewed. The implications of a combined D2 and 5-HT2A receptor blockade, which is obtained by several current antipsychotic drugs, are discussed, and the rationale for the development of more selective 5-HT2A...