Distinct BOLD fMRI Responses of Capsaicin-Induced Thermal Sensation Reveal Pain-Related Brain Activation in Nonhuman Primates.

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Abu Bakar Ali Asad

Full Text Available Approximately 20% of the adult population suffer from chronic pain that is not adequately treated by current therapies, highlighting a great need for improved treatment options. To develop effective analgesics, experimental human and animal models of pain are critical. Topically/intra-dermally applied capsaicin induces hyperalgesia and allodynia to thermal and tactile stimuli that mimics chronic pain and is a useful translation from preclinical research to clinical investigation. Many behavioral and self-report studies of pain have exploited the use of the capsaicin pain model, but objective biomarker correlates of the capsaicin augmented nociceptive response in nonhuman primates remains to be explored.Here we establish an aversive capsaicin-induced fMRI model using non-noxious heat stimuli in Cynomolgus monkeys (n = 8. BOLD fMRI data were collected during thermal challenge (ON:20 s/42°C; OFF:40 s/35°C, 4-cycle at baseline and 30 min post-capsaicin (0.1 mg, topical, forearm application. Tail withdrawal behavioral studies were also conducted in the same animals using 42°C or 48°C water bath pre- and post- capsaicin application (0.1 mg, subcutaneous, tail.Group comparisons between pre- and post-capsaicin application revealed significant BOLD signal increases in brain regions associated with the 'pain matrix', including somatosensory, frontal, and cingulate cortices, as well as the cerebellum (paired t-test, p<0.02, n = 8, while no significant change was found after the vehicle application. The tail withdrawal behavioral study demonstrated a significant main effect of temperature and a trend towards capsaicin induced reduction of latency at both temperatures.These findings provide insights into the specific brain regions involved with aversive, 'pain-like', responses in a nonhuman primate model. Future studies may employ both behavioral and fMRI measures as translational biomarkers to gain deeper understanding of pain processing and evaluate

C-fiber-related EEG-oscillations induced by laser radiant heat stimulation of capsaicin-treated skin

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Domnick, Claudia; Hauck, Michael; Casey, Kenneth L; Engel, Andreas K; Lorenz, Jürgen

2009-01-01

Nociceptive input reaches the brain via two different types of nerve fibers, moderately fast A-delta and slowly conducting C-fibers, respectively. To explore their distinct roles in normal and inflammatory pain we used laser stimulation of normal and capsaicin treated skin at proximal and distal arm sites in combination with time frequency transformation of electroencephalography (EEG) data. Comparison of phase-locked (evoked) and non-phase-locked (total) EEG to laser stimuli revealed three significant pain-related oscillatory responses. First, an evoked response in the delta-theta band, mediated by A-fibers, was reduced by topical capsaicin treatment. Second, a decrease of total power in the alpha-to-gamma band reflected both an A- and C-nociceptor-mediated response with only the latter being reduced by capsaicin treatment. Finally, an enhancement of total power in the upper beta band was mediated exclusively by C-nociceptors and appeared strongly augmented by capsaicin treatment. These findings suggest that phase-locking of brain activity to stimulus onset is a critical feature of A-delta nociceptive input, allowing rapid orientation to salient and potentially threatening events. In contrast, the subsequent C-nociceptive input exhibits clearly less phase coupling to the stimulus. It may primarily signal the tissue status allowing more long-term behavioral adaptations during ongoing inflammatory events that accompany tissue damage. PMID:21197293

Role of capsaicin- and heat-sensitive afferents in stimulation of acupoint-induced pain and analgesia in humans.

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Lei, Jing; Ye, Gang; Wu, Jiang-Tao; Pertovaara, Antti; You, Hao-Jun

2017-09-01

We investigated role of capsaicin-sensitive afferents within and without the areas of Zusanli (ST36)/Shangjuxu (ST37) acupoints along the stomach (ST) meridian in the perception and modulation of pain assessed by visual analog scale of pain and its distribution rated by subjects, pressure pain threshold (PPT), and heat pain threshold (HPT) in humans. Compared with the treatment of non-acupoint area, capsaicin (100µg/50µl) administered into either ST36 or ST37 acupoint caused the strongest pain intensity and the most extensive pain distribution, followed by rapid onset, bilateral, long-lasting secondary mechanical hyperalgesia and slower onset secondary heat hypoalgesia (1day after the capsaicin treatment). Between treatments of different acupoints, capsaicin administrated into the ST36 acupoint exhibited the stronger pain intensity and more widespread pain distribution compared with the treatment of ST37 acupoint. A period of 30- to 45-min, but not 15-min, 43°C heating-needle stimulation applied to the ST36 acupoint significantly enhanced the HPT, and had no effect on PPT. Upon trapezius muscle pain elicited by the i.m. injection of 5.8% saline, pre-emptive treatment of the contralateral ST36 acupoint with 43°C heating-needle stimulation alleviated the ongoing muscle pain, reduced painful area, and reversed the decrease in HPT. It is suggested that (1) pain elicited from the acupoint and non-acupoint areas differs significantly, which are supposed to be dependent on the different distributions and contributions of capsaicin-sensitive afferents. (2) Non-painful heat stimulation is a valid approach in prevention of ongoing muscle pain with associated post-effects of peripheral and central sensitization. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

C-fiber-related EEG-oscillations induced by laser radiant heat stimulation of capsaicin-treated skin

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Claudia Domnick

2009-03-01

Full Text Available Claudia Domnick1, Michael Hauck1,2,3, Kenneth L Casey3, Andreas K Engel1, Jürgen Lorenz1,3,41Department of Neurophysiology and Pathophysiology; 2Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 3Department of Neurology, University of Michigan, Ann Arbor, MI, USA; 4Faculty of Life Sciences, Hamburg University of Applied Sciences, Hamburg, GermanyAbstract: Nociceptive input reaches the brain via two different types of nerve fibers, moderately fast A-delta and slowly conducting C-fibers, respectively. To explore their distinct roles in normal and inflammatory pain we used laser stimulation of normal and capsaicin treated skin at proximal and distal arm sites in combination with time frequency transformation of electroencephalography (EEG data. Comparison of phase-locked (evoked and non-phase-locked (total EEG to laser stimuli revealed three significant pain-related oscillatory responses. First, an evoked response in the delta-theta band, mediated by A-fibers, was reduced by topical capsaicin treatment. Second, a decrease of total power in the alpha-to-gamma band reflected both an A- and C-nociceptor-mediated response with only the latter being reduced by capsaicin treatment. Finally, an enhancement of total power in the upper beta band was mediated exclusively by C-nociceptors and appeared strongly augmented by capsaicin treatment. These findings suggest that phase-locking of brain activity to stimulus onset is a critical feature of A-delta nociceptive input, allowing rapid orientation to salient and potentially threatening events. In contrast, the subsequent C-nociceptive input exhibits clearly less phase coupling to the stimulus. It may primarily signal the tissue status allowing more long-term behavioral adaptations during ongoing inflammatory events that accompany tissue damage.Keywords: C-fibers, oscillations, EEG, laser, capsaicin, inflammatory pain

The effect of wound instillation of a novel purified capsaicin formulation on postherniotomy pain

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Aasvang, Eske K; Hansen, Jeanette B; Malmstrøm, Jørgen

2008-01-01

, preclinical, and clinical studies, and may be an effective adjunct to postoperative pain management. METHODS: We performed a single-center, randomized, double-blind, placebo-controlled study of the analgesic efficacy of a single intraoperative wound instillation of 1000 microg ultrapurified capsaicin (ALGRX......BACKGROUND: Acute postoperative pain is common after most surgical procedures. Despite the availability of many analgesic options, postoperative pain management is often unsatisfactory. Purified capsaicin (ALGRX 4975 98% pure) has demonstrated prolong inhibition of C-fiber function in in vitro...... 4975) after open mesh groin hernia repair in 41 adult male patients. The primary end-point was average daily visual analog scale (VAS) pain scores during the first week after surgery assessed as area under the curve (AUC). Pain was recorded twice daily in a pain diary for 4 wk. Physical examination...

Identifying the Integrated Neural Networks Involved in Capsaicin-Induced Pain Using fMRI in Awake TRPV1 Knockout and Wild-Type Rats

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Jason Richard Yee

2015-02-01

Full Text Available In the present study, we used functional MRI in awake rats to investigate the pain response that accompanies intradermal injection of capsaicin into the hindpaw. To this end, we used BOLD imaging together with a 3D segmented, annotated rat atlas and computational analysis to identify the integrated neural circuits involved in capsaicin-induced pain. The specificity of the pain response to capsaicin was tested in a transgenic model that contains a biallelic deletion of the gene encoding for the transient receptor potential cation channel subfamily V member 1 (TRPV1. Capsaicin is an exogenous ligand for the TRPV1 receptor, and in wild-type rats, activated the putative pain neural circuit. In addition, capsaicin-treated wild-type rats exhibited activation in brain regions comprising the Papez circuit and habenular system, systems that play important roles in the integration of emotional information, and learning and memory of aversive information, respectively. As expected, capsaicin administration to TRPV1-KO rats failed to elicit the robust BOLD activation pattern observed in wild-type controls. However, the intradermal injection of formalin elicited a significant activation of the putative pain pathway as represented by such areas as the anterior cingulate, somatosensory cortex, parabrachial nucleus, and periaqueductal gray. Notably, comparison of neural responses to capsaicin in wild-type versus knock-out rats uncovered evidence that capsaicin may function in an antinociceptive capacity independent of TRPV1 signaling. Our data suggest that neuroimaging of pain in awake, conscious animals has the potential to inform the neurobiological basis of full and integrated perceptions of pain.

CAPSAICIN-SENSITIVE SENSORY NERVE FIBERS CONTRIBUTE TO THE GENERATION AND MAINTENANCE OF SKELETAL FRACTURE PAIN

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Jimenez-Andrade, Juan Miguel; Bloom, Aaron P.; Mantyh, William G.; Koewler, Nathan J.; Freeman, Katie T.; Delong, David; Ghilardi, Joseph R.; Kuskowski, Michael A.; Mantyh, Patrick W.

2009-01-01

Although skeletal pain can have a marked impact on a patient’s functional status and quality of life, relatively little is known about the specific populations of peripheral nerve fibers that drive non-malignant bone pain. In the present report, neonatal male Sprague Dawley rats were treated with capsaicin or vehicle and femoral fracture was produced when the animals were young adults (15–16 weeks old). Capsaicin treatment, but not vehicle, resulted in a significant (>70%) depletion in the de...

Pain-relieving effectiveness, quality of life and tolerability of repeated capsaicin 8% patch treatment of peripheral neuropathic pain in Scandinavian clinical practice

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Hansson, P; Jensen, Troels Staehelin; Kvarstein, G

2018-01-01

CONTEXT: Clinical trials have demonstrated the efficacy and safety of the capsaicin 8% patch in patients with peripheral neuropathic pain (PNP); however, few studies have assessed this treatment in a clinical practice. OBJECTIVE: To determine whether treatment and re-treatment with the capsaicin ...

A human experimental model of episodic pain

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Petrini, Laura; Hennings, Kristian; Li, Xi

2014-01-01

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

Peripheral Glutamate Receptors Are Required for Hyperalgesia Induced by Capsaicin

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You-Hong Jin

2012-01-01

Full Text Available Transient receptor potential vanilloid1 (TRPV1 and glutamate receptors (GluRs are located in small diameter primary afferent neurons (nociceptors, and it was speculated that glutamate released in the peripheral tissue in response to activation of TRPV1 might activate nociceptors retrogradely. But, it was not clear which types of GluRs are functioning in the nociceptive sensory transmission. In the present study, we examined the c-Fos expression in spinal cord dorsal horn following injection of drugs associated with glutamate receptors with/without capsaicin into the hindpaw. The subcutaneous injection of capsaicin or glutamate remarkably evoked c-Fos expression in ipsilateral sides of spinal cord dorsal horn. This capsaicin evoked increase of c-Fos expression was significantly prevented by concomitant administration of MK801, CNQX, and CPCCOEt. On the other hand, there were not any significant changes in coinjection of capsaicin and MCCG or MSOP. These results reveal that the activation of iGluRs and group I mGluR in peripheral afferent nerves play an important role in mechanisms whereby capsaicin evokes/maintains nociceptive responses.

Comparison of topical capsaicin and topical turpentine oil for treatment of painful diabetic neuropathy

International Nuclear Information System (INIS)

Musharraf, M.U.; Ahmed, Z.

2017-01-01

Background: Diabetes Mellitus is a pandemic of the modern era owing to our rapidly deteriorating lifestyle. Painful diabetic neuropathy is one of the costliest and disabling complications of diabetes mellitus. No single treatment exists to prevent or reverse neuropathic changes or to provide total pain relief. Topical Capsaicin and Turpentine Oil are found to be effective in treatment of painful diabetic neuropathy. Methods: Patients of either gender with ages between 18 and 70 years having painful diabetic neuropathy already taking one oral drug for painful neuropathy and treatment for diabetes mellitus and an HbA1C less than 8.5% were included while Pregnant or lactating mothers, patients with chronic liver disease and patients with renal insufficiency (creatinine >3.0 mg/dl) and peripheral arterial disease were excluded from study. Patients were randomly divided into two groups (A and B) using computer generated random number table. Group A was given topical application of capsaicin while Group B was given topical application of commercially available turpentine oil over painful site on feet. Results: 300 patients were equally divided in two groups. The patients in group A had a Visual Analog Pain Score of 7.91±5.10 at baseline and 5.10±1.343 after 3 months of treatment (p-value 0.0001). The patients in group B had a Visual Analog Pain Score of 7.83±1.012 at baseline and 5.20±1.187 after 3 months of treatment (p-value 0.0001). Chi Square test was applied to compare efficacy of both groups. It was noted that 71 (53%) had efficacy in group A and 63 (47%) had efficacy in the group B but the difference was not statistically significant. (p-value=0.399). Conclusion: It has been concluded that turpentine oil is effective in managing diabetic neuropathic pain similar to capsaicin cream.

Pain flare following external beam radiotherapy and meaningful change in pain scores in the treatment of bone metastases

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Chow, Edward; Ling, Alison; Davis, Lori; Panzarella, Tony; Danjoux, Cyril

2005-01-01

Background and purpose: To examine the incidence of pain flare following external beam radiotherapy and to determine what constitutes a meaningful change in pain scores in the treatment of bone metastases. Patients and methods: Patients with bone metastases treated with external beam radiotherapy were asked to score their pain on a scale of 0-10 before the treatment (baseline), daily during the treatment and for 10 days after completion of external beam radiation. Pain flare was defined as a two-point increase from baseline pain in the pain scale of 0-10 with no decrease in analgesic intake or a 25% increase in analgesic intake employing daily oral morphine equivalent with no decrease in pain score. To distinguish pain flare from progression of pain, we required the pain score and analgesic intake to return back to baseline levels after the increase/flare. They were also asked to indicate if their pain changed during that time compared to pre-treatment level. The change in pain score was compared with patient perception. Results: Eighty-eight patients were evaluated in this study. There were 49 male and 39 female patients with the median age of 70 years. Twelve of 88 patients (14%) had pain flare on day 1. The overall incidence of pain flare during the study period ranged from 2 to 16%. A total of 797 pain scorings were obtained. Patients perceived an improvement in pain when their self-reported pain score decreased by at least two points. Conclusions: Our study confirms the occurrence of pain flare following the external beam radiotherapy in the treatment of bone metastases. Further studies are required to predict who are at risk for flare. Appropriate measures can be taken to alleviate the pain flare. The finding in the meaningful change in pain scores supports the investigator-defined partial response used in some clinical trials

Application of the capsaicin 8% cutaneous patch in neuropathic pain of the head and face: A case series.

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Gaul, Charly; Resch, Sonja

2015-05-01

Treatment of neuropathic or neuralgic head and facial pain due to dental, traumatic or surgical nerve lesions or post-herpetic neuropathy is often challenging. We are reporting on four patients with neuropathic pain syndromes successfully treated with a capsaicin 8% patch in the affected area of the head or face. Treatment with the capsaicin 8% patch seems to be effective and safe for application to the facial and head region. The capsaicin 8% patch might be an additional treatment option if first-line treatment with anticonvulsants or antidepressants was ineffective or limited by side effects. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Effects of intra-fourth ventricle injection of crocin on capsaicin-induced orofacial pain in rats.

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Tamaddonfard, Esmaeal; Tamaddonfard, Sina; Pourbaba, Salar

2015-01-01

Crocin, a constituent of saffron and yellow gardenia, possesses anti-nociceptive effects. In the present study, we investigated the effects of intra-fourth ventricle injection of crocin in a rat model of orofacial pain. The contribution of opioid system was assessed using intra-fourth ventricle injection of naloxone, an opioid receptor antagonist. A guide cannula was implanted into the fourth ventricle of brain in anesthetized rats. Orofacial pain was induced by subcutaneous (s.c.) injection of capsaicin (1.5 µg/20 µl) into the right vibrissa pad. The time spent face rubbing/grooming was recorded for a period of 20 min. Locomotor activity was measured using an open-field test. Intra-fourth ventricle injection of crocin (10 and 40 µg/rat) and morphine (10 and 40 µg/rat) and their co-administration (2.5 and 10 µg/rat of each) suppressed capsaicin-induced orofacial pain. The analgesic effect induced by 10 µg/rat of morphine, but not crocin (10 µg/rat), was prevented by 20 µg/rat of naloxone pretreatment. The above-mentioned chemical compounds did not affect locomotor activity. The results of this study showed that the injection of crocin into the cerebral fourth ventricle attenuates capsaicin-induced orofacial pain in rats. The anti-nociceptive effect of crocin was not attributed to the central opioid receptors.

Effects of intra-fourth ventricle injection of crocin on capsaicin-induced orofacial pain in rats

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Esmaeal Tamaddonfard

2015-08-01

Full Text Available Objectives: Crocin, a constituent of saffron and yellow gardenia, possesses anti-nociceptive effects. In the present study, we investigated the effects of intra-fourth ventricle injection of crocin in a rat model of orofacial pain. The contribution of opioid system was assessed using intra-fourth ventricle injection of naloxone, an opioid receptor antagonist. Materials and Methods: A guide cannula was implanted into the fourth ventricle of brain in anesthetized rats. Orofacial pain was induced by subcutaneous (s.c. injection of capsaicin (1.5 µg/20 µl into the right vibrissa pad. The time spent face rubbing/grooming was recorded for a period of 20 min. Locomotor activity was measured using an open-field test. Results: Intra-fourth ventricle injection of crocin (10 and 40 µg/rat and morphine (10 and 40 µg/rat and their co-administration (2.5 and 10 µg/rat of each suppressed capsaicin-induced orofacial pain. The analgesic effect induced by 10 µg/rat of morphine, but not crocin (10 µg/rat, was prevented by 20 µg/rat of naloxone pretreatment. The above-mentioned chemical compounds did not affect locomotor activity. Conclusion: The results of this study showed that the injection of crocin into the cerebral fourth ventricle attenuates capsaicin-induced orofacial pain in rats. The anti-nociceptive effect of crocin was not attributed to the central opioid receptors.

Capsaicin 8% Patch for Central and Peripheral Neuropathic Pain of Persons with Incomplete Spinal Cord Injury: Two Case Reports.

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Trbovich, Michelle; Yang, Huiqing

2015-08-01

Neuropathic pain after spinal cord injury is common and often refractory to standard treatments. The capsaicin 8% patch is a Food and Drug Administration-approved treatment of neuropathic pain in postherpetic neuralgia and has demonstrated significant efficacy in human immunodeficiency virus-autonomic neuropathy. The patch defunctionalizes transient receptor potential vanilloid 1 receptors, impairing cutaneous nociceptors for a prolonged period (i.e., 8-12 wks) with no systemic side effects. A retrospective review was conducted on the effects of the patch in two patients with spinal cord injury and neuropathic pain refractory to standard treatments. Two weeks after application, both patients reported complete pain relief. Average onset of relief of 4 days and average duration of relief of 197 days, requiring only one to four applications per year, paralleled findings reported in postherpetic neuralgia and human immunodeficiency virus-autonomic neuropathy trials. Upregulation of capsaicin-sensitive transient receptor potential vanilloid 1 receptors after spinal cord injury has been reported. The capsaicin 8% patch is a promising therapeutic agent for neuropathic pain in spinal cord injury.

Differential effect of ketamine and lidocaine on spontaneous and mechanical evoked pain in patients with nerve injury pain

DEFF Research Database (Denmark)

Gottrup, Hanne; Bach, Flemming Winther; Juhl, Gitte Irene

2006-01-01

ketamine, an N-methyl-D-aspartate receptor antagonist and lidocaine, a sodium channel blocker, on spontaneous pain, brush-evoked pain, and pinprick-evoked pain in patients with nerve injury pain. METHODS: Twenty patients participated in two randomized, double-blinded, placebo-controlled, crossover...... experiments in which they, on four different days, received a 30-minute intravenous infusion of ketamine (0.24 mg/kg), lidocaine (5 mg/kg), or saline. Ongoing pain, pain evoked by brush and repetitive pinprick stimuli, and acetone was measured before, during, and after infusion. RESULTS: Ketamine...... significantly reduced ongoing pain and evoked pain to brush and pinprick, whereas lidocaine only reduced evoked pain to repetitive pinprick stimuli. In individual patients, there was no correlation between the pain-relieving effect of lidocaine and ketamine on ongoing or mechanically evoked pains. CONCLUSIONS...

Tolerability of the capsaicin 8% patch following pretreatment with lidocaine or tramadol in patients with peripheral neuropathic pain: a multicentre, randomized, assessor-blinded study.

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Jensen, T S; Høye, K; Fricová, J; Vanelderen, P; Ernault, E; Siciliano, T; Marques, S

2014-10-01

Application of the capsaicin 8% patch is associated with treatment-related discomfort. Consequently, pretreatment for 60 min with anaesthetic cream is recommended; however, this may be uncomfortable and time consuming. We conducted a multicentre, randomized (1:1), assessor-blinded study in patients with peripheral neuropathic pain to assess tolerability of the capsaicin patch following topical lidocaine (4%) or oral tramadol (50 mg) pretreatment. The primary endpoint was the proportion of patients tolerating capsaicin patch application (ability to receive ≥90% of a 60-min application). Numeric Pain Rating Scale (NPRS) scores were assessed before, during and after treatment. Overall, 122 patients were included (61 per arm). The capsaicin patch was tolerated by 121 patients. Tolerability of the capsaicin patch was similar following pretreatment with lidocaine and tramadol. Following patch application, pain levels increased up to 55 min (change from baseline of 1.3 for lidocaine and 1.4 for tramadol). After patch removal, tramadol-treated patients experienced greater pain relief up to the end of day 1; in the evening, mean changes in NPRS scores from baseline were 0 for lidocaine and -1 for tramadol. Proportions of patients reporting increases of ≥2 NPRS points or >33% from baseline at one or more time point(s) on the day of treatment were similar between arms. Adverse event incidence was comparable between arms. Capsaicin 8% patch tolerability was similar in the two arms, with comparable results for most secondary endpoints. Tramadol given 30 min before patch application should be considered as an alternative pretreatment option in patients receiving capsaicin patch treatment. © 2014 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

Pain and flare-up after endodontic treatment procedures.

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Sipavičiūtė, Eglė; Manelienė, Rasmutė

2014-01-01

Flare-ups can occur after root canal treatment and consist of acute exacerbations of an asymptomatic pulpal and/or periradicular pathologic condition. The causative factors of interappointment pain encompass mechanical, chemical, and/or microbial injury to the pulp or periradicular tissues. Microorganisms can participate in causation of interappointment pain in the following situations: apical extrusion of debris; incomplete instrumentation leading to changes in the endodontic microbiota or in environmental conditions; and secondary intraradicular infections. Interappointment pain is almost exclusively due to the development of acute inflammation at the periradicular tissues in response to an increase in the intensity of injury coming from the root canal system. The mechanical irritation of apical periodontal tissue is caused by overinstrumentation of the root canal and filling material extrusion through the apical foramen. Incorrectly measured working length of the root canal has inherent connection with these causative factors of endodontic flare - up. This review article discusses these many facets of the flare-up: definition, incidence causes and predisposing factors.

Norepinephrine-evoked pain in fibromyalgia. A randomized pilot study [ISRCTN70707830

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Casanova Jose-Miguel

2002-01-01

Full Text Available Abstract Background Fibromyalgia syndrome displays sympathetically maintained pain features such as frequent post-traumatic onset and stimuli-independent pain accompanied by allodynia and paresthesias. Heart rate variability studies showed that fibromyalgia patients have changes consistent with ongoing sympathetic hyperactivity. Norepinephrine-evoked pain test is used to assess sympathetically maintained pain syndromes. Our objective was to define if fibromyalgia patients have norepinephrine-evoked pain. Methods Prospective double blind controlled study. Participants: Twenty FM patients, and two age/sex matched control groups; 20 rheumatoid arthritis patients and 20 healthy controls. Ten micrograms of norepinephrine diluted in 0.1 ml of saline solution were injected in a forearm. The contrasting substance, 0.1 ml of saline solution alone, was injected in the opposite forearm. Maximum local pain elicited during the 5 minutes post-injection was graded on a visual analog scale (VAS. Norepinephrine-evoked pain was diagnosed when norepinephrine injection induced greater pain than placebo injection. Intensity of norepinephrine-evoked pain was calculated as the difference between norepinephrine minus placebo-induced VAS scores. Results Norepinephrine-evoked pain was seen in 80 % of FM patients (95% confidence intervals 56.3 – 94.3%, in 30 % of rheumatoid arthritis patients and in 30 % of healthy controls (95% confidence intervals 11.9 – 54.3 (p Conclusions Fibromyalgia patients have norepinephrine-evoked pain. This finding supports the hypothesis that fibromyalgia may be a sympathetically maintained pain syndrome.

Effect of Capsaicin Cream on Chronic Low Back Pain in Patients With Inter-Vertebral Disc Herniation

OpenAIRE

Fayazi; Farokhpyam; Talali

2015-01-01

Background Low back pain is one of the most common debilitating disorders worldwide and the third cause of visiting a physician. One of the most common causes of low back pain is spinal disc herniation. Still there is no general agreement on the most effective treatment for it. Objectives This study aimed to determine the effect of Capsaicin cream on low back pain in patients with inter-vertebral disc herniation in Ahvaz. ...

Objective correlate of subjective pain perception by contact heat-evoked potentials.

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Granovsky, Yelena; Granot, Michal; Nir, Rony-Reuven; Yarnitsky, David

2008-01-01

The method of pain-evoked potentials has gained considerable acceptance over the last 3 decades regarding its objectivity, repeatability, and quantifiability. The present study explored whether the relationship between pain-evoked potentials and pain psychophysics obtained by contact heat stimuli is similar to those observed for the conventionally used laser stimulation. Evoked potentials (EPs) were recorded in response to contact heat stimuli at different body sites in 24 healthy volunteers. Stimuli at various temperatures were applied to the forearm (43 degrees C, 46 degrees C, 49 degrees C, and 52 degrees C) and leg (46 degrees C and 49 degrees C). The amplitudes of both components (N2 and P2) were strongly associated with the intensity of the applied stimuli and with subjective pain perception. Yet, regression analysis revealed pain perception and not stimulus intensity as the major contributing factor. A significant correlation was found between the forearm and the leg for both psychophysics and EPs amplitude. Contact heat can generate readily distinguishable evoked potentials on the scalp, consistent between upper and lower limbs. Although these potentials bear positive correlation with both stimulus intensity and pain magnitude, the latter is the main contributor to the evoked brain response.

Effect of Capsaicin Cream on Chronic Low Back Pain in Patients With Inter-Vertebral Disc Herniation

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Fayazi

2015-07-01

Full Text Available Background Low back pain is one of the most common debilitating disorders worldwide and the third cause of visiting a physician. One of the most common causes of low back pain is spinal disc herniation. Still there is no general agreement on the most effective treatment for it. Objectives This study aimed to determine the effect of Capsaicin cream on low back pain in patients with inter-vertebral disc herniation in Ahvaz. Patients and Methods This was a double blind clinical trial in which 43 patients with chronic low back pain, according to characteristics of the subjects, were randomly divided into two groups of treatment (n = 23 and control (n = 20. Data collection instruments included demographic specifications and visual analogue scale (VAS questionnaire completed on arrival and at the first, second and third weeks after intervention. The treatment and placebo groups used the ointment for three weeks and three times a day as a thin layer on the painful position. Data entered SPSS (version 18 and analyzed using the analytical descriptive statistics. Results There was a significant difference in the average pain intensity between the groups of study pre-and post-intervention (P = 0.0001 and the rate of using analgesics in the treatment group significantly decreased (P = 0.008. Also patients’ satisfaction was significantly different between the two groups using the ointment (P = 0.0001. Conclusions Capsaicin cream has beneficial effects on pain relieving and reducing analgesic use in patients with inter-vertebral disc herniation. Therefore, the ointment can be recommended in the treatment of low back pain caused by inter-vertebral disc herniation.

Painful Intercourse Is Significantly Associated with Evoked Pain Perception and Cognitive Aspects of Pain in Women with Pelvic Pain

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Meryl J. Alappattu, DPT, PhD

2015-03-01

Conclusions: Differences in local pain ratings suggest that women with pelvic pain perceive stimuli in this region as more painful than pain-free women although the magnitude of stimuli does not differ. Alappattu MJ, George SZ, Robinson ME, Fillingim RB, Moawad N, LeBrun EW, and Bishop MD. Painful intercourse is significantly associated with evoked pain perception and cognitive aspects of pain in women with pelvic pain. Sex Med 2015;3:14–23.

Late sensory function after intraoperative capsaicin wound instillation

DEFF Research Database (Denmark)

Aasvang, E K; Hansen, J B; Kehlet, H

2010-01-01

is partly re-established after skin injection of capsaicin. However, no study has evaluated the long-term effects of wound instillation of purified capsaicin on sensory functions. METHODS: Patients included in a double-blind placebo-controlled randomized study of the analgesic effect of capsaicin after....... placebo group at the 1-week follow-up (Pfunction on the operated side between groups at the pre-operative, 1-week or 2 1/2 year post-operative follow-up (P>0.05). The sensory function......BACKGROUND: Intense capsaicin-induced C-fiber stimulation results in reversible lysis of the nerve soma, thereby making capsaicin wound instillation of potential interest for the treatment of post-operative pain. Clinical histological and short-term sensory studies suggest that the C-fiber function...

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

Science.gov (United States)

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

2010-09-01

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

Clinical and evoked pain, personality traits, and emotional states: can familial confounding explain the associations?

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Strachan, Eric; Poeschla, Brian; Dansie, Elizabeth; Succop, Annemarie; Chopko, Laura; Afari, Niloofar

2015-01-01

Pain is a complex phenomenon influenced by context and person-specific factors. Affective dimensions of pain involve both enduring personality traits and fleeting emotional states. We examined how personality traits and emotional states are linked with clinical and evoked pain in a twin sample. 99 female twin pairs were evaluated for clinical and evoked pain using the McGill Pain Questionnaire (MPQ) and dolorimetry, and completed the 120-item International Personality Item Pool (IPIP), the Positive and Negative Affect Scale (PANAS), and ratings of stress and mood. Using a co-twin control design we examined a) the relationship of personality traits and emotional states with clinical and evoked pain and b) whether genetics and common environment (i.e. familial factors) may account for the associations. Neuroticism was associated with the sensory component of the MPQ; this relationship was not confounded by familial factors. None of the emotional state measures was associated with the MPQ. PANAS negative affect was associated with lower evoked pressure pain threshold and tolerance; these associations were confounded by familial factors. There were no associations between IPIP traits and evoked pain. A relationship exists between neuroticism and clinical pain that is not confounded by familial factors. There is no similar relationship between negative emotional states and clinical pain. In contrast, the relationship between negative emotional states and evoked pain is strong while the relationship with enduring personality traits is weak. The relationship between negative emotional states and evoked pain appears to be non-causal and due to familial factors. Copyright © 2014 Elsevier Inc. All rights reserved.

Incidence and Predictive Factors of Pain Flare After Spine Stereotactic Body Radiation Therapy: Secondary Analysis of Phase 1/2 Trials

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Pan, Hubert Y.; Allen, Pamela K.; Wang, Xin S.; Chang, Eric L.; Rhines, Laurence D.; Tatsui, Claudio E.; Amini, Behrang; Wang, Xin A.; Tannir, Nizar M.; Brown, Paul D.; Ghia, Amol J.

2014-01-01

Purpose/Objective(s): To perform a secondary analysis of institutional prospective spine stereotactic body radiation therapy (SBRT) trials to investigate posttreatment acute pain flare. Methods and Materials: Medical records for enrolled patients were reviewed. Study protocol included baseline and follow-up surveys with pain assessment by Brief Pain Inventory and documentation of pain medications. Patients were considered evaluable for pain flare if clinical note or follow-up survey was completed within 2 weeks of SBRT. Pain flare was defined as a clinical note indicating increased pain at the treated site or survey showing a 2-point increase in worst pain score, a 25% increase in analgesic intake, or the initiation of steroids. Binary logistic regression was used to determine predictive factors for pain flare occurrence. Results: Of the 210 enrolled patients, 195 (93%) were evaluable for pain flare, including 172 (88%) clinically, 135 (69%) by survey, and 112 (57%) by both methods. Of evaluable patients, 61 (31%) had undergone prior surgery, 57 (29%) had received prior radiation, and 34 (17%) took steroids during treatment, mostly for prior conditions. Pain flare was observed in 44 patients (23%). Median time to pain flare was 5 days (range, 0-20 days) after the start of treatment. On multivariate analysis, the only independent factor associated with pain flare was the number of treatment fractions (odds ratio = 0.66, P=.004). Age, sex, performance status, spine location, number of treated vertebrae, prior radiation, prior surgery, primary tumor histology, baseline pain score, and steroid use were not significant. Conclusions: Acute pain flare after spine SBRT is a relatively common event, for which patients should be counseled. Additional study is needed to determine whether prophylactic or symptomatic intervention is preferred

Incidence and Predictive Factors of Pain Flare After Spine Stereotactic Body Radiation Therapy: Secondary Analysis of Phase 1/2 Trials

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Pan, Hubert Y.; Allen, Pamela K. [Department of Radiation Oncology, University of Texas MD Anderson Cancer, Houston, Texas (United States); Wang, Xin S. [Department of Symptom Research, University of Texas MD Anderson Cancer, Houston, Texas (United States); Chang, Eric L. [Department of Radiation Oncology, University of Texas MD Anderson Cancer, Houston, Texas (United States); Department of Radiation Oncology, USC Norris Cancer Center, Los Angeles, California (United States); Rhines, Laurence D.; Tatsui, Claudio E. [Department of Neurosurgery, University of Texas MD Anderson Cancer, Houston, Texas (United States); Amini, Behrang [Department of Diagnostic Radiology, University of Texas MD Anderson Cancer, Houston, Texas (United States); Wang, Xin A. [Department of Radiation Physics, University of Texas MD Anderson Cancer, Houston, Texas (United States); Tannir, Nizar M. [Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer, Houston, Texas (United States); Brown, Paul D. [Department of Radiation Oncology, University of Texas MD Anderson Cancer, Houston, Texas (United States); Ghia, Amol J., E-mail: AJGhia@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer, Houston, Texas (United States)

2014-11-15

Purpose/Objective(s): To perform a secondary analysis of institutional prospective spine stereotactic body radiation therapy (SBRT) trials to investigate posttreatment acute pain flare. Methods and Materials: Medical records for enrolled patients were reviewed. Study protocol included baseline and follow-up surveys with pain assessment by Brief Pain Inventory and documentation of pain medications. Patients were considered evaluable for pain flare if clinical note or follow-up survey was completed within 2 weeks of SBRT. Pain flare was defined as a clinical note indicating increased pain at the treated site or survey showing a 2-point increase in worst pain score, a 25% increase in analgesic intake, or the initiation of steroids. Binary logistic regression was used to determine predictive factors for pain flare occurrence. Results: Of the 210 enrolled patients, 195 (93%) were evaluable for pain flare, including 172 (88%) clinically, 135 (69%) by survey, and 112 (57%) by both methods. Of evaluable patients, 61 (31%) had undergone prior surgery, 57 (29%) had received prior radiation, and 34 (17%) took steroids during treatment, mostly for prior conditions. Pain flare was observed in 44 patients (23%). Median time to pain flare was 5 days (range, 0-20 days) after the start of treatment. On multivariate analysis, the only independent factor associated with pain flare was the number of treatment fractions (odds ratio = 0.66, P=.004). Age, sex, performance status, spine location, number of treated vertebrae, prior radiation, prior surgery, primary tumor histology, baseline pain score, and steroid use were not significant. Conclusions: Acute pain flare after spine SBRT is a relatively common event, for which patients should be counseled. Additional study is needed to determine whether prophylactic or symptomatic intervention is preferred.

Cross-sectional evaluation of post-operative pain and flare-ups in endodontic treatments using a type of rotary instruments.

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Tanalp, Jale; Sunay, Hakki; Bayirli, Gündüz

2013-01-01

The purpose of this clinical study was to evaluate the general incidence of post-operative pain and flare-ups in patients who were endodontically treated by two endodontics specialists using rotary instruments (Hero 642, Micro Mega, France) with the same treatment protocol. Records of 382 teeth belonging to 268 patients treated by two endodontics specialists during a 6-month period were kept and evaluated. Post-operative pain between treatment visits was categorized using a pre-established scoring system. Ninety-five patients were males, whereas 173 were females. Pulpal necrosis without periapical pathosis was determined as the most common indication for endodontic treatment (21.7%) followed by irreversible pulpitis and re-treatment without periapical lesions (18.3%, 18.3%, respectively). The general prevalence of post-operative pain and flare-ups was determined as 8.1%, whereas cases that could be classified as real flare-ups which were severe and required an unscheduled visit (scores 2 and 3) comprised 3.4% of the cases. No statistically significant correlation was determined between gender and post-operative pain and flare-up (p = 0.05). There was a significant correlation between number of appointments and the presence of pain and flare-ups. Teeth undergoing multiple visits had a higher risk of developing post-operative pain and flare-ups compared to those with single appointments with a statistical significance (p = 0.03). Teeth with pre-operative pain were more prone to developing post-operative pain and discomfort with a statistically significant difference (p = 0.02). While no significant correlation was determined between tooth vitality and pain and flare-ups (p = 0.5), a statistically significant relationship existed between the presence of a periapical pathosis and post-operative pain and flare-ups. Cases with a periapical lesion had a higher risk of developing pain and flare-ups compared to those with no periapical involvement (p = 0.0001). Future

Methodology for self-report of rest pain (or spontaneous pain) vs evoked pain in chronic neuropathic conditions: a prospective observational pilot study

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He, David; Grant, Brian; Holden, Ronald R.; Gilron, Ian

2017-01-01

Abstract. Introduction:. The distinction between pain at rest and pain evoked by touch or movement has important clinical implications and may be associated with different mechanisms. However, current methods of clinical pain assessment pay little attention to directly distinguishing between these contrasting components of symptom burden. Objectives:. We developed the 10-item “Functional Impact of Neuropathic Evoked and Spontaneous Symptom Evaluation” questionnaire designed to distinguish ...

Changes in symptoms during urologic chronic pelvic pain syndrome symptom flares: findings from one site of the MAPP Research Network.

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Sutcliffe, Siobhan; Colditz, Graham A; Pakpahan, Ratna; Bradley, Catherine S; Goodman, Melody S; Andriole, Gerald L; Lai, H Henry

2015-02-01

To provide the first description and quantification of symptom changes during interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome symptom exacerbations ("flares"). Participants at one site of the Trans-Multidisciplinary Approaches to the study of chronic Pelvic Pain Epidemiology and Phenotyping Study completed two 10-day diaries over the 1-year study follow-up period, one at baseline and one during their first flare (if not at baseline). On each day of the diary, participants reported whether they were currently experiencing a flare, defined as "symptoms that are much worse than usual" for at least 1 day, and their levels of urination-related pain, pelvic pain, urgency, and frequency on a scale of 0-10. Linear mixed models were used to calculate mean changes in symptoms between non-flare and flare days from the same participant. Eighteen of 27 women and 9 of 29 men reported at least one flare during follow-up, for a total of 281 non-flare and 210 flare days. Of these participants, 44.4% reported one flare, 29.6% reported two flares, and 25.9% reported ≥ 3 flares over the combined 20-day diary observation period, with reported flares ranging in duration from 1 day to >2 weeks. During these flares, each of the main symptoms worsened significantly by a mean of at least two points and total symptoms worsened by a mean of 11 points for both sexes (all P ≤ 0.01). Flares are common and correspond to a global worsening of urologic and pelvic pain symptoms. © 2013 Wiley Periodicals, Inc.

Measures of spontaneous and movement-evoked pain are associated with disability in patients with whiplash injuries.

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Mankovsky-Arnold, Tsipora; Wideman, Timothy H; Larivière, Christian; Sullivan, Michael J L

2014-09-01

This study examined the degree to which measures of spontaneous and movement-evoked pain accounted for shared or unique variance in functional disability associated with whiplash injury. The study also addressed the role of fear of movement as a mediator or moderator of the relation between different indices of pain and functional disability. Measures of spontaneous pain, single-point movement-evoked pain, repetition-induced summation of activity-related pain (RISP), and fear of movement and disability were obtained on a sample of 142 individuals who had sustained whiplash injuries. Participants' pain ratings, provided after lifting a weighted canister, were used as the index of single-point movement-evoked pain. RISP was computed as the increase in pain reported by participants over successive lifts of 18 weighted canisters. Measures of functional disability included physical lift tolerance and self-reported disability. Hierarchical regression analyses revealed that measures of single-point movement-evoked pain and RISP accounted for significant unique variance in self-reported disability, beyond the variance accounted for by the measure of spontaneous pain. Only RISP accounted for significant unique variance in lift tolerance. The results suggest that measures of movement-evoked pain represent a disability-relevant dimension of pain that is not captured by measures of spontaneous pain. The clinical and conceptual implications of the findings are discussed. This study examined the degree to which measures of spontaneous and movement-evoked pain accounted for shared or unique variance in functional disability associated with whiplash injury. The findings suggest that approaches to the clinical evaluation of pain would benefit from the inclusion of measures of movement-evoked pain. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

The μ opioid agonist morphine modulates potentiation of capsaicin-evoked TRPV1 responses through a cyclic AMP-dependent protein kinase A pathway

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Roberts-Thomson Sarah J

2006-07-01

Full Text Available Abstract Background The vanilloid receptor 1 (TRPV1 is critical in the development of inflammatory hyperalgesia. Several receptors including G-protein coupled prostaglandin receptors have been reported to functionally interact with the TRPV1 through a cAMP-dependent protein kinase A (PKA pathway to potentiate TRPV1-mediated capsaicin responses. Such regulation may have significance in inflammatory pain. However, few functional receptor interactions that inhibit PKA-mediated potentiation of TRPV1 responses have been described. Results In the present studies we investigated the hypothesis that the μ opioid receptor (MOP agonist morphine can modulate forskolin-potentiated capsaicin responses through a cAMP-dependent PKA pathway. HEK293 cells were stably transfected with TRPV1 and MOP, and calcium (Ca2+ responses to injection of the TRPV1 agonist capsaicin were monitored in Fluo-3-loaded cells. Pre-treatment with morphine did not inhibit unpotentiated capsaicin-induced Ca2+ responses but significantly altered capsaicin responses potentiated by forskolin. TRPV1-mediated Ca2+ responses potentiated by the direct PKA activator 8-Br-cAMP and the PKC activator Phorbol-12-myristate-13-acetatewere not modulated by morphine. Immunohistochemical studies confirmed that the TRPV1 and MOP are co-expressed on cultured Dorsal Root Ganglion neurones, pointing towards the existence of a functional relationship between the G-protein coupled MOP and nociceptive TRPV1. Conclusion The results presented here indicate that the opioid receptor agonist morphine acts via inhibition of adenylate cyclase to inhibit PKA-potentiated TRPV1 responses. Targeting of peripheral opioid receptors may therefore have therapeutic potential as an intervention to prevent potentiation of TRPV1 responses through the PKA pathway in inflammation.

Harnessing the Therapeutic Potential of Capsaicin and Its Analogues in Pain and Other Diseases

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Shaherin Basith

2016-07-01

Full Text Available Capsaicin is the most predominant and naturally occurring alkamide found in Capsicum fruits. Since its discovery in the 19th century, the therapeutic roles of capsaicin have been well characterized. The potential applications of capsaicin range from food flavorings to therapeutics. Indeed, capsaicin and few of its analogues have featured in clinical research covered by more than a thousand patents. Previous records suggest pleiotropic pharmacological activities of capsaicin such as an analgesic, anti-obesity, anti-pruritic, anti-inflammatory, anti-apoptotic, anti-cancer, anti-oxidant, and neuro-protective functions. Moreover, emerging data indicate its clinical significance in treating vascular-related diseases, metabolic syndrome, and gastro-protective effects. The dearth of potent drugs for management of such disorders necessitates the urge for further research into the pharmacological aspects of capsaicin. This review summarizes the historical background, source, structure and analogues of capsaicin, and capsaicin-triggered TRPV1 signaling and desensitization processes. In particular, we will focus on the therapeutic roles of capsaicin and its analogues in both normal and pathophysiological conditions.

Intramuscular temperature modulates glutamate-evoked masseter muscle pain intensity in humans.

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Sato, Hitoshi; Castrillon, Eduardo E; Cairns, Brian E; Bendixen, Karina H; Wang, Kelun; Nakagawa, Taneaki; Wajima, Koichi; Svensson, Peter

2015-01-01

To determine whether glutamate-evoked jaw muscle pain is altered by the temperature of the solution injected. Sixteen healthy volunteers participated and received injections of hot (48°C), neutral (36°C), or cold (3°C) solutions (0.5 mL) of glutamate or isotonic saline into the masseter muscle. Pain intensity was assessed with an electronic visual analog scale (eVAS). Numeric rating scale (NRS) scores of unpleasantness and temperature perception, pain-drawing areas, and pressure pain thresholds (PPTs) were also measured. Participants filled out the McGill Pain Questionnaire (MPQ). Two-way or three-way repeated measures ANOVA were used for data analyses. Injection of hot glutamate and cold glutamate solutions significantly increased and decreased, respectively, the peak pain intensity compared with injection of neutral glutamate solution. The duration of glutamate-evoked pain was significantly longer when hot glutamate was injected than when cold glutamate was injected. No significant effect of temperature on pain intensity was observed when isotonic saline was injected. No effect of solution temperature was detected on unpleasantness, heat perception, cold perception, area of pain drawings, or PPTs. There was a significantly greater use of the "numb" term in the MPQ to describe the injection of cold solutions compared to the injection of both neutral and hot solutions. Glutamate-evoked jaw muscle pain was significantly altered by the temperature of the injection solution. Although temperature perception in the jaw muscle is poor, pain intensity is increased when the muscle tissue temperature is elevated.

Evoked potentials after painful cutaneous electrical stimulation depict pain relief during a conditioned pain modulation.

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Höffken, Oliver; Özgül, Özüm S; Enax-Krumova, Elena K; Tegenthoff, Martin; Maier, Christoph

2017-08-29

Conditioned pain modulation (CPM) evaluates the pain modulating effect of a noxious conditioning stimulus (CS) on another noxious test stimulus (TS), mostly based solely on subjective pain ratings. We used painful cutaneous electrical stimulation (PCES) to induce TS in a novel CPM-model. Additionally, to evaluate a more objective parameter, we recorded the corresponding changes of cortical evoked potentials (PCES-EP). We examined the CPM-effect in 17 healthy subjects in a randomized controlled cross-over design during immersion of the non-dominant hand into 10 °C or 24 °C cold water (CS). Using three custom-built concentric surface electrodes, electrical stimuli were applied on the dominant hand, inducing pain of 40-60 on NRS 0-100 (TS). At baseline, during and after CS we assessed the electrically induced pain intensity and electrically evoked potentials recorded over the central electrode (Cz). Only in the 10 °C-condition, both pain (52.6 ± 4.4 (baseline) vs. 30.3 ± 12.5 (during CS)) and amplitudes of PCES-EP (42.1 ± 13.4 μV (baseline) vs. 28.7 ± 10.5 μV (during CS)) attenuated during CS and recovered there after (all p pain ratings during electrical stimulation and amplitudes of PCES-EP correlated significantly with each other (r = 0.5) and with CS pain intensity (r = 0.5). PCES-EPs are a quantitative measure of pain relief, as changes in the electrophysiological response are paralleled by a consistent decrease in subjective pain ratings. This novel CPM paradigm is a feasible method, which could help to evaluate the function of the endogenous pain modulation processes. German Clinical Trials Register DRKS-ID: DRKS00012779 , retrospectively registered on 24 July 2017.

Pharmacodynamic analysis of the analgesic effect of capsaicin 8% patch (QutenzaTM in diabetic neuropathic pain patients: detection of distinct response groups

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Martini C

2012-03-01

Full Text Available Christian Martini1,*, Ashraf Yassen2,*, Erik Olofsen1, Paul Passier2, Malcom Stoker3, Albert Dahan1 1Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands; 2Global Clinical Pharmacology and Exploratory Development, Astellas Pharma Global Development Europe, Leiderdorp, The Netherlands; 3Global Medical Sciences, Astellas Pharma Global Development Europe, Leiderdorp, The Netherlands*These authors contributed equally to this workAbstract: Treatment of chronic pain is associated with high variability in the response to pharmacological interventions. A mathematical pharmacodynamic model was developed to quantify the magnitude and onset/offset times of effect of a single capsaicin 8% patch application in the treatment of painful diabetic peripheral neuropathy in 91 patients. In addition, a mixture model was applied to objectively match patterns in pain-associated behavior. The model identified four distinct subgroups that responded differently to treatment: 3.3% of patients (subgroup 1 showed worsening of pain; 31% (subgroup 2 showed no change; 32% (subgroup 3 showed a quick reduction in pain that reached a nadir in week 3, followed by a slow return towards baseline (16% ± 6% pain reduction in week 12; 34% (subgroup 4 showed a quick reduction in pain that persisted (70% ± 5% reduction in week 12. The estimate of the response-onset rate constant, obtained for subgroups 1, 3, and 4, was 0.76 ± 0.12 week-1 (median ± SE, indicating that every 0.91 weeks the pain score reduces or increases by 50% relative to the score of the previous week (= t½. The response-offset rate constant could be determined for subgroup 3 only and was 0.09 ± 0.04 week-1 (t½ 7.8 weeks. The analysis allowed separation of a heterogeneous neuropathic pain population into four homogenous subgroups with distinct behaviors in response to treatment with capsaicin. It is argued that this model-based approach may have added value in analyzing

Role of ventrolateral orbital cortex muscarinic and nicotinic receptors in modulation of capsaicin-induced orofacial pain-related behaviors in rats.

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Tamaddonfard, Esmaeal; Erfanparast, Amir; Abbas Farshid, Amir; Delkhosh-Kasmaie, Fatmeh

2017-11-15

Acetylcholine, as a major neurotransmitter, mediates many brain functions such as pain. This study was aimed to investigate the effects of microinjection of muscarinic and nicotinic acetylcholine receptor antagonists and agonists into the ventrolateral orbital cortex (VLOC) on capsaicin-induced orofacial nociception and subsequent hyperalgesia. The right side of VLOC was surgically implanted with a guide cannula in anaesthetized rats. Orofacial pain-related behaviors were induced by subcutaneous injection of a capsaicin solution (1.5µg/20µl) into the left vibrissa pad. The time spent face rubbing with ipsilateral forepaw and general behavior were recorded for 10min, and then mechanical hyperalgesia was determined using von Frey filaments at 15, 30, 45 and 60min post-capsaicin injection. Alone intra-VLOC microinjection of atropine (a muscarinic acetylcholine receptor antagonist) and mecamylamine (a nicotinic acetylcholine receptor antagonist) at a similar dose of 200ng/site did not alter nocifensive behavior and hyperalgesia. Microinjection of oxotremorine (a muscarinic acetylcholine receptor agonist) at doses of 50 and 100ng/site and epibatidine (a nicotinic acetylcholine receptor agonist) at doses of 12.5, 25, 50 and 100ng/site into the VLOC suppressed pain-related behaviors. Prior microinjections of 200ng/site atropine and mecamylamine (200ng/site) prevented oxotremorine (100ng/site)-, and epibatidine (100ng/site)-induced antinociception, respectively. None of the above-mentioned chemicals changed general behavior. These results showed that the VLOC muscarinic and nicotinic acetylcholine receptors might be involved in modulation of orofacial nociception and hypersensitivity. Copyright © 2017 Elsevier B.V. All rights reserved.

Capsaicin-loaded nanolipoidal carriers for topical application: design, characterization, and in vitro/in vivo evaluation

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Wang XR

2017-05-01

Full Text Available Xia-Rong Wang,1 Si-Qian Gao,1 Xiao-Qian Niu,1 Long-Jian Li,2 Xiao-Ying Ying,1 Zhong-Jie Hu,2 Jian-Qing Gao1,3 1Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 2Zhejiang Provincial Corps Hospital of Chinese People’s Armed Police Forces, Jiaxing, Zhejiang, 3Jiangsu Engineering Research Center for New-Type External and Transdermal Preparations, Jiangsu, People’s Republic of China Abstract: Capsaicin has been used in clinical applications for the treatment of pain disorders and inflammatory diseases. Given the strong pungency and high oil/water partition coefficient of capsaicin, capsaicin-loaded nanolipoidal carriers (NLCs were designed to increase permeation and achieve the analgesic, anti-inflammatory effect with lower skin irritation. Capsaicin-loaded NLCs were prepared and later optimized by the Box–Behnken design. The physicochemical characterizations, morphology, and encapsulation of the capsaicin-loaded NLCs were subsequently confirmed. Capsaicin-loaded NLCs and capsaicin-loaded NLCs gel exhibited sustained release and no cytotoxicity properties. Also, they could significantly enhance the penetration amount, permeation flux, and skin retention amounts of capsaicin due to the application of NLCs. To study the topical permeation mechanism of capsaicin, 3,3'-dioctadecyloxacarbocyanine perchlorate (Dio was used as a fluorescent dye. Dio-loaded NLCs and Dio-loaded NLCs gel could effectively deliver Dio up to a skin depth of 260 and 210 µm, respectively, primarily through the appendage route on the basis of version skin sections compared with Dio solution, which only delivered Dio up to 150 µm. In vivo therapeutic experiments demonstrated that capsaicin-loaded NLCs and capsaicin-loaded NLCs gel could improve the pain threshold in a dose-dependent manner and inhibit inflammation, primarily by reducing the prostaglandin E2 levels in the tissue compared with capsaicin cream and capsaicin solution

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

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

2015-02-12

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

A modification of a previous model fo r inflammatory tooth pain: Effects of different capsaicin and formalin concentrations and ibuprofen

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Maryam Raoof DDS, MS

2012-09-01

Full Text Available BACKGROUND AND AIM:This study aimed to solve the problems faced with the previous model of inflammatory tooth painin rats.METHODS:After cutting 2 mm of the distal extremities, the polyethylene crownswere placed on the mandibularincisors. In contrast to the original model, we used flow composite instead of wire in order to maximize the retention ofcrowns. Different concentrations of capsaicin (10, 25 and 100 mg/ml and formalin were administrated into the cavitiesunder the crowns. The algesic agent-induced behaviors were evaluated.RESULTS:The modified model had no liquid leakage. Furthermore, composite allowed the crowns to remain for alonger period of time. Capsaicin 25, 100 mg/ml and formalin applications induced significantly more painfulstimulation compared with control groups (P < 0.001. These responses were significantly reduced by theadministration of ibuprofen, 20 minutes prior to the capsaicin 100 mg/ml injection.CONCLUSIONS:This model seems to be adequate for long-term pain related experiments in which fluid leakageelimination is important.

Capsaicin-induced neurogenic inflammation in pig skin: A behavioural study

DEFF Research Database (Denmark)

di Giminiani, Pierpaolo; Petersen, Lars Jelstrup; Herskin, Mette S

2014-01-01

Topical capsaicin is a well-established model of experimental hyperalgesia. Its application to the study of animals has been limited to few species. The effect of topical capsaicin on hyperalgesia in porcine skin was evaluated as part of a study of inflammatory pain in the pig. Two experiments were...... carried out on pigs of 27 ± 5 kg (n = 8) and 57 ± 3 kg (n = 16). Thermal and mechanical noxious stimuli were provided (CO2 laser and Pressure Application Measurement device) to assess avoidance behaviours. Capsaicin induced significant thermal hyperalgesia in the smaller pigs (P

Is physician supervision of the capsaicin 8% patch administration procedure really necessary? An opinion from health care professionals

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Kern KU

2013-07-01

Full Text Available Kai-Uwe Kern,1 Janice England,2 Andrea Roth-Daniek,3 Till Wagner3 1Institute for Pain Medicine/Pain Practice, Wiesbaden, Germany; 2Pain Medicine and Anaesthesia, The Christie National Health Service Foundation Trust, Manchester, UK; 3Pain Therapy and Palliative Care Department, Medizinisches Zentrum Städteregion Aachen, Aachen, Germany Abstract: Neuropathic pain is difficult to treat and can have a severe effect on quality of life. The capsaicin 8% patch is a novel treatment option that directly targets the source of peripheral neuropathic pain. It can provide pain relief for up to 12 weeks in patients with peripheral neuropathic pain. Treatment with the capsaicin 8% patch follows a clearly defined procedure, and patch application must be carried out by a physician or a health care professional under the supervision of a physician. Nonetheless, in our experience, nurses often take the lead role in capsaicin 8% patch application without the involvement of a physician. We believe that the nurse's key role is of benefit to the patients, as he or she may be better placed, because of time constraints and patient relationships, to support the patient through the application procedure than a physician. Moreover, a number of frequently prescribed drugs, including botulinum toxin and infliximab, can be administered by health care professionals without the requirement for physician supervision. Here we argue that current guidance should be amended to remove the requirement for physician supervision during application of the capsaicin 8% patch. Keywords: capsaicin, neuropathic pain, topical, health care professional, physician, nurse

High-dose 8% capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy: single-center experience.

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Filipczak-Bryniarska, Iwona; Krzyzewski, Roger M; Kucharz, Jakub; Michalowska-Kaczmarczyk, Anna; Kleja, Justyna; Woron, Jarosław; Strzepek, Katarzyna; Kazior, Lucyna; Wordliczek, Jerzy; Grodzicki, Tomasz; Krzemieniecki, Krzysztof

2017-08-17

High-dose capsaicin patch is effective in treatment of neuropathic pain in HIV-associated neuropathy and diabetic neuropathy. There are no studies assessing effectiveness of high-dose capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy. We sought to determine the effectiveness of treatment of pain associated with chemotherapy-induced peripheral neuropathy with high-dose capsaicin patch. Our study group consisted of 18 patients with clinically confirmed oxaliplatin-induced neuropathy. Baseline characteristic including underling disease, received cumulative dose of neurotoxic agent, neuropathic symptoms, prior treatment and initial pain level were recorded. Pain was evaluated with Numeric Rating Scale prior to treatment with high-dose capsaicin and after 1.8 day and after 8 and 12 weeks after introducing treatment. Patients were divided into two groups accordingly to the amount of neurotoxic agent that caused neuropathy (high sensitivity and low sensitivity group). Most frequent symptoms of chemotherapy-induced neuropathy were: pain (88.89%), paresthesis (100%), sock and gloves sensation (100%) and hypoesthesis (100%). Initial pain level was 7.45 ± 1.14. Mean cumulative dose of oxaliplatin after which patients developed symptoms was 648.07 mg/m 2 . Mean pain level after 12 weeks of treatment was 0.20 ± 0.41. When examined according to high and low sensitivity to neurotoxic agent patients with low sensitivity had higher pain reduction, especially after 8 days after introducing treatment (69.55 ± 12.09 vs. 49.40 ± 20.34%; p = 0.02) and after 12 weeks (96.96 ± 5.56 vs. 83.93 ± 18.59%; p = 0.04). High-dose capsaicin patch is an effective treatment for pain associated with chemotherapy-induced neuropathy in patients treated with oxaliplatin. Patients with lower sensitivity to neurotoxic agents have better response to treatment and pain reduction.

Antipruritic effect of pretreatment with topical capsaicin 8% on histamine- and cowhage-evoked itch in healthy volunteers

DEFF Research Database (Denmark)

Andersen, Hjalte Holm; Marker, Jens Broch; Hoeck, Emil A.

2017-01-01

capsaicin 8% pretreatment for 24 h reduced histaminergic and nonhistaminergic itch by about 75%, while a significant reduction (≈60%) was achieved for only nonhistaminergic itch in a standard 1-h treatment. Further investigations are needed to elucidate the clinical potential of high-concentration capsaicin...

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

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Arjun eMuralidharan

2016-05-01

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

Stress-evoked opioid release inhibits pain in major depressive disorder.

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Frew, Ashley K; Drummond, Peter D

2008-10-15

To determine whether stress-evoked release of endogenous opioids might account for hypoalgesia in major depressive disorder (MDD), the mu-opioid antagonist naltrexone (50mg) or placebo was administered double-blind to 24 participants with MDD and to 31 non-depressed controls. Eighty minutes later participants completed a painful foot cold pressor test and, after a 5-min interval, began a 25-min arithmetic task interspersed with painful electric shocks. Ten minutes later participants completed a second cold pressor test. Negative affect was greater in participants with MDD than in non-depressed controls throughout the experiment, and increased significantly in both groups during mental arithmetic. Before the math task, naltrexone unmasked direct linear relationships between severity of depression, negative affect while resting quietly, and cold-induced pain in participants with MDD. In contrast, facilitatory effects of naltrexone on cold- and shock-induced pain were greatest in controls with the lowest depression scores. Naltrexone strengthened the relationship between negative affect and shock-induced pain during the math task, particularly in the depressed group, and heightened anxiety in both groups toward the end of the task. Thus, mu-opioid activity apparently masked a positive association between negative affect and pain in the most distressed participants. These findings suggest that psychological distress inhibits pain via stress-evoked release of opioid peptides in severe cases of MDD. In addition, tonic endogenous opioid neurotransmission could inhibit depressive symptoms and pain in people with low depression scores.

The TRPV1 channel in rodents is a major target for antinociceptive effect of the probiotic Lactobacillus reuteri DSM 17938

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Perez-Burgos, Azucena; Wang, Lu; McVey Neufeld, Karen-Anne; Mao, Yu-Kang; Ahmadzai, Mustafa; Janssen, Luke J; Stanisz, Andrew M; Bienenstock, John; Kunze, Wolfgang A

2015-01-01

Abstract Certain bacteria exert visceral antinociceptive activity, but the mechanisms involved are not determined. Lactobacillus reuteri DSM 17938 was examined since it may be antinociceptive in children. Since transient receptor potential vanilloid 1 (TRPV1) channel activity may mediate nociceptive signals, we hypothesized that TRPV1 current is inhibited by DSM. We tested this by examining the effect of DSM on the firing frequency of spinal nerve fibres in murine jejunal mesenteric nerve bundles following serosal application of capsaicin. We also measured the effects of DSM on capsaicin-evoked increase in intracellular Ca2+ or ionic current in dorsal root ganglion (DRG) neurons. Furthermore, we tested the in vivo antinociceptive effects of oral DSM on gastric distension in rats. Live DSM reduced the response of capsaicin- and distension-evoked firing of spinal nerve action potentials (238 ± 27.5% vs. 129 ± 17%). DSM also reduced the capsaicin-evoked TRPV1 ionic current in DRG neuronal primary culture from 83 ± 11% to 41 ± 8% of the initial response to capsaicin only. Another lactobacillus (Lactobacillus rhamnosus JB-1) with known visceral anti-nociceptive activity did not have these effects. DSM also inhibited capsaicin-evoked Ca2+ increase in DRG neurons; an increase in Ca2+ fluorescence intensity ratio of 2.36 ± 0.31 evoked by capsaicin was reduced to 1.25 ± 0.04. DSM releasable products (conditioned medium) mimicked DSM inhibition of capsaicin-evoked excitability. The TRPV1 antagonist 6-iodonordihydrocapsaicin or the use of TRPV1 knock-out mice revealed that TRPV1 channels mediate about 80% of the inhibitory effect of DSM on mesenteric nerve response to high intensity gut distension. Finally, feeding with DSM inhibited perception in rats of painful gastric distension. Our results identify a specific target channel for a probiotic with potential therapeutic properties. Key points Certain probiotic bacteria have been shown to reduce distension

Dietary Capsaicin Protects Cardiometabolic Organs from Dysfunction

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Fang Sun

2016-04-01

Full Text Available Chili peppers have a long history of use for flavoring, coloring, and preserving food, as well as for medical purposes. The increased use of chili peppers in food is very popular worldwide. Capsaicin is the major pungent bioactivator in chili peppers. The beneficial effects of capsaicin on cardiovascular function and metabolic regulation have been validated in experimental and population studies. The receptor for capsaicin is called the transient receptor potential vanilloid subtype 1 (TRPV1. TRPV1 is ubiquitously distributed in the brain, sensory nerves, dorsal root ganglia, bladder, gut, and blood vessels. Activation of TRPV1 leads to increased intracellular calcium signaling and, subsequently, various physiological effects. TRPV1 is well known for its prominent roles in inflammation, oxidation stress, and pain sensation. Recently, TRPV1 was found to play critical roles in cardiovascular function and metabolic homeostasis. Experimental studies demonstrated that activation of TRPV1 by capsaicin could ameliorate obesity, diabetes, and hypertension. Additionally, TRPV1 activation preserved the function of cardiometabolic organs. Furthermore, population studies also confirmed the beneficial effects of capsaicin on human health. The habitual consumption of spicy foods was inversely associated with both total and certain causes of specific mortality after adjustment for other known or potential risk factors. The enjoyment of spicy flavors in food was associated with a lower prevalence of obesity, type 2 diabetes, and cardiovascular diseases. These results suggest that capsaicin and TRPV1 may be potential targets for the management of cardiometabolic vascular diseases and their related target organs dysfunction.

Postoperative Pain and Flare-Ups: Comparison of Incidence Between Single and Multiple Visit Pulpectomy in Primary Molars

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Gowda, Subhadra Halemane Nagaraj

2017-01-01

Introduction Endodontic treatment performed in either single- or multiple visit can be followed by numerous short- and long term complications. One of the short term complications include postoperative pain and flare–ups. The ability to predict its prevalence and forewarn the patient may go some way towards enabling coping strategies and help dentist in pain management treatment decisions Aim To compare the incidence and intensity of postoperative pain and flare-ups between single- and multiple visit pulpectomy in primary molars. Also, to correlate the preoperative status of the pulp to postoperative pain and flare-ups. Materials and Methods Eighty primary molars indicated for pulpectomy were included in the study and divided into two groups. Tooth treated and preoperative status of the pulp vitality was recorded. All the conventional steps in pulpectomy were followed. Teeth in Group 1 (single visit pulpectomy) were obturated on the same visit. Teeth in Group 2 (multiple visit pulpectomy) were obturated in the subsequent appointment. The recording of postoperative pain, flare-ups, use of medication were done after 24 hours, seven days and one month. Results Four cases in both the groups reported postoperative pain (10%) at 24 hour recall, p=0.74. One flare-up (2.5%) was recorded in each group p=0.67. None of the patients reported pain at seventh day and one month recall. Postoperative pain was recorded in five non-vital teeth (13.5%) and three vital teeth (6.9%). However, it was statistically not significant p=0.53. Conclusion From the perspective of our study there was a low incidence of postoperative pain. The majority of patients in both groups reported no pain or only minimal pain within 24 hours of treatment. There were no differences between single- and multi visit treatment protocols with respect to the incidence of postoperative pain. No significant correlation could be found between pulp vitality and the incidence of postoperative pain. PMID:28511499

Dexamethasone for the prevention of a pain flare after palliative radiotherapy for painful bone metastases : a multicenter double-blind placebo-controlled randomized trial

NARCIS (Netherlands)

Westhoff, Paulien G.; de Graeff, Alexander; Geerling, Jenske I.; Reyners, Anna K. L.; van der Linden, Yvette M.

2014-01-01

Background: Radiotherapy has a good effect in palliation of painful bone metastases, with a pain response rate of more than 60%. However, shortly after treatment, in approximately 40% of patients a temporary pain flare occurs, which is defined as a two-point increase of the worst pain score on an

Functional deficits in peripheral nerve mitochondria in rats with paclitaxel- and oxaliplatin-evoked painful peripheral neuropathy

OpenAIRE

Zheng, Huaien; Xiao, Wen Hua; Bennett, Gary J.

2011-01-01

Cancer chemotherapeutics like paclitaxel and oxaliplatin produce a dose-limiting chronic sensory peripheral neuropathy that is often accompanied by neuropathic pain. The cause of the neuropathy and pain is unknown. In animal models, paclitaxel-evoked and oxaliplatin-evoked painful peripheral neuropathies are accompanied by an increase in the incidence of swollen and vacuolated mitochondria in peripheral nerve axons. It has been proposed that mitochondrial swelling and vacuolation are indicati...

Bi-phasic activation of the primary motor cortex by pain and its relation to pain-evoked potentials - an exploratory study.

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Kisler, Lee-Bareket; Weissman-Fogel, Irit; Sinai, Alon; Sprecher, Elliot; Chistyakov, Andrei V; Shamay-Tsoory, Simone; Moscovitz, Nadav; Granovsky, Yelena

2017-06-15

The primary motor cortex (M1) is a known target for brain stimulation aimed at pain alleviation in chronic pain patients, yet the mechanisms through which analgesia occurs, and the exact pain-motor interrelations are not fully understood. We used noxious contact heat evoked potentials (CHEPs) and cortical source analysis to further explore the relevance of M1 in pain processing. Twenty-four healthy young females received brief noxious heat stimuli to their left non-dominant volar forearm, simultaneously with CHEPs recordings. Thereafter, the pain-evoked activity of M1 and a control area in the occipital cortex (OC) was analyzed and estimated using sLORETA (standardized low-resolution brain electromagnetic tomography). This analysis revealed two phases of M1 pain-evoked activation (phase 1: the peak at 261.5±25.7ms; phase 2: the peak at 381.3±28.3ms). Canonical correlations revealed that M1, but not the OC, was the main factor contributing to the relation with the CHEPs components. In detail, the activity magnitude of M1 first and second phases was related to the N2 and P2 amplitude, respectively. The latency of the second phase was associated with both N2 and P2 latencies. In relation to pain, the latency of M1's first activity phase was positively correlated with pain ratings, suggesting pain interference to synchronized activity in M1. Our results confirm the established relevance of the primary motor cortex to pain processing. Copyright © 2017 Elsevier B.V. All rights reserved.

Biomarkers of neuropathic pain in skin nerve degeneration neuropathy: contact heat-evoked potentials as a physiological signature.

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Wu, Shao-Wei; Wang, Yi-Chia; Hsieh, Paul-Chen; Tseng, Ming-Tsung; Chiang, Ming-Chang; Chu, Chih-Pang; Feng, Fang-Ping; Lin, Yea-Huey; Hsieh, Sung-Tsang; Chao, Chi-Chao

2017-03-01

Contact heat-evoked potentials (CHEPs) have become an established method of assessing small-fiber sensory nerves; however, their potential as a physiological signature of neuropathic pain symptoms has not been fully explored. To investigate the diagnostic efficacy in examining small-fiber sensory nerve degeneration, the relationship with skin innervations, and clinical correlates with sensory symptoms, we recruited 188 patients (115 men) with length-dependent sensory symptoms and reduced intraepidermal nerve fiber (IENF) density at the distal leg to perform CHEP, quantitative sensory testing, and nerve conduction study. Fifty-seven age- and sex-matched controls were enrolled for comparison of CHEP and skin innervation. Among patients with neuropathy, 144 patients had neuropathic pain and 64 cases had evoked pain. Compared with quantitative sensory testing and nerve conduction study parameters, CHEP amplitudes showed the highest sensitivity for diagnosing small-fiber sensory nerve degeneration and exhibited the strongest correlation with IENF density in multiple linear regression. Contact heat-evoked potential amplitudes were strongly correlated with the degree of skin innervation in both patients with neuropathy and controls, and the slope of the regression line between CHEP amplitude and IENF density was higher in patients with neuropathy than in controls. Patients with evoked pain had higher CHEP amplitude than those without evoked pain, independent of IENF density. Receiver operating characteristic analysis showed that CHEP had better performance in diagnosing small-fiber sensory nerve degeneration than thermal thresholds. Furthermore, CHEPs showed superior classification accuracy with respect to evoked pain. In conclusion, CHEP is a sensitive tool to evaluate pathophysiology of small-fiber sensory nerve and serves as a physiological signature of neuropathic pain symptoms.

In vitro and in vivo evaluation of capsaicin-loaded microemulsion for enhanced oral bioavailability.

Science.gov (United States)

Zhu, Yuan; Zhang, Jiajia; Zheng, Qianfeng; Wang, Miaomiao; Deng, Wenwen; Li, Qiang; Firempong, Caleb Kesse; Wang, Shengli; Tong, Shanshan; Xu, Ximing; Yu, Jiangnan

2015-10-01

Capsaicin, as a food additive, has attracted worldwide concern owing to its pungency and multiple pharmacological effects. However, poor water solubility and low bioavailability have limited its application. This study aims to develop a capsaicin-loaded microemulsion to enhance the oral bioavailability of the anti-neuropathic-pain component, capsaicin, which is poorly water soluble. In this study, the microemulsion consisting of Cremophor EL, ethanol, medium-chain triglycerides (oil phase) and water (external phase) was prepared and characterized (particle size, morphology, stability and encapsulation efficiency). The gastric mucosa irritation test of formulated capsaicin was performed in rats to evaluate its oral feasibility, followed by the pharmacokinetic study in vivo. Under these conditions, the encapsulated capsaicin revealed a faster capsaicin release in vitro coupled with a greater absorption in vivo when compared to the free capsaicin. The oral bioavailability of the formulated capsaicin-loaded microemulsions was 2.64-fold faster than that of free capsaicin. No significant irritation was observed on the mucosa from the pathological section of capsaicin-loaded microemulsion treated stomach. These results indicate that the developed microemulsion represents a safe and orally effective carrier for poorly soluble substances. The formulation could be used for clinical trials and expand the application of capsaicin. © 2014 Society of Chemical Industry.

Modulation of oral heat and cold pain by irritant chemicals.

Science.gov (United States)

Albin, Kelly C; Carstens, Mirela Iodi; Carstens, E

2008-01-01

Common food irritants elicit oral heat or cool sensations via actions at thermosensitive transient receptor potential (TRP) channels. We used a half-tongue, 2-alternative forced-choice procedure coupled with bilateral pain intensity ratings to investigate irritant effects on heat and cold pain. The method was validated in a bilateral thermal difference detection task. Capsaicin, mustard oil, and cinnamaldehyde enhanced lingual heat pain elicited by a 49 degrees C stimulus. Mustard oil and cinnamaldehyde weakly enhanced lingual cold pain (9.5 degrees C), whereas capsaicin had no effect. Menthol significantly enhanced cold pain and weakly reduced heat pain. To address if capsaicin's effect was due to summation of perceptually similar thermal and chemical sensations, one-half of the tongue was desensitized by application of capsaicin. Upon reapplication, capsaicin elicited little or no irritant sensation yet still significantly enhanced heat pain on the capsaicin-treated side, ruling out summation. In a third experiment, capsaicin significantly enhanced pain ratings to graded heat stimuli (47 degrees C to 50 degrees C) resulting in an upward shift of the stimulus-response function. Menthol may induce cold hyperalgesia via enhanced thermal gating of TRPM8 in peripheral fibers. Capsaicin, mustard oil, and cinnamaldehyde may induce heat hyperalgesia via enhanced thermal gating of TRPV1 that is coexpressed with TRPA1 in peripheral nociceptors.

Effects of insomnia disorder and knee osteoarthritis on resting and pain-evoked inflammatory markers.

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Quartana, Phillip J; Finan, Patrick H; Page, Gayle G; Smith, Michael T

2015-07-01

Osteoarthritis is the most prevalent arthritic condition. Systemic inflammatory cytokines appear to have an important role in the onset and maintenance of the disease. Sleep disturbances are prevalent in osteoarthritis and associated with alterations in systemic inflammatory cytokines, suggesting a common pathophysiology across these conditions. A comparative investigation of the effects of insomnia disorder and osteoarthritis on pain-evoked cytokine responses has yet to be undertaken. We examined the influence of symptomatic knee osteoarthritis and insomnia disorder on resting C-reactive protein (CRP), interleukin (IL)-6, and IL-10 levels, and pain-evoked IL-6 and IL-10 responses. Participants were N=117 older adults (mean age=59.7years; 61.8% women) rigorously evaluated for knee osteoarthritis and insomnia disorder using established diagnostic guidelines. Results revealed no association of osteoarthritis or insomnia disorder with CRP. Resting IL-6 was greater in osteoarthritis participants versus those without osteoarthritis, although this association was largely attributable to BMI. IL-10 was highest among participants with osteoarthritis or insomnia disorder. Growth curve modeling revealed that participants with insomnia disorder had greater pain-evoked IL-6 responses than participants without insomnia disorder or osteoarthritis. These findings highlight the utility of laboratory pain testing methods for understanding individual differences in inflammatory cytokines. Moreover, our findings provide evidence for amplified pain-evoked pro-inflammatory cytokine reactivity among older adults with clinically diagnosed insomnia disorder, even after controlling for individual differences in BMI and age. Additional research will be required determine whether an amplified pain-related cytokine response contributes to OA, and possibly other age-related disease, associated with insomnia disorder. Published by Elsevier Inc.

Inhibition of calcineurin inhibits the desensitization of capsaicin evoked currents in cultured dorsal root ganglion neurones from adult rats

NARCIS (Netherlands)

Docherty, RJ; Yeats, JC; Bevan, S; Boddeke, HWGM

Capsaicin activates a non-specific cation conductance in mammalian sensory neurones. If capsaicin is applied continuously or repeatedly then there is a progressive decline in responsiveness. We have studied the mechanism of this desensitization using electrophysiological methods in cultured dorsal

Acidification of rat TRPV1 alters the kinetics of capsaicin responses

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Faltynek Connie R

2005-09-01

Full Text Available Abstract TRPV1 (vanilloid receptor 1 receptors are activated by a variety of ligands such as capsaicin, as well as by acidic conditions and temperatures above 42°C. These activators can enhance the potency of one another, shifting the activation curve for TRPV1 to the left. In this study, for example, we observed an approximately 10-fold shift in the capsaicin EC50 (640 nM to 45 nM for rat TRPV1 receptors expressed in HEK-293 cells when the pH was lowered from 7.4 to 5.5. To investigate potential causes for this shift in capsaicin potency, the rates of current activation and deactivation of whole-cell currents were measured in individual cells exposed to treatments of pH 5.5, 1 μM capsaicin or in combination. Acidic pH was found to both increase the activation rate and decrease the deactivation rate of capsaicin-activated currents providing a possible mechanism for the enhanced potency of capsaicin under acidic conditions. Utilizing a paired-pulse protocol, acidic pH slowed the capsaicin deactivation rate and was readily reversible. Moreover, the effect could occur under modestly acidic conditions (pH 6.5 that did not directly activate TRPV1. When TRPV1 was maximally activated by capsaicin and acidic pH, the apparent affinity of the novel and selective capsaicin-site competitive TRPV1 antagonist, A-425619, was reduced ~35 fold. This shift was overcome by reducing the capsaicin concentration co-applied with acidic pH. Since inflammation is associated with tissue acidosis, these findings enhance understanding of TRPV1 receptor responses in inflammatory pain where tissue acidosis is prevalent.

Prolonged maintenance of capsaicin-induced hyperalgesia by brief daily vibration stimuli.

Science.gov (United States)

Kim, Hee Kee; Schattschneider, Jörn; Lee, Inhyung; Chung, Kyungsoon; Baron, Ralf; Chung, Jin Mo

2007-05-01

This study tests the hypothesis that central sensitization initiated by nociceptive input can be maintained by repeated brief innocuous peripheral inputs. Capsaicin was injected intradermally into the hind paw of adult rats. Three different types of daily cutaneous mechanical stimulations (vibration, soft brush, or pressure) were applied to the capsaicin-injected paw for a period of 2 weeks. Daily stimulation consisted of a 10-s stimulation repeated every 30s for 30 min. Foot withdrawal thresholds to von Frey stimuli applied to the paw were measured once a day for 4 weeks. The capsaicin-only group (control rats without daily stimulation) showed hyperalgesia lasting for 3 days. In contrast, hyperalgesia persisted for 2 weeks in the group that received vibration stimulation. Neither the soft brush nor the pressure group showed a significant difference in mechanical threshold from the control group (capsaicin only). The vibration-induced prolonged hyperalgesia was significantly reduced by systemic injection of ifenprodil, an NMDA-receptor antagonist, but it was not influenced by either an AMPA-receptor blocker or a reactive oxygen species (ROS) scavenger. Furthermore, a dorsal column lesion did not interfere with the prolongation of hyperalgesia. Data suggest that vibration-induced prolongation of hyperalgesia is mediated by spinal NMDA-receptors, and a similar mechanism may underlie some forms of chronic pain with no obvious causes, such as complex regional pain syndrome type 1 (CRPS-1).

Pain Flare Is a Common Adverse Event in Steroid-Naïve Patients After Spine Stereotactic Body Radiation Therapy: A Prospective Clinical Trial

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Chiang, Andrew [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON (Canada); Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, ON (Canada); Zeng, Liang; Zhang, Liying; Lochray, Fiona; Korol, Renee; Loblaw, Andrew; Chow, Edward [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON (Canada); Sahgal, Arjun, E-mail: arjun.sahgal@sunnybrook.ca [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON (Canada); Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, ON (Canada)

2013-07-15

Purpose: To determine the incidence of pain flare after spine stereotactic body radiation therapy (SBRT) in steroid-naïve patients and identify predictive factors. Methods and Materials: Forty-one patients were treated with spine SBRT between February 2010 and April 2012. All patients had their pain assessed at baseline, during, and for 10 days after SBRT using the Brief Pain Inventory. All pain medications were recorded daily and narcotics converted to an oral morphine equivalent dose. Pain flare was defined as a 2-point increase in worst pain score as compared with baseline with no decrease in analgesic intake, a 25% increase in analgesic intake as compared with baseline with no decrease in worst pain score, or if corticosteroids were initiated at any point during or after SBRT because of pain. Results: The median age and Karnofsky performance status were 57.5 years (range, 27-80 years) and 80 (range, 50-100), respectively. Eighteen patients were treated with 20-24 Gy in a single fraction, whereas 23 patients were treated with 24-35 Gy in 2-5 fractions. Pain flare was observed in 68.3% of patients (28 of 41), most commonly on day 1 after SBRT (29%, 8 of 28). Multivariate analysis identified a higher Karnofsky performance status (P=.02) and cervical (P=.049) or lumbar (P=.02) locations as significant predictors of pain flare. In those rescued with dexamethasone, a significant decrease in pain scores over time was subsequently observed (P<.0001). Conclusions: Pain flare is a common adverse event after spine SBRT and occurs most commonly the day after treatment completion. Patients should be appropriately consented for this adverse event.

The prevalence of postoperative pain and flare-up in single- and multiple-visit endodontic treatment: a systematic review.

Science.gov (United States)

Sathorn, C; Parashos, P; Messer, H

2008-02-01

The aim of this systematic review was to assess the evidence regarding postoperative pain and flare-up of single- or multiple-visit root canal treatment. CENTRAL, MEDLINE and EMBASE databases were searched. Reference lists from identified articles were scanned. A forward search was undertaken on the authors of the identified articles. Papers that had cited these articles were also identified through Science Citation Index to identify potentially relevant subsequent primary research. The included clinical studies compared the prevalence/severity of postoperative pain or flare-up in single- and multiple-visit root canal treatment. Data in those studies were extracted independently. Sixteen studies fitted the inclusion criteria in the review, with sample size varying from 60 to 1012 cases. The prevalence of postoperative pain ranged from 3% to 58%. The heterogeneity amongst included studies was far too great to conduct meta-analysis and yield meaningful results. Compelling evidence indicating a significantly different prevalence of postoperative pain/flare-up of either single- or multiple-visit root canal treatment is lacking.

Pain trajectory and exercise-induced pain flares during 8 weeks of neuromuscular exercise in individuals with knee and hip pain.

Science.gov (United States)

Sandal, L F; Roos, E M; Bøgesvang, S J; Thorlund, J B

2016-04-01

Patients considering or engaged in exercise as treatment may expect or experience transient increases in joint pain, causing fear of exercise and influencing compliance. This study investigated the pain trajectory during an 8-week neuromuscular exercise (NEMEX) program together with acute exercise-induced pain flares in persons with knee or hip pain. Individuals above 35 years self-reporting persistent knee or hip pain for the past 3 months were offered 8 weeks of supervised NEMEX, performed in groups twice weekly. The program consisted of 11 exercises focusing on joint stability and neuromuscular control. Participants self-reported joint pain on a 0-10 numerical rating scale (NRS) at baseline and 8-weeks follow-up. NRS pain ratings were also collected before and immediately after every attended exercise session. Joint pain was reduced from baseline (NRS 3.6; 95% CI 3.2-4.1) to 8-weeks follow-up (2.6; 95% CI 2.1-3.1), (P neuromuscular exercise. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Early event related fields during visually evoked pain anticipation.

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Gopalakrishnan, Raghavan; Burgess, Richard C; Plow, Ela B; Floden, Darlene P; Machado, Andre G

2016-03-01

Pain experience is not only a function of somatosensory inputs. Rather, it is strongly influenced by cognitive and affective pathways. Pain anticipatory phenomena, an important limitation to rehabilitative efforts in the chronic state, are processed by associative and limbic networks, along with primary sensory cortices. Characterization of neurophysiological correlates of pain anticipation, particularly during very early stages of neural processing is critical for development of therapeutic interventions. Here, we utilized magnetoencephalography to study early event-related fields (ERFs) in healthy subjects exposed to a 3 s visual countdown task that preceded a painful stimulus, a non-painful stimulus or no stimulus. We found that the first countdown cue, but not the last cue, evoked critical ERFs signaling anticipation, attention and alertness to the noxious stimuli. Further, we found that P2 and N2 components were significantly different in response to first-cues that signaled incoming painful stimuli when compared to non-painful or no stimuli. The findings indicate that early ERFs are relevant neural substrates of pain anticipatory phenomena and could be potentially serve as biomarkers. These measures could assist in the development of neurostimulation approaches aimed at curbing the negative effects of pain anticipation during rehabilitation. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Effect of neonatal capsaicin treatment on neural activity in the medullary dorsal horn of neonatal rats evoked by electrical stimulation to the trigeminal afferents: an optical, electrophysiological, and quantitative study.

Science.gov (United States)

Takuma, S

2001-07-06

To elucidate which glutamate receptors, NMDA or non-NMDA, have the main role in synaptic transmission via unmyelinated afferents in the trigeminal subnucleus caudalis (the medullary dorsal horn), and to examine the early functional effects of neonatal capsaicin treatment to the subnucleus caudalis, optical recording, field potential recording, and quantitative study using electron micrographs were employed. A medulla oblongata isolated from a rat 5--7 days old was sectioned horizontally 400-microm thick or parasagittally and stained with a voltage-sensitive dye, RH482 or RH795. Single-pulse stimulation with high intensity to the trigeminal afferents evoked optical responses mainly in the subnucleus caudalis. The optical signals were composed of two phases, a fast component followed by a long-lasting component. The spatiotemporal properties of the optical signals were well correlated to those of the field potentials recorded simultaneously. The fast component was eliminated by 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX; 10 microM), while the long-lasting component was not. The latter increased in amplitude under a condition of low Mg(2+) but was significantly reduced by DL-2-amino-5-phosphonovaleric acid (AP5; 30 microM). Neonatal capsaicin treatment also reduced the long-lasting component markedly. In addition, the decreases in the ratio of unmyelinated axons to myelinated axons and in the ratio of unmyelinated axons to Schwann cell subunits of trigeminal nerve roots both showed significant differences (P<0.05, Student's t-test) between the control group and the neonatal capsaicin treatment group. This line of evidence indirectly suggests that synaptic transmission via unmyelinated afferents in the subnucleus caudalis is mediated substantially by NMDA glutamate receptors and documented that neonatal capsaicin treatment induced a functional alteration of the neural transmission in the subnucleus caudalis as well as a morphological alteration of primary afferents

Facilitation and inhibition by capsaicin of cholinergic neurotransmission in the guinea-pig small intestine.

Science.gov (United States)

Geber, Christian; Mang, Christian F; Kilbinger, Heinz

2006-01-01

The effects of capsaicin on [3H]acetylcholine release and muscle contraction were studied on the myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum preincubated with [3H]choline. Capsaicin concentration-dependently increased both basal [3H]acetylcholine release (pEC50 7.0) and muscle tone (pEC50 6.1). The facilitatory effects of capsaicin were antagonized by 1 microM capsazepine (pK (B) 7.0 and 7.6), and by the combined blockade of NK1 and NK3 tachykinin receptors with the antagonists CP99994 plus SR142801 (each 0.1 microM). This suggests that stimulation by capsaicin of TRPV1 receptors on primary afferent fibres causes a release of tachykinins which, in turn, mediate via NK1 and NK3 receptors an increase in acetylcholine release. The capsaicin-induced acetylcholine release was significantly enhanced by the NO synthase inhibitor L-NG-nitroarginine (100 microM). This indicates that tachykinins released from sensory neurons also stimulate nitrergic neurons and thus lead, via NO release, to inhibition of acetylcholine release. Capsaicin concentration-dependently reduced the electrically-evoked [3H]acetylcholine release (pEC50 6.4) and twitch contractions (pEC50 5.9). The inhibitory effects were not affected by either capsazepine, NK1 and NK3 receptor antagonists, the cannabinoid CB1 antagonist SR141716A or by L-NG-nitroarginine. Desensitization of TRPV1 receptors by a short exposure to 3 microM capsaicin abolished the facilitatory responses to a subsequent administration, but did not modify the inhibitory effects. In summary, capsaicin has a dual effect on cholinergic neurotransmission. The facilitatory effect is indirect and involves tachykinin release and excitation of NK1 and NK3 receptors on cholinergic neurons. The inhibition of acetylcholine release may be due to a decrease of Ca2+ influx into cholinergic neurons.

Thermal grill-evoked sensations of heat correlate with cold pain threshold and are enhanced by menthol and cinnamaldehyde.

Science.gov (United States)

Averbeck, B; Rucker, F; Laubender, R P; Carr, R W

2013-05-01

Thunberg's thermal grill produces a sensation of strong heat upon skin contact with spatially interlaced innocuous warm and cool stimuli. To examine the classes of peripheral axons that might contribute to this illusion, the effects of topical l-menthol, an activator of TRPM8, and cinnamaldehyde, a TRPA1 agonist, on the magnitude of thermal sensations were examined during grill stimulation in healthy volunteers. Under control conditions, cutaneous grill stimulation (interlaced 20/40 °C) evoked a sensation of heat, and for individual subjects, the magnitude of this heat sensation was positively correlated with cold pain threshold (CPT). Menthol increased the CPT and enhanced the magnitude of grill-evoked heat. Cinnamaldehyde intensified warm sensations, reduced heat pain threshold and also enhanced grill-evoked heat. Both TRPM8-expressing and TRPA1-expressing afferent axons can affect grill-evoked thermal sensations. The enhancement of grill-evoked sensations of temperature with menthol and cinnamaldehyde may provide an additional clinically relevant means of testing altered thermal sensitivity, which is often affected in neuropathic patient groups. © 2012 European Federation of International Association for the Study of Pain Chapters.

Predictability of painful stimulation modulates the somatosensory-evoked potential in the rat

NARCIS (Netherlands)

Schaap, M.W.H.; van Oostrom, H.; Doornenbal, A.; Baars, A.M.; Arndt, S.S.; Hellebrekers, L.J.

2013-01-01

Abstract Somatosensory-evoked potentials (SEPs) are used in humans and animals to increase knowledge about nociception and pain. Since the SEP in humans increases when noxious stimuli are administered unpredictably, predictability potentially influences the SEP in animals as well. To assess the

Fibromyalgia Flares: A Qualitative Analysis.

Science.gov (United States)

Vincent, Ann; Whipple, Mary O; Rhudy, Lori M

2016-03-01

Patients with fibromyalgia report periods of symptom exacerbation, colloquially referred to as "flares" and despite clinical observation of flares, no research has purposefully evaluated the presence and characteristics of flares in fibromyalgia. The purpose of this qualitative study was to describe fibromyalgia flares in a sample of patients with fibromyalgia. Using seven open-ended questions, patients were asked to describe how they perceived fibromyalgia flares and triggers and alleviating factors associated with flares. Patients were also asked to describe how a flare differs from their typical fibromyalgia symptoms and how they cope with fibromyalgia flares. Content analysis was used to analyze the text. A total of 44 participants completed the survey. Responses to the seven open-ended questions revealed three main content areas: causes of flares, flare symptoms, and dealing with a flare. Participants identified stress, overdoing it, poor sleep, and weather changes as primary causes of flares. Symptoms characteristic of flares included flu-like body aches/exhaustion, pain, fatigue, and variety of other symptoms. Participants reported using medical treatments, rest, activity and stress avoidance, and waiting it out to cope with flares. Our results demonstrate that periods of symptom exacerbation (i.e., flares) are commonly experienced by patients with fibromyalgia and symptoms of flares can be differentiated from every day or typical symptoms of fibromyalgia. Our study is the first of its kind to qualitatively explore characteristics, causes, and management strategies of fibromyalgia flares. Future studies are needed to quantitatively characterize fibromyalgia flares and evaluate mechanisms of flares. © 2015 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Preliminary protocol for systemic administration of capsaicin for the treatment of the burning mouth syndrome].

Science.gov (United States)

Lauritano, D; Petruzzi, M; Baldoni, M

2003-06-01

Burning mouth syndrome could be considered an expression of atypical facial pain. The recent neuropathological findings in BMS may suggest the need for alternative therapies. This paper aims to evaluate if systemic capsaicin could be used for BMS the- rapy. Eighty-four BMS patients (19 males and 63 females, aged 36 to 74 years, mean 54.6) were referred to the Oral Medicine and Oral Pathology Department, Dental University Institute, Milan-Bicocca University. They were divided in 2 groups: 1(st) Group: the first group (42 patients) received 3 capsules of capsaicin (50 mg of powder of red pepper with 0,25% of capsaicin) a day for one month. 2(nd) Group: the control group (42 patients) received 3 capsules of placebo (empty capsules) a day for one month. The intensity of pain was measured on the visuo-analogical scale VAS. T test of Student was applied to analyse results of VAS. P values of less than 0.05 were interpreted as significant, and the level in confidence intervals was 95%. Significant differences were noted between the two groups at the end of our study (p<0.05). No important side effects were reported. Systemic capsaicin could be considered a successful therapeutical approach for BMS patients.

Tolerability of NGX-4010, a capsaicin 8% patch, in conjunction with three topical anesthetic formulations for the treatment of neuropathic pain

Directory of Open Access Journals (Sweden)

Webster LR

2012-01-01

Full Text Available Lynn R Webster1, John F Peppin2, Frederick T Murphy3,4, Jeffrey K Tobias5, Geertrui F Vanhove51Lifetree Clinical Research and Pain Clinic, Lifetree Medical Inc, Salt Lake City, UT, USA; 2Clinical Research Division, The Pain Treatment Center of the Bluegrass, Lexington, KY, USA; 3Altoona Center for Clinical Research, Duncansville, PA, USA; 4University of Pennsylvania, School of Medicine, Philadelphia, PA, USA; 5NeurogesX Inc, San Mateo, CA, USABackground: The objective of this study was to assess the safety, tolerability, and preliminary efficacy of NGX-4010, a capsaicin 8% patch, following pretreatment with three different topical anesthetics in patients with peripheral neuropathic pain.Methods: This open-label, multicenter study enrolled 117 patients with post-herpetic neuralgia, HIV-associated distal sensory polyneuropathy, or painful diabetic neuropathy. Patients received pretreatment with one of three lidocaine 4%-based topical anesthetics (L.M.X.4® [Ferndale Laboratories Inc, Ferndale, MI], Topicaine® Gel [Estela Basso, Jupiter, FL], or Betacaine Enhanced Gel 4 [Tiberius Inc, Tampa, FL] for 60 minutes followed by a single 60- or 90-minute NGX-4010 application, and were followed for 12 weeks. Tolerability and safety measures included “pain now” Numeric Pain Rating Scale (NPRS scores, dermal assessments, medication use for treatment-related pain, adverse events (AEs, clinical laboratory parameters, physical examinations, and vital signs. The primary efficacy variable was the percentage change in mean NPRS scores for “average pain for the past 24 hours” from baseline to weeks 2 through 12.Results: Treatment with NGX-4010 following pretreatment with any of the three topical anesthetics was generally safe and well tolerated. Nearly all patients completed ≥90% of the planned NGX-4010 application duration. The most common treatment-related AEs, application-site burning and application-site pain, were transient, mostly mild or moderate

Acid and stretch, but not capsaicin, are effective stimuli for ATP release in the porcine bladder mucosa: Are ASIC and TRPV1 receptors involved?

Science.gov (United States)

Sadananda, Prajni; Kao, Felicity C L; Liu, Lu; Mansfield, Kylie J; Burcher, Elizabeth

2012-05-15

Stretch-evoked ATP release from the bladder mucosa is a key event in signaling bladder fullness. Our aim was to examine whether acid and capsaicin can also release ATP and to determine the receptors involved, using agonists and antagonists at TRPV1 and acid-sensing ion channels (ASICs). Strips of porcine bladder mucosa were exposed to acid, capsaicin or stretch. Strip tension was monitored. Bath fluid was collected for ATP measurement. Gene expression of ASICs and TRPV1 in porcine bladders was quantified using quantitative real-time PCR (qRT-PCR). Stretch stimulus (150% of original length) repeatedly and significantly increased ATP release to approximately 45 times basal release. Acid (pH 6.5, 6.0, 5.6) contracted mucosal strips and also increased ATP release up to 30-fold, without evidence of desensitization. Amiloride (0.3 μM) reduced the acid-evoked ATP release by approximately 70%, while capsazepine (10 μM) reduced acid-evoked ATP release at pH 6.0 and pH 5.6 (by 68% and 61%, respectively). Capsaicin (0.1-10 μM) was ineffective in causing ATP release, and also failed to contract porcine mucosal or detrusor strips. Gene expression for ASIC1, ASIC2, ASIC3 and TRPV1 was seen in the lateral wall, dome, trigone and neck of both detrusor and mucosa. In conclusion, stretch and acid induce ATP release in the porcine bladder mucosa, but capsaicin is ineffective. The pig bladder is a well-known model for the human bladder, however these data suggest that it should be used with caution, particularly for TRPV1 related studies. Copyright © 2012 Elsevier B.V. All rights reserved.

Antinociceptive interaction between benfotiamine and resveratrol in capsaicin-induced licking.

Science.gov (United States)

Montiel-Ruiz, Rosa Mariana; Reyes-García, Gerardo; Flores-Murrieta, Francisco; Déciga-Campos, Myrna

2009-01-01

In an attempt to provide more direct evidence concerning the possible antinociceptive effect of resveratrol-benfotiamine combination on neurogenic pain, we investigated whether resveratrol and benfotiamine administered alone or in combination decrease capsaicin induced nociception in mice. Before testing, the animals were placed individually in transparent glass cylinders, 20 cm in diameter, serving as observation chambers. After the adaptation period, 20 microL of capsaicin (1.6 microg/paw) were injected under the skin of the dorsal of the right hind paw. Animals were observed individually for 5 min after capsaicin injection. The amount of time spent licking the injected paw was timed with a chronometer and was considered as indicative of nociception. Animals were pretreated with resveratrol (56.2-177 mg/kg, i.p.), benfotiamine (100-1000 mg/kg, p.o.) and their combinations (11:1, 22:2, 44:4; 88:8 mg/kg benfotiamine:resveratrol). It was observed that resveratrol (ED50 = 104 +/- 8.2 mg/kg) was able to produce more important decrement of capsaicin-induced licking than benfotiamine (ED50 = 529.4 +/- 85.2 mg/kg). In addition, a synergistic interaction was observed between benfotiamine and resveratrol, suggesting that this combination could be useful in neurogenic nociception.

Bioconversion of Capsaicin by Aspergillus oryzae.

Science.gov (United States)

Lee, Minji; Cho, Jeong-Yong; Lee, Yu Geon; Lee, Hyoung Jae; Lim, Seong-Il; Park, So-Lim; Moon, Jae-Hak

2015-07-08

This study identified metabolites of capsaicin bioconverted by Aspergillus oryzae, which is generally used for mass production of gochujang prepared by fermenting red pepper powder in Korea. A. oryzae was incubated with capsaicin in potato dextrose broth. Capsaicin decreased depending on the incubation period, but new metabolites increased. Five capsaicin metabolites purified from the ethyl acetate fraction of the capsaicin culture were identified as N-vanillylcarbamoylbutyric acid, N-vanillyl-9-hydroxy-8-methyloctanamide, ω-hydroxycapsaicin, 8-methyl-N-vanillylcarbamoyl-6(E)-octenoic acid, and 2-methyl-N-vanillylcarbamoyl-6(Z)-octenoic acid by nuclear magnetic resonance (NMR) and mass spectrometry (MS). The capsaicin metabolites in gochujang were confirmed and quantitated by selective multiple reaction monitoring detection after liquid chromatography electrospray ionization MS using the isolated compounds as external standards. On the basis of the structures of the capsaicin metabolites, it is proposed that capsaicin metabolites were converted by A. oryzae by ω-hydroxylation, alcohol oxidation, hydrogenation, isomerization, and α- and/or β-oxidation.

Early life vincristine exposure evokes mechanical pain hypersensitivity in the developing rat.

Science.gov (United States)

Schappacher, Katie A; Styczynski, Lauren; Baccei, Mark L

2017-09-01

Vincristine (VNC) is commonly used to treat pediatric cancers, including the most prevalent childhood malignancy, acute lymphoblastic leukemia. Although clinical evidence suggests that VNC causes peripheral neuropathy in children, the degree to which pediatric chemotherapeutic regimens influence pain sensitivity throughout life remains unclear, in part because of the lack of an established animal model of chemotherapy-induced neuropathic pain during early life. Therefore, this study investigated the effects of VNC exposure between postnatal days (P) 11 and 21 on mechanical and thermal pain sensitivity in the developing rat. Low doses of VNC (15 or 30 μg/kg) failed to alter nociceptive withdrawal reflexes at any age examined compared with vehicle-injected littermate controls. Meanwhile, high dose VNC (60 μg/kg) evoked mechanical hypersensitivity in both sexes beginning at P26 that persisted until adulthood and included both static and dynamic mechanical allodynia. Hind paw withdrawal latencies to noxious heat and cold were unaffected by high doses of VNC, suggesting a selective effect of neonatal VNC on mechanical pain sensitivity. Gross and fine motor function appeared normal after VNC treatment, although a small decrease in weight gain was observed. The VNC regimen also produced a significant decrease in intraepidermal nerve fiber density in the hind paw skin by P33. Overall, the present results demonstrate that high-dose administration of VNC during the early postnatal period selectively evokes a mechanical hypersensitivity that is slow to emerge during adolescence, providing further evidence that aberrant sensory input during early life can have prolonged consequences for pain processing.

Knee joint mobilization reduces secondary mechanical hyperalgesia induced by capsaicin injection into the ankle joint.

Science.gov (United States)

Sluka, K A; Wright, A

2001-01-01

Joint mobilization is a treatment approach commonly used by physical therapists for the management of a variety of painful conditions. However, the clinical effectiveness when compared to placebo and the neurophysiological mechanism of action are not known. The purpose of this study was to establish that application of a manual therapy technique will produce antihyperalgesia in an animal model of joint inflammation and that the antihyperalgesia produced by joint mobilization depends on the time of treatment application. Capsaicin (0.2%, 50 microl) was injected into the lateral aspect of the left ankle joint and mechanical withdrawal threshold assessed before and after capsaicin injection in Sprague-Dawley rats. Joint mobilization of the ipsilateral knee joint was performed 2 h after capsaicin injection for a total of 3 min, 9 min or 15 min under halothane anaesthesia. Control groups included animals that received halothane for the same time as the group that received joint mobilization and those whose limbs were held for the same duration as the mobilization (no halothane). Capsaicin resulted in a decreased mechanical withdrawal threshold by 2 h after injection that was maintained through 4 h. Both 9 and 15 min of mobilization, but not 3 min of mobilization, increased the withdrawal threshold to mechanical stimuli to baseline values when compared with control groups. The antihyperalgesic effect of joint mobilization lasted 30 min. Thus, joint mobilization (9 or 15 min duration) produces a significant reversal of secondary mechanical hyperalgesia induced by intra-articular injection of capsaicin. Copyright 2001 European Federation of Chapters of the International Association for the Study of Pain.

Blocking proteinase-activated receptor 2 alleviated neuropathic pain evoked by spinal cord injury.

Science.gov (United States)

Wei, H; Wei, Y; Tian, F; Niu, T; Yi, G

2016-01-01

Spinal cord injury (SCI) is an extremely serious type of physical trauma observed in clinics. Especially, neuropathic pain resulting from SCI has a lasting and significant impact on most aspects of daily life. Thus, a better understanding of the molecular pathways responsible for the cause of neuropathic pain observed in SCI is important to develop effectively therapeutic agents and treatment strategies. Proteinase-activated receptors (PARs) are a family member of G-protein-coupled receptors and are activated by a proteolytic mechanism. One of its subtypes PAR2 has been reported to be engaged in mechanical and thermal hyperalgesia. Thus, in this study we specifically examined the underlying mechanisms responsible for SCI evoked-neuropathic pain in a rat model. Overall, we demonstrated that SCI increases PAR2 and its downstream pathways TRPV1 and TRPA1 expression in the superficial dorsal horn of the spinal cord. Also, we showed that blocking spinal PAR2 by intrathecal injection of FSLLRY-NH2 significantly inhibits neuropathic pain responses induced by mechanical and thermal stimulation whereas FSLLRY-NH2 decreases the protein expression of TRPV1 and TRPA1 as well as the levels of substance P and calcitonin gene-related peptide. Results of this study have important implications, i.e. targeting one or more of these signaling molecules involved in activation of PAR2 and TRPV1/TRPA1 evoked by SCI may present new opportunities for treatment and management of neuropathic pain often observed in patients with SCI.

The effect of wound instillation of a novel purified capsaicin formulation on postherniotomy pain: A double-blind, randomized, placebo-controlled study

DEFF Research Database (Denmark)

Aasvang, Eske Kvanner; Hansen, J.B.; Malmstrom, J.

2008-01-01

and laboratory tests were done before and I wk after surgery, together with recordings of adverse events up to 28 days. Adverse events were recorded. Data were also analyzed using a mixed-effects analysis with NONMEM. RESULTS: VAS AUC was significantly lower during the first 3 days postoperatively (P ....05), but not for the whole I or 4 wk postoperatively. Mixed-effects analysis with NONMEM revealed that pain scores were significantly lower (P adverse events were observed, although a mild transient increase in liver enzymes was seen......, preclinical, and clinical studies, and may be an effective adjunct to postoperative pain management. METHODS: We performed a single-center, randomized, double-blind, placebo-controlled study of the analgesic efficacy of a single intraoperative wound instillation of 1000 mu g ultrapurified capsaicin (ALGRX...

Topical Pain Relievers May Cause Burns

Science.gov (United States)

... joint pain relievers containing the active ingredients menthol, methyl salicylate and capsaicin. These cases were uncovered by FDA ... people who purchase these products, Tan notes. Menthol, methyl salicylate and capsaicin create sensations of local warmth or ...

Effect profile of paracetamol, Δ9-THC and promethazine using an evoked pain test battery in healthy subjects.

Science.gov (United States)

van Amerongen, G; Siebenga, P; de Kam, M L; Hay, J L; Groeneveld, G J

2018-04-10

A battery of evoked pain tasks (PainCart) was developed to investigate the pharmacodynamic properties of novel analgesics in early-phase clinical research. As part of its clinical validation, compounds with different pharmacological mechanisms of actions are investigated. The aim was to investigate the analgesic effects of classic and nonclassic analgesics compared to a sedating negative control in a randomized placebo-controlled crossover study in 24 healthy volunteers using the PainCart. The PainCart consisted of pain tasks eliciting electrical, pressure, heat, cold and inflammatory pain. Subjective scales for cognitive functioning and psychotomimetic effects were included. Subjects were administered each of the following oral treatments: paracetamol (1000 mg), Δ9-THC (10 mg), promethazine (50 mg) or matching placebo. Pharmacodynamic measurements were performed at baseline and repeated up to 10 h postdose. Paracetamol did not show a significant reduction in pain sensation or subjective cognitive functioning compared to placebo. Promethazine induced a statistically significant reduction in PTT for cold pressor and pressure stimulation. Furthermore, reduced subjective alertness was observed. Δ9-THC showed a statistically significant decrease in PTT for electrical and pressure stimulation. Δ9-THC also demonstrated subjective effects, including changes in alertness and calmness, as well as feeling high and psychotomimetic effects. This study found a decreased pain tolerance due to Δ9-THC and promethazine, or lack thereof, using an evoked pain task battery. Pain thresholds following paracetamol administration remained unchanged, which may be due to insufficient statistical power. We showed that pain thresholds determined using this pain test battery are not driven by sedation. The multimodal battery of evoked pain tasks utilized in this study may play an important role in early-phase clinical drug development. This battery of pain tasks is not sensitive to the

["Flare-up" during endodontic treatment--etiology and management].

Science.gov (United States)

Zuckerman, O; Metzger, Z; Sela, G; Lin, S

2007-04-01

"Flare-ups" during or following endodontic treatment are not uncommon. A "Flare-up" refers to post-operative pain and/or swelling resulting from bacterial, mechanical or chemical irritation. Prompt diagnosis and treatment are essential for reducing patients' pain and discomfort. Prevention of bacterial, chemical or mechanical invasion to the periapical tissues is the best approach. Other treatment modalities which reduce the probability of periradicular tissue irritation should also be adopted. Etiology, prevention, diagnosis and treatment options of "flare-up" cases are discussed as well as indications for analgesics, in accordance with the severity of the pain.

Endodontic flare up: incidence and association of possible risk factors.

Science.gov (United States)

Gbadebo, S O; Sulaiman, A O; Anifowose, O O

2016-06-01

Endodontic emergency during root canal treatment (flare up) is a common occurrence in multivisit root canal treatment (RCT) and it may be associated with many factors. The occurrence however can affect the prognosis of the tooth and the patient -clinician relationship. To determine the incidence and risk factors associated with occurrence of flare up in a multi visit RCT. Patients planned for multi-visit (RCT) were recruited for the research. Standard protocol was followed in all cases. After the first visit, the patients were followed up for possible development of flare up. Patients' demographics, presence or absence of preoperative pain, status of the pulp and occurrence of flare up were among the data collected. Data was analyzed using SPSS version 20 with level of significance set at P flare up was 8.5%. Prior to treatment, 47% of the cases had pain, 61.3% had apical radioluscency and 83% had pulpal necrosis. Majority (7, 77.8%) of the flare up occurred after the first visit (p=0.000). Only pre- treatment pain had a statistical significant ielationship with occurrence of flare up (p=0.009). Incidence of flare up was 8.5% and the major risk factor was preoperative pain. First visit in a multi visit RCT is an important stage which if well handled, can reduce the incidence of flare up.

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.

Brain potentials evoked by intraepidermal electrical stimuli reflect the central sensitization of nociceptive pathways.

Science.gov (United States)

Liang, M; Lee, M C; O'Neill, J; Dickenson, A H; Iannetti, G D

2016-08-01

Central sensitization (CS), the increased sensitivity of the central nervous system to somatosensory inputs, accounts for secondary hyperalgesia, a typical sign of several painful clinical conditions. Brain potentials elicited by mechanical punctate stimulation using flat-tip probes can provide neural correlates of CS, but their signal-to-noise ratio is limited by poor synchronization of the afferent nociceptive input. Additionally, mechanical punctate stimulation does not activate nociceptors exclusively. In contrast, low-intensity intraepidermal electrical stimulation (IES) allows selective activation of type II Aδ-mechano-heat nociceptors (II-AMHs) and elicits reproducible brain potentials. However, it is unclear whether hyperalgesia from IES occurs and coexists with secondary mechanical punctate hyperalgesia, and whether the magnitude of the electroencephalographic (EEG) responses evoked by IES within the hyperalgesic area is increased. To address these questions, we explored the modulation of the psychophysical and EEG responses to IES by intraepidermal injection of capsaicin in healthy human subjects. We obtained three main results. First, the intensity of the sensation elicited by IES was significantly increased in participants who developed robust mechanical punctate hyperalgesia after capsaicin injection (i.e., responders), indicating that hyperalgesia from IES coexists with punctate mechanical hyperalgesia. Second, the N2 peak magnitude of the EEG responses elicited by IES was significantly increased after the intraepidermal injection of capsaicin in responders only. Third, a receiver-operator characteristics analysis showed that the N2 peak amplitude is clearly predictive of the presence of CS. These findings suggest that the EEG responses elicited by IES reflect secondary hyperalgesia and therefore represent an objective correlate of CS. Copyright © 2016 the American Physiological Society.

Analgesic effect of topical oral capsaicin gel in burning mouth syndrome.

Science.gov (United States)

Jørgensen, Mette Rose; Pedersen, Anne Marie Lynge

2017-03-01

To investigate the effectiveness of repeated topical application of oral capsaicin gel in two different concentrations for relief of burning/stinging sensations in patients with burning mouth syndrome (BMS). This randomized double-blind cross-over study included 22 female patients with BMS. The patients were randomized for topical application of either 0.01% or 0.025% oral capsaicin gel on the dorsal part of tongue three times daily for 14 days, followed by 14 days wash-out period, and finally treatment with the other concentration of oral gel three times daily for 14 days. A visual analogue scale (VAS) was used to assess the severity of pain five times during the intervention period. 18 patients completed the intervention. Their VAS score at baseline was 5.5 ± 0.6 cm (mean ± SD). Treatment with the two concentrations of capsaicin gels significantly improved the burning/stinging symptoms assessed on VAS compared with baseline (p = 0.002). There was no statistically significant difference between the two concentrations of the gels on relieving symptoms. Four patients dropped out during the intervention period due to gastrointestinal side-effects. Topical capsaicin might be an alternative for the short-term treatment of BMS. However, further studies are needed to investigate especially the gastro-intestinal side-effects which may limit its long-term use.

TRPA1 contributes to capsaicin-induced facial cold hyperalgesia in rats.

Science.gov (United States)

Honda, Kuniya; Shinoda, Masamichi; Furukawa, Akihiko; Kita, Kozue; Noma, Noboru; Iwata, Koichi

2014-12-01

Orofacial cold hyperalgesia is known to cause severe persistent pain in the face following trigeminal nerve injury or inflammation, and transient receptor potential (TRP) vanilloid 1 (TRPV1) and TRP ankylin 1 (TRPA1) are thought to be involved in cold hyperalgesia. However, how these two receptors are involved in cold hyperalgesia is not fully understood. To clarify the mechanisms underlying facial cold hyperalgesia, nocifensive behaviors to cold stimulation, the expression of TRPV1 and TRPA1 in trigeminal ganglion (TG) neurons, and TG neuronal excitability to cold stimulation following facial capsaicin injection were examined in rats. The head-withdrawal reflex threshold (HWRT) to cold stimulation of the lateral facial skin was significantly decreased following facial capsaicin injection. This reduction of HWRT was significantly recovered following local injection of TRPV1 antagonist as well as TRPA1 antagonist. Approximately 30% of TG neurons innervating the lateral facial skin expressed both TRPV1 and TRPA1, and about 64% of TRPA1-positive neurons also expressed TRPV1. The TG neuronal excitability to noxious cold stimulation was significantly increased following facial capsaicin injection and this increase was recovered by pretreatment with TRPA1 antagonist. These findings suggest that TRPA1 sensitization via TRPV1 signaling in TG neurons is involved in cold hyperalgesia following facial skin capsaicin injection. © 2014 Eur J Oral Sci.

Characterization of capsaicin synthase and identification of its gene (csy1) for pungency factor capsaicin in pepper (Capsicum sp.)

Science.gov (United States)

Prasad, B. C. Narasimha; Kumar, Vinod; Gururaj, H. B.; Parimalan, R.; Giridhar, P.; Ravishankar, G. A.

2006-01-01

Capsaicin is a unique alkaloid of the plant kingdom restricted to the genus Capsicum. Capsaicin is the pungency factor, a bioactive molecule of food and of medicinal importance. Capsaicin is useful as a counterirritant, antiarthritic, analgesic, antioxidant, and anticancer agent. Capsaicin biosynthesis involves condensation of vanillylamine and 8-methyl nonenoic acid, brought about by capsaicin synthase (CS). We found that CS activity correlated with genotype-specific capsaicin levels. We purified and characterized CS (≈35 kDa). Immunolocalization studies confirmed that CS is specifically localized to the placental tissues of Capsicum fruits. Western blot analysis revealed concomitant enhancement of CS levels and capsaicin accumulation during fruit development. We determined the N-terminal amino acid sequence of purified CS, cloned the CS gene (csy1) and sequenced full-length cDNA (981 bp). The deduced amino acid sequence of CS from full-length cDNA was 38 kDa. Functionality of csy1 through heterologous expression in recombinant Escherichia coli was also demonstrated. Here we report the gene responsible for capsaicin biosynthesis, which is unique to Capsicum spp. With this information on the CS gene, speculation on the gene for pungency is unequivocally resolved. Our findings have implications in the regulation of capsaicin levels in Capsicum genotypes. PMID:16938870

Anticancer Properties of Capsaicin Against Human Cancer.

Science.gov (United States)

Clark, Ruth; Lee, Seong-Ho

2016-03-01

There is persuasive epidemiological and experimental evidence that dietary phytochemicals have anticancer activity. Capsaicin is a bioactive phytochemical abundant in red and chili peppers. While the preponderance of the data strongly indicates significant anticancer benefits of capsaicin, more information to highlight molecular mechanisms of its action is required to improve our knowledge to be able to propose a potential therapeutic strategy for use of capsaicin against cancer. Capsaicin has been shown to alter the expression of several genes involved in cancer cell survival, growth arrest, angiogenesis and metastasis. Recently, many research groups, including ours, found that capsaicin targets multiple signaling pathways, oncogenes and tumor-suppressor genes in various types of cancer models. In this review article, we highlight multiple molecular targets responsible for the anticancer mechanism of capsaicin. In addition, we deal with the benefits of combinational use of capsaicin with other dietary or chemotherapeutic compounds, focusing on synergistic anticancer activities. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

The role of trigeminal nucleus caudalis orexin 1 receptors in orofacial pain transmission and in orofacial pain-induced learning and memory impairment in rats.

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Kooshki, Razieh; Abbasnejad, Mehdi; Esmaeili-Mahani, Saeed; Raoof, Maryam

2016-04-01

It is widely accepted that the spinal trigeminal nuclear complex, especially the subnucleus caudalis (Vc), receives input from orofacial structures. The neuropeptides orexin-A and -B are expressed in multiple neuronal systems. Orexin signaling has been implicated in pain-modulating system as well as learning and memory processes. Orexin 1 receptor (OX1R) has been reported in trigeminal nucleus caudalis. However, its roles in trigeminal pain modulation have not been elucidated so far. This study was designed to investigate the role of Vc OX1R in the modulation of orofacial pain as well as pain-induced learning and memory deficits. Orofacial pain was induced by subcutaneous injection of capsaicin in the right upper lip of the rats. OX1R agonist (orexin-A) and antagonist (SB-334867-A) were microinjected into Vc prior capsaicin administration. After recording nociceptive times, learning and memory was investigated using Morris water maze (MWM) test. The results indicated that, orexin-A (150 pM/rat) significantly reduced the nociceptive times, while SB334867-A (80 nM/rat) exaggerated nociceptive behavior in response to capsaicin injection. In MWM test, capsaicin-treated rats showed a significant learning and memory impairment. Moreover, SB-334867-A (80 nM/rat) significantly exaggerated learning and memory impairment in capsaicin-treated rats. However, administration of orexin-A (100 pM/rat) prevented learning and memory deficits. Taken together, these results indicate that Vc OX1R was at least in part involved in orofacial pain transmission and orexin-A has also a beneficial inhibitory effect on orofacial pain-induced deficits in abilities of spatial learning and memory. Copyright © 2016 Elsevier Inc. All rights reserved.

Antimicrobial and anti-virulence activity of capsaicin against erythromycin-resistant, cell-invasive Group A streptococci

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Emanuela eMarini

2015-11-01

Full Text Available Capsaicin (8-methyl-N-vanillyl-6-nonenamide is the active component of Capsicum plants (chilli peppers, which are grown as food and for medicinal purposes since ancient times, and is responsible for the pungency of their fruit. Besides its multiple pharmacological and physiological properties (pain relief, cancer prevention, and beneficial cardiovascular, and gastrointestinal effects capsaicin has recently attracted considerable attention because of its antimicrobial and anti-virulence activity. This is the first study of its in vitro antibacterial and anti-virulence activity against Streptococcus pyogenes [Group A streptococci (GAS], a major human pathogen. The test strains were previously characterized, erythromycin-susceptible (n=5 and erythromycin-resistant (n=27, cell-invasive pharyngeal isolates. The MICs of capsaicin were 64-128 μg/mL (the most common MIC was 128 µg/mL. The action of capsaicin was bactericidal, as suggested by MBC values that were equal or close to the MICs, and by early detection of dead cells in the live/dead assay. No capsaicin-resistant mutants were obtained in single-step resistance selection studies. Interestingly, growth in presence of sublethal capsaicin concentrations induced an increase in biofilm production (p ≤ 0.05 and in the number of bacteria adhering to A549 monolayers, and a reduction in cell-invasiveness and haemolytic activity (both p ≤ 0.05. Cell invasiveness fell so dramatically that a highly invasive strain became non-invasive. The dose-response relationship, characterized by opposite effects of low and high capsaicin doses, suggests a hormetic response. The present study documents that capsaicin has promising bactericidal activity against erythromycin-resistant, cell-invasive pharyngeal GAS isolates. The fact that sublethal concentrations inhibited cell invasion and reduced haemolytic activity, two important virulence traits of GAS, is also interesting, considering that cell

Neural correlates of heat-evoked pain memory in humans.

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Wang, Liping; Gui, Peng; Li, Lei; Ku, Yixuan; Bodner, Mark; Fan, Gaojie; Zhou, Yong-Di; Dong, Xiao-Wei

2016-03-01

The neural processes underlying pain memory are not well understood. To explore these processes, contact heat-evoked potentials (CHEPs) were recorded in humans with electroencephalography (EEG) technique during a delayed matching-to-sample task, a working memory task involving presentations of two successive painful heat stimuli (S-1 and S-2) with different intensities separated by a 2-s interval (the memorization period). At the end of the task, the subject was required to discriminate the stimuli by indicating which (S-1 or S-2) induced more pain. A control task was used, in which no active discrimination was required between stimuli. All event-related potential (ERP) analysis was aligned to the onset of S-1. EEG activity exhibited two successive CHEPs: an N2-P2 complex (∼400 ms after onset of S-1) and an ultralate component (ULC, ∼900 ms). The amplitude of the N2-P2 at vertex, but not the ULC, was significantly correlated with stimulus intensity in these two tasks, suggesting that the N2-P2 represents neural coding of pain intensity. A late negative component (LNC) in the frontal recording region was observed only in the memory task during a 500-ms period before onset of S-2. LNC amplitude differed between stimulus intensities and exhibited significant correlations with the N2-P2 complex. These indicate that the frontal LNC is involved in maintenance of intensity of pain in working memory. Furthermore, alpha-band oscillations observed in parietal recording regions during the late delay displayed significant power differences between tasks. This study provides in the temporal domain previously unidentified neural evidence showing the neural processes involved in working memory of painful stimuli. Copyright © 2016 the American Physiological Society.

Electroencephalographic evoked pain response is suppressed by spinal cord stimulation in complex regional pain syndrome: a case report.

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Hylands-White, Nicholas; Duarte, Rui V; Beeson, Paul; Mayhew, Stephen D; Raphael, Jon H

2016-12-01

Pain is a subjective response that limits assessment. The purpose of this case report was to explore how the objectivity of the electroencephalographic response to thermal stimuli would be affected by concurrent spinal cord stimulation. A patient had been implanted with a spinal cord stimulator for the management of complex regional pain syndrome of both hands for 8 years. Following ethical approval and written informed consent we induced thermal stimuli using the Medoc PATHWAY Pain & Sensory Evaluation System on the right hand of the patient with the spinal cord stimulator switched off and with the spinal cord stimulator switched on. The patient reported a clinically significant reduction in thermal induced pain using the numerical rating scale (71.4 % reduction) with spinal cord stimulator switched on. Analysis of electroencephalogram recordings indicated the occurrence of contact heat evoked potentials (N2-P2) with spinal cord stimulator off, but not with spinal cord stimulator on. This case report suggests that thermal pain can be reduced in complex regional pain syndrome patients with the use of spinal cord stimulation and offers objective validation of the reported outcomes with this treatment.

Small-fibre neuropathy in female Fabry patients: reduced allodynia and skin blood flow after topical capsaicin

DEFF Research Database (Denmark)

Møller, Anette Torvin; Feldt-Rasmussen, Ulla; Rasmussen, Åse K.

2006-01-01

affected. Recently, attention has been drawn to female patients whether they also show signs of nerve involvement. An early sign of the disease is painful small-fibre neuropathy. The aim of this study was to evaluate a small-fibre dysfunction in female Fabry patients by using capsaicin applied topically......Fabry disease is a rare X-linked lysosomal storage disorder. The mutations result in a deficiency of the lysosomal enzyme α-galactosidase A causing accumulation of glycosphingolipids in the vascular endothelial cells and many other tissues. Given the X-linked inheritance, male patients are severely....... The response to capsaicin was evaluated by laser Doppler imaging. We found that the female Fabry patients had a significantly smaller increase in blood flow (p = 0.0003) after capsaicin application. The area of static mechanical allodynia and dynamic mechanical hyperalgesia was also significantly smaller (p...

Reproducibility of the heat/capsaicin skin sensitization model in healthy volunteers

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Cavallone LF

2013-11-01

Full Text Available Laura F Cavallone,1 Karen Frey,1 Michael C Montana,1 Jeremy Joyal,1 Karen J Regina,1 Karin L Petersen,2 Robert W Gereau IV11Department of Anesthesiology, Washington University in St Louis, School of Medicine, St Louis, MO, USA; 2California Pacific Medical Center Research Institute, San Francisco, CA, USAIntroduction: Heat/capsaicin skin sensitization is a well-characterized human experimental model to induce hyperalgesia and allodynia. Using this model, gabapentin, among other drugs, was shown to significantly reduce cutaneous hyperalgesia compared to placebo. Since the larger thermal probes used in the original studies to produce heat sensitization are now commercially unavailable, we decided to assess whether previous findings could be replicated with a currently available smaller probe (heated area 9 cm2 versus 12.5–15.7 cm2.Study design and methods: After Institutional Review Board approval, 15 adult healthy volunteers participated in two study sessions, scheduled 1 week apart (Part A. In both sessions, subjects were exposed to the heat/capsaicin cutaneous sensitization model. Areas of hypersensitivity to brush stroke and von Frey (VF filament stimulation were measured at baseline and after rekindling of skin sensitization. Another group of 15 volunteers was exposed to an identical schedule and set of sensitization procedures, but, in each session, received either gabapentin or placebo (Part B.Results: Unlike previous reports, a similar reduction of areas of hyperalgesia was observed in all groups/sessions. Fading of areas of hyperalgesia over time was observed in Part A. In Part B, there was no difference in area reduction after gabapentin compared to placebo.Conclusion: When using smaller thermal probes than originally proposed, modifications of other parameters of sensitization and/or rekindling process may be needed to allow the heat/capsaicin sensitization protocol to be used as initially intended. Standardization and validation of

Sensory Disturbances, but Not Motor Disturbances, Induced by Sensorimotor Conflicts Are Increased in the Presence of Acute Pain

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Clémentine Brun

2017-07-01

Full Text Available Incongruence between our motor intention and the sensory feedback of the action (sensorimotor conflict induces abnormalities in sensory perception in various chronic pain populations, and to a lesser extent in pain-free individuals. The aim of this study was to simultaneously investigate sensory and motor disturbances evoked by sensorimotor conflicts, as well as to assess how they are influenced by the presence of acute pain. It was hypothesized that both sensory and motor disturbances would be increased in presence of pain, which would suggest that pain makes body representations less robust. Thirty healthy participants realized cyclic asymmetric movements of flexion-extension with both upper limbs in a robotized system combined to a 2D virtual environment. The virtual environment provided a visual feedback (VF about movements that was either congruent or incongruent, while the robotized system precisely measured motor performance (characterized by bilateral amplitude asymmetry and medio-lateral drift. Changes in sensory perception were assessed with a questionnaire after each trial. The effect of pain (induced with capsaicin was compared to three control conditions (no somatosensory stimulation, tactile distraction and proprioceptive masking. Results showed that while both sensory and motor disturbances were induced by sensorimotor conflicts, only sensory disturbances were enhanced during pain condition comparatively to the three control conditions. This increase did not statistically differ across VF conditions (congruent or incongruent. Interestingly however, the types of sensations evoked by the conflict in the presence of pain (changes in intensity of pain or discomfort, changes in temperature or impression of a missing limb were different than those evoked by the conflict alone (loss of control, peculiarity and the perception of having an extra limb. Finally, results showed no relationship between the amount of motor and sensory

CAPSAICIN: ITS BIOLOGICAL ACTIVITIES AND IN SILICO TARGET FISHING.

Science.gov (United States)

Akhtar, Fahad; Muhammad Sharif, Hajra; Arshad Mallick, Muhammad; Zahoor, Fareeha; Abdulmalik, Attiya; Baig, Warda; Shujaat, Nodia; Gul, Sundas; Bibi, Gulfam; Ramzan, Rahdia; Murtaza, Ghulam

2017-03-01

Capsicum annuum L. is a rich source of capsaicin, an alkaloid, which is a very pungent compound. Due to ever growing need of capsaicin, an extensive research on its efficient cultivation as well as chemical synthesis is underway. Owing to the pungent nature of capsaicin, its analogous molecules without pungent effect are being explored. The objective of this descriptive review is to comprehensively present the updates on the bioactivities of capsaicin. Additionally, the in silico target fishing approach has been used to identify the possible protein targets of capsaicin. This article will definitely provide future perspectives of research on capsaicin.

[A clinical study of endodontic flare-ups].

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Yeh, S J; Lin, Y T; Lu, S Y

1994-06-01

The purpose of this study was to investigate the clinical variables influencing endodontic flare-ups. Three hundred and thirteen teeth receiving endodontic treatment at the Endodontic Department, Chang Gung Memorial Hospital were studied from December 1992 to February 1993. Among them, 21 teeth with significant pain and 9 with apical swelling were noted after the first appointment of treatment. Three teeth with persistent pain and one with apical swelling were also found one week after completion of endodontic therapy. The results showed significant improvement of clinical symptoms and signs one week after completion of endodontic treatment in comparison with pretreatment and after the first appointment (p endodontic flare-ups after the first appointment of treatment (P endodontic flare-ups.

Correction to: Ephedra Herb extract activates/desensitizes transient receptor potential vanilloid 1 and reduces capsaicin-induced pain.

Science.gov (United States)

Nakamori, Shunsuke; Takahashi, Jun; Hyuga, Sumiko; Tanaka-Kagawa, Toshiko; Jinno, Hideto; Hyuga, Masashi; Hakamatsuka, Takashi; Odaguchi, Hiroshi; Goda, Yukihiro; Hanawa, Toshihiko; Kobayashi, Yoshinori

2018-03-01

The article Ephedra Herb extract activates/desensitizes transient receptor potential vanilloid 1 and reduces capsaicin-induced pain, written by Shunsuke Nakamori, Jun Takahashi, Sumiko Hyuga, Toshiko Tanaka-Kagawa, Hideto Jinno, Masashi Hyuga, Takashi Hakamatsuka, Hiroshi Odaguchi, Yukihiro Goda, Toshihiko Hanawa and Yoshinori Kobayashi, was originally published Online First without open access. After publication in volume 71, issue 1, page 105-113 the author decided to opt for Open Choice and to make the article an open access publication. Therefore, the copyright of the article has been changed to © The Author(s) 2018 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Integrating TRPV1 Receptor Function with Capsaicin Psychophysics

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Gregory Smutzer

2016-01-01

Full Text Available Capsaicin is a naturally occurring vanilloid that causes a hot, pungent sensation in the human oral cavity. This trigeminal stimulus activates TRPV1 receptors and stimulates an influx of cations into sensory cells. TRPV1 receptors function as homotetramers that also respond to heat, proinflammatory substances, lipoxygenase products, resiniferatoxin, endocannabinoids, protons, and peptide toxins. Kinase-mediated phosphorylation of TRPV1 leads to increased sensitivity to both chemical and thermal stimuli. In contrast, desensitization occurs via a calcium-dependent mechanism that results in receptor dephosphorylation. Human psychophysical studies have shown that capsaicin is detected at nanomole amounts and causes desensitization in the oral cavity. Psychophysical studies further indicate that desensitization can be temporarily reversed in the oral cavity if stimulation with capsaicin is resumed at short interstimulus intervals. Pretreatment of lingual epithelium with capsaicin modulates the perception of several primary taste qualities. Also, sweet taste stimuli may decrease the intensity of capsaicin perception in the oral cavity. In addition, capsaicin perception and hedonic responses may be modified by diet. Psychophysical studies with capsaicin are consistent with recent findings that have identified TRPV1 channel modulation by phosphorylation and interactions with membrane inositol phospholipids. Future studies will further clarify the importance of capsaicin and its receptor in human health and nutrition.

Discrepancy between perceived pain and cortical processing: A voxel-based morphometry and contact heat evoked potential study.

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Kramer, J L K; Jutzeler, C R; Haefeli, J; Curt, A; Freund, P

2016-01-01

The purpose of this study was to determine if local gray and white matter volume variations between subjects could account for variability in responses to CHEP stimulation. Structural magnetic resonance imaging was used to perform voxel-based morphometry (VBM) of gray and white matter in 30 neurologically healthy subjects. Contact heat stimulation was performed on the dorsum of the right hand at the base of the thumb. Evoked potentials were acquired from a vertex-recording electrode referenced to linked ears. Controlling for age, total intracranial volume, and skull/scalp thickness, CHEP amplitude and pain rating were not significantly correlated between subjects. A VBM region of interest approach demonstrated a significant interaction between pain rating and N2 amplitude in the right insular cortex (ppain rating. This finding suggests that the discrepancy between pain ratings and the amplitude of evoked potentials is not solely related to measurement artifact, but rather attributable, in part, to anatomical differences between subjects. Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.

Protein phosphatase 2A regulates central sensitization in the spinal cord of rats following intradermal injection of capsaicin

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Fang Li

2006-03-01

Full Text Available Abstract Background Intradermal injection of capsaicin into the hind paw of rats induces spinal cord central sensititzation, a process in which the responsiveness of central nociceptive neurons is amplified. In central sensitization, many signal transduction pathways composed of several cascades of intracellular enzymes are involved. As the phosphorylation state of neuronal proteins is strictly controlled and balanced by the opposing activities of protein kinases and phosphatases, the involvement of phosphatases in these events needs to be investigated. This study is designed to determine the influence of serine/threonine protein phosphatase type 2A (PP2A on the central nociceptive amplification process, which is induced by intradermal injection of capsaicin in rats. Results In experiment 1, the expression of PP2A protein in rat spinal cord at different time points following capsaicin or vehicle injection was examined using the Western blot method. In experiment 2, an inhibitor of PP2A (okadaic acid, 20 nM or fostriecin, 30 nM was injected into the subarachnoid space of the spinal cord, and the spontaneous exploratory activity of the rats before and after capsaicin injection was recorded with an automated photobeam activity system. The results showed that PP2A protein expression in the spinal cord was significantly upregulated following intradermal injection of capsaicin in rats. Capsaicin injection caused a significant decrease in exploratory activity of the rats. Thirty minutes after the injection, this decrease in activity had partly recovered. Infusion of a phosphatase inhibitor into the spinal cord intrathecal space enhanced the central sensitization induced by capsaicin by making the decrease in movement last longer. Conclusion These findings indicate that PP2A plays an important role in the cellular mechanisms of spinal cord central sensitization induced by intradermal injection of capsaicin in rats, which may have implications in

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

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

2008-01-01

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

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

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Thomas J Park

2008-01-01

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

Capsaicin-sensitive intestinal mucosal afferent mechanism and body fat distribution.

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Leung, Felix W

2008-07-04

This report summarizes clinical and experimental data in support of the hypothesis that capsaicin-sensitive intestinal mucosal afferent mechanism plays a role in regulating body fat distribution. Epidemiological data have revealed that the consumption of foods containing capsaicin is associated with a lower prevalence of obesity. Rural Thai people consume diets containing 0.014% capsaicin. Rodents fed a diet containing 0.014% capsaicin showed no change in caloric intake but a significant 24% and 29% reduction in the visceral (peri-renal) fat weight. Increase in intestinal blood flow facilitates nutrient energy absorption and decrease in adipose tissue blood flow facilitates storage of nutrient energy in adipose tissue. Stimulation of intestinal mucosal afferent nerves increases intestinal blood flow, but decreases visceral (mesenteric) adipost tissue blood flow. In in vitro cell studies capsaicin has a direct effect on adipocytes. Intravenous capsaicin produces measurable plasma level and subcutaneous capsaicin retards accumulation of adipose tissue. The data on a direct effect of oral capsaicin on adipose tissue at remote sites, however, are conflicting. Capsaicin absorbed from the gut lumen is almost completely metabolized before reaching the general circulation. Oral capsaicin significantly increases transient receptor potential vanilloid type-1 (TRPV1) channel expression as well as TRPV1 messenger ribonucleic acid (mRNA) in visceral adipose tissue. In TRPV1 knockout mice on a high fat diet the body weight was not significantly different in the absence or presence of oral capsaicin. In rodent experiments, daily intragastric administration of capsaicin for two weeks led to defunctionalization of intestinal mucosal afferent nerves, manifested by loss of acute mucosal capsaicin-induced effects; but not the corneal afferent nerves, with preservation of the paw wiping reflex of the eye exposed briefly to dilute capsaicin. The latter indicated the absence of an oral

Antinociceptive effect and interaction of uncompetitive and competitive NMDA receptor antagonists upon capsaicin and paw pressure testing in normal and monoarthritic rats.

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Pelissier, Teresa; Infante, Claudio; Constandil, Luis; Espinosa, Jeannette; Lapeyra, Carolina De; Hernández, Alejandro

2008-01-01

We assessed whether intrathecal administration of the uncompetitive and competitive NMDA receptor antagonists ketamine and (+/-)CPP, respectively, could produce differential modulation on chemical and mechanical nociception in normal and monoarthritic rats. In addition, the antinociceptive interaction of ketamine and (+/-)CPP on monoarthritic pain was also studied using isobolographic analysis. Monoarthritis was produced by intra-articular injection of complete Freund's adjuvant into the tibio-tarsal joint. Four weeks later, the antinociceptive effect of intrathecal administration of the drugs alone or combined was evaluated by using the intraplantar capsaicin and the paw pressure tests. Ketamine (0.1, 1, 10, 30, 100, 300 and 1000 microg i.t.) and (+/-)CPP (0.125, 2.5, 7.5, 12.5, 25 and 50 microg i.t.) produced significantly greater dose-dependent antinociception in the capsaicin than in the paw pressure test. Irrespective of the nociceptive test employed, both antagonists showed greater antinociceptive activity in monoarthritic than in healthy rats. Combinations produced synergy of a supra-additive nature in the capsaicin test, but only additive antinociception in paw pressure testing. The efficacy of the drugs, alone or combined, is likely to depend on the differential sensitivity of tonic versus phasic pain and/or chemical versus mechanical pain to NMDA antagonists.

Blocking mammalian target of rapamycin (mTOR) improves neuropathic pain evoked by spinal cord injury.

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Wang, Xiaoping; Li, Xiaojia; Huang, Bin; Ma, Shuai

2016-01-01

Spinal cord injury (SCI) is an extremely serious type of physical trauma observed in clinics. Neuropathic pain resulting from SCI has a lasting and significant impact on most aspects of daily life. Thus, a better understanding of the molecular pathways responsible for the cause of neuropathic pain observed in SCI is important to develop effective therapeutic agents and treatment strategies. Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that is well known for its critical roles in regulating protein synthesis and growth. Furthermore, compelling evidence supports the notion that widespread dysregulation of mTOR and its downstream pathways are involved in neuropathic pain. Thus, in this study we specifically examined the underlying mechanisms by which mTOR and its signaling pathways are involved in SCI-evoked neuropathic pain in a rat model. Overall, we demonstrated that SCI increased the protein expression of p-mTOR, and mTORmediated- phosphorylation of 4E-binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) in the superficial dorsal horn of the spinal cord. Also, we showed that blocking spinal mTOR by intrathecal injection of rapamycin significantly inhibited pain responses induced by mechanical and thermal stimulation. In addition, blocking spinal phosphatidylinositide 3-kinase (p-PI3K) pathway significantly attenuated activities of p-mTOR pathways as well as mechanical and thermal hyperalgesia in SCI rats. Moreover, blocking mTOR and PI3K decreased the enhanced levels of substance P and calcitonin gene-related peptide (CGRP) in the dorsal horn of SCI rats. We revealed specific signaling pathways leading to SCI-evoked neuropathic pain, including the activation of PI3K, mTOR and its downstream signaling pathways. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of neuropathic pain often observed in patients with SCI.

Blocking mammalian target of rapamycin (mTOR improves neuropathic pain evoked by spinal cord injury

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Wang Xiaoping

2016-01-01

Full Text Available Spinal cord injury (SCI is an extremely serious type of physical trauma observed in clinics. Neuropathic pain resulting from SCI has a lasting and significant impact on most aspects of daily life. Thus, a better understanding of the molecular pathways responsible for the cause of neuropathic pain observed in SCI is important to develop effective therapeutic agents and treatment strategies. Mammalian target of rapamycin (mTOR is a serine/threonine protein kinase that is well known for its critical roles in regulating protein synthesis and growth. Furthermore, compelling evidence supports the notion that widespread dysregulation of mTOR and its downstream pathways are involved in neuropathic pain. Thus, in this study we specifically examined the underlying mechanisms by which mTOR and its signaling pathways are involved in SCI-evoked neuropathic pain in a rat model. Overall, we demonstrated that SCI increased the protein expression of p-mTOR, and mTORmediated- phosphorylation of 4E–binding protein 4 (4E-BP1 and p70 ribosomal S6 protein kinase 1 (S6K1 in the superficial dorsal horn of the spinal cord. Also, we showed that blocking spinal mTOR by intrathecal injection of rapamycin significantly inhibited pain responses induced by mechanical and thermal stimulation. In addition, blocking spinal phosphatidylinositide 3-kinase (p-PI3K pathway significantly attenuated activities of p-mTOR pathways as well as mechanical and thermal hyperalgesia in SCI rats. Moreover, blocking mTOR and PI3K decreased the enhanced levels of substance P and calcitonin gene-related peptide (CGRP in the dorsal horn of SCI rats. We revealed specific signaling pathways leading to SCI-evoked neuropathic pain, including the activation of PI3K, mTOR and its downstream signaling pathways. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of neuropathic pain often observed in patients with SCI.

Repeated oral administration of capsaicin increases anxiety-like ...

Indian Academy of Sciences (India)

This study was conducted to examine the psycho-emotional effects of repeated oral exposure to capsaicin, the principal active component of chili peppers. Each rat received 1 mL of 0.02% capsaicin into its oral cavity daily, and was subjected to behavioural tests following 10 daily administrations of capsaicin. Stereotypy ...

Flare-up rate of single-visit endodontics.

Science.gov (United States)

Trope, M

1991-01-01

The purpose of the study was to compare the flare-up rate for single-visit endodontics among teeth without radiographic or clinical signs of apical periodontitis, those with radiographic or clinical signs of apical periodontitis not previously root-treated, and those with apical periodontitis where retreatment was performed. All teeth were instrumented to a predetermined minimum size with a 0.5 per cent solution of sodium hypochlorite being used as the irrigant. The root canal was obturated without regard to the presence or absence of symptoms or diagnosis of the apical condition. The patients were given written post-operative instructions and a prescription for 600 mg ibuprofen to be taken if mild to moderate pain developed. If severe pain and/or swelling developed, the patient was instructed to telephone immediately and was considered to have had a flare-up. Teeth without signs of apical periodontitis did not have any flare-ups. One flare-up occurred in 69 teeth with signs of apical periodontitis not previously root-treated. The majority of the flare-ups (3 of 22 teeth) occurred in teeth with signs of apical periodontitis requiring retreatment.

A change in the parameters of P300 evoked potentials in relation to the degree of exacerbation of pain syndrome

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A P Rachin

2012-01-01

Full Text Available In chronic pain, the state of suprasegmental brain structures (the cortex, limbic system, truncodiencephalic structures, which form the motivational-affective and cognitive components of pain behavior, actively affects pain afferentation as well. The purpose of the study was to comparatively analyze the parameters and topographic distribution of P300 cognitive evoked potential in patients with lower back pain. Sixty patients aged 22 to 60 years were examined. The authors made their clinical and neurological examinations, collected medical history data, and assessed back pain intensity by a visual analog scale. The findings were compared with the parameters of cognitive evoked potentials (the separating of P300 to count; keystroke in the recognition of significant stimuli; elaboration of a verbal and nonverbal visual stimulation protocol, by using emotionally significant stimuli. The processes of recognition and differentiation, those of directed attention, and the rate of information processing slowed down in patients with different stages of pain syndrome. The P300 separating procedure using the emotionally significant stimuli allows one to assess the specific features of chronization of pain syndromes and the presence of pain memory in the central nervous system of such patients. The estimation of P300 parameters over time or during treatment are of particular value for the optimization and evaluation of its efficiency.

Relationship of intracanal medicaments to endodontic flare-ups.

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Trope, M

1990-10-01

The purpose of the study was to compare the effect of three intracanal medicaments on the incidence of post-instrumentation flare-ups. All teeth were instrumented to a predetermined minimum size using a 0.5% solution of sodium hypochlorite as the irrigant. Formocresol, Ledermix, and calcium hydroxide were placed in strict sequence irrespective of the presence or absence of symptoms or radiographic signs of apical periodontitis. The patients were given written post-operative instructions and a prescription for 600 mg ibuprofen to be taken if mild to moderate pain developed. If severe pain and/or swelling developed the patient was instructed to call the office immediately and was considered to have had a flare-up. Twelve flare-ups occurred in teeth with radiographic signs of apical periodontitis; none in teeth without periapical radiolucencies. Six of the twelve flare-ups occurred in retreatment cases and the other six occurred in teeth without previous endodontic treatment. No significant difference was found in the flare-up rate among the three intracanal medicaments.

Moderate extracellular acidification inhibits capsaicin-induced cell death through regulating calcium mobilization, NF-κB translocation and ROS production in synoviocytes

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Hu, Fen; Yang, Shuang; Zhao, Dan; Zhu, Shuyan; Wang, Yuxiang; Li, Junying

2012-01-01

Highlights: ► Moderate extracellular acidification regulates intracellular Ca 2+ mobilization. ► Moderate acidification activates NF-κB nuclear translocation in synoviocytes. ► Moderate acidification depresses the ROS production induced by capsaicin. ► Moderate acidification inhibits capsaicin-caused synoviocyte death. -- Abstract: We previously show the expression of transient receptor potential vanilloid 1 (TRPV1) in primary synoviocytes from collagen-induced arthritis (CIA) rats. Capsaicin and lowered extracellular pH from 7.4 to 5.5 induce cell death through TRPV1-mediated Ca 2+ entry and reactive oxygen species (ROS) production. However, under the pathological condition in rheumatoid arthritis, the synovial fluid is acidified to a moderate level (about pH 6.8). In the present study, we examined the effects of pH 6.8 on the TRPV1-mediated cell death. Our finding is different or even opposite from what was observed at pH 5.5. We found that the moderate extracellular acidification (from pH 7.4 to 6.8) inhibited the capsaicin-induced Ca 2+ entry through attenuating the activity of TRPV1. In the mean time, it triggered a phospholipse C (PLC)-related Ca 2+ release from intracellular stores. The nuclear translocation of NF-κB was found at pH 6.8, and this also depends on PLC activation. Moreover, the capsaicin-evoked massive ROS production and cell death were depressed at pH 6.8, both of which are dependent on the activation of PLC and NF-κB. Taken together, these results suggested that the moderate extracellular acidification inhibited the capsaicin-induced synoviocyte death through regulating Ca 2+ mobilization, activating NF-κB nuclear translocation and depressing ROS production.

Moderate extracellular acidification inhibits capsaicin-induced cell death through regulating calcium mobilization, NF-{kappa}B translocation and ROS production in synoviocytes

Energy Technology Data Exchange (ETDEWEB)

Hu, Fen; Yang, Shuang; Zhao, Dan; Zhu, Shuyan; Wang, Yuxiang [Department of Biophysics, School of Physics and Key Laboratory of Bioactive Materials of Education Ministry, Nankai University, Tianjin 300071 (China); Li, Junying, E-mail: jyli04@nankai.edu.cn [Department of Biophysics, School of Physics and Key Laboratory of Bioactive Materials of Education Ministry, Nankai University, Tianjin 300071 (China)

2012-07-20

Highlights: Black-Right-Pointing-Pointer Moderate extracellular acidification regulates intracellular Ca{sup 2+} mobilization. Black-Right-Pointing-Pointer Moderate acidification activates NF-{kappa}B nuclear translocation in synoviocytes. Black-Right-Pointing-Pointer Moderate acidification depresses the ROS production induced by capsaicin. Black-Right-Pointing-Pointer Moderate acidification inhibits capsaicin-caused synoviocyte death. -- Abstract: We previously show the expression of transient receptor potential vanilloid 1 (TRPV1) in primary synoviocytes from collagen-induced arthritis (CIA) rats. Capsaicin and lowered extracellular pH from 7.4 to 5.5 induce cell death through TRPV1-mediated Ca{sup 2+} entry and reactive oxygen species (ROS) production. However, under the pathological condition in rheumatoid arthritis, the synovial fluid is acidified to a moderate level (about pH 6.8). In the present study, we examined the effects of pH 6.8 on the TRPV1-mediated cell death. Our finding is different or even opposite from what was observed at pH 5.5. We found that the moderate extracellular acidification (from pH 7.4 to 6.8) inhibited the capsaicin-induced Ca{sup 2+} entry through attenuating the activity of TRPV1. In the mean time, it triggered a phospholipse C (PLC)-related Ca{sup 2+} release from intracellular stores. The nuclear translocation of NF-{kappa}B was found at pH 6.8, and this also depends on PLC activation. Moreover, the capsaicin-evoked massive ROS production and cell death were depressed at pH 6.8, both of which are dependent on the activation of PLC and NF-{kappa}B. Taken together, these results suggested that the moderate extracellular acidification inhibited the capsaicin-induced synoviocyte death through regulating Ca{sup 2+} mobilization, activating NF-{kappa}B nuclear translocation and depressing ROS production.

Effect of prophylactic amoxicillin on endodontic flare-up in asymptomatic, necrotic teeth.

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Pickenpaugh, L; Reader, A; Beck, M; Meyers, W J; Peterson, L J

2001-01-01

The purpose of this prospective, randomized, double-blind, placebo-controlled study was to determine the effect of prophylactic amoxicillin on the occurrence of endodontic flare-up in asymptomatic, necrotic teeth. Seventy patients participated and had a clinical diagnosis of an asymptomatic, necrotic tooth with associated periapical radiolucency. One hour before endodontic treatment, patients randomly received either 3 g of amoxicillin or 3 g of a placebo control in a double-blind manner. After endodontic treatment, each patient received: ibuprofen; acetaminophen with codeine (30 mg); and a 5 1/2-day diary to record pain, swelling, percussion pain, and number and type of pain medication taken. The results demonstrated 10% of the 70 patients had a flare-up characterized by moderate-to-severe postoperative pain or swelling that began approximately 30 h after endodontic treatment and persisted for an average of 74 h. Of the seven patients who had flare-ups, 4 were in the amoxicillin group and 3 were not. Prophylactic amoxicillin did not significantly (p = 0.80) influence the endodontic flare-up. We concluded that a prophylactic dose of amoxicillin before endodontic treatment of asymptomatic, necrotic teeth had no effect on the endodontic flare-up.

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

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Kanako So

2015-03-01

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

Dehydration enhances pain-evoked activation in the human brain compared with rehydration.

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Ogino, Yuichi; Kakeda, Takahiro; Nakamura, Koji; Saito, Shigeru

2014-06-01

Negative effects of dehydration on the human brain and cognitive function have been reported. In this study, we examined the effects of dehydration on pain thresholds and cortical activations in response to pain, compared with rehydration with an oral rehydration solution (ORS) by functional magnetic resonance imaging. Five healthy adult men were subjected to dehydration and rehydration on 2 different days. The condition on the first day was randomly assigned to each subject. They completed a 40-minute exercise protocol using a walking machine after 12 hours of fasting under both conditions. For rehydration, the subjects consumed up to 3000 mL ORS starting from the night before the test day. After exercise, a painful stimulus (cold pressor test) was applied to the subjects' medial forearm in a magnetic resonance imaging scanning gantry, and pain-evoked brain activation was analyzed. On the rehydration day, each of the subjects consumed an average of 2040 mL (range; 1800-2500 mL) ORS. Physiological data revealed that subjects when dehydrated lost more weight from exercise than subjects when rehydrated had a larger heart rate increase, a higher tympanic temperature, and a higher urine osmolality. Subjective data revealed that the subjects reported significantly stronger thirst while dehydrated than while rehydrated with ORS, although the levels of hunger and anxiety and mood did not significantly differ between conditions. The cold pressor test robustly activated the pain-related neural network, notably the anterior cingulate cortex, insula, and thalamus. Such activations in the dehydrated subjects were greater than those in the rehydrated subjects in terms of peak and cluster, accompanied by a decrease in pain threshold (P = 0.001). Our findings suggest that dehydration brings about increased brain activity related to painful stimuli together with enhanced thirst, whereas rehydration with ORS alleviates thirst and decreases brain activity related to painful stimuli.

Increased Evoked Potentials and Behavioral Indices in Response to Pain Among Individuals with Intellectual Disability.

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Benromano, Tali; Pick, Chaim G; Granovsky, Yelena; Defrin, Ruth

2017-09-01

Previous studies on the sensitivity and reactivity to pain of individuals with intellectual disability (ID) are inconsistent. The inconsistency may result from the reliance on self-reports and facial expressions of pain that are subject to internal and external biases. The aim was therefore to evaluate the reactivity to pain of individuals with ID by recording pain-evoked potentials (EPs), here for the first time, and testing their association with behavioral pain indices. Forty-one healthy adults, 16 with mild-moderate ID and 25 controls. Subjects received series of phasic heat stimuli and rated their pain on self-report scales. Changes in facial expressions and in pain EPs were recorded and analyzed offline. Pain self-reports, facial expressions, and the N2P2 amplitudes of the EPs exhibited stimulus-response relationship with stimulation intensity in both groups. The facial expressions and N2P2 amplitudes of individuals with ID were increased and N2P2 latency prolonged compared with controls. N2P2 amplitudes correlated with self-reports only in controls. Individuals with ID are hypersensitive/reactive to pain, a finding bearing clinical implications. Although pain EPs may reflect a somewhat different aspect of pain than the behavioral indices do, there is evidence to support their use to record pain in noncommunicative individuals, pending further validation. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

The effects of Hot Pepper Extract and Capsaicin on Adipocyte Metabolism

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Ching Sheng, Chu

2008-03-01

Full Text Available Objectives : The purpose of this study is to investigate the effects of hot pepper extract and capsaicin on the adipogenesis in 3T3-L1 cells, lipolysis in rat epididymal adipocytes and histological changes in porcine adipose tissue. Methods : Inhibiton of preadipocyte differentiation and/or stimulation of lipolysis play important roles in reducing obesity. 3T3-L1 preadipocytes were differentiated with adipogenic reagents by incubating for 3 days in the absence or presence of hot pepper extract or capsaicin ranging from 0.01 to 1㎎/㎖. The effects of hot pepper extract and capsaicin on adipogenesis were examined by measuring GPDH activity and by Oil Red O staining. Mature adipocytes from rat epididymal fat pad was incubated with hot pepper extract or capsaicin ranging from 0.01 to 1㎎/㎖ for 3 hrs. The effects of hot pepper extract and capsaicin on lipolysis were examined by measuring free glycerol released. Fat tissue from pig skin was injected with hot pepper extract or capsaicinCFP ranging from 0.1 to 10㎎/㎖ to examine the effects of hot pepper extract and capsaicin on histological changes under light microscopy. Results : The following results were obtained from present study on adipogenesis of preadipocytes, lipolysis of adipocytes and histological changes in fat tissue. 1. Hot pepper extract and capsaicin inhibited adipogenic differentiation at the concentration of 0.1 and 0.01㎎/㎖, respectively, indicating that capsaicin was more effective in inhibiting adipogenesis than hot pepper extract. 2. Hot pepper extract and capsaicin decreased the activity of glycerol-3-phosphate dehydrogenase(GPDH at the concentration of 0.1 and 0.01㎎/㎖, respectively, indicating that capsaicin was more effective in inhibiting adipogenic differentiation than hot pepper extract. 3. Hot pepper extract and capsaicin increased glycerol release at the concentration of 0.1㎎/㎖. There was no difference in lipolytic activity between hot pepper extract and

Tlx3 Function in the Dorsal Root Ganglion is Pivotal to Itch and Pain Sensations

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Chengcheng Huang

2017-06-01

Full Text Available Itch, a sensation eliciting a desire to scratch, is distinct from but not completely independent of pain. Inspiring achievements have been made in the characterization of itch-related receptors and neurotransmitters, but the molecular mechanisms controlling the development of pruriceptors remain poorly understood. Here, our RNAseq and in situ hybridization data show that the transcription factor Tlx3 is required for the expression of a majority of itch-related molecules in the dorsal root ganglion (DRG. As a result, Tlx3F/F;Nav1.8-cre mice exhibit significantly attenuated acute and dry skin-induced chronic itch. Furthermore, our study indicates that TRPV1 plays a pivotal role in the chronic itch evoked by dry skin and allergic contact dermatitis (ACD. The mutants also display impaired response to cold and inflammatory pain and elevated response to capsaicin, whereas the responses to acute mechanical, thermal stimuli and neuropathic pain remain normal. In Tlx3F/F;Nav1.8-cre mice, TRPV1 is derepressed and expands predominantly into IB4+ non-peptidergic (NP neurons. Collectively, our data reveal a molecular mechanism in regulating the development of pruriceptors and controlling itch and pain sensations.

Acute low back pain is marked by variability: An internet-based pilot study

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Katz Jeffrey N

2011-10-01

Full Text Available Abstract Background Pain variability in acute LBP has received limited study. The objectives of this pilot study were to characterize fluctuations in pain during acute LBP, to determine whether self-reported 'flares' of pain represent discrete periods of increased pain intensity, and to examine whether the frequency of flares was associated with back-related disability outcomes. Methods We conducted a cohort study of acute LBP patients utilizing frequent serial assessments and Internet-based data collection. Adults with acute LBP (lasting ≤3 months completed questionnaires at the time of seeking care, and at both 3-day and 1-week intervals, for 6 weeks. Back pain was measured using a numerical pain rating scale (NPRS, and disability was measured using the Oswestry Disability Index (ODI. A pain flare was defined as 'a period of increased pain lasting at least 2 hours, when your pain intensity is distinctly worse than it has been recently'. We used mixed-effects linear regression to model longitudinal changes in pain intensity, and multivariate linear regression to model associations between flare frequency and disability outcomes. Results 42 of 47 participants (89% reported pain flares, and the average number of discrete flare periods per patient was 3.5 over 6 weeks of follow-up. More than half of flares were less than 4 hours in duration, and about 75% of flares were less than one day in duration. A model with a quadratic trend for time best characterized improvements in pain. Pain decreased rapidly during the first 14 days after seeking care, and leveled off after about 28 days. Patients who reported a pain flare experienced an almost 3-point greater current NPRS than those not reporting a flare (mean difference [SD] 2.70 [0.11]; p ß [SE} 0.28 (0.08; p = 0.002. Conclusions Acute LBP is characterized by variability. Patients with acute LBP report multiple distinct flares of pain, which correspond to discrete increases in pain intensity. A

Investigation of the predictive validity of laser-EPs in normal, UVB-inflamed and capsaicin-irritated skin with four analgesic compounds in healthy volunteers.

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Schaffler, Klaus; Nicolas, Laurent B; Borta, Andreas; Brand, Tobias; Reitmeir, Peter; Roebling, Robert; Scholpp, Joachim

2017-07-01

The aim of the present study was to assess the predictivity of laser-(radiant-heat)-evoked potentials (LEPs) from the vertex electroencephalogram, using an algesimetric procedure, testing the anti-nociceptive/anti-hyperalgesic effects of single oral doses of four marketed analgesics (of different compound classes) vs. placebo, in healthy volunteers with three skin types. This was a randomized, placebo-controlled, single-blind, five-way-crossover trial. Twenty-five healthy male/female Caucasians were included (receiving celecoxib 200 mg, pregabalin 150 mg, duloxetine 60 mg, lacosamide 100 mg or placebo) in a Williams design, with CO 2 laser-induced painful stimuli to normal, ultraviolet (UV) B-inflamed and capsaicin-irritated skin. LEPs and visual analogue scale ratings were taken at baseline and hourly for 6 h postdose from all three skin types. In normal skin, the averaged postdose LEP peak-to-peak-(PtP)-amplitudes were reduced by pregabalin (-2.68 μV; 95% confidence interval (CI) -4.16, 1.19) and duloxetine (-1.73 μV; 95% CI -3.21, -0.26) but not by lacosamide and celecoxib vs. placebo. On UVB-irradiated skin, reflecting inflammatory pain, celecoxib induced a pronounced reduction in LEP PtP amplitudes vs. placebo (-6.2 μV; 95% CI -7.88, -4.51), with a smaller reduction by duloxetine (-4.54 μV; 95% CI -6.21, -2.87) and pregabalin (-3.72 μV; 95% CI -5.40, -2.04), whereas lacosamide was inactive. LEP PtP amplitudes on capsaicin-irritated skin, reflecting peripheral/spinal sensitization, as in neuropathic pain, were reduced by pregabalin (-3.78 μV; 95% CI -5.31, -2.25) and duloxetine (-2.32 μV; 95% CI -3.82, -0.82) but not by celecoxib or lacosamide vs. placebo, which was in agreement with known clinical profiles. Overall, PtP amplitude reductions were in agreement with subjective ratings. LEP algesimetry is sensitive to analgesics with different modes of action and may enable the effects of novel analgesics to be assessed during early clinical

Effects of capsaicin in the motor nerve.

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Pettorossi, V E; Bortolami, R; Della Torre, G; Brunetti, O

1994-08-01

The injection of capsaicin into the lateral gastrocnemius (LG) muscle of the rat induced an immediate and sustained reduction in the A delta and C components of the compound action potential (CAP) of the LG motor nerve. Conversely, the drug did not immediately affect the CAP wave belonging to fast-conducting fibers or the motor responses to LG nerve stimulation. It seems that capsaicin only affects the group III and IV afferents of LG nerve. However, a week after the injection the capsaicin also altered the motor responses, as shown by the threshold enhancement and amplitude reduction of the muscle twitch and by the decrease of the A alpha-beta CAP components. This late motor impairment was attributed to a central depression following a reduction of capsaicin-sensitive neuron input into the CNS. However, this motor effect was transient since the LG nerve regained the preinjection excitability level in a week and the muscle twitch amplitude reached the control value in a month.

Endodontic flare-ups: a prospective study.

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Alves, Vanessa de Oliveira

2010-11-01

The objective of this prospective clinical study was to evaluate the incidence of flare-ups (pain and/or swelling requiring endodontic interappointment and emergency treatment) and identify the risk factors associated with their occurrence in patients who received endodontic treatment from June 2006 to June 2007 at the endodontics clinic of the São Paulo Dental Association (APCD), Jardim Paulista branch, São Paulo, Brazil. The incidence of flare-ups was 1.71% out of 408 teeth that had received endodontic therapy. Statistical analysis using the chi-squared test (P flare-up rate and the presence of a periradicular radiolucency. Copyright © 2010 Mosby, Inc. All rights reserved.

Tris-hydroxymethyl-aminomethane enhances capsaicin-induced intracellular Ca2+ influx through transient receptor potential V1 (TRPV1 channels

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Satoshi Murakami

2016-02-01

Full Text Available Non-selective transient receptor potential vanilloid (TRPV cation channels are activated by various insults, including exposure to heat, acidity, and the compound capsaicin, resulting in sensations of pain in the skin, visceral organs, and oral cavity. Recently, TRPV1 activation was also demonstrated in response to basic pH elicited by ammonia and intracellular alkalization. Tris-hydroxymethyl aminomethane (THAM is widely used as an alkalizing agent; however, the effects of THAM on TRPV1 channels have not been defined. In this study, we characterized the effects of THAM-induced TRPV1 channel activation in baby hamster kidney cells expressing human TRPV1 (hTRPV1 and the Ca2+-sensitive fluorescent sensor GCaMP2 by real-time confocal microscopy. Notably, both capsaicin (1 μM and pH 6.5 buffer elicited steep increases in the intracellular Ca2+ concentration ([Ca2+]i, while treatment with THAM (pH 8.5 alone had no effect. However, treatment with THAM (pH 8.5 following capsaicin application elicited a profound, long-lasting increase in [Ca2+]i that was completely inhibited by the TRPV1 antagonist capsazepine. Taken together, these results suggest that hTRPV1 pre-activation is required to provoke enhanced, THAM-induced [Ca2+]i increases, which could be a mechanism underlying pain induced by basic pH.

Test imf kursus - Referred Pain and Sensations Evoked by Standardized Palpation of the Masseter Muscle in Healthy Participants

DEFF Research Database (Denmark)

Masuda, Manabu; Iida, Takashi; Exposto, Fernando G

2018-01-01

, Tukey post hoc, and McNemar's tests with a 5% level of significance. RESULTS: Referred pain/sensations were most commonly evoked with the 2.0-kg stimulus (34.4% of participants; P significant effects of stimulus intensity on NRS...... scores for pain and unpleasantness, as well as for aftersensation (P significant effects on NRS scores for pain and unpleasantness for the 1.0- and 2.0-kg stimuli (P 2.0-kg stimulus (P .... The right masseter muscle was divided into 15 test sites. Mechanical sensitivity of the masseter was assessed with three mechanical stimuli (0.5 kg, 1.0 kg, or 2.0 kg) applied by palpometers to the 15 test sites for 5 seconds each site. Participants scored the perceived intensity of pain and unpleasantness...

Cannabinoid hyperemesis syndrome: potential mechanisms for the benefit of capsaicin and hot water hydrotherapy in treatment.

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Richards, John R; Lapoint, Jeff M; Burillo-Putze, Guillermo

2018-01-01

Cannabinoid hyperemesis syndrome is a clinical disorder that has become more prevalent with increasing use of cannabis and synthetic cannabinoids, and which is difficult to treat. Standard antiemetics commonly fail to alleviate the severe nausea and vomiting characteristic of the syndrome. Curiously, cannabinoid hyperemesis syndrome patients often report dramatic relief of symptoms with hot showers and baths, and topical capsaicin. In this review, we detail the pharmacokinetics and pharmacodynamics of capsaicin and explore possible mechanisms for its beneficial effect, including activation of transient receptor potential vanilloid 1 and neurohumoral regulation. Putative mechanisms responsible for the benefit of hot water hydrotherapy are also investigated. An extensive search of PubMed, OpenGrey, and Google Scholar from inception to April 2017 was performed to identify known and theoretical thermoregulatory mechanisms associated with the endocannabinoid system. The searches resulted in 2417 articles. These articles were screened for relevant mechanisms behind capsaicin and heat activation having potential antiemetic effects. References from the selected articles were also hand-searched. A total of 137 articles were considered relevant and included. Capsaicin: Topical capsaicin is primarily used for treatment of neuropathic pain, but it has also been used successfully in some 20 cases of cannabinoid hyperemesis syndrome. The pharmacokinetics and pharmacodynamics of capsaicin as a transient receptor potential vanilloid 1 agonist may explain this effect. Topical capsaicin has a longer half-life than oral administration, thus its potential duration of benefit is longer. Capsaicin and transient receptor potential vanilloid 1: Topical capsaicin binds and activates the transient receptor potential vanilloid 1 receptor, triggering influx of calcium and sodium, as well as release of inflammatory neuropeptides leading to transient burning, stinging, and itching. This elicits

Impact of visual learning on facial expressions of physical distress: a study on voluntary and evoked expressions of pain in congenitally blind and sighted individuals.

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Kunz, Miriam; Faltermeier, Nicole; Lautenbacher, Stefan

2012-02-01

The ability to facially communicate physical distress (e.g. pain) can be essential to ensure help, support and clinical treatment for the individual experiencing physical distress. So far, it is not known to which degree this ability represents innate and biologically prepared programs or whether it requires visual learning. Here, we address this question by studying evoked and voluntary facial expressions of pain in congenitally blind (N=21) and sighted (N=42) individuals. The repertoire of evoked facial expressions was comparable in congenitally blind and sighted individuals; however, blind individuals were less capable of facially encoding different intensities of experimental pain. Moreover, blind individuals were less capable of voluntarily modulating their pain expression. We conclude that the repertoire of facial muscles being activated during pain is biologically prepared. However, visual learning is a prerequisite in order to encode different intensities of physical distress as well as for up- and down-regulation of one's facial expression. Copyright © 2011 Elsevier B.V. All rights reserved.

Scaling Up Cortical Control Inhibits Pain

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Jahrane Dale

2018-05-01

Full Text Available Summary: Acute pain evokes protective neural and behavioral responses. Chronic pain, however, disrupts normal nociceptive processing. The prefrontal cortex (PFC is known to exert top-down regulation of sensory inputs; unfortunately, how individual PFC neurons respond to an acute pain signal is not well characterized. We found that neurons in the prelimbic region of the PFC increased firing rates of the neurons after noxious stimulations in free-moving rats. Chronic pain, however, suppressed both basal spontaneous and pain-evoked firing rates. Furthermore, we identified a linear correlation between basal and evoked firing rates of PFC neurons, whereby a decrease in basal firing leads to a nearly 2-fold reduction in pain-evoked response in chronic pain states. In contrast, enhancing basal PFC activity with low-frequency optogenetic stimulation scaled up prefrontal outputs to inhibit pain. These results demonstrate a cortical gain control system for nociceptive regulation and establish scaling up prefrontal outputs as an effective neuromodulation strategy to inhibit pain. : Dale et al. find that acute pain increases activity levels in the prefrontal cortex. Chronic pain reduces both basal spontaneous and pain-evoked activity in this region, whereas neurostimulation to restore basal activities can in turn enhance nociception-evoked prefrontal activities to inhibit pain. Keywords: chronic pain, neuromodulation, prefrontal cortex, PFC, cortical gain control

Capsaicin induces cell cycle arrest and apoptosis in human KB cancer cells.

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Lin, Chia-Han; Lu, Wei-Cheng; Wang, Che-Wei; Chan, Ya-Chi; Chen, Mu-Kuan

2013-02-25

Capsaicin, a pungent phytochemical in a variety of red peppers of the genus Capsicum, has shown an anti-proliferative effect on various human cancer cell lines. In contrast, capsaicin has also been considered to promote the growth of cancer cells. Thus, the effects of capsaicin on various cell types need to be explored. The anti-proliferative effects of capsaicin on human KB cancer cells are still unknown. Therefore, we examined the viability, cell cycle progression, and factors associated with apoptosis in KB cells treated with capsaicin. The cell proliferation/viability and cytotoxicity of KB cells exposed to capsaicin were determined by a sulforhodamine B colorimetric assay and trypan blue exclusion. Apoptosis was detected by Hoechst staining and confirmed by western blot analysis of poly-(ADP-ribose) polymerase cleavage. Cell cycle distribution and changes of the mitochondrial membrane potential were analyzed by flow cytometry. Furthermore, the expression of caspase 3, 8 and 9 was evaluated by immunoblotting. We found that treatment of KB cells with capsaicin significantly reduced cell proliferation/viability and induced cell death in a dose-dependent manner compared with that in the untreated control. Cell cycle analysis indicated that exposure of KB cells to capsaicin resulted in cell cycle arrest at G2/M phase. Capsaicin-induced growth inhibition of KB cells appeared to be associated with induction of apoptosis. Moreover, capsaicin induced disruption of the mitochondrial membrane potential as well as activation of caspase 9, 3 and poly-(ADP-ribose) polymerase in KB cells. Our data demonstrate that capsaicin modulates cell cycle progression and induces apoptosis in human KB cancer cells through mitochondrial membrane permeabilization and caspase activation. These observations suggest an anti-cancer activity of capsaicin.

How is symptom flare defined in musculoskeletal conditions: A systematic review.

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Costa, Nathalia; Ferreira, Manuela L; Cross, Marita; Makovey, Joanna; Hodges, Paul W

2018-01-31

To systematically review the definitions for "flare" in musculoskeletal conditions, the derivation processes, and validation of definitions for the 12 most burdensome musculoskeletal conditions. A literature search was conducted in MEDLINE, EMBASE, CINAHL, AMED, PsycInfo and Lilacs to identify studies that investigated derivation or validation of a flare definition, which we considered as a phrase or group of domains. Reports of derivation of flare definitions were identified for 9/12 musculoskeletal conditions. Validation of flare definitions was initiated for 4/12. For each condition, different derivation and validation methods have been used, with variable levels of consumer involvement, and in some cases different groups have worked on the process in parallel. Although some flare definitions began simply as "symptom worsening" or "change in treatment", most evolved into multidimensional definitions that include: pain, impact on function, joint symptoms, and emotional elements. Frequently initial attempts to create phrase to define the term flare evolved into consensus on the breadth of domains involved. Validation has compared flare definitions/domains against measures of disease activity, clinicians' diagnosis, response to drug therapy, or a combination. This review suggests that greater characterisation and definition of flares in musculoskeletal conditions are linked to the inclusion of multiple perspectives, multifaceted domains and compound comparators for their validation. Further work is required to optimise and test the derived definitions for most musculoskeletal conditions. As some elements are disease-specific, flare definitions cannot be extrapolated to other conditions. Research regarding flare in back pain (most burdensome disease) is limited. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of experimental diabetes on cholinergic, purinergic and peptidergic motor responses of the isolated rat bladder to electrical field stimulation or capsaicin.

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Benkó, Rita; Lázár, Zsófia; Pórszász, Róbert; Somogyi, George T; Barthó, Loránd

2003-09-30

An attempt has been made to pharmacologically isolate cholinergic, P(2) purinoceptor-mediated and peptidergic (capsaicin-sensitive, tachykinin-mediated) contraction of the guanethidine-treated rat bladder detrusor preparation, in vitro. The effect of experimental diabetes was assessed on these types of contraction. Responses were evoked by electrical field stimulation (single shocks or 1 Hz for 30 s or 10 Hz for 40 s). Single shocks and 1-Hz stimulation were applied in the presence of (a). atropine (1 microM) or (b). P(2) purinoceptor antagonists (50 microM pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid) [PPADS] plus 100 microM suramin. Long-term electrical field stimulation (10 Hz for 40 s) (c). was applied with both atropine and the P(2) purinoceptor antagonists present in the organ bath. The effects of capsaicin (d). and ATP (e). were also studied. Three groups of experimental animals were used: streptozotocin-treated (50 mg.kg(-1) i.p., 8 weeks before the experiment), parallel solvent-treated and untreated rats. (a). Responses to electrical field stimulation in the presence of atropine were reduced by half by PPADS plus suramin, but were resistant to capsaicin tachyphylaxis. They were enhanced in preparations taken from diabetic rats. (b). Contractions to electrical field stimulation in the presence of PPADS plus suramin were reduced by 2/3 by atropine, but were left unchanged by capsaicin or diabetes. (c). Contractions to long-term stimulation had a quick and a sustained phase. Especially the latter was inhibited by capsaicin tachypyhlaxis; it was also strongly reduced in preparations taken from diabetic rats. (d). Contractions to capsaicin (30 nM and 1 microM) were resistant to tetrodotoxin, strongly reduced by a combination of tachykinin NK(1) and NK(2) receptor antagonists, and slightly reduced in preparations from diabetic animals. Capsaicin (1 microM) had no acute inhibitory action on cholinergic or purinergic responses, nor did it cause relaxation

Activation of TRPV1 by capsaicin induces functional Kinin B1 receptor in rat spinal cord microglia

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Talbot Sébastien

2012-01-01

Full Text Available Abstract Background The kinin B1 receptor (B1R is upregulated by pro-inflammatory cytokines and oxydative stress, which are enhanced by transient receptor potential vanilloid subtype 1 (TRPV1 activation. To examine the link between TRPV1 and B1R in inflammatory pain, this study aimed to determine the ability of TRPV1 to regulate microglial B1R expression in the spinal cord dorsal horn, and the underlying mechanism. Methods B1R expression (mRNA, protein and binding sites was measured in cervical, thoracic and lumbar spinal cord in response to TRPV1 activation by systemic capsaicin (1-50 mg/kg, s.c in rats pre-treated with TRPV1 antagonists (capsazepine or SB-366791, the antioxidant N-acetyl-L-cysteine (NAC, or vehicle. B1R function was assessed using a tail-flick test after intrathecal (i.t. injection of a selective B1R agonist (des-Arg9-BK, and its microglial localization was investigated by confocal microscopy with the selective fluorescent B1R agonist, [Nα-bodipy]-des-Arg9-BK. The effect of i.t. capsaicin (1 μg/site was also investigated. Results Capsaicin (10 to 50 mg/kg, s.c. enhanced time-dependently (0-24h B1R mRNA levels in the lumbar spinal cord; this effect was prevented by capsazepine (10 mg/kg, i.p.; 10 μg/site, i.t. and SB-366791 (1 mg/kg, i.p.; 30 μg/site, i.t.. Increases of B1R mRNA were correlated with IL-1β mRNA levels, and they were significantly less in cervical and thoracic spinal cord. Intrathecal capsaicin (1 μg/site also enhanced B1R mRNA in lumbar spinal cord. NAC (1 g/kg/d × 7 days prevented B1R up-regulation, superoxide anion production and NF-kB activation induced by capsaicin (15 mg/kg. Des-Arg9-BK (9.6 nmol/site, i.t. decreased by 25-30% the nociceptive threshold at 1 min post-injection in capsaicin-treated rats (10-50 mg/kg while it was without effect in control rats. Des-Arg9-BK-induced thermal hyperalgesia was blocked by capsazepine, SB-366791 and by antagonists/inhibitors of B1R (SSR240612, 10 mg/kg, p

Feasibility and Domain Validation of Rheumatoid Arthritis (RA) Flare Core Domain Set

DEFF Research Database (Denmark)

Bartlett, Susan J; Bykerk, Vivian P; Cooksey, Roxanne

2015-01-01

, and stiffness scores averaged ≥ 2 times higher (2 of 11 points) in flaring individuals. Correlations between flare domains and corresponding legacy instruments were obtained: r = 0.46 to 0.93. A combined definition (patient report of flare and 28-joint Disease Activity Score increase) was evaluated in 2 other...... provided input for stiffness, self-management, contextual factors, and measurement considerations. RESULTS: Flare data from 501 patients in an observational study indicated 39% were in flare, with mean (SD) severity of 6.0 (2.6) and 55% lasting > 14 days. Pain, physical function, fatigue, participation...

Supercritical CO2 as a reaction medium for synthesis of capsaicin analogues by lipase-catalyzed transacylation of capsaicin.

Science.gov (United States)

Kobata, Kenji; Kobayashi, Mamiko; Kinpara, Sachiyo; Watanabe, Tatsuo

2003-09-01

Capsaicin analogues having different acyl moiety were synthesized by lipase-catalyzed transacylation of capsaicin with a corresponding acyl donor in supercritical CO2 as a reaction medium. Transacylation with methyl tetradecanoate using Novozym 435 as a catalyst gave vanillyl tetradecanamide in a 54% yield at 80 degrees C and 19 MPa over 72 h. Vanillyl (Z)-9-octadecenamide, olvanil, was synthesized from triolein in a 21% yield over 7 d.

Differences in cortical coding of heat evoked pain beyond the perceived intensity: an fMRI and EEG study.

Science.gov (United States)

Haefeli, Jenny; Freund, Patrick; Kramer, John L K; Blum, Julia; Luechinger, Roger; Curt, Armin

2014-04-01

Imaging studies have identified a wide network of brain areas activated by nociceptive stimuli and revealed differences in somatotopic representation of highly distinct stimulation sites (foot vs. hand) in the primary (S1) and secondary (S2) somatosensory cortices. Somatotopic organization between adjacent dermatomes and differences in cortical coding of similarly perceived nociceptive stimulation are less well studied. Here, cortical processing following contact heat nociceptive stimulation of cervical (C4, C6, and C8) and trunk (T10) dermatomes were recorded in 20 healthy subjects using functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Stimulation of T10 compared with the C6 and C8 revealed significant higher response intensity in the left S1 (contralateral) and the right S2 (ipsilateral) even when the perceived pain was equal between stimulation sites. Accordingly, contact heat evoked potentials following stimulation of T10 showed significantly higher N2P2 amplitudes compared to C6 and C8. Adjacent dermatomes did not reveal a distinct somatotopical representation. Within the assessed cervical and trunk dermatomes, nociceptive cortical processing to heat differs significantly in magnitude even when controlling for pain perception. This study provides evidence that controlling for pain perception is not sufficient to compare directly the magnitude of cortical processing [blood oxygen level dependence (BOLD) response and amplitude of evoked potentials] between body sites. Copyright © 2013 Wiley Periodicals, Inc.

Upregulation of T-type Ca2+ channels in long-term diabetes determines increased excitability of a specific type of capsaicin-insensitive DRG neurons.

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Duzhyy, Dmytro E; Viatchenko-Karpinski, Viacheslav Y; Khomula, Eugen V; Voitenko, Nana V; Belan, Pavel V

2015-05-20

Previous studies have shown that increased excitability of capsaicin-sensitive DRG neurons and thermal hyperalgesia in rats with short-term (2-4 weeks) streptozotocin-induced diabetes is mediated by upregulation of T-type Ca(2+) current. In longer-term diabetes (after the 8th week) thermal hyperalgesia is changed to hypoalgesia that is accompanied by downregulation of T-type current in capsaicin-sensitive small-sized nociceptors. At the same time pain symptoms of diabetic neuropathy other than thermal persist in STZ-diabetic animals and patients during progression of diabetes into later stages suggesting that other types of DRG neurons may be sensitized and contribute to pain. In this study, we examined functional expression of T-type Ca(2+) channels in capsaicin-insensitive DRG neurons and excitability of these neurons in longer-term diabetic rats and in thermally hypoalgesic diabetic rats. Here we have demonstrated that in STZ-diabetes T-type current was upregulated in capsaicin-insensitive low-pH-sensitive small-sized nociceptive DRG neurons of longer-term diabetic rats and thermally hypoalgesic diabetic rats. This upregulation was not accompanied by significant changes in biophysical properties of T-type channels suggesting that a density of functionally active channels was increased. Sensitivity of T-type current to amiloride (1 mM) and low concentration of Ni(2+) (50 μM) implicates prevalence of Cav3.2 subtype of T-type channels in the capsaicin-insensitive low-pH-sensitive neurons of both naïve and diabetic rats. The upregulation of T-type channels resulted in the increased neuronal excitability of these nociceptive neurons revealed by a lower threshold for action potential initiation, prominent afterdepolarizing potentials and burst firing. Sodium current was not significantly changed in these neurons during long-term diabetes and could not contribute to the diabetes-induced increase of neuronal excitability. Capsaicin-insensitive low-pH-sensitive type

Endodontic interappointment flare-ups: a prospective study of incidence and related factors.

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Walton, R; Fouad, A

1992-04-01

Severe pain and/or swelling following a root canal treatment appointment are serious sequelae. Information varies or is incomplete as to the incidence of these conditions and related factors. In this study, data were collected at root canal treatment appointments on demographics, pulp/periapical diagnoses, presenting symptoms, treatment procedures, and number of appointments. Patients that then experienced a flare-up (a severe problem requiring an unscheduled visit and treatment) had the correlating factors examined. Statistical determinations were by chi-square analysis with significance at 0.05 or less. Nine hundred forty-six visits resulted in an incidence of 3.17% flare-ups. Flare-ups were positively correlated with more severe presenting symptoms, pulp necrosis with painful apical pathosis, and patients on analgesics. Fewer flare-ups occurred in undergraduate patients and following obturation procedures. There was no correlation between patient demographics or systemic conditions, number of appointments, treatment procedures, or taking antibiotics.

Treatment options in painful diabetic neuropathy.

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Nash, T P

1999-01-01

Diabetic neuropathy is common in patients with diabetes mellitus, and 7.5% of diabetics experience pain from diabetic neuropathy. Complications of diabetes mellitus are more common where control of the disease is not optimal. By improving the control of the disease, both the neuropathy and the pain it can produce may be improved. The pain of diabetic neuropathy can frequently be controlled using analgesics, antidepressants, anticonvulsants, topical capsaicin, and neuromodulation, either alone or in any combination.

Incidence and factors related to flare-ups in a graduate endodontic programme.

Science.gov (United States)

Iqbal, M; Kurtz, E; Kohli, M

2009-02-01

To investigate the incidence and factors related to endodontic flare-ups in nonsurgical root canal treatment (NSRCT) cases completed by graduate endodontic residents at University of Pennsylvania, USA. Residents at University of Pennsylvania enter all clinical patient records into an electronic database called PennEndo database. Analysis of records of 6580 patients treated from September 2000 to July 2005 revealed a total of 26 patients with flare-ups (0.39%). Patients were categorized to have undergone flare-up when they attended for an unscheduled visit and active treatment, and when they suffered from severe pain and or swelling after initiation or continuation of NSRCT. SAS software was used to develop a logistic regression model with flare-up as a dependent variable. Independent variables included in the model were: history of previous pain, one vs. two visit NSRCT, periapical diagnosis, tooth type, rotary versus hand instrumentation, and lateral versus vertical compaction of gutta-percha. The odds for developing a flare-up in teeth with a periapical radiolucency were 9.64 times greater than teeth without a periapical radiolucency (P = 0.0090). There was no statistically significant difference in flare-ups between one and two visits NSRCT. The odds of developing a flare-up increased 40 fold when NSRCT was completed in three or more visits. However, this result may have been confounded by addition of an unscheduled visit in patients suffering from flare-ups. Other independent variables did not have any statistically significant correlations. A low percentage of patients experienced flare-ups during NSRCT procedures. The presence of a periapical lesion was the single most important predictor of flare-ups during NSRCT.

Flare-ups in endodontics and their relationship to various medicaments.

Science.gov (United States)

Ehrmann, Ernest H; Messer, Harold H; Clark, Robert M

2007-12-01

The purpose of this research is to investigate the frequency of endodontic flare-ups using a visual analogue scale. Definitions of flare-ups vary widely as does their reported frequency. A flare-up was defined as an increase of 20 or more points on the visual analogue scale for a given tooth, within the periods of 4 h and 24 h after the initial treatment appointment. The data from a previous study were used to determine the incidence of flare-ups after using three modalities (Ledermix, calcium hydroxide and no medication) to manage patients presenting for relief of pain of endodontic origin. A statistical analysis showed that there were no significant differences in flare-up rates at both the 4-h and 24-h periods between the three modalities. Further research is required using the above definition of a flare-up and standardising treatment protocols.

Abdominal acupuncture reduces laser-evoked potentials in healthy subjects

DEFF Research Database (Denmark)

Pazzaglia, C.; Liguori, S.; Minciotti, I.

2015-01-01

Objective: Acupuncture is known to reduce clinical pain, although the exact mechanism is unknown. The aim of the current study was to investigate the effect of acupuncture on laser-evoked potential amplitudes and laser pain perception. Methods: In order to evaluate whether abdominal acupuncture...... is able to modify pain perception, 10 healthy subjects underwent a protocol in which laser-evoked potentials (LEPs) and laser pain perception were collected before the test (baseline), during abdominal acupuncture, and 15. min after needle removal. The same subjects also underwent a similar protocol...... in which, however, sham acupuncture without any needle penetration was used. Results: During real acupuncture, both N1 and N2/P2 amplitudes were reduced, as compared to baseline (p . < 0.01). The reduction lasted up to 15. min after needle removal. Furthermore, laser pain perception was reduced during...

Endodontic flare-ups: comparison of incidence between single and multiple visits procedures in patients attending a Nigerian teaching hospital.

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Oginni, Ao; Udoye, C I

2004-12-01

The present study was performed to compare the incidence of endodontic flare ups in single with multiple visits treatment procedures, to establish the relationship between pre-operative and post obturation pain in patients attending for endodontic therapy in a Nigerian teaching Hospital. Patients were randomly assigned to either single visit or multiple visits group. Data collected at root canal treatment appointment and recall visits (1st, 7th and 30th day post obturation) include pulp vitality status, the presence or absence of pre-operative pain, presence and degree of post obturation pain. Presence of endodontic flare-ups (defined as either patient's report of pain not controlled with over the counter medication and or increasing swelling). The compiled data were analyzed using chi-square where applicable. P level endodontic flare-ups (8.1 %) were recorded in the multiple visits group compared to 19 (18,3%) flare-ups for the single visit group, P = 0.02. For both single and multiple visits procedures, there were statistically significant correlations between pre operative and post obturation pain (P = 0.002 and P = 0.0004 respectively). Teeth with vital pulps reported the lowest frequency of post obturation pain (48.8%), while those with non vital pulps were found to have the highest frequency oh post obturation pain (50,3%), P = 0.9. Although the present study reported higher incidences for post obturation pain and flare-ups following the single visit procedures, single visit endodontic therapy has been shown to be a safe and effective alternative to multiple visits treatment.

Advances in pain control in palliative care

African Journals Online (AJOL)

2011-07-02

Jul 2, 2011 ... pain evoked by light touch or pain evoked by change in temperature. This type of pain is .... the drugs; drug interactions; co-morbidities that can be alleviated by .... AIDS and cancer. • Because pain in palliative care is multi-.

Capsaicin: Friend or Foe in Skin Cancer and Other Related Malignancies?

Science.gov (United States)

Georgescu, Simona-Roxana; Sârbu, Maria-Isabela; Matei, Clara; Ilie, Mihaela Adriana; Caruntu, Constantin; Constantin, Carolina; Neagu, Monica; Tampa, Mircea

2017-12-16

Capsaicin is the main pungent in chili peppers, one of the most commonly used spices in the world; its analgesic and anti-inflammatory properties have been proven in various cultures for centuries. It is a lipophilic substance belonging to the class of vanilloids and an agonist of the transient receptor potential vanilloid 1 receptor. Taking into consideration the complex neuro-immune impact of capsaicin and the potential link between inflammation and carcinogenesis, the effect of capsaicin on muco-cutaneous cancer has aroused a growing interest. The aim of this review is to look over the most recent data regarding the connection between capsaicin and muco-cutaneous cancers, with emphasis on melanoma and muco-cutaneous squamous cell carcinoma.

Structural mechanism underlying capsaicin binding and activation of TRPV1 ion channel

Science.gov (United States)

Cheng, Wei; Yang, Wei; Yu, Peilin; Song, Zhenzhen; Yarov-Yarovoy, Vladimir; Zheng, Jie

2015-01-01

Capsaicin bestows spiciness by activating TRPV1 channel with exquisite potency and selectivity. Capsaicin-bound channel structure was previously resolved by cryo-EM at 4.2-to-4.5 Å resolution, however important details required for mechanistic understandings are unavailable: capsaicin was registered as a small electron density, reflecting neither its chemical structure nor specific ligand-channel interactions. We obtained the missing atomic-level details by iterative computation, which were confirmed by systematic site-specific functional tests. We observed that the bound capsaicin takes “tail-up, head-down” configurations. The vanillyl and amide groups form specific interactions to anchor its bound position, while the aliphatic tail may sample a range of conformations, making it invisible in cryo-EM images. Capsaicin stabilizes the open state by “pull-and-contact” interactions between the vanillyl group and the S4-S5 linker. Our study provided a structural mechanism for the agonistic function of capsaicin and its analogs, and demonstrated an effective approach to obtain atomic level information from cryo-EM structures. PMID:26053297

Validation of OMERACT preliminary rheumatoid arthritis flare domains in the NOR-DMARD study

DEFF Research Database (Denmark)

Lie, Elisabeth; Woodworth, Thasia G; Christensen, Robin

2014-01-01

'. Convergent and divergent construct validity and content validity were assessed by correlation analyses and logistic regression analysis, respectively. RESULTS: Applying the flare working definition based on patient-reported worsening, standardised mean differences (SMDs) were >0.5 for the majority...... of outcomes. The largest SMDs were observed for Pain visual analogue scale (1.30), SF-36 Bodily pain (1.24), Patient global (1.20) and morning stiffness intensity (1.17). The flare working definition based on treatment change yielded lower SMDs (

Capsaicin and Dihydrocapsaicin Determination in Chili Pepper Genotypes Using Ultra-Fast Liquid Chromatography

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Magaji G. Usman

2014-05-01

Full Text Available Research was carried out to estimate the levels of capsaicin and dihydrocapsaicin that may be found in some heat tolerant chili pepper genotypes and to determine the degree of pungency as well as percentage capsaicin content of each of the analyzed peppers. A sensitive, precise, and specific ultra fast liquid chromatographic (UFLC system was used for the separation, identification and quantitation of the capsaicinoids and the extraction solvent was acetonitrile. The method validation parameters, including linearity, precision, accuracy and recovery, yielded good results. Thus, the limit of detection was 0.045 µg/kg and 0.151 µg/kg for capsaicin and dihydrocapsaicin, respectively, whereas the limit of quantitation was 0.11 µg/kg and 0.368 µg/kg for capsaicin and dihydrocapsaicin. The calibration graph was linear from 0.05 to 0.50 µg/g for UFLC analysis. The inter- and intra-day precisions (relative standard deviation were <5.0% for capsaicin and <9.9% for dihydrocapsaicin while the average recoveries obtained were quantitative (89.4%–90.1% for capsaicin, 92.4%–95.2% for dihydrocapsaicin, indicating good accuracy of the UFLC method. AVPP0705, AVPP0506, AVPP0104, AVPP0002, C05573 and AVPP0805 showed the highest concentration of capsaicin (12,776, 5,828, 4,393, 4,760, 3,764 and 4,120 µg/kg and the highest pungency level, whereas AVPP9703, AVPP0512, AVPP0307, AVPP0803 and AVPP0102 recorded no detection of capsaicin and hence were non-pungent. All chili peppers studied except AVPP9703, AVPP0512, AVPP0307, AVPP0803 and AVPP0102 could serve as potential sources of capsaicin. On the other hand, only genotypes AVPP0506, AVPP0104, AVPP0002, C05573 and AVPP0805 gave a % capsaicin content that falls within the pungency limit that could make them recommendable as potential sources of capsaicin for the pharmaceutical industry.

Liposomal topical capsaicin in post-herpetic neuralgia: a safety pilot study

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Manoel Jacobsen Teixeira

2015-03-01

Full Text Available Topical treatments have gained popularity for general use as an adjunct to systemic drugs in neuropathic pain, but their use produces variable clinical results and local adverse events. Objective To evaluate the safety and analgesic effect of a formulation of liposomal capsaicin (LC (0.025% in patients with post herpetic neuralgia (PHN. Method Patients who remained symptomatic after first-and second-line treatment were randomized to receive LC for six weeks in a placebo-controlled, crossover design study. Clinical assessment was performed at baseline, in the second, fourth and sixth week of treatment. Results Thirteen patients completed both treatment periods. Visual Analog Scale (VAS was significantly decreased after the end of the study (p = 0.008, however the effect of treatment was not significant (p = 0.076. There was no difference on global impression of change and other pain characteristics. LC was safe and well tolerated. However, at the concentration used, its analgesic effects were marginal and not significant.

Fusobacterium nucleatum in endodontic flare-ups.

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Chávez de Paz Villanueva, Luis Eduardo

2002-02-01

The extent to which Fusobacterium nucleatum is recovered from root canals of teeth that present with an interappointment flare-up following endodontic instrumentation was investigated. Included in the study were 28 patients that sought emergency treatment after initiation of root canal therapy. Only non-painful teeth that had been treated because of a necrotic pulp and periapical inflammatory lesion were studied. Root canal samples for bacterial analysis were taken, transported to a bacteriological laboratory, and processed for a semiquantitative assessment of bacterial isolates. Bacterial findings were correlated with self-assessed pain intensity as recorded by means of a Visual Analogue Scale. Clinical presentation of swelling and presence of exudate in the treated root canals were also linked. Bacteria were recovered from all teeth examined. Gram-negative anaerobic coccoid rods (Prevotella species and Porphyromonas species) were frequent isolates. All teeth in patients who were reported to be in severe pain (Visual Analogue Scale > or = 6) displayed F nucleatum. Nine out of 10 of these teeth also had swelling and exudate in the root canals. Samples from the remaining patients that had teeth with less pain score showed a variable bacterial recovery. None of these teeth displayed F nucleatum. F nucleatum appears to be associated with the development of the most severe forms of interappointment endodontic flare-ups.

Capsaicin binds to prohibitin 2 and displaces it from the mitochondria to the nucleus

International Nuclear Information System (INIS)

Kuramori, Chikanori; Azuma, Motoki; Kume, Kanako; Kaneko, Yuki; Inoue, Atsushi; Yamaguchi, Yuki; Kabe, Yasuaki; Hosoya, Takamitsu; Kizaki, Masahiro; Suematsu, Makoto; Handa, Hiroshi

2009-01-01

Capsaicin is widely used as a food additive and as an analgesic agent. Besides its well-known role in nociception, which is mediated by vanilloid receptor 1 specifically expressed in dorsal root ganglion neurons, capsaicin has also been considered as a potential anticancer agent, as it inhibits cell proliferation and induces apoptosis in various types of cancer cells. Here we identified a new molecular target of capsaicin from human myeloid leukemia cells. We show that capsaicin binds to prohibitin (PHB) 2, which is normally localized to the inner mitochondrial membrane, and induces its translocation to the nucleus. PHB2 is implicated in the maintenance of mitochondrial morphology and the control of apoptosis. We also provide evidence suggesting that capsaicin causes apoptosis directly through the mitochondria and that PHB2 contributes to capsaicin-induced apoptosis at multiple levels. This work will serve as an important foundation for further understanding of anticancer activity of capsaicin.

Pain Processing and Vegetative Dysfunction in Fibromyalgia: A Study by Sympathetic Skin Response and Laser Evoked Potentials

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Marina de Tommaso

2017-01-01

Full Text Available Background. A dysfunction of pain processing at central and peripheral levels was reported in fibromyalgia (FM. We aimed to correlate laser evoked potentials (LEPs, Sympathetic Skin Response (SSR, and clinical features in FM patients. Methods. Fifty FM patients and 30 age-matched controls underwent LEPs and SSR by the right hand and foot. The clinical evaluation included FM disability (FIQ and severity scores (WPI, anxiety (SAS and depression (SDS scales, and questionnaires for neuropathic pain (DN4. Results. The LEP P2 latency and amplitude and the SSR latency were increased in FM group. This latter feature was more evident in anxious patients. The LEPs habituation was reduced in FM patients and correlated to pain severity scores. In a significant number of patients (32% with higher DN4 and FIQ scores, SSR or LEP responses were absent. Conclusions. LEPs and SSR might contribute to clarifying the peripheral and central nervous system involvement in FM patients.

Brief Report: Validation of a Definition of Flare in Patients With Established Gout.

Science.gov (United States)

Gaffo, Angelo L; Dalbeth, Nicola; Saag, Kenneth G; Singh, Jasvinder A; Rahn, Elizabeth J; Mudano, Amy S; Chen, Yi-Hsing; Lin, Ching-Tsai; Bourke, Sandra; Louthrenoo, Worawit; Vazquez-Mellado, Janitzia; Hernández-Llinas, Hansel; Neogi, Tuhina; Vargas-Santos, Ana Beatriz; da Rocha Castelar-Pinheiro, Geraldo; Amorim, Rodrigo B C; Uhlig, Till; Hammer, Hilde B; Eliseev, Maxim; Perez-Ruiz, Fernando; Cavagna, Lorenzo; McCarthy, Geraldine M; Stamp, Lisa K; Gerritsen, Martijn; Fana, Viktoria; Sivera, Francisca; Taylor, William

2018-03-01

To perform external validation of a provisional definition of disease flare in patients with gout. Five hundred nine patients with gout were enrolled in a cross-sectional study during a routine clinical care visit at 17 international sites. Data were collected to classify patients as experiencing or not experiencing a gout flare, according to a provisional definition. A local expert rheumatologist performed the final independent adjudication of gout flare status. Sensitivity, specificity, predictive values, and receiver operating characteristic (ROC) curves were used to determine the diagnostic performance of gout flare definitions. The mean ± SD age of the patients was 57.5 ± 13.9 years, and 89% were male. The definition requiring fulfillment of at least 3 of 4 criteria (patient-defined gout flare, pain at rest score of >3 on a 0-10-point numerical rating scale, presence of at least 1 swollen joint, and presence of at least 1 warm joint) was 85% sensitive and 95% specific in confirming the presence of a gout flare, with an accuracy of 92%. The ROC area under the curve was 0.97. The definition based on a classification and regression tree algorithm (entry point, pain at rest score >3, followed by patient-defined flare "yes") was 73% sensitive and 96% specific. The definition of gout flare that requires fulfillment of at least 3 of 4 patient-reported criteria is now validated to be sensitive, specific, and accurate for gout flares, as demonstrated using an independent large international patient sample. The availability of a validated gout flare definition will improve the ascertainment of an important clinical outcome in studies of gout. © 2017, American College of Rheumatology.

Capsaicin: Friend or Foe in Skin Cancer and Other Related Malignancies?

Directory of Open Access Journals (Sweden)

Simona-Roxana Georgescu

2017-12-01

Full Text Available Capsaicin is the main pungent in chili peppers, one of the most commonly used spices in the world; its analgesic and anti-inflammatory properties have been proven in various cultures for centuries. It is a lipophilic substance belonging to the class of vanilloids and an agonist of the transient receptor potential vanilloid 1 receptor. Taking into consideration the complex neuro-immune impact of capsaicin and the potential link between inflammation and carcinogenesis, the effect of capsaicin on muco-cutaneous cancer has aroused a growing interest. The aim of this review is to look over the most recent data regarding the connection between capsaicin and muco-cutaneous cancers, with emphasis on melanoma and muco-cutaneous squamous cell carcinoma.

Endodontic inter-appointment flare-ups: An example of chaos?

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Poorya Jalali

2015-01-01

Full Text Available Introduction: Pain and/or swelling after instrumentation of a root canal constitute a significant complication during endodontic treatment. Despite a large number of articles discussing the causative factors behind endodontic flare-ups, the exact mechanism is still not understood. The Hypothesis: The seemingly irrational behavior of endodontic inter-appointment flare-ups may be due to sensitive dependence on initial conditions. A model based on Lorenz′ chaos theory is presented as a possible explanation for the sudden emergence and unpredictability of flare-ups. Evaluation of the Hypothesis: All studies agree on some common traits regarding inter-appointment flare-ups: Careful instrumentation can still cause flare-up; the host inflammatory response behaves as a complex nonlinear network; and also the poly-etiologic nature of this phenomenon all illustrate the sensitive dependence on initial conditions of the system. Integrating more variables (e.g., different species of bacteria into this already complex system will make it increasingly chaotic reflecting its unpredictable behavior.

Intravesical Capsaicin in Patients with Detrusor Hyper-reflexia. A Placebo-controlled Cross-over Study

DEFF Research Database (Denmark)

Petersen, T; Nielsen, J B; Schrøder, H D

1999-01-01

to anticholinergic treatment underwent intravesical administration of 50 ml 2% lignocaine. followed by either 100 ml 1 mmol/l capsaicin or 100 ml physiological saline for 30 min. Cross-over to the alternative treatment took place after 4 weeks. Varying degrees of burning sensation were experienced by all but one...... patient during the capsaicin treatment and precluded the possibility of conducting studies of this type in a blind manner. No preference for capsaicin treatment was found, and micturition and VAS scores were unchanged after treatment with capsaicin. The mean volume of the contents of the bladder at which...... DH first appeared was 175 ml after saline and 195 ml after capsaicin (mean difference 20 ml with a 5% confidence interval from -25 to 65). Bladder biopsies taken 2 weeks after treatment with capsaicin showed more pronounced inflammation, superficial haemorrhage, squamous epithelial metaplasia...

Structural mechanism underlying capsaicin binding and activation of TRPV1 ion channel

OpenAIRE

Yang, Fan; Xiao, Xian; Cheng, Wei; Yang, Wei; Yu, Peilin; Song, Zhenzhen; Yarov-Yarovoy, Vladimir; Zheng, Jie

2015-01-01

Capsaicin bestows spiciness by activating TRPV1 channel with exquisite potency and selectivity. Capsaicin-bound channel structure was previously resolved by cryo-EM at 4.2-to-4.5 ? resolution, however important details required for mechanistic understandings are unavailable: capsaicin was registered as a small electron density, reflecting neither its chemical structure nor specific ligand-channel interactions. We obtained the missing atomic-level details by iterative computation, which were c...

Peripheral and central components of habituation of heat pain perception and evoked potentials in humans.

Science.gov (United States)

Greffrath, Wolfgang; Baumgärtner, Ulf; Treede, Rolf-Detlef

2007-12-05

For the neurophysiological examination of nociceptive pathways, contact-heat evoked potentials (contact-heat EPs) are elicited by repetitive brief noxious heat stimuli. Suppression of heat responses in primary nociceptive neurons during repetitive stimulation has been shown in animal models in vivo and in vitro. We now investigated whether heat pain and contact-heat EPs in humans display equivalent signs of habituation. Heat pain and EPs were elicited in 16 volunteers with a contact thermode (30 degrees Cs(-1)). Heat pulses at three intensities (pain threshold, moderate noxious and maximum available) were applied to the right forearm either by moving the thermode after each pulse to variable locations or when fixed to one location (inter-stimulus intervals 8-10s). Contact-heat EPs consisted of an early negativity in temporal leads (N1), followed by a biphasic response at the vertex (N2-P2). Pain ratings and contact-heat EPs (N1 and N2-P2 components) displayed significant temperature dependence. N2-P2 correlated positively with ratings. With stimulation at variable locations, both measures slowly decreased with time constants tau of 2 min (ratings) and 12 min (EPs). With stimulation at a fixed location, habituation was much faster for both, ratings (tau=10s) and EPs (tau=33 s). As a consequence, both measures were significantly reduced (pheat pain perception and contact-heat EPs display signs of rapid habituation when stimulation is restricted to a fixed location and thus, reflect fatigue of peripheral nociceptive neurons. Habituation within the central nervous system is slower and less pronounced.

Brain Activity Associated with Slow Temporal Summation of C-fiber Evoked Pain in Fibromyalgia Patients and Healthy Controls

OpenAIRE

Staud, Roland; Craggs, Jason G.; Perlstein, William M.; Robinson, Michael E.; Price, Donald D.

2008-01-01

Temporal summation of “second pain” (TSSP) is the result of C-fiber-evoked responses of dorsal-horn neurons, termed ‘windup’. This phenomenon is dependent on stimulus frequency (≥0.33 Hz) and relevant for central sensitization as well as chronic pain. Whereas our previous functional magnetic resonance imaging (fMRI) study characterized neural correlates of TSSP in eleven healthy volunteers, the present study was designed to compare brain responses associated with TSSP across these healthy par...

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

Science.gov (United States)

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

2014-01-01

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

Pharmacologic and non-pharmacologic treatments for chronic pain in individuals with HIV: a systematic review

Science.gov (United States)

Merlin, Jessica S.; Bulls, Hailey W.; Vucovich, Lee A.; Edelman, E. Jennifer; Starrels, Joanna L.

2016-01-01

Chronic pain occurs in as many as 85% of individuals with HIV and is associated with substantial functional impairment. Little guidance is available for HIV providers seeking to address their patients’ chronic pain. We conducted a systematic review to identify clinical trials and observational studies that examined the impact of pharmacologic or non-pharmacologic interventions on pain and/or functional outcomes among HIV-infected individuals with chronic pain in high-development countries. Eleven studies met inclusion criteria and were mostly low or very low quality. Seven examined pharmacologic interventions (gabapentin, pregabalin, capsaicin, analgesics including opioids) and four examined non-pharmacologic interventions (cognitive behavioral therapy, self-hypnosis, smoked cannabis). The only controlled studies with positive results were of capsaicin and cannabis, and had short-term follow-up (≤12 weeks). Among the seven studies of pharmacologic interventions, five had substantial pharmaceutical industry sponsorship. These findings highlight several important gaps in the HIV/chronic pain literature that require further research. PMID:27267445

Evaluation of an automated analysis for pain-related evoked potentials

Directory of Open Access Journals (Sweden)

Wulf Michael

2017-09-01

Full Text Available This paper presents initial steps towards an auto-mated analysis for pain-related evoked potentials (PREP to achieve a higher objectivity and non-biased examination as well as a reduction in the time expended during clinical daily routines. While manually examining, each epoch of an en-semble of stimulus-locked EEG signals, elicited by electrical stimulation of predominantly intra-epidermal small nerve fibers and recorded over the central electrode (Cz, is in-spected for artifacts before calculating the PREP by averag-ing the artifact-free epochs. Afterwards, specific peak-latencies (like the P0-, N1 and P1-latency are identified as certain extrema in the PREP’s waveform. The proposed automated analysis uses Pearson’s correlation and low-pass differentiation to perform these tasks. To evaluate the auto-mated analysis’ accuracy its results of 232 datasets were compared to the results of the manually performed examina-tion. Results of the automated artifact rejection were compa-rable to the manual examination. Detection of peak-latencies was more heterogeneous, indicating some sensitivity of the detected events upon the criteria used during data examina-tion.

Pain Report and Pain-Related Evoked Potentials Operantly Conditioned

NARCIS (Netherlands)

Lousberg, Richel; Vuurman, Eric; Lamers, Theo; van Breukelen, Gerard; Jongen, Ellen; Rijnen, Heidi; Maessen, Christa; Hermens, Hermanus J.

Objective: The purpose of the present study was to answer the ques- tion whether pain report can be increased and decreased by operant conditioning. We predicted that the conditioned pain effects would remain significant after correction for social desirability and fantasy proneness. Furthermore, we

Flaring fix: better technologies green flaring

International Nuclear Information System (INIS)

Stastny, P.

2004-01-01

Recent advances in reducing solution gas flaring and venting are discussed, highlighting the 2002 report of the Clean Air Strategic Alliance (CASA) and its 39 recommendations targeting a 50 per cent reduction in flaring from a 1996 baseline. Much of the improvement to date (62 per cent at the end of 2002 on an annual basis) has come from collecting and sending gas down pipelines for processing, but improvements in technologies such as incineration, in combustion efficiency, and the use of micro-turbines, also helped to make a difference. Improvements in smokeless flares, through the addition of a special flare tip to flare stacks, has similarly contributed to higher combustion efficiency, and further improvements are expected from sonic flare technology currently under development. Expectations are also high for advances in incinerator technology, particularly enclosed burner systems, which almost completely burn flare gas while having no visible flame, smoke or odor

The capsaicin cough reflex in eczema patients with respiratory symptoms elicited by perfume.

Science.gov (United States)

Elberling, Jesper; Dirksen, Asger; Johansen, Jeanne Duus; Mosbech, Holger

2006-03-01

Respiratory symptoms elicited by perfume are common in the population but have unclear pathophysiology. Increased capsaicin cough responsiveness has been associated with the symptoms, but it is unknown whether the site of the symptoms in the airways influences this association. The aim of this study was to investigate the association between the site of airway symptoms elicited by perfume and cough responsiveness to bronchial challenge with capsaicin. 21 eczema patients with respiratory symptoms elicited by perfume were compared with 21 healthy volunteers in a sex- and age-matched case control study. The participants completed a symptom questionnaire and underwent a bronchial challenge with capsaicin. Lower, but not upper, respiratory symptoms elicited by perfume were associated with increased capsaicin cough responsiveness. Having severe symptoms to perfume (n=11) did not relate to the site of the symptoms in the airways and was not associated with increased capsaicin cough responsiveness. In conclusion, respiratory symptoms elicited by perfume may reflect local hyperreactivity related to defensive reflexes in the airways, and measurements of the capsaicin cough reflex are relevant when patients with lower respiratory symptoms related to environmental perfume exposures are investigated.

Contact Heat Evoked Potentials (CHEPs) in Patients with Mild-Moderate Alzheimer's Disease and Matched Control-A Pilot Study

DEFF Research Database (Denmark)

Jensen-Dahm, Christina; Madsen, Caspar Skau; Waldemar, Gunhild

2016-01-01

OBJECTIVE: Clinical studies have found that patients with Alzheimer's disease report pain of less intensity and with a lower affective response, which has been thought to be due to altered pain processing. The authors wished to examine the cerebral processing of non-painful and painful stimuli...... threshold and heat pain threshold. Somatosensory evoked potentials, amplitude, and latency were within normal range and similar for the two groups. CONCLUSIONS: The findings suggest that the processing of non-painful and painful stimuli is preserved in patients with mild to moderate Alzheimer's disease....... using somatosensory evoked potentials and contact heat evoked potentials in patients with Alzheimer's disease and in healthy elderly controls. DESIGN: Case-control study SETTING AND SUBJECTS: Twenty outpatients with mild-moderate Alzheimer's disease and in 17 age- and gender-matched healthy controls...

Preclinical characterization of three transient receptor potential vanilloid receptor 1 antagonists for early use in human intradermal microdose analgesic studies.

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Sjögren, E; Halldin, M M; Stålberg, O; Sundgren-Andersson, A K

2018-05-01

The transient receptor potential vanilloid receptor 1 (TRPV1) is a nonselective cation channel involved in the mediation of peripheral pain to the central nervous system. As such, the TRPV1 is an accessible molecular target that lends itself well to the understanding of nociceptive signalling. This study encompasses preclinical investigations of three molecules with the prospect to establish them as suitable analgesic model compounds in human intradermal pain relief studies. The inhibitory effectiveness was evaluated by means of in vitro assays, TRPV1 expressing Chinese hamster ovary cells (CHO-K1) and rat dorsal root ganglion cultures in fluorescent imaging plate reader and whole cell patch clamp systems, as well as in vivo by capsaicin-evoked pain-related behavioural response studies in rat. Secondary pharmacology, pharmacokinetics and preclinical safety were also assessed. In vitro, all three compounds were effective at inhibiting capsaicin-activated TRPV1. The concentration producing 50% inhibition (IC 50 ) determined was in the range of 3-32 nmol/L and 10-501 nmol/L using CHO-K1 and dorsal root ganglion cultures, respectively. In vivo, all compounds showed dose-dependent reduction in capsaicin-evoked pain-related behavioural responses in rat. None of the three compounds displayed any significant activity on any of the secondary targets tested. The compounds were also shown to be safe from a toxicological, drug metabolism and pharmacokinetic perspective, for usage in microgram doses in the human skin. The investigated model compounds displayed ideal compound characteristics as pharmacological and translational tools to address efficacy on the human native TRPV1 target in human skin in situ. This work details the pharmaceutical work-up of three TRPV1-active investigational compounds, to obtain regulatory approval, for subsequent use in humans. This fast and cost-effective preclinical development path may impact research beyond the pain management area, as

Efficacy and safety profile of combination of tramadol-diclofenac versus tramadol-paracetamol in patients with acute musculoskeletal conditions, postoperative pain, and acute flare of osteoarthritis and rheumatoid arthritis: a Phase III, 5-day open-label study

Science.gov (United States)

Chandanwale, Ajay S; Sundar, Subramanian; Latchoumibady, Kaliaperumal; Biswas, Swati; Gabhane, Mukesh; Naik, Manoj; Patel, Kamlesh

2014-01-01

Objective We aimed to evaluate the safety and efficacy of a fixed-dose combination (FDC) of tramadol and diclofenac versus a standard approved FDC of tramadol and paracetamol, in patients with acute moderate to severe pain. Methods A total of 204 patients with moderate to severe pain due to acute musculoskeletal conditions (n=52), acute flare of osteoarthritis (n=52), acute flare of rheumatoid arthritis (n=50), or postoperative pain (n=50) were enrolled in the study at baseline. Each disease category was then randomized to receive either of two treatments for 5 days: group A received an FDC of immediate-release tramadol hydrochloride (50 mg) and sustained-release diclofenac sodium (75 mg) (one tablet, twice daily), and group B received an FDC of tramadol hydrochloride (37.5 mg) and paracetamol (325 mg) (two tablets every 4–6 hours, up to a maximum of eight tablets daily). The primary efficacy end points were reductions in pain intensity from baseline at day 3 and day 5 as assessed by a Visual Analog Scale (VAS) score. Results Group A showed a significant reduction in the VAS score for overall pain from baseline on day 3 (P=0.001) and day 5 (Ppain, and gastritis), which required minimal management, without any treatment discontinuation. The number of adverse events in group A was nine (8.82%) compared with 22 (21.78%) in group B, after 5 days of treatment. Conclusion An FDC of tramadol-diclofenac showed a significantly greater reduction in pain intensity and was well tolerated compared with tramadol-paracetamol, resulting in better analgesia in patients suffering from moderate to severe pain due to acute musculoskeletal conditions, postoperative pain following orthopedic surgery, or acute flare of osteoarthritis and rheumatoid arthritis. PMID:25152629

Hot Chili Peppers: Extraction, Cleanup, and Measurement of Capsaicin

Science.gov (United States)

Huang, Jiping; Mabury, Scott A.; Sagebiel, John C.

2000-12-01

Capsaicin, the pungent ingredient of the red pepper or Capsicum annuum, is widely used in food preparation. The purpose of this experiment was to acquaint students with the active ingredients of hot chili pepper (capsaicin and dihydrocapsaicin), the extraction, cleanup, and analysis of these chemicals, as a fun and informative analytical exercise. Fresh peppers were prepared and extracted with acetonitrile, removing plant co-extractives by addition to a C-18 solid-phase extraction cartridge. Elution of the capsaicinoids was accomplished with a methanol-acetic acid solution. Analysis was completed by reverse-phase HPLC with diode-array or variable wavelength detection and calibration with external standards. Levels of capsaicin and dihydrocapsaicin were typically found to correlate with literature values for a specific hot pepper variety. Students particularly enjoyed relating concentrations of capsaicinoids to their perceived valuation of "hotness".

A study on the comparison of antioxidant effects between hot pepper extract and capsaicin

Directory of Open Access Journals (Sweden)

Hyeon Min Gang

2008-03-01

Full Text Available Objective : The objective of this study was to compare the antioxidant effects of hot pepper extract and capsaicin. Methods : In vitro, antioxidant activities were examined by DPPH radical scavenging activity, total antioxidant capacity(TAC, oxygen radical scavenging capacity(ORAC, inhibition of induced lipid peroxidation using liver mitochonria and total phenolic contents. Results : 1. DPPH free radical scavenging actiivities at the concentrations of both 1 and 10㎎/㎖ were 1.2 to 1.9 times higher in capsaicin than in hot pepper extract. The concentration of capsaicin required for 50% radical scavenging was lower than that of hot pepper extract(3.9 vs 5.9㎎/㎖, indicating that capsaicin had higher DPPH radical scavenging activity than hot pepper extract. 2. Total antioxidant capacities of capsaicin at the concentrations of 0.1 and 1mg/ml(13.8 and 41.3 nmol Trolox equivalent were not significantly different from those at the concentrations of 1 and 10㎎/㎖(11.4 and 41.2nmol Trolox equivalent, indicating that capsaicin showed 10 times higher ABTS radical scavenging activity compared to hot pepper extract. 3. ORAC of capsaicin at the concentrations of 1, 5, 10 and 100 mg/ml were 0.04, 0.17, 0.29 and 1.74nmol gallic acid equivalent, respectively. On the other hand, ORAC of hot pepper extract at the concentrations of 1, 5, 10 and 100㎍/㎖ were 0.15, 0.44, 0.75 and 2.49nmol gallic acid equivalent, respectively, indicating that capsaicin showed higher peroxyl radical scavenging activity than hot pepper extract. 4. Inhibition of lipid peroxidation caused by hot pepper extract at the concentrations of 1 and 10mg/㎖ were 12.2 and 61.4%, respectively. Inhibition of lipid peroxidation caused by capsaicin at the concentrations of 1 and 10㎎/㎖l were 64.0 and 96.8%, respectively. Thus capsaicin showed 10 times stronger effect in inhibiton of lipid peroxidation than hot pepper extract. 5. Total phenolic contents of hot pepper extract at the

Symptom-Based Treatment of Neuropathic Pain in Spinal Cord-Injured Patients: A Randomized Crossover Clinical Trial.

Science.gov (United States)

Min, Kyunghoon; Oh, Yoongul; Lee, Sang-Hyuk; Ryu, Ju Seok

2016-05-01

The objective of this study was to identify the differences in medication effect according to pain characteristics in spinal cord-injured patients. This study is a prospective, randomized, crossover study. Fifty-five patients and 66 locations of neuropathic pain were included. Pain was classified into four spontaneous characteristics and three evoked pain characteristics. Oxcarbazepine (Na channel blocker) and pregabalin (calcium channel α2-δ ligand medication) were tried. Patients were divided into two groups: evoked pain present and evoked pain absent. Overall average visual analog scale was obtained. Oxcarbazepine was significantly more effective for patients without evoked pain than in those with it for electrical, burning, and pricking pain. The effect of pregabalin was not different regarding the presence or absence of evoked pain for all pain categories, except burning pain. In patients with evoked pain, pregabalin was shown to be significantly more effective for electrical pain, allodynia, and heat hyperalgesia than oxcarbazepine. In the evoked pain absent group, oxcarbazepine showed greater improvement than pregabalin but was not significant. In summary, the phenotype of neuropathic pain was associated with the efficacy of different pharmacologic treatments. Symptom-based treatment, therefore, can lead to more efficient analgesia.

Involvement of Endoplasmic Reticulum Stress in Capsaicin-Induced Apoptosis of Human Pancreatic Cancer Cells

Directory of Open Access Journals (Sweden)

Shengzhang Lin

2013-01-01

Full Text Available Capsaicin, main pungent ingredient of hot chilli peppers, has been shown to have anticarcinogenic effect on various cancer cells through multiple mechanisms. In this study, we investigated the apoptotic effect of capsaicin on human pancreatic cancer cells in both in vitro and in vivo systems, as well as the possible mechanisms involved. In vitro, treatment of both the pancreatic cancer cells (PANC-1 and SW1990 with capsaicin resulted in cells growth inhibition, G0/G1 phase arrest, and apoptosis in a dose-dependent manner. Knockdown of growth arrest- and DNA damage-inducible gene 153 (GADD153, a marker of the endoplasmic-reticulum-stress- (ERS- mediated apoptosis pathway, by specific siRNA attenuated capsaicin-induced apoptosis both in PANC-1 and SW1990 cells. Moreover, in vivo studies capsaicin effectively inhibited the growth and metabolism of pancreatic cancer and prolonged the survival time of pancreatic cancer xenograft tumor-induced mice. Furthermore, capsaicin increased the expression of some key ERS markers, including glucose-regulated protein 78 (GRP78, phosphoprotein kinase-like endoplasmic reticulum kinase (phosphoPERK, and phosphoeukaryotic initiation factor-2α (phospho-eIF2α, activating transcription factor 4 (ATF4 and GADD153 in tumor tissues. In conclusion, we for the first time provide important evidence to support the involvement of ERS in the induction of apoptosis in pancreatic cancer cells by capsaicin.

Thermal conditions influence changes in body temperature induced by intragastric administration of capsaicin in mice.

Science.gov (United States)

Mori, Noriyuki; Urata, Tomomi; Fukuwatari, Tsutomu

2016-08-01

Capsaicin has been reported to have unique thermoregulatory actions. However, changes in core temperature after the administration of capsaicin are a controversial point. Therefore, we investigated the effects of environmental thermal conditions on changes in body temperature caused by capsaicin in mice. We showed that intragastric administration of 10 and 15 mg/kg capsaicin increased tail temperature and decreased colonic temperatures in the core temperature (CT)-constant and CT-decreasing conditions. In the CT-increasing condition, 15 mg/kg capsaicin increased tail temperature and decreased colonic temperature. However, 10 mg/kg capsaicin increased colonic temperature. Furthermore, the amount of increase in tail temperature was greater in the CT-decreasing condition and lower in the CT-increasing condition, compared with that of the CT-constant condition. These findings suggest that the changes in core temperature were affected by the environmental thermal conditions and that preliminary thermoregulation state might be more important than the constancy of temperature to evaluate the effects of heat diffusion and thermogensis.

Organization of pERK-immunoreactive cells in trigeminal spinal nucleus caudalis, upper cervical cord, NTS and Pa5 following capsaicin injection into masticatory and swallowing-related muscles in rats.

Science.gov (United States)

Tsujimura, Takanori; Shinoda, Masamichi; Honda, Kuniya; Hitomi, Suzuro; Kiyomoto, Masaaki; Matsuura, Shingo; Katagiri, Ayano; Tsuji, Kojun; Inoue, Makoto; Shiga, Yoshi; Iwata, Koichi

2011-10-12

Many phosphorylated extracellular signal-regulated kinase (pERK)-immunoreactive (IR) cells are expressed in the trigeminal spinal subnucleus caudalis (Vc), upper cervical spinal cord (C1-C2), nucleus tractus solitarii (NTS) and paratrigeminal nucleus (Pa5) after capsaicin injection into the whisker pad (WP), masseter muscle (MM), digastric muscle (DM) or sternohyoideus muscle (SM). The pERK-IR cells also showed NeuN immunoreactivity, indicating that ERK phosphorylation occurs in neurons. The pERK-IR cells were significantly reduced after intrathecal injection of MEK 1/2 inhibitor PD98059. The pERK-IR cells expressed bilaterally in the Vc and C1-C2 after capsaicin injection into the unilateral DM or SM, whereas unilaterally in the Vc and C1-C2 after unilateral WP or MM injection. After capsaicin injection into the WP or MM, the pERK-IR cell expression in the Vc was restricted rostrocaudally within a narrow area. However, the distribution of pERK-IR cells was more wide spread without a clear peak in the Vc and C1-C2 after capsaicin injection into the DM or SM. In the NTS, the unimodal pERK-IR cell expression peaked at 0-720μm rostral from the obex following capsaicin injection into WP, MM, DM or SM. In the ipsilateral Pa5, many pERK-IR cells were observed following capsaicin injection into the SM. The number of swallows elicited by distilled water administration was significantly smaller after capsaicin injection into the WP, MM or DM but not SM compared to that of vehicle-injected rats. Various noxious inputs due to the masticatory or swallowing-related muscle inflammation may be differentially involved in muscle pain and swallowing reflex activity. Copyright © 2011 Elsevier B.V. All rights reserved.

Single high-concentration capsaicin application prevents c-Fos expression in spinothalamic and postsynaptic dorsal column neurons after surgical incision

Czech Academy of Sciences Publication Activity Database

Uchytilová, Eva; Špicarová, Diana; Paleček, Jiří

2015-01-01

Roč. 19, č. 10 (2015), s. 1496-1505 ISSN 1090-3801 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) LH12058; GA ČR(CZ) GPP303/12/P510; GA MŠk(CZ) EE2.3.30.0025; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 Keywords : pain * spinothalamic * capsaicin * TRPV1 * PSDC Subject RIV: FH - Neurology Impact factor: 2.900, year: 2015

Quantitative sensory testing and pain-evoked cytokine reactivity: comparison of patients with sickle cell disease to healthy matched controls.

Science.gov (United States)

Campbell, Claudia M; Carroll, C Patrick; Kiley, Kasey; Han, Dingfen; Haywood, Carlton; Lanzkron, Sophie; Swedberg, Lauren; Edwards, Robert R; Page, Gayle G; Haythornthwaite, Jennifer A

2016-04-01

Sickle cell disease (SCD) is an inherited blood disorder associated with significant morbidity, which includes severe episodic pain, and, often, chronic pain. Compared to healthy individuals, patients with SCD report enhanced sensitivity to thermal detection and pain thresholds and have altered inflammatory profiles, yet no studies to date have examined biomarker reactivity after laboratory-induced pain. We sought to examine this relationship in patients with SCD compared to healthy control participants. We completed quantitative sensory testing in 83 patients with SCD and sequential blood sampling in 27 of them, whom we matched (sex, age, race, body mass index, and education) to 27 healthy controls. Surprisingly, few quantitative sensory testing differences emerged between groups. Heat pain tolerance, pressure pain threshold at the trapezius, thumb, and quadriceps, and thermal temporal summation at 45°C differed between groups in the expected direction, whereas conditioned pain modulation and pain ratings to hot water hand immersion were counterintuitive, possibly because of tailoring the water temperature to a perceptual level; patients with SCD received milder temperatures. In the matched subsample, group differences and group-by-time interactions were observed in biomarkers including tumor necrosis factor alpha, interleukin-1ß, interleukin-4, and neuropeptide Y. These findings highlight the utility of laboratory pain testing methods for understanding individual differences in inflammatory cytokines. Our findings suggest amplified pain-evoked proinflammatory cytokine reactivity among patients with SCD relative to carefully matched controls. Future research is warranted to evaluate the impact of enhanced pain-related cytokine response and whether it is predictive of clinical characteristics and the frequency/severity of pain crises in patients with SCD.

Electrochemical impedance spectroscopy versus cyclic voltammetry for the electroanalytical sensing of capsaicin utilising screen printed carbon nanotube electrodes.

Science.gov (United States)

Randviir, Edward P; Metters, Jonathan P; Stainton, John; Banks, Craig E

2013-05-21

Screen printed carbon nanotube electrodes (SPEs) are explored as electroanalytical sensing platforms for the detection of capsaicin in both synthetic capsaicin solutions and capsaicin extracted from chillies and chilli sauces utilising both cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). It is found that the technique which is most applicable to the electroanalytical detection of capsaicin depends upon the analyte concentration: for the case of low capsaicin concentrations, CV is a more appropriate method as capsaicin exhibits characteristic voltammetric waves of peak heights relevant to the capsaicin concentration; but for the case of high capsaicin concentrations where the voltammetric waves merge and migrate out of the potential window, EIS is shown to be a more appropriate technique, owing to the observed linear increases in R(ct) with increasing concentration. Furthermore, we explore different types of screen printed carbon nanotube electrodes, namely single- and multi- walled carbon nanotubes, finding that they are technique-specific: for the case of low capsaicin concentrations, single-walled carbon nanotube SPEs are preferable (SW-SPE); yet for the case of EIS at high capsaicin concentrations, multi-walled carbon nanotube SPEs (MW-SPE) are preferred, based upon analytical responses. The analytical performance of CV and EIS is applied to the sensing of capsaicin in grown chillies and chilli sauces and is critically compared to 'gold standard' HPLC analysis.

Cold suppresses agonist-induced activation of TRPV1.

Science.gov (United States)

Chung, M-K; Wang, S

2011-09-01

Cold therapy is frequently used to reduce pain and edema following acute injury or surgery such as tooth extraction. However, the neurobiological mechanisms of cold therapy are not completely understood. Transient receptor potential vanilloid 1 (TRPV1) is a capsaicin- and heat-gated nociceptive ion channel implicated in thermosensation and pathological pain under conditions of inflammation or injury. Although capsaicin-induced nociception, neuropeptide release, and ionic currents are suppressed by cold, it is not known if cold suppresses agonist-induced activation of recombinant TRPV1. We demonstrate that cold strongly suppressed the activation of recombinant TRPV1 by multiple agonists and capsaicin-evoked currents in trigeminal ganglia neurons under normal and phosphorylated conditions. Cold-induced suppression was partially impaired in a TRPV1 mutant that lacked heat-mediated activation and potentiation. These results suggest that cold-induced suppression of TRPV1 may share a common molecular basis with heat-induced potentiation, and that allosteric inhibition may contribute, in part, to the cold-induced suppression. We also show that combination of cold and a specific antagonist of TRPV1 can produce an additive suppression. Our results provide a mechanistic basis for cold therapy and may enhance anti-nociceptive approaches that target TRPV1 for managing pain under inflammation and tissue injury, including that from tooth extraction.

A heteromeric Texas coral snake toxin targets acid-sensing ion channels to produce pain.

Science.gov (United States)

Bohlen, Christopher J; Chesler, Alexander T; Sharif-Naeini, Reza; Medzihradszky, Katalin F; Zhou, Sharleen; King, David; Sánchez, Elda E; Burlingame, Alma L; Basbaum, Allan I; Julius, David

2011-11-16

Natural products that elicit discomfort or pain represent invaluable tools for probing molecular mechanisms underlying pain sensation. Plant-derived irritants have predominated in this regard, but animal venoms have also evolved to avert predators by targeting neurons and receptors whose activation produces noxious sensations. As such, venoms provide a rich and varied source of small molecule and protein pharmacophores that can be exploited to characterize and manipulate key components of the pain-signalling pathway. With this in mind, here we perform an unbiased in vitro screen to identify snake venoms capable of activating somatosensory neurons. Venom from the Texas coral snake (Micrurus tener tener), whose bite produces intense and unremitting pain, excites a large cohort of sensory neurons. The purified active species (MitTx) consists of a heteromeric complex between Kunitz- and phospholipase-A2-like proteins that together function as a potent, persistent and selective agonist for acid-sensing ion channels (ASICs), showing equal or greater efficacy compared with acidic pH. MitTx is highly selective for the ASIC1 subtype at neutral pH; under more acidic conditions (pH 100-fold) proton-evoked activation of ASIC2a channels. These observations raise the possibility that ASIC channels function as coincidence detectors for extracellular protons and other, as yet unidentified, endogenous factors. Purified MitTx elicits robust pain-related behaviour in mice by activation of ASIC1 channels on capsaicin-sensitive nerve fibres. These findings reveal a mechanism whereby snake venoms produce pain, and highlight an unexpected contribution of ASIC1 channels to nociception. © 2011 Macmillan Publishers Limited. All rights reserved

Role played by acid-sensitive ion channels in evoking the exercise pressor reflex.

Science.gov (United States)

Hayes, Shawn G; McCord, Jennifer L; Rainier, Jon; Liu, Zhuqing; Kaufman, Marc P

2008-10-01

The exercise pressor reflex arises from contracting skeletal muscle and is believed to play a role in evoking the cardiovascular responses to static exercise, effects that include increases in arterial pressure and heart rate. This reflex is believed to be evoked by the metabolic and mechanical stimulation of thin fiber muscle afferents. Lactic acid is known to be an important metabolic stimulus evoking the reflex. Until recently, the only antagonist for acid-sensitive ion channels (ASICs), the receptors to lactic acid, was amiloride, a substance that is also a potent antagonist for both epithelial sodium channels as well as voltage-gated sodium channels. Recently, a second compound, A-317567, has been shown to be an effective and selective antagonist to ASICs in vitro. Consequently, we measured the pressor responses to the static contraction of the triceps surae muscles in decerebrate cats before and after a popliteal arterial injection of A-317567 (10 mM solution; 0.5 ml). We found that this ASIC antagonist significantly attenuated by half (Pacid injection into the popliteal artery. In contrast, A-317567 had no effect on the pressor responses to tendon stretch, a pure mechanical stimulus, and to a popliteal arterial injection of capsaicin, which stimulated transient receptor potential vanilloid type 1 channels. We conclude that ASICs on thin fiber muscle afferents play a substantial role in evoking the metabolic component of the exercise pressor reflex.

The capsaicin cough reflex in eczema patients with respiratory symptoms elicited by perfume

DEFF Research Database (Denmark)

Elberling, Jesper; Dirksen, Asger; Johansen, Jeanne Duus

2006-01-01

Respiratory symptoms elicited by perfume are common in the population but have unclear pathophysiology. Increased capsaicin cough responsiveness has been associated with the symptoms, but it is unknown whether the site of the symptoms in the airways influences this association. The aim of this st......Respiratory symptoms elicited by perfume are common in the population but have unclear pathophysiology. Increased capsaicin cough responsiveness has been associated with the symptoms, but it is unknown whether the site of the symptoms in the airways influences this association. The aim...... of this study was to investigate the association between the site of airway symptoms elicited by perfume and cough responsiveness to bronchial challenge with capsaicin. 21 eczema patients with respiratory symptoms elicited by perfume were compared with 21 healthy volunteers in a sex- and age-matched case...... control study. The participants completed a symptom questionnaire and underwent a bronchial challenge with capsaicin. Lower, but not upper, respiratory symptoms elicited by perfume were associated with increased capsaicin cough responsiveness. Having severe symptoms to perfume (n=11) did not relate...

Factors associated with endodontic flare-ups: a prospective study.

Science.gov (United States)

Imura, N; Zuolo, M L

1995-09-01

The purpose of this prospective study was to assess the incidence of flare-ups (a severe problem requiring an unscheduled visit and treatment) among patients who received endodontic treatment by the two authors in their respective practices during a period of one year, and also to examine the correlation with pre-operative and operative variables. The results showed an incidence of 1.58% for flare-ups from 1012 endodontically treated teeth. Statistical analysis using the chi-square test (Pflare-ups were found to be positively correlated with multiple appointments, retreatment cases, periradicular pain prior to treatment, presence of radiolucent lesions, and patients taking analgesic or anti-inflammatory drugs. In contrast, there was no correlation between flare-up, and age, sex, different arch/tooth groups and the status of the pulp.

Feasibility of Topical Applications of Natural High-Concentration Capsaicinoid Solutions in Patients with Peripheral Neuropathic Pain: A Retrospective Analysis

Directory of Open Access Journals (Sweden)

Fanny Bauchy

2016-01-01

Full Text Available Background. Capsaicin, one of several capsaicinoid compounds, is a potent TRPV1 agonist. Topical application at high concentration (high concentration, >1% induces a reversible disappearance of epidermal free nerve endings and is used to treat peripheral neuropathic pain (PNP. While the benefit of low-concentration capsaicin remains controversial, the 8%-capsaicin patch (Qutenza®, 2010, Astellas, Netherlands has shown its effectiveness. This patch is, however, costly and natural high-concentration capsaicinoid solutions may represent a cheaper alternative to pure capsaicin. Methods. In this retrospective study, 149 patients were screened, 132 were included with a diagnosis of neuropathic pain, and eighty-four were retained in the final analyses (median age: 57.5 years [IQR25–75: 44.7–67.1], male/female: 30/54 with PNP who were treated with topical applications of natural high-concentration capsaicinoid solutions (total number of applications: 137. Indications were postsurgical PNP (85.7% and nonsurgical PNP (14.3% (posttraumatic, HIV-related, postherpetic, and radicular PNP. Objectives. To assess the feasibility of topical applications of natural high-concentration capsaicinoid solutions for the treatment of PNP. Results. The median treated area was 250 cm2 [IQR25–75: 144–531]. The median amount of capsaicinoids was 55.1 mg [IQR25–75: 28.7–76.5] per plaster and the median concentration was 172.3 μg/cm2 [IQR25–75: 127.6–255.2]. Most patients had local adverse effects on the day of treatment, such as mild to moderate burning pain and erythema. 13.6–19.4% of the patients experienced severe pain or erythema. Following treatment, 62.5% of patients reported a lower pain intensity or a smaller pain surface, and 35% reported a sustained pain relief lasting for at least 4 weeks. Conclusion. Analgesic topical treatment with natural high-concentration capsaicinoid is feasible and may represent a low cost alternative to alleviate

Dietary Capsaicin Improves Glucose Homeostasis and Alters the Gut Microbiota in Obese Diabetic ob/ob Mice

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Jun-Xian Song

2017-08-01

Full Text Available Background: The effects of capsaicin on obesity and glucose homeostasis are still controversial and the mechanisms underlying these effects remain largely unknown. This study aimed to investigate the potential relationship between the regulation of obesity and glucose homeostasis by dietary capsaicin and the alterations of gut microbiota in obese diabetic ob/ob mice.Methods: The ob/ob mice were subjected to a normal, low-capsaicin (0.01%, or high-capsaicin (0.02% diet for 6 weeks, respectively. Obesity phenotypes, glucose homeostasis, the gut microbiota structure and composition, short-chain fatty acids, gastrointestinal hormones, and pro-inflammatory cytokines were measured.Results: Both the low- and high-capsaicin diets failed to prevent the increase in body weight, adiposity index, and Lee's obesity index. However, dietary capsaicin at both the low and high doses significantly inhibited the increase of fasting blood glucose and insulin levels. These inhibitory effects were comparable between the two groups. Similarly, dietary capsaicin resulted in remarkable improvement in glucose and insulin tolerance. In addition, neither the low- nor high-capsaicin diet could alter the α-diversity and β-diversity of the gut microbiota. Taxonomy-based analysis showed that both the low- and high-capsaicin diets, acting in similar ways, significantly increased the Firmicutes/Bacteroidetes ratio at the phylum level as well as increased the Roseburia abundance and decreased the Bacteroides and Parabacteroides abundances at the genus level. Spearman's correlation analysis revealed that the Roseburia abundance was negatively while the Bacteroides and Parabacteroides abundances were positively correlated to the fasting blood glucose level and area under the curve by the oral glucose tolerance test. Finally, the low- and high-capsaicin diets significantly increased the fecal butyrate and plasma total GLP-1 levels, but decreased plasma total ghrelin, TNF-α, IL-1�

Synthesis of Capsaicin Glycosides and 8-Nordihydrocapsaicin Glycosides as Potential Weight-Loss Formulations

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Hisashi Katsuragi

2010-03-01

Full Text Available The enzymatic synthesis of capsaicin glycosides and 8-nordihydrocapsaicin glycosides was investigated using almond β-glucosidase and cyclodextrin glucanotransferase (CGTase. Capsaicin and 8-nordihydrocapsaicin were converted into their β-glucoside and β-maltooligosaccharide (amylose conjugate, i.e. β-maltoside and β-maltotrioside, by sequencial glycosylation with almond β-glucosidase and CGTase. The β-glucoside and β-maltoside of capsaicin and β-glucoside of 8-nordihydrocapsaicin showed inhibitory effects on high-fat-diet-induced elevations in body weight of mice.

Synthesis of Capsaicin Glycosides and 8-Nordihydrocapsaicin Glycosides as Potential Weight-Loss Formulations

Directory of Open Access Journals (Sweden)

Hisashi Katsuragi

2010-01-01

Full Text Available The enzymatic synthesis of capsaicin glycosides and 8-nordihydrocapsaicin glycosides was investigated using almond β-glucosidase and cyclodextrin glucanotransferase (CGTase. Capsaicin and 8-nordihydrocapsaicin were converted into their β-glucoside and β-maltooligosaccharide (amylose conjugate, i.e. β-maltoside and β-maltotrioside, by sequencial glycosylation with almond β-glucosidase and CGTase. The β-glucoside and β-maltoside of capsaicin and β-glucoside of 8-nordihydrocapsaicin showed inhibitory effects on high-fat-diet-induced elevations in body weight of mice.

Medication overuse reinstates conditioned pain modulation in women with migraine.

Science.gov (United States)

Guy, Nathalie; Voisin, Daniel; Mulliez, Aurélien; Clavelou, Pierre; Dallel, Radhouane

2018-05-01

Background This study investigated the effects of medication overuse and withdrawal on modulation of pain processing in women with migraine. Temporal summation of laser-evoked thermal pain was used to measure the effects of conditioned pain modulation. Methods 36 female participants (12 healthy volunteers, 12 with episodic migraine and 12 with medication overuse headache) were included in a two session protocol. Medication overuse headache subjects were also tested three weeks after medication overuse headache withdrawal. Mechanical and laser-evoked thermal pain thresholds were measured on the back of the non-dominant hand where, later, temporal summation of laser-evoked thermal pain to repetitive thermal stimuli was elicited for 30 min, at an intensity producing moderate pain. Between the 10 th and 20 th minutes, the contralateral foot was immersed into a water bath at a not painful (30℃) or painfully cold (8℃; conditioned pain modulation) temperature. Results Episodic migraine, medication overuse headache and medication overuse headache withdrawal were associated with an increase in extracephalic temporal summation of laser-evoked thermal pain as compared to healthy volunteer subjects, while there was no alteration of laser-evoked thermal and mechanical extracephalic pain thresholds in these subjects. Conditioned pain modulation was highly efficient in temporal summation of laser-evoked thermal pain in healthy volunteer subjects, with a solid post-effect (reduction of pain). Conditioned pain modulation was still present, but reduced, in episodic migraine. By contrast, conditioned pain modulation was normal in medication overuse headache and strongly reduced in medication overuse headache withdrawal. Furthermore, in medication overuse headache withdrawal, the post-effect was no longer a decrease, but a facilitation of pain. Conclusions These data show that a decrease in conditioned pain modulation does not underlie medication overuse headache in women. On

Central projections and entries of capsaicin-sensitive muscle afferents.

Science.gov (United States)

Della Torre, G; Lucchi, M L; Brunetti, O; Pettorossi, V E; Clavenzani, P; Bortolami, R

1996-03-25

The entry pathway and central distribution of A delta and C muscle afferents within the central nervous system (CNS) were investigated by combining electron microscopy and electrophysiological analysis after intramuscular injection of capsaicin. The drug was injected into the rat lateral gastrocnemius (LG) and extraocular (EO) muscles. The compound action potentials of LG nerve and the evoked field potentials recorded in semilunar ganglion showed an immediate and permanent reduction in A delta and C components. The morphological data revealed degenerating unmyelinated axons and terminals in the inner sublamina II and in the border of laminae I-II of the dorsal horn at L4-L5 and C1-C2 (subnucleus caudalis trigemini) spinal cord segments. Most degenerating terminals were the central bouton (C) of type I and II synaptic glomeruli. Furthermore, degenerating peripheral axonal endings (V2) presynaptic to normal C were found. Since V2 were previously found degenerated after cutting the oculomotor nerve (ON) or L4 ventral root, we conclude that some A delta and C afferents from LG and EO muscles entering the CNS by ON or ventral roots make axoaxonic synapses on other primary afferents to promote an afferent control of sensory input.

Experimental knee pain evoke spreading hyperalgesia and facilitated temporal summation of pain

DEFF Research Database (Denmark)

Jørgensen, Tanja Schjødt; Henriksen, Marius; Danneskiold-Samsøe, Bente

2013-01-01

OBJECTIVES: This study evaluated the deep-tissue pressure pain sensitivity and temporal summation of pain within and around healthy knees exposed to experimental pain. DESIGN: The study was designed as a randomized crossover trial, with each subject tested on 1 day. SETTING: All tests were carried...... occasions: baseline, immediately after the injection, and when pain had vanished. Assessments sites were located in the peripatellar region, vastus lateralis, and tibialis anterior muscles. RESULTS: The experimental knee pain model demonstrated 1) hyperalgesia to pressure stimulation on the infrapatellar...... fat pad during experimental pain, and 2) facilitated temporal summation of pressure pain at the infrapatellar fat pad and knee-related muscles. CONCLUSION: The increased sensitivity and temporal summation found in this study were exclusive to deep -tissue with no contralateral decreased pain...

Capsaicin, a novel inhibitor of the NorA efflux pump, reduces the intracellular invasion of Staphylococcus aureus.

Science.gov (United States)

Kalia, Nitin Pal; Mahajan, Priya; Mehra, Rukmankesh; Nargotra, Amit; Sharma, Jai Parkash; Koul, Surrinder; Khan, Inshad Ali

2012-10-01

To delineate the role of capsaicin (8-methyl-N-vanillyl-6-nonenamide) as an inhibitor of the NorA efflux pump and its impact on invasion of macrophages by Staphylococcus aureus. Capsaicin in combination with ciprofloxacin was tested for activity against S. aureus SA-1199B (NorA overproducing), SA-1199 (wild-type) and SA-K1758 (norA knockout). The role of NorA in the intracellular invasion of S. aureus and the ability of capsaicin to inhibit this invasion was established in J774 macrophage cell lines. The three-dimensional structure of NorA was predicted using an in silico approach and docking studies of capsaicin were performed. Capsaicin significantly reduced the MIC of ciprofloxacin for S. aureus SA-1199 and SA-1199B. Furthermore, capsaicin also extended the post-antibiotic effect of ciprofloxacin by 1.1 h at MIC concentration. There was a decrease in mutation prevention concentration of ciprofloxacin when combined with capsaicin. Inhibition of ethidium bromide efflux by NorA-overproducing S. aureus SA-1199B confirmed the role of capsaicin as a NorA efflux pump inhibitor (EPI). The most significant finding of this study was the ability of capsaicin to reduce the intracellular invasion of S. aureus SA-1199B (NorA overproducing) in J774 macrophage cell lines by 2 log(10). This study, for the first time, has shown that capsaicin, a novel EPI, not only inhibits the NorA efflux pump of S. aureus but also reduces the invasiveness of S. aureus, thereby reducing its virulence.

Microbial causes of endodontic flare-ups.

Science.gov (United States)

Siqueira, Jose F

2003-07-01

Inter-appointment flare-up is characterized by the development of pain, swelling or both, following endodontic intervention. The causative factors of flare-ups encompass mechanical, chemical and/or microbial injury to the pulp or periradicular tissues. Of these factors, microorganisms are arguably the major causative agents of flare-ups. Even though the host is usually unable to eliminate the root canal infection, mobilization and further concentration of defence components at the periradicular tissues impede spreading of infection, and a balance between microbial aggression and host defences is commonly achieved. There are some situations during endodontic therapy in which such a balance may be disrupted in favour of microbial aggression, and an acute periradicular inflammation can ensue. Situations include apical extrusion of infected debris, changes in the root canal microbiota and/or in environmental conditions caused by incomplete chemo-mechanical preparation, secondary intraradicular infections and perhaps the increase in the oxidation-reduction potential within the root canal favouring the overgrowth of the facultative bacteria. Based on these situations, preventive measures against infective flare-ups are proposed, including selection of instrumentation techniques that extrude lesser amounts of debris apically; completion of the chemo-mechanical procedures in a single visit; use of an antimicrobial intracanal medicament between appointments in the treatment of infected cases; not leaving teeth open for drainage and maintenance of the aseptic chain throughout endodontic treatment. Knowledge about the microbial causes of flare-ups and adoption of appropriate preventive measures can significantly reduce the incidence of this highly distressing and undesirable clinical phenomenon.

Influence of repeated infusion of capsaicin-contained red pepper sauce on esophageal secondary peristalsis in humans.

Science.gov (United States)

Liu, T T; Yi, C H; Lei, W Y; Hung, X S; Yu, H C; Chen, C L

2014-10-01

The transient receptor potential vanilloid 1 has been implicated as a target mediator for heartburn perception and modulation of esophageal secondary peristalsis. Our aim was to determine the effect of repeated esophageal infusion of capsaicin-contained red pepper sauce on heartburn perception and secondary peristalsis in healthy adults. Secondary peristalsis was performed with mid-esophageal injections of air in 15 healthy adults. Two separate protocols including esophageal infusion with saline and capsaicin-contained red pepper sauce and 2 consecutive sessions of capsaicin-contained red pepper sauce were randomly performed. After repeated infusion of capsaicin-contained red pepper sauce, the threshold volume to activate secondary peristalsis was significantly increased during slow (p sauce enhanced heartburn perception (p sauce infusion (p = 0.007). Acute infusion of capsaicin-contained red pepper sauce significantly increased pressure wave amplitudes of distal esophagus during slow (p = 0.003) and rapid air injections (p = 0.01), but repeated infusion of capsaicin-contained red pepper sauce significantly decreased pressure wave amplitude of distal esophagus during slow (p = 0.0005) and rapid air injections (p = 0.003). Repeated esophageal infusion of capsaicin appears to attenuate heartburn perception and inhibit distension-induced secondary peristalsis in healthy adults. These results suggest capsaicin-sensitive afferents in modulating sensorimotor function of secondary peristalsis in human esophagus. © 2014 John Wiley & Sons Ltd.

Conditioned pain modulation and situational pain catastrophizing as preoperative predictors of pain following chest wall surgery: a prospective observational cohort study.

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Kasper Grosen

Full Text Available Variability in patients' postoperative pain experience and response to treatment challenges effective pain management. Variability in pain reflects individual differences in inhibitory pain modulation and psychological sensitivity, which in turn may be clinically relevant for the disposition to acquire pain. The aim of this study was to investigate the effects of conditioned pain modulation and situational pain catastrophizing on postoperative pain and pain persistency.Preoperatively, 42 healthy males undergoing funnel chest surgery completed the Spielberger's State-Trait Anxiety Inventory and Beck's Depression Inventory before undergoing a sequential conditioned pain modulation paradigm. Subsequently, the Pain Catastrophizing Scale was introduced and patients were instructed to reference the conditioning pain while answering. Ratings of movement-evoked pain and consumption of morphine equivalents were obtained during postoperative days 2-5. Pain was reevaluated at six months postoperatively.Patients reporting persistent pain at six months follow-up (n = 15 were not significantly different from pain-free patients (n = 16 concerning preoperative conditioned pain modulation response (Z = 1.0, P = 0.3 or level of catastrophizing (Z = 0.4, P = 1.0. In the acute postoperative phase, situational pain catastrophizing predicted movement-evoked pain, independently of anxiety and depression (β = 1.0, P = 0.007 whereas conditioned pain modulation predicted morphine consumption (β = -0.005, P = 0.001.Preoperative conditioned pain modulation and situational pain catastrophizing were not associated with the development of persistent postoperative pain following funnel chest repair. Secondary outcome analyses indicated that conditioned pain modulation predicted morphine consumption and situational pain catastrophizing predicted movement-evoked pain intensity in the acute postoperative phase. These findings may have

Solar flares

International Nuclear Information System (INIS)

Zirin, H.

1974-01-01

A review of the knowledge about solar flares which has been obtained through observations from the earth and from space by various methods is presented. High-resolution cinematography is best carried out at H-alpha wavelengths to reveal the structure, time history, and location of flares. The classification flares in H alpha according to either physical or morphological criteria is discussed. The study of flare morphology, which shows where, when, and how flares occur, is important for evaluating theories of flares. Consideration is given to studies of flares by optical spectroscopy, radio emissions, and at X-ray and XUV wavelengths. Research has shown where and possibly why flares occur, but the physics of the instability involved, of the particle acceleration, and of the heating are still not understood. (IAA)

Capsaicin sensitizes TRAIL-induced apoptosis through Sp1-mediated DR5 up-regulation: Involvement of Ca2+ influx

International Nuclear Information System (INIS)

Moon, Dong-Oh; Kang, Chang-Hee; Kang, Sang-Hyuck; Choi, Yung-Hyun; Hyun, Jin-Won; Chang, Weon-Young; Kang, Hee-Kyoung; Koh, Young-Sang; Maeng, Young-Hee; Kim, Young-Ree; Kim, Gi-Young

2012-01-01

Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various malignant cells, several cancers including human hepatocellular carcinoma (HCC) exhibit potent resistance to TRAIL-induced cell death. The aim of this study is to evaluate the anti-cancer potential of capsaicin in TRAIL-induced cancer cell death. As indicated by assays that measure phosphatidylserine exposure, mitochondrial activity and activation of caspases, capsaicin potentiated TRAIL-resistant cells to lead to cell death. In addition, we found that capsaicin induces the cell surface expression of TRAIL receptor DR5, but not DR4 through the activation Sp1 on its promoter region. Furthermore, we investigated that capsaicin-induced DR5 expression and apoptosis are inhibited by calcium chelator or inhibitors for calmodulin-dependent protein kinase. Taken together, our data suggest that capsaicin sensitizes TRAIL-mediated HCC cell apoptosis by DR5 up-regulation via calcium influx-dependent Sp1 activation. Highlights: ► Capsaicin sensitizes TRAIL-induced apoptosis through activation of caspases. ► Capsaicin induces expression of DR5 through Sp1 activation. ► Capsaicin activates calcium signaling pathway.

Involvement of AMPK signaling cascade in capsaicin-induced apoptosis of HT-29 colon cancer cells.

Science.gov (United States)

Kim, Young Min; Hwang, Jin-Taek; Kwak, Dong Wook; Lee, Yun Kyung; Park, Ock Jin

2007-01-01

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is activated during ATP-depleting metabolic states, such as hypoxia, heat shock, oxidative stress, and exercise. As a highly conserved heterotrimeric kinase that functions as a major metabolic switch to maintain energy homeostasis, AMPK has been shown to exert as an intrinsic regulator of mammalian cell cycle. Moreover, AMPK cascade has emerged as an important pathway implicated in cancer control. In this article, we have investigated the effects of capsaicin on apoptosis in relation to AMPK activation in colon cancer cell. Capsaicin-induced apoptosis was revealed by the presence of nucleobodies in the capsaicin-treated HT-29 colon cancer cells. Concomitantly, the activation of AMPK and the increased expression of the inactive form of acetyl-CoA carboxylase (ACC) were detected in capsaicin-treated colon cancer cells. We showed that both capsaicin and 5'-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR), an AMPK activator possess the AMPK-activating capacity as well as apoptosis-inducing properties. Evidence of the association between AMPK activation and the increased apoptosis in HT-29 colon cancer cells by capsaicin treatment, and further findings of the correlation of the activated AMPK and the elevated apoptosis by cotreatment of AICAR and capsaicin support AMPK as an important component of apoptosis, as well as a possible target of cancer control.

Flare stars

International Nuclear Information System (INIS)

Nicastro, A.J.

1981-01-01

The least massive, but possibly most numerous, stars in a galaxy are the dwarf M stars. It has been observed that some of these dwarfs are characterized by a short increase in brightness. These stars are called flare stars. These flare stars release a lot of energy in a short amount of time. The process producing the eruption must be energetic. The increase in light intensity can be explained by a small area rising to a much higher temperature. Solar flares are looked at to help understand the phenomenon of stellar flares. Dwarfs that flare are observed to have strong magnetic fields. Those dwarf without the strong magnetic field do not seem to flare. It is believed that these regions of strong magnetic fields are associated with star spots. Theories on the energy that power the flares are given. Astrophysicists theorize that the driving force of a stellar flare is the detachment and collapse of a loop of magnetic flux. The mass loss due to stellar flares is discussed. It is believed that stellar flares are a significant contributor to the mass of interstellar medium in the Milky Way

Extraction and purification of capsaicin from capsicum oleoresin using an aqueous two-phase system combined with chromatography.

Science.gov (United States)

Fan, Yong; Lu, Yan-Min; Yu, Bin; Tan, Cong-Ping; Cui, Bo

2017-09-15

Capsaicin was extracted from capsicum oleoresin using an aqueous two-phase system (ATPS) composed of an ethylene oxide-propylene oxide (EOPO) copolymer, salt and ethanol. Capsaicin was concentrated in the top polymer-rich phase. To determine the optimal conditions, the partitioning of capsaicin in the ATPS was investigated, considering a single-factor experiment including the salt concentration, polymer concentration, buffer pH, ethanol concentration, sample loading and extraction duration. Response surface methodology was applied to investigate the effects of the polymer concentration, buffer pH and sample loading on capsaicin partitioning. A capsaicin yield of 95.5% was obtained using the optimal extraction system, which consisted of 16.3% UCON 50-HB-5100/10% K 2 HPO 4 /1% ethanol, a buffer pH of 4.35 and 0.24g of capsicum oleoresin. Capsaicin was purified from the capsaicinoid extract using a two-step macroporous adsorption resin (MAR) method. After purification using non-polar MAR ADS-17, the recovery and purity of capsaicin were 83.7% and 50.3%, respectively. After purification using weakly polar MAR AB-8, the recovery and purity of capsaicin were 88.0% and 85.1%, respectively. Copyright © 2017. Published by Elsevier B.V.

Novel Approaches to Extraction Methods in Recovery of Capsaicin from Habanero Pepper (CNPH 15.192).

Science.gov (United States)

Martins, Frederico S; Borges, Leonardo L; Ribeiro, Claudia S C; Reifschneider, Francisco J B; Conceição, Edemilson C

2017-07-01

The objective of this study was to compare three capsaicin extraction methods: Shoxlet, Ultrasound-assisted Extraction (UAE), and Shaker-assisted Extraction (SAE) from Habanero pepper, CNPH 15.192. The different parameters evaluated were alcohol degree, time extraction, and solid-solvent ratio using response surface methodology (RSM). The three parameters found significant ( p Soxhlet increased the extraction in 10-25%; however, long extraction times (45 minutes) degraded 2% capsaicin. The extraction of capsaicin was influenced by extraction method and by the operating conditions chosen. The optimized conditions provided savings of time, solvent, and herbal material. Prudent choice of the extraction method is essential to ensure optimal yield of extract, thereby making the study relevant and the knowledge gained useful for further exploitation and application of this resource. Habanero pepper , line CNPH 15.192, possess capsaicin in higher levels when compared with others speciesHigher levels of ethanolic strength are more suitable to obtain a higher levels of capsaicinBox-Behnken design indicates to be useful to explore the best conditions of ultrasound assisted extraction of capsaicin. Abbreviations used: Nomenclature UAE: Ultrasound-assisted Extraction; SAE: Shaker-assisted Extraction.

Suramin affects capsaicin responses and capsaicin-noxious heat interactions in rat dorsal root ganglia neurones

Czech Academy of Sciences Publication Activity Database

Vlachová, Viktorie; Lyfenko, Alla; Vyklický st., Ladislav; Orkand, R. K.

2002-01-01

Roč. 51, č. 2 (2002), s. 193-198 ISSN 0862-8408 R&D Projects: GA ČR GA305/00/1639; GA MŠk LN00B122 Institutional research plan: CEZ:AV0Z5011922 Keywords : dorsal root ganglia neurones * vanilloid receptor * capsaicin-noxious heat Subject RIV: ED - Physiology Impact factor: 0.984, year: 2002

Effects of Capsaicin on Older Patients with Oropharyngeal Dysphagia: A Double-Blind, Placebo-Controlled, Crossover Study.

Science.gov (United States)

Nakato, Rui; Manabe, Noriaki; Shimizu, Sayako; Hanayama, Kozo; Shiotani, Akiko; Hata, Jiro; Haruma, Ken

2017-01-01

The standard of care for older patients with oropharyngeal dysphagia (OD) is poor. Stimulation of transient receptor potential vanilloid 1 might become a pharmacological strategy for these patients. This study aimed to compare the therapeutic effect of film food containing 0.75 µg of capsaicin in these patients. In a crossover, randomized trial, 49 patients with OD were provided capsaicin or identical placebo at least 7 days apart. Patients' reported symptoms during repeated swallowing, the volume, pH and substance P (SP) concentrations in saliva, and cervical esophageal wall motion evaluated by ultrasonographic tissue Doppler imaging were obtained before and after capsaicin or placebo administration. Significantly more patients with OD who took capsaicin experienced improvement in symptoms than those who took placebo. Salivary SP levels were significantly increased after capsaicin administration compared with placebo in the effective group. The duration of cervical esophageal wall opening was significantly shorter in capsaicin administration in the effective group. Furthermore, a significant negative correlation was found between the duration of cervical esophageal wall opening and salivary SP levels. Elevated salivary SP concentrations stimulated by capsaicin greatly improve the safety and efficacy of swallowing, and shorten the swallow response in older patients with OD. © 2017 S. Karger AG, Basel.

Combined treatment with capsaicin and resveratrol enhances neuroprotection against glutamate-induced toxicity in mouse cerebral cortical neurons

NARCIS (Netherlands)

Lee, J.G.; Yon, J.M.; Lin, C.; Jung, A.Y.; Jung, K.Y.; Nam, S.Y.

2012-01-01

Capsaicin and resveratrol as natural products have a variety of beneficial effects. However, capsaicin is also a neurotoxic agent, rendering its effect on the nervous system confusing. The aim of this study was to investigate whether capsaicin and/or resveratrol have a protective effect against

Dopaminergic tone does not influence pain levels during placebo interventions in patients with chronic neuropathic pain.

Science.gov (United States)

Skyt, Ina; Moslemi, Kurosh; Baastrup, Cathrine; Grosen, Kasper; Benedetti, Fabrizio; Petersen, Gitte L; Price, Donald D; Hall, Kathryn T; Kaptchuk, Ted J; Svensson, Peter; Jensen, Troels S; Vase, Lene

2017-10-23

Placebo effects have been reported in patients with chronic neuropathic pain. Expected pain levels and positive emotions are involved in the observed pain relief, but the underlying neurobiology is largely unknown. Patients with neuropathic pain are highly motivated for pain relief, and as motivational factors such as expectations of reward, as well as pain processing in itself, are related to the dopaminergic system, it can be speculated that dopamine release contributes to placebo effects in neuropathic pain. Nineteen patients with neuropathic pain after thoracic surgery were tested during a placebo intervention consisting of open and hidden applications of the pain-relieving agent lidocaine (2 mL) and no treatment. The dopamine antagonist haloperidol (2 mg) and the agonist levodopa/carbidopa (100/25 mg) were administered to test the involvement of dopamine. Expected pain levels, desire for pain relief, and ongoing and evoked pain were assessed on mechanical visual analog scales (0-10). Significant placebo effects on ongoing (P ≤ 0.003) and evoked (P ≤ 0.002) pain were observed. Expectancy and desire accounted for up to 41.2% and 71.5% of the variance in ongoing and evoked pain, respectively, after the open application of lidocaine. We found no evidence for an effect of haloperidol and levodopa/carbidopa on neuropathic pain levels (P = 0.071-0.963). Dopamine seemed to influence the levels of expectancy and desire, yet there was no evidence for indirect or interaction effects on the placebo effect. This is the first study to suggest that dopamine does not contribute to placebo effects in chronic neuropathic pain.

Flare energetics

Science.gov (United States)

Wu, S. T.; Dejager, C.; Dennis, B. R.; Hudson, H. S.; Simnett, G. M.; Strong, K. T.; Bentley, R. D.; Bornmann, P. L.; Bruner, M. E.; Cargill, P. J.

1986-01-01

In this investigation of flare energetics, researchers sought to establish a comprehensive and self-consistent picture of the sources and transport of energy within a flare. To achieve this goal, they chose five flares in 1980 that were well observed with instruments on the Solar Maximum Mission, and with other space-borne and ground-based instruments. The events were chosen to represent various types of flares. Details of the observations available for them and the corresponding physical parameters derived from these data are presented. The flares were studied from two perspectives, the impulsive and gradual phases, and then the results were compared to obtain the overall picture of the energics of these flares. The role that modeling can play in estimating the total energy of a flare when the observationally determined parameters are used as the input to a numerical model is discussed. Finally, a critique of the current understanding of flare energetics and the methods used to determine various energetics terms is outlined, and possible future directions of research in this area are suggested.

Neuropathic low back pain in clinical practice.

Science.gov (United States)

Baron, R; Binder, A; Attal, N; Casale, R; Dickenson, A H; Treede, R-D

2016-07-01

Low back pain (LBP) is one of the most common chronic pain conditions. This paper reviews the available literature on the role of neuropathic mechanisms in chronic LBP and discusses implications for its clinical management, with a particular focus on pharmacological treatments. Literature searches were performed in PubMed, key pain congresses and ProQuest Dialog to identify published evidence on neuropathic back pain and its management. All titles were assessed for relevant literature. Chronic LBP comprises both nociceptive and neuropathic components, however, the neuropathic component appears under-recognized and undertreated. Neuropathic pain (NP) is challenging to manage. Many patients with chronic LBP have pain that is refractory to existing treatments. Typically, less than half of patients experience clinically meaningful analgesia with oral pharmacotherapies; these are also associated with risks of adverse effects. Paracetamol and NSAIDs, although widely used for LBP, are unlikely to ameliorate the neuropathic component and data on the use of NP medications such as antidepressants and gabapentin/pregabalin are limited. While there is an unmet need for improved treatment options, recent data have shown tapentadol to have efficacy in the neuropathic component of LBP, and studies suggest that the capsaicin 8% patch and lidocaine 5% medicated plaster, topical analgesics available for the treatment of peripheral NP, may be a valuable additional approach for the management of neuropathic LBP. Chronic LBP often has an under-recognized neuropathic component, which can be challenging to manage, and requires improved understanding and better diagnosis and treatment. WHAT DOES THIS REVIEW ADD?: Increased recognition and improved understanding of the neuropathic component of low back pain raises the potential for the development of mechanism-based therapies. Open and retrospective studies suggest that agents like tapentadol and topical analgesics - such as the capsaicin

Application of a capsaicin rinse in the treatment of burning mouth syndrome

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Silvestre-Rangil, Javier; Tamarit-Santafé, Carmen; Bautista, Daniel

2012-01-01

Objective: To examine the efficacy of a new topical capsaicin presentation as an oral rinse in improving the symptoms of burning mouth syndrome (BMS). Study design: A prospective, double-blind, cross-over study was made of 30 patients with BMS. There were 7 dropouts; the final study series thus comprised 23 individuals. The patients were randomized to two groups: (A) capsaicin rinse (0.02%) or (B) placebo rinse, administered during one week. After a one-week washout period, the patients were then assigned to the opposite group. Burning discomfort was scored using a visual analog scale (VAS): in the morning before starting the treatment, in the afternoon on the first day of treatment, and at the end of the week of treatment in the morning and in the afternoon. The same scoring sequence was again applied one week later with the opposite rinse. Results: The mean patient age was 72.65 ± 12.10 years, and the duration of BMS was 5.43 ± 3.23 years on average. Significant differences in VAS score were recorded in the capsaicin group between baseline in the morning (AM1) or afternoon (AA1) and the end of the week of treatment (AA7)(p=0.003 and p=0.002, respectively). Conclusion: The topical application of capsaicin may be useful in treating the discomfort of BMS, but has some limitations. Key words: Burning mouth syndrome, stomatodynia, capsaicin, treatment, clinical management. PMID:21743415

Capsaicin-sensitive muscle afferents modulate the monosynaptic reflex in response to muscle ischemia and fatigue in the rat.

Science.gov (United States)

Della Torre, G; Brunetti, O; Pettorossi, V E

2002-01-01

The role of muscle ischemia and fatigue in modulating the monosynaptic reflex was investigated in decerebrate and spinalized rats. Field potentials and fast motoneuron single units in the lateral gastrocnemious (LG) motor pool were evoked by dorsal root stimulation. Muscle ischemia was induced by occluding the LG vascular supply and muscle fatigue by prolonged tetanic electrical stimulation of the LG motor nerve. Under muscle ischemia the monosynaptic reflex was facilitated since the size of the early and late waves of the field potential and the excitability of the motoneuron units increased. This effect was abolished after L3-L6 dorsal rhizotomy, but it was unaffected after L3-L6 ventral rhizotomy. By contrast, the monosynaptic reflex was inhibited by muscle fatiguing stimulation, and this effect did not fully depend on the integrity of the dorsal root. However, when ischemia was combined with repetitive tetanic muscle stimulation the inhibitory effect of fatigue was significantly enhanced. Both the ischemia and fatigue effects were abolished by capsaicin injected into the LG muscle at a dose that blocked a large number of group III and IV muscle afferents. We concluded that muscle ischemia and fatigue activate different groups of muscle afferents that are both sensitive to capsaicin, but enter the spinal cord through different roots. They are responsible for opposite effects, when given separately: facilitation during ischemia and inhibition during fatigue; however, in combination, ischemia enhances the responsiveness of the afferent fibres to fatigue.

The evolution of flaring and non-flaring active regions

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Kilcik, A.; Yurchyshyn, V.; Sahin, S.; Sarp, V.; Obridko, V.; Ozguc, A.; Rozelot, J. P.

2018-06-01

According to the modified Zurich classification, sunspot groups are classified into seven different classes (A, B, C, D, E, F and H) based on their morphology and evolution. In this classification, classes A and B, which are small groups, describe the beginning of sunspot evolution, while classes D, E and F describe the large and evolved groups. Class C describes the middle phase of sunspot evolution and the class H describes the end of sunspot evolution. Here, we compare the lifetime and temporal evolution of flaring and non-flaring active regions (ARs), and the flaring effect on ARs in these groups in detail for the last two solar cycles (1996 through 2016). Our main findings are as follows: (i) Flaring sunspot groups have longer lifetimes than non-flaring ones. (ii) Most of the class A, B and C flaring ARs rapidly evolve to higher classes, while this is not applicable for non-flaring ARs. More than 50 per cent of the flaring A, B and C groups changed morphologically, while the remaining D, E, F and H groups did not change remarkably after the flare activity. (iii) 75 per cent of all flaring sunspot groups are large and complex. (iv) There is a significant increase in the sunspot group area in classes A, B, C, D and H after flaring activity. In contrast, the sunspot group area of classes E and F decreased. The sunspot counts of classes D, E and F decreased as well, while classes A, B, C and H showed an increase.

A comparative study between clinical grading of anterior chamber flare and flare reading using the Kowa laser flare meter.

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Konstantopoulou, Kallirroi; Del'Omo, Roberto; Morley, Anne M; Karagiannis, Dimitris; Bunce, Catey; Pavesio, Carlos

2015-10-01

To assess the accuracy of standard clinical grading of aqueous flare in uveitis according to the Standardization of Uveitis Nomenclature consensus, and compare the results with the readings of the laser flare meter, Kowa 500. Two examiners clinically graded the flare in 110 eyes. The flare was then measured using the Kowa laser flare meter. Twenty-nine eyes were graded as anterior chamber flare +2; for 18 of these, the clinicians were in agreement, the rest differed by the order of one grade. The range of the laser flare meter for these eyes was 5.2-899.1 photons/ms. The median value was 41.4. Seventy-four eyes were graded with flare +1. Agreement was established in 51 of these eyes. Disagreement for the rest was again by the order of 1, and the flare meter range was 1.1-169.9 photons/ms, median value 18.4. For the clinical measure of flare 0, the clinicians disagreed on three out of five eyes. The flare meter readings ranged from 2.5 to 14.1 photons/ms, median value 9.9. Only two eyes were graded with flare +3 and there was one step disagreement on both of them. We found little evidence of association between the flare readings and intraocular pressure or age. Our findings suggest that clinical evaluation of aqueous flare is subjective. Compared with the Kowa laser flare meter's numeric readings, the discrepancies observed indicate that clinical grading is an approximate science. The laser flare meter provides an accurate, reproducible, non-invasive assessment of aqueous flare that can prove valuable in research and clinical decisions.

Histologic evaluation of pulpal response to MTA and capsaicin in cats

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Zahrasadat Madani

2012-09-01

Full Text Available Introduction: In direct pup capping, the exposed pulp is directly capped with a capping material to provoke a dentinal bridge formation to seal the exposed area.The aim of this study was to evaluate the pulpal response to MTA and capsaicin in cats. Methods: The sample for this experimental study consisted of 24 canines of cats, weighed approximately 3-4kg. After sedation, the teeth were cut and exposed at 3mm above cementoenamel junction, then divided into two groups: 1 direct pulp capping with MTA 2 direct pulp capping with Capsaicin. The cavities were filled with glass ionomer cement (Fuji IX. The cats were sacrificed in the first, second, and fourth weeks 4 canine teeth were extracted for the purpose of histologic analysis. 6Serial sections were cut parallel to the longitudinal axis of the canines. The sections were stained with hematoxylin & eosin, and were observed and analyzed using a light microscope. Results: In both groups treated with MTA and capsaicin, the inflammation decreased during weeks1, 2, and 4. Less inflammation was seen in MTA group but there was no statistical difference between the two groups (p=0.22. In the group treated with capsaicin, necrosis was observed in every 12 samples, but in the other group treated with MTA, only 1 pulp necrosis was seen in the first week (p=0.000. There was no significant difference in dentinal barrier formation, inflammatory response, and soft tissue changes between the two groups. Conclusions: The results of this study showed that capsaicin can decrease the severity of inflammation, but it is ineffective in dentinal barrier formation.

Prolonged maintenance of capsaicin-induced hyperalgesia by brief daily vibration stimuli

OpenAIRE

Kim, Hee Kee; Schattschneider, Jörn; Lee, Inhyung; Chung, Kyungsoon; Baron, Ralf; Chung, Jin Mo

2006-01-01

This study tests the hypothesis that central sensitization initiated by nociceptive input can be maintained by repeated brief innocuous peripheral inputs. Capsaicin was injected intradermally into the hind paw of adult rats. Three different types of daily cutaneous mechanical stimulations (vibration, soft brush, or pressure) were applied to the capsaicin-injected paw for a period of 2 weeks. Daily stimulation consisted of a 10-second stimulation repeated every 30 seconds for 30 minutes. Foot ...

Pain Modulation after Oromucosal Cannabinoid Spray (SATIVEX® in Patients with Multiple Sclerosis: A Study with Quantitative Sensory Testing and Laser-Evoked Potentials

Directory of Open Access Journals (Sweden)

Mara Turri

2018-06-01

Full Text Available Background. Delta-9-tetrahydrocannabinol (THC/cannabidiol (CBD (nabiximols or Sativex® is an oromucosal spray formulation containing THC and CBD at an approximately 1:1 fixed ratio. Its administration for the treatment of pain in patients with multiple sclerosis (MS has been established. MS patients generally complain of different kinds of pain, including spasticity-related and neuropathic pain. In this study, we compared and evaluated pain modulation and thermal/pain threshold of MS patients before and after THC/CBD administration. Methods. 19 MS patients underwent clinical examination, numerical rating scale (NRS, quantitative sensory testing (QST, and laser-evoked potentials (LEPs before and after 1 month of therapy. Psychophysiological and neurophysiological data were compared to sex- and age-matched controls. Results. Patients reported a significant reduction in pain. We found statistically significant differences in LEP parameters between patients and controls but no significant change in LEP measures after THC/CBD therapy. Cold and heat detection thresholds were altered in patients but did not change after THC/CBD therapy. There was a significant increase in cold pain threshold by hand stimulation and a significant reduction in abnormal cold perception thresholds. Conclusions. Our results indicate that Sativex® therapy provides pain relief in MS patients and suggest that it might modulate peripheral cold-sensitive TRP channels.

Effects of cocoa-enriched diet on orofacial pain in a murine model.

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Bowden, L N; Rohrs, E L; Omoto, K; Durham, P L; Holliday, L S; Morris, A D; Allen, K D; Caudle, R M; Neubert, J K

2017-06-01

To investigate and discuss the effects of cocoa on orofacial pain. The Department of Orthodontics at the University of Florida (UF). Male and female hairless rats (N=20/group) were tested. Rats were tested using the Orofacial Pain Assessment Device (OPAD) before and after changing their food from the standard chow to a cocoa-enriched or control-equivalent diet. Male rats fed the cocoa diet had a significantly higher operant pain index when tested at 37°C as compared to control diet-fed animals. Female rats on the cocoa diet had a significantly higher pain index when tested at 18°C and 44°C, as compared to animals fed the control diet. Capsaicin-induced pain was inhibited, with cocoa-diet male rats having a significantly higher pain index than control-diet male rats and cocoa-diet female rats at both 37°C and 44°C. Cocoa-diet female rats had a significantly higher pain index at 44°C than control-diet females. Mechanical sensitivity was affected following capsaicin cream, with a significantly decreased tolerated bottle distance in both cocoa- and control-diet animals, but there was no difference between cocoa- and control-diet groups. Using the OPAD operant system, we demonstrated that a diet rich in cocoa was effective in inhibiting neurogenic inflammatory pain in rats. This has implications for the use of novel alternative therapies such as diet modification for pain control. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Deep Flare Net (DeFN) Model for Solar Flare Prediction

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Nishizuka, N.; Sugiura, K.; Kubo, Y.; Den, M.; Ishii, M.

2018-05-01

We developed a solar flare prediction model using a deep neural network (DNN) named Deep Flare Net (DeFN). This model can calculate the probability of flares occurring in the following 24 hr in each active region, which is used to determine the most likely maximum classes of flares via a binary classification (e.g., ≥M class versus statistically predict flares, the DeFN model was trained to optimize the skill score, i.e., the true skill statistic (TSS). As a result, we succeeded in predicting flares with TSS = 0.80 for ≥M-class flares and TSS = 0.63 for ≥C-class flares. Note that in usual DNN models, the prediction process is a black box. However, in the DeFN model, the features are manually selected, and it is possible to analyze which features are effective for prediction after evaluation.

Modulation of itch by conditioning itch and pain stimulation in healthy humans

DEFF Research Database (Denmark)

Andersen, Hjalte Holm; van Laarhoven, Antoinette I. M.; Elberling, Jesper

2017-01-01

Little is known about endogenous descending control of itch. In chronic pain, descending pain inhibition is reduced as signified by lowered conditioned pain modulation (CPM). There are indications that patients with chronic itch may also exhibit reduced endogenous descending inhibition of itch......-evoked itch, while the test stimuli were electrical stimulation paradigms designed to evoke itch or pain. Pain was significantly reduced (CPM-effect) by the conditioning pain stimulus (p

Race effects on temporal summation to heat pain in youth.

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Morris, Matthew C; Walker, Lynn; Bruehl, Stephen; Hellman, Natalie; Sherman, Amanda L; Rao, Uma

2015-05-01

Racial differences in pain responsiveness have been demonstrated in adults. However, it is unclear whether racial differences are also present in youth and whether they extend to experimental pain indices assessing temporal summation of second pain (TSSP). Temporal summation of second pain provides an index of pain sensitivity and may be especially relevant in determining risk for chronic pain. This study assessed pain tolerance and TSSP to evoked thermal pain in 78 healthy youth (age range, 10-17), 51% of whom were African American and 49% were non-Hispanic white. Multilevel models revealed within-individual increases in pain ratings during the temporal summation task in non-Hispanic white youth that were consistent with TSSP. Pain ratings did not change significantly during the temporal summation task in African-American youth. Baseline evoked pain ratings were significantly higher in African-American compared with non-Hispanic white youth. These findings suggest that enhanced responsiveness to evoked thermal pain in African Americans is present in adolescence but is unlikely to be related to elevated TSSP. These results may have implications for understanding racial differences in chronic pain experience in adulthood.

Tolerability of the capsaicin 8% patch following pretreatment with lidocaine or tramadol in patients with peripheral neuropathic pain: A multicentre, randomized, assessor-blinded study

NARCIS (Netherlands)

Jensen, T.S.; Hoye, K.; Fricova, J.; Vanelderen, P.J.L.; Ernault, E.; Siciliano, T.; Marques, S.

2014-01-01

BACKGROUND: Application of the capsaicin 8% patch is associated with treatment-related discomfort. Consequently, pretreatment for 60 min with anaesthetic cream is recommended; however, this may be uncomfortable and time consuming. METHODS: We conducted a multicentre, randomized (1:1),

Glutamate Receptor GluA1 Subunit Is Implicated in Capsaicin Induced Modulation of Amygdala LTP but Not LTD

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Gebhardt, Christine; Albrecht, Doris

2018-01-01

Capsaicin has been shown to modulate synaptic plasticity in various brain regions including the amygdala. Whereas in the lateral amygdala the modulatory effect of capsaicin on long-term potentiation (LA-LTP) is mediated by TRPV1 channels, we have recently shown that capsaicin-induced enhancement of long term depression (LA-LTD) is mediated by…

The capsaicin cough reflex in patients with symptoms elicited by odorous chemicals

DEFF Research Database (Denmark)

Holst, H; Arendt-Nielsen, L; Mosbech, H

2010-01-01

Patients with multiple chemical sensitivity and eczema patients with airway symptoms elicited by odorous chemicals have enhanced cough reflex to capsaicin when applying the tidal breathing method. The aims of the present study were to test whether the capsaicin induced cough reflex was enhanced...... when applying the single breath inhalation method in similar groups of patients with symptoms related to odorous chemicals e.g. other persons wearing of perfume; and to investigate to what extent the reporting of lower airway symptoms influenced the cough reflex. Sixteen patients fulfilling Cullen......'s criteria for multiple chemical sensitivity and 15 eczema patients with airway symptoms elicited by odorous chemicals were compared with 29 age-matched, healthy controls. We measured C5--the capsaicin concentration causing five coughs or more--using the single breath inhalation test. No difference was found...

A Pilot Study: Evaluation of the Effects of Treatment with 0.75% Topical Capsaicin in Patients with Reflex Sympathetic Dystrophy Using Three Phase Bone Scintigraphy

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1991-01-28

years topical capsaicin has recieved growing attention in the treatment of specific pain syndromes. Derived primarily from neonatal and adult rat...dorsal roots19󈧚, cornea19, and coeliac ganglion23 . Similar, and generally parallel, depletions have been shown for cholecystokinin.16-23 A review this...stimulation. Therapy of causalgia has its roots in S. Wier Mitchell’s civil war experience beginning at the United States Army Hospital for Diseases on

Involvement of the phosphoinositide 3-kinase/Akt pathway in apoptosis induced by capsaicin in the human pancreatic cancer cell line PANC-1.

Science.gov (United States)

Zhang, Jian-Hong; Lai, Fu-Ji; Chen, Hui; Luo, Jiang; Zhang, Ri-Yuan; Bu, He-Qi; Wang, Zhao-Hong; Lin, Hong-Hai; Lin, Sheng-Zhang

2013-01-01

Capsaicin, one of the major pungent ingredients found in red peppers, has been recently demonstrated to induce apoptosis in various malignant cell lines through an unclear mechanism. In this study, the effect of capsaicin on proliferation and apoptosis in the human pancreatic cancer cell line PANC-1 and its possible mechanism(s) of action were investigated. The results of a Cell Counting Kit-8 (CCK-8) assay revealed that capsaicin significantly decreased the viability of PANC-1 cells in a dose-dependent manner. Capsaicin induced G0/G1 phase cell cycle arrest and apoptosis in PANC-1 cells as demonstrated by a flow cytometric assessment. Caspase-3 expression at both the protein and mRNA level was promoted following capsaicin treatment. Furthermore, we revealed that phospho-PI3 Kinase p85 (Tyr458) and phospho-Akt (Ser473) in PANC-1 cells were downregulated in response to capsaicin. Moreover, capsaicin gavage significantly inhibited the growth of pancreatic cancer PANC-1 cell xenografts in athymic nude mice. An increased number of TUNEL-positive cells and cleaved caspase-3 were observed in capsaicin-treated mice. In vivo, capsaicin downregulated the expression of phospho-PI3 Kinase p85 (Tyr458) and phospho-Akt (Ser473). In conclusion, we have demonstrated that capsaicin is an inhibitor of growth of PANC-1 cells, and downregulation of the phosphoinositide 3-kinase/Akt pathway may be involved in capsaicin-induced apoptosis in vitro and in vivo.

The Effects of Flare Definitions on the Statistics of Derived Flare Distrubtions

Science.gov (United States)

Ryan, Daniel; Dominique, Marie; Seaton, Daniel B.; Stegen, Koen; White, Arthur

2016-05-01

The statistical examination of solar flares is crucial to revealing their global characteristics and behaviour. However, statistical flare studies are often performed using standard but basic flare detection algorithms relying on arbitrary thresholds which may affect the derived flare distributions. We explore the effect of the arbitrary thresholds used in the GOES event list and LYRA Flare Finder algorithms. We find that there is a small but significant relationship between the power law exponent of the GOES flare peak flux frequency distribution and the algorithms’ flare start thresholds. We also find that the power law exponents of these distributions are not stable but appear to steepen with increasing peak flux. This implies that the observed flare size distribution may not be a power law at all. We show that depending on the true value of the exponent of the flare size distribution, this deviation from a power law may be due to flares missed by the flare detection algorithms. However, it is not possible determine the true exponent from GOES/XRS observations. Additionally we find that the PROBA2/LYRA flare size distributions are clearly non-power law. We show that this is consistent with an insufficient degradation correction which causes LYRA absolute irradiance values to be unreliable. This means that they should not be used for flare statistics or energetics unless degradation is adequately accounted for. However they can be used to study time variations over shorter timescales and for space weather monitoring.

Capsaicin affects brain function in a model of hepatic encephalopathy associated with fulminant hepatic failure in mice

Science.gov (United States)

Avraham, Y; Grigoriadis, NC; Magen, I; Poutahidis, T; Vorobiav, L; Zolotarev, O; Ilan, Y; Mechoulam, R; Berry, EM

2009-01-01

Background and purpose: Hepatic encephalopathy is a neuropsychiatric syndrome caused by liver failure. In view of the effects of cannabinoids in a thioacetamide-induced model of hepatic encephalopathy and liver disease and the beneficial effect of capsaicin (a TRPV1 agonist) in liver disease, we assumed that capsaicin may also affect hepatic encephalopathy. Experimental approach: Fulminant hepatic failure was induced in mice by thioacetamide and 24 h later, the animals were injected with one of the following compound(s): 2-arachidonoylglycerol (CB1, CB2 and TRPV1 receptor agonist); HU308 (CB2 receptor agonist), SR141716A (CB1 receptor antagonist); SR141716A+2-arachidonoylglycerol; SR144528 (CB2 receptor antagonist); capsaicin; and capsazepine (TRPV1 receptor agonist and antagonist respectively). Their neurological effects were evaluated on the basis of activity in the open field, cognitive function in an eight-arm maze and a neurological severity score. The mice were killed 3 or 14 days after thioacetamide administration. 2-arachidonoylglycerol and 5-hydroxytryptamine (5-HT) levels were determined by gas chromatography-mass spectrometry and high-performance liquid chromatography with electrochemical detection, respectively. Results: Capsaicin had a neuroprotective effect in this animal model as shown by the neurological score, activity and cognitive function. The effect of capsaicin was blocked by capsazepine. Thioacetamide induced astrogliosis in the hippocampus and the cerebellum and raised brain 5-hydroxytryptamine levels, which were decreased by capsaicin, SR141716A and HU-308. Thioacetamide lowered brain 2-arachidonoylglycerol levels, an effect reversed by capsaicin. Conclusions: Capsaicin improved both liver and brain dysfunction caused by thioacetamide, suggesting that both the endocannabinoid and the vanilloid systems play important roles in hepatic encephalopathy. Modulation of these systems may have therapeutic value. PMID:19764982

Solar flares

International Nuclear Information System (INIS)

Kaastra, J.S.

1985-01-01

In this thesis an electrodynamic model for solar flares is developed. The main theoretical achievements underlying the present study are treated briefly and the observable flare parameters are described within the framework of the flare model of this thesis. The flare model predicts large induced electric fields. Therefore, acceleration processes of charged particles by direct electric fields are treated. The spectrum of the accelerated particles in strong electric fields is calculated, 3 with the electric field and the magnetic field perpendicular and in the vicinity of an X-type magnetic neutral line. An electromagnetic field configuration arises in the case of a solar flare. A rising current filament in a quiescent background bipolar magnetic field causes naturally an X-type magnetic field configuration below the filament with a strong induced electric field perpendicular to the ambient magnetic field. This field configuration drives particles and magnetic energy towards the neutral line, where a current sheet is generated. The global evolution of the fields in the flare is determined by force balance of the Lorentz forces on the filament and the force balance on the current sheet. The X-ray, optical and radio observations of a large solar flare on May 16, 1981 are analyzed. It is found that these data fit the model very well. (Auth.)

Cancer-promoting effect of capsaicin on DMBA/TPA-induced skin tumorigenesis by modulating inflammation, Erk and p38 in mice.

Science.gov (United States)

Liu, Zhaoguo; Zhu, Pingting; Tao, Yu; Shen, Cunsi; Wang, Siliang; Zhao, Lingang; Wu, Hongyan; Fan, Fangtian; Lin, Chao; Chen, Chen; Zhu, Zhijie; Wei, Zhonghong; Sun, Lihua; Liu, Yuping; Wang, Aiyun; Lu, Yin

2015-07-01

Epidemiologic and animal studies revealed that capsaicin (8-methyl-N-vanillyl-6-noneamide) can act as a carcinogen or cocarcinogen. However, the influence of consumption of capsaicin-containing foods or vegetables on skin cancer patients remains largely unknown. In the present study, we demonstrated that capsaicin has a cocarcinogenic effect on 9, 10-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumorigenesis. Our results showed that topical application of capsaicin on the dorsal skin of DMBA-initiated and TPA-promoted mice could significantly accelerate tumor formation and growth and induce more and larger skin tumors than the model group (DMBA + TPA). Moreover, capsaicin could promote TPA-induced skin hyperplasia and tumor proliferation. Mechanistic study found that inflammation-related factors cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were highly elevated by pretreatment with capsaicin, suggesting an inflammation-dependent mechanism. Furthermore, mice that were administered capsaicin exhibited significant up-regulation of phosphorylation of nuclear factor kappaB (NF-κB), Erk and p38 but had no effect on JNK. Thus, our results indicated that inflammation, Erk and P38 collectively played a crucial role in cancer-promoting effect of capsaicin on carcinogen-induced skin cancer in mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Comparison of the differences in pain and the effect of ibuprofen in reducing endodontic flare-up after single-visit root canal therapy between Uyghur and Han patients with chronic apical periodontitis].

Science.gov (United States)

Yan, Lei; Wang, Xin-Ying; Wan, Na; Wu, Pei-Ling

2017-04-01

To compare the incidence of postoperative pain of chronic periapical periodontitis patients with root canal therapy between Han and Uygur, and the effect of ibuprofen in reducing endodontic flare-up after single-visit root canal therapy between Uyghur and Han patients with chronic apical periodontitis, in order to provide a basis for clinical administration. Two hundred and fifty Uyghur and 250 Han patients with chronic apical periodontitis in their incisor, canine and premolar were collected, and randomly divided into 2 groups: experimental group and control group. After single-visit root canal therapy, Uyghur patients in the experimental group (UEG) and Han patients in the experimental group (HEG) took ibuprofen capsules according to the drug instructions; while Uyghur patients in the control group (UCG) and Han patients in the control group(HCG) took placebo capsules. Both doctors and patient kept blind from the drug capsules and group of the patients. The incidence, degree of endodontic Flare-up at 6, 12, 24, 48, 72 hours and 1 week after root canal therapy were recorded and analyzed by χ 2 test using SPSS11.0 software package. During the experiment, the incidence of E flare-up in Uygur patients was higher than in Han patients; the incidence of E flare-up in different groups in orders from high to low was: UCG>HCG>UEG>HEG. Chi-square test showed that there were significant differences between the two groups. In view of time distribution, most of flare-up happened between 24~48 hours after root canal therapy with the highest degree in all 4 groups. Regardless of the incidence or degree of flare-up, HEG and HCG were significantly greater than UEG and UCG. Ibuprofen can reduce and prevent flare-up for both Uyghur and Han patients, but it has better effect on Han patients.

Postoperative pain after endodontic retreatment: single- versus two-visit treatment.

Science.gov (United States)

Yoldas, Oguz; Topuz, Aysin; Isçi, A Sehnaz; Oztunc, Haluk

2004-10-01

The purpose of this clinical study was to determine the effect of 1- or 2-visit root canal treatment on the postoperative pain in the retreatment cases. Two hundred eighteen cases that required retreatment were included in the study. Obturated and unfilled canal space and the status of periapical tissues were evaluated according to the PAI index. The patients were subcategorized in regard to the presence or the absence of preoperative pain. Approximately half of each category was treated in 1 appointment. After removing the previous root canal obturation materials and biomechanic preparation of root canals, the teeth in the 1-visit group were obturated at the first appointment by using AH 26 sealer and laterally compacted gutta-percha, and those in the 2-visit group were medicated with calcium hydroxide-chlorhexidine combination and then closed with a temporary filling material. One week after the initial appointment, patients were asked about the occurrence of postoperative pain. The level of discomfort was rated as no pain, mild pain, moderate pain, or severe pain (flare-up). Data were statistically analyzed using the chi-squared and Fischer exact tests. Eight patients from the 1-visit group and 2 patients from the 2-visit group had flare-ups. There was a statistical difference between the groups (P endodontic treatment with intracanal medication was found to be effective in reducing postoperative pain of previously symptomatic teeth and decreased the number of flare-ups in all retreatment cases.

Chronic Oral Capsaicin Exposure During Development Leads to Adult Rats with Reduced Taste Bud Volumes.

Science.gov (United States)

Omelian, Jacquelyn M; Samson, Kaeli K; Sollars, Suzanne I

2016-09-01

Cross-sensory interaction between gustatory and trigeminal nerves occurs in the anterior tongue. Surgical manipulations have demonstrated that the strength of this relationship varies across development. Capsaicin is a neurotoxin that affects fibers of the somatosensory lingual nerve surrounding taste buds, but not fibers of the gustatory chorda tympani nerve which synapse with taste receptor cells. Since capsaicin is commonly consumed by many species, including humans, experimental use of this neurotoxin provides a naturalistic perturbation of the lingual trigeminal system. Neonatal or adults rats consumed oral capsaicin for 40 days and we examined the cross-sensory effect on the morphology of taste buds across development. Rats received moderate doses of oral capsaicin, with chronic treatments occurring either before or after taste system maturation. Tongue morphology was examined either 2 or 50 days after treatment cessation. Edema, which has been previously suggested as a cause of changes in capsaicin-related gustatory function, was also assessed. Reductions in taste bud volume occurred 50 days, but not 2 days post-treatment for rats treated as neonates. Adult rats at either time post-treatment were unaffected. Edema was not found to occur with the 5 ppm concentration of capsaicin we used. Results further elucidate the cooperative relationship between these discrete sensory systems and highlight the developmentally mediated aspect of this interaction. Chronic exposure to even moderate levels of noxious stimuli during development has the ability to impact the orosensory environment, and these changes may not be evident until long after exposure has ceased.

Ultraviolet radiation-induced lipid peroxidation in liposomal membrane: modification by capsaicin

International Nuclear Information System (INIS)

De, A.K.; Ghosh, J.J.; Mandal, T.K.

1993-01-01

Ultraviolet-radiation has been reported to cause lipid peroxidation in the liposomal membrane. In the present study, treatment with capsaicin, (8-methyl-n-vanillyl-6-nonenamide), the pungent principle of red hot pepper, was shown to modify UV-induced lipid peroxidation in the liposomal membrane. Treatment with low doses of capsaicin (less than 0.1 μg/mL of phosphatidyl choline liposome) produced a significant increase in UV-induced lipid peroxidation, while high doses (0.1-0.5 μg/mL of PC liposome) caused a significant decrease of UV-induced peroxidation

Ultraviolet radiation-induced lipid peroxidation in liposomal membrane: modification by capsaicin

Energy Technology Data Exchange (ETDEWEB)

De, A. K.; Ghosh, J. J.; Mandal, T. K. [University College of Science, Department of Biochemistry, 35 Ballygunge Circular Road, Calcutta 700-019 (India)

1993-07-01

Ultraviolet-radiation has been reported to cause lipid peroxidation in the liposomal membrane. In the present study, treatment with capsaicin, (8-methyl-n-vanillyl-6-nonenamide), the pungent principle of red hot pepper, was shown to modify UV-induced lipid peroxidation in the liposomal membrane. Treatment with low doses of capsaicin (less than 0.1 μg/mL of phosphatidyl choline liposome) produced a significant increase in UV-induced lipid peroxidation, while high doses (0.1-0.5 μg/mL of PC liposome) caused a significant decrease of UV-induced peroxidation.

Repeated oral administration of capsaicin increases anxiety-like ...

Indian Academy of Sciences (India)

2013-07-22

Jul 22, 2013 ... open arms was reduced in capsaicin-treated rats compared with control rats. In forced ... TRPV1 receptors was also observed in the prefrontal cortex, nucleus ... its implication in the control of psycho-motor activities. Indeed ...

KEPLER FLARES. II. THE TEMPORAL MORPHOLOGY OF WHITE-LIGHT FLARES ON GJ 1243

Energy Technology Data Exchange (ETDEWEB)

Davenport, James R. A.; Hawley, Suzanne L.; Johnson, Emily C.; Peraza, Jesus; Jansen, Tiffany C.; Larsen, Daniel M. [Department of Astronomy, University of Washington, P.O. Box 351580, Seattle, WA 98195 (United States); Hebb, Leslie [Department of Physics, Hobart and William Smith Colleges, 300 Pulteney Street, Geneva, NY 14456 (United States); Wisniewski, John P.; Malatesta, Michael; Keil, Marcus; Silverberg, Steven M.; Scheffler, Matthew S.; Berdis, Jodi R. [HL Dodge Department of Physics and Astronomy, University of Oklahoma, 440 W Brooks Street, Norman, OK 73019 (United States); Kowalski, Adam F. [NASA Goddard Space Flight Center, Code 671, Greenbelt, MD 20771 (United States); Hilton, Eric J., E-mail: jrad@astro.washington.edu [Universe Sandbox, 911 E. Pike Street #333, Seattle, WA 98122 (United States)

2014-12-20

We present the largest sample of flares ever compiled for a single M dwarf, the active M4 star GJ 1243. Over 6100 individual flare events, with energies ranging from 10{sup 29} to 10{sup 33} erg, are found in 11 months of 1 minute cadence data from Kepler. This sample is unique for its completeness and dynamic range. We have developed automated tools for finding flares in short-cadence Kepler light curves, and performed extensive validation and classification of the sample by eye. From this pristine sample of flares we generate a median flare template. This template shows that two exponential cooling phases are present during the white-light flare decay, providing fundamental constraints for models of flare physics. The template is also used as a basis function to decompose complex multi-peaked flares, allowing us to study the energy distribution of these events. Only a small number of flare events are not well fit by our template. We find that complex, multi-peaked flares occur in over 80% of flares with a duration of 50 minutes or greater. The underlying distribution of flare durations for events 10 minutes and longer appears to follow a broken power law. Our results support the idea that sympathetic flaring may be responsible for some complex flare events.

KEPLER FLARES. II. THE TEMPORAL MORPHOLOGY OF WHITE-LIGHT FLARES ON GJ 1243

International Nuclear Information System (INIS)

Davenport, James R. A.; Hawley, Suzanne L.; Johnson, Emily C.; Peraza, Jesus; Jansen, Tiffany C.; Larsen, Daniel M.; Hebb, Leslie; Wisniewski, John P.; Malatesta, Michael; Keil, Marcus; Silverberg, Steven M.; Scheffler, Matthew S.; Berdis, Jodi R.; Kowalski, Adam F.; Hilton, Eric J.

2014-01-01

We present the largest sample of flares ever compiled for a single M dwarf, the active M4 star GJ 1243. Over 6100 individual flare events, with energies ranging from 10 29 to 10 33 erg, are found in 11 months of 1 minute cadence data from Kepler. This sample is unique for its completeness and dynamic range. We have developed automated tools for finding flares in short-cadence Kepler light curves, and performed extensive validation and classification of the sample by eye. From this pristine sample of flares we generate a median flare template. This template shows that two exponential cooling phases are present during the white-light flare decay, providing fundamental constraints for models of flare physics. The template is also used as a basis function to decompose complex multi-peaked flares, allowing us to study the energy distribution of these events. Only a small number of flare events are not well fit by our template. We find that complex, multi-peaked flares occur in over 80% of flares with a duration of 50 minutes or greater. The underlying distribution of flare durations for events 10 minutes and longer appears to follow a broken power law. Our results support the idea that sympathetic flaring may be responsible for some complex flare events

Single-sweep spectral analysis of contact heat evoked potentials

DEFF Research Database (Denmark)

Hansen, Tine M; Graversen, Carina; Frøkjaer, Jens B

2015-01-01

AIMS: The cortical response to nociceptive thermal stimuli recorded as contact heat evoked potentials (CHEPs) may be altered by morphine. However, previous studies have averaged CHEPs over multiple stimuli, which are confounded by jitter between sweeps. Thus, the aim was to assess single-sweep ch......AIMS: The cortical response to nociceptive thermal stimuli recorded as contact heat evoked potentials (CHEPs) may be altered by morphine. However, previous studies have averaged CHEPs over multiple stimuli, which are confounded by jitter between sweeps. Thus, the aim was to assess single...... by 13% (P = 0.04) and 9% (P = 0.007), while the beta and gamma bands were increased by 10% (P = 0.006) and 24% (P = 0.04). CONCLUSION: The decreases in the delta and theta band are suggested to represent a decrease in the pain specific morphology of the CHEPs, which indicates a diminished pain response...

Transdermal and Topical Drug Administration in the Treatment of Pain

Directory of Open Access Journals (Sweden)

Wojciech Leppert

2018-03-01

Full Text Available The comprehensive treatment of pain is multidimodal, with pharmacotherapy playing a key role. An effective therapy for pain depends on the intensity and type of pain, the patients’ age, comorbidities, and appropriate choice of analgesic, its dose and route of administration. This review is aimed at presenting current knowledge on analgesics administered by transdermal and topical routes for physicians, nurses, pharmacists, and other health care professionals dealing with patients suffering from pain. Analgesics administered transdermally or topically act through different mechanisms. Opioids administered transdermally are absorbed into vessels located in subcutaneous tissue and, subsequently, are conveyed in the blood to opioid receptors localized in the central and peripheral nervous system. Non–steroidal anti–inflammatory drugs (NSAIDs applied topically render analgesia mainly through a high concentration in the structures of the joint and a provision of local anti–inflammatory effects. Topically administered drugs such as lidocaine and capsaicin in patches, capsaicin in cream, EMLA cream, and creams containing antidepressants (i.e., doxepin, amitriptyline act mainly locally in tissues through receptors and/or ion channels. Transdermal and topical routes offer some advantages over systemic analgesic administration. Analgesics administered topically have a much better profile for adverse effects as they relieve local pain with minimal systemic effects. The transdermal route apart from the above-mentioned advantages and provision of long period of analgesia may be more convenient, especially for patients who are unable to take drugs orally. Topically and transdermally administered opioids are characterised by a lower risk of addiction compared to oral and parenteral routes.

Sex differences in the neural representation of pain unpleasantness.

Science.gov (United States)

Girard-Tremblay, Lydia; Auclair, Vincent; Daigle, Kathya; Léonard, Guillaume; Whittingstall, Kevin; Goffaux, Philippe

2014-08-01

Sex differences in pain perception are still poorly understood, but they may be related to the way the brains of men and women respond to the affective dimensions of pain. Using a matched pain intensity paradigm, where pain intensity was kept constant across participants but pain unpleasantness was left free to vary among participants, we studied the relationship between pain unpleasantness and pain-evoked brain activity in healthy men and women separately. Experimental pain was provoked using transcutaneous electrical stimulation of the sural nerve while pain-related brain activity was measured using somatosensory-evoked brain potentials with source localization. Cardiac responses to pain were also measured using electrocardiac recordings. Results revealed that subjective pain unpleasantness was strongly associated with increased perigenual anterior cingulate cortex activity in women, whereas it was strongly associated with decreased ventromedial prefrontal cortex activity in men. Only ventromedial prefrontal cortex deactivations in men were additionally associated with increased autonomic cardiac arousal. These results suggest that in order to deal with pain's objectionable properties, men preferentially deactivate prefrontal suppression regions, leading to the mobilization of threat-control circuits, whereas women recruit well-known emotion-processing areas of the brain. This article presents neuroimaging findings demonstrating that subjective pain unpleasantness ratings are associated with different pain-evoked brain responses in men and women, which has potentially important implications regarding sex differences in the risk of developing chronic pain. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

Flare Observations

Directory of Open Access Journals (Sweden)

Benz Arnold O.

2008-02-01

Full Text Available Solar flares are observed at all wavelengths from decameter radio waves to gamma-rays at 100 MeV. This review focuses on recent observations in EUV, soft and hard X-rays, white light, and radio waves. Space missions such as RHESSI, Yohkoh, TRACE, and SOHO have enlarged widely the observational base. They have revealed a number of surprises: Coronal sources appear before the hard X-ray emission in chromospheric footpoints, major flare acceleration sites appear to be independent of coronal mass ejections (CMEs, electrons, and ions may be accelerated at different sites, there are at least 3 different magnetic topologies, and basic characteristics vary from small to large flares. Recent progress also includes improved insights into the flare energy partition, on the location(s of energy release, tests of energy release scenarios and particle acceleration. The interplay of observations with theory is important to deduce the geometry and to disentangle the various processes involved. There is increasing evidence supporting reconnection of magnetic field lines as the basic cause. While this process has become generally accepted as the trigger, it is still controversial how it converts a considerable fraction of the energy into non-thermal particles. Flare-like processes may be responsible for large-scale restructuring of the magnetic field in the corona as well as for its heating. Large flares influence interplanetary space and substantially affect the Earth’s lower ionosphere. While flare scenarios have slowly converged over the past decades, every new observation still reveals major unexpected results, demonstrating that solar flares, after 150 years since their discovery, remain a complex problem of astrophysics including major unsolved questions.

Flare Observations

Science.gov (United States)

Benz, Arnold O.

2017-12-01

Solar flares are observed at all wavelengths from decameter radio waves to gamma-rays beyond 1 GeV. This review focuses on recent observations in EUV, soft and hard X-rays, white light, and radio waves. Space missions such as RHESSI, Yohkoh, TRACE, SOHO, and more recently Hinode and SDO have enlarged widely the observational base. They have revealed a number of surprises: Coronal sources appear before the hard X-ray emission in chromospheric footpoints, major flare acceleration sites appear to be independent of coronal mass ejections, electrons, and ions may be accelerated at different sites, there are at least 3 different magnetic topologies, and basic characteristics vary from small to large flares. Recent progress also includes improved insights into the flare energy partition, on the location(s) of energy release, tests of energy release scenarios and particle acceleration. The interplay of observations with theory is important to deduce the geometry and to disentangle the various processes involved. There is increasing evidence supporting magnetic reconnection as the basic cause. While this process has become generally accepted as the trigger, it is still controversial how it converts a considerable fraction of the energy into non-thermal particles. Flare-like processes may be responsible for large-scale restructuring of the magnetic field in the corona as well as for its heating. Large flares influence interplanetary space and substantially affect the Earth's ionosphere. Flare scenarios have slowly converged over the past decades, but every new observation still reveals major unexpected results, demonstrating that solar flares, after 150 years since their discovery, remain a complex problem of astrophysics including major unsolved questions.

Regulation of early and delayed radiation responses in rat small intestine by capsaicin-sensitive nerves

International Nuclear Information System (INIS)

Wang Junru; Zheng Huaien; Kulkarni, Ashwini; Ou Xuemei; Hauer-Jensen, Martin

2006-01-01

Purpose: Mast cells protect against the early manifestations of intestinal radiation toxicity, but promote chronic intestinal wall fibrosis. Intestinal sensory nerves are closely associated with mast cells, both anatomically and functionally, and serve an important role in the regulation of mucosal homeostasis. This study examined the effect of sensory nerve ablation on the intestinal radiation response in an established rat model. Methods and Materials: Rats underwent sensory nerve ablation with capsaicin or sham ablation. Two weeks later, a localized segment of ileum was X-irradiated or sham irradiated. Structural, cellular, and molecular changes were examined 2 weeks (early injury) and 26 weeks (chronic injury) after irradiation. The mast cell dependence of the effect of sensory nerve ablation on intestinal radiation injury was assessed using c-kit mutant (Ws/Ws) mast cell-deficient rats. Results: Capsaicin treatment caused a baseline reduction in mucosal mast cell density, crypt cell proliferation, and expression of substance P and calcitonin gene-related peptide, two neuropeptides released by sensory neurons. Sensory nerve ablation strikingly exacerbated early intestinal radiation toxicity (loss of mucosal surface area, inflammation, intestinal wall thickening), but attenuated the development of chronic intestinal radiation fibrosis (collagen I accumulation and transforming growth factor β immunoreactivity). In mast cell-deficient rats, capsaicin treatment exacerbated postradiation epithelial injury (loss of mucosal surface area), but none of the other aspects of radiation injury were affected by capsaicin treatment. Conclusions: Ablation of capsaicin-sensitive enteric neurons exacerbates early intestinal radiation toxicity, but attenuates development of chronic fibroproliferative changes. The effect of capsaicin treatment on the intestinal radiation response is partly mast cell dependent

On the possible cyclic recurrence of flare activity of flare stars in the pleiades

International Nuclear Information System (INIS)

Mirzoyan, L.V.; Oganyan, G.V.

1977-01-01

The flare activity of flare stars in Pleiades is investigated. It is shown that according to flare statistics only one half of the probable Pleiades members with low luminosities have flare activity throughout the observation period. Two assumptions are suggested to explain this contradiction with the concept on the evolutionary importance of the flare star phase which all the dwarf stars go through: cyclic nature of the flare activity and large dispersion in flare activity phase durations for equally luminous stars. Certain evidences to support cyclic flare activity assumption are adduced

Modulation of Itch by Conditioning Itch and Pain Stimulation in Healthy Humans.

Science.gov (United States)

Andersen, Hjalte H; van Laarhoven, Antoinette I M; Elberling, Jesper; Arendt-Nielsen, Lars

2017-12-01

Little is known about endogenous descending control of itch. In chronic pain, descending pain inhibition is reduced as signified by lowered conditioned pain modulation. There are indications that patients with chronic itch may also exhibit reduced endogenous descending inhibition of itch and pain. This study aimed to investigate whether and the extent to which itch can be modulated by conditioning itch and pain stimuli. Twenty-six healthy volunteers participated. The study consisted of 5 conditions designed to systematically assess endogenous modulation of itch or pain: 1) itch-induced modulation of contralateral itch, 2) pain-induced modulation of contralateral itch, 3) pain-induced modulation of ipsilateral itch, 4) pain-induced modulation of contralateral pain, and 5) itch-induced modulation of contralateral pain. Conditioning stimuli were cold pressor-induced pain and histamine-evoked itch, whereas the test stimuli were electrical stimulation paradigms designed to evoke itch or pain. Pain was significantly reduced (conditioned pain modulation-effect) by the conditioning pain stimulus (P modulation-effect) by contra- as well as ipsilateral applied conditioning pain (both P modulation of itch as well as pain in humans. Future studies addressing potential aberrations in pain-evoked descending modulation of itch in chronic itch patients are warranted. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

Vasomotor response to cold stimulation in human capsaicin-induced hyperalgesic area.

Science.gov (United States)

Pud, Dorit; Andersen, Ole Kaeseler; Arendt-Nielsen, Lars; Eisenberg, Elon; Yarnitsky, David

2005-07-01

Cooling the skin induces sympathetically driven vasoconstriction, with some vasoparalytic dilatation at the lowest temperatures. Neurogenic inflammation, on the other hand, entails vasodilatation. In this study we investigated the balance between vasoconstriction and vasodilatation in an area of experimentally induced secondary hyperalgesia (2 degrees HA), in response to low-temperature stimulations. Fourteen healthy volunteers were exposed to three 30-s long cold stimuli (20, 10, and 0 degrees C) applied, at three adjacent sites, before (baseline) and 8 min after intradermal injection of 50 microg capsaicin to the volar forearm. The cold stimuli were applied distally to the injection site within the 2 degrees HA. Blood flux (BF) and skin temperatures were measured at four different regions (proximally, and distally to the capsaicin injection and at the 0, 10, and 20 degrees C thermode sites) all within the 2 degrees HA. The vascular measurements were conducted five times. Results showed a marked increase in BF after baseline cold stimulation (Peffect (elevated BF) was found following the capsaicin injection compared with baseline for all regions (Pcooled area was dilated by 450+/-5.1%; The vasoconstrictive effect for the 10 and 20 degrees C did not overcome the capsaicin vasodilatation, but did reduce it, with dilatation of 364+/-7.0% and 329+/-7.3%, respectively. For 0 degrees C, a dilatation of 407+/-6.5% was seen. It is concluded that in this experimental model, and potentially in the equivalent clinical syndromes, vasodilatation induced by the inflammation is only slightly reduced by cold stimulation such that it is still dominant, despite some cold-induced vasoconstriction.

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

DEFF Research Database (Denmark)

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

2013-01-01

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

The effects of cellulase on capsaicin production in freely suspended cells and immobilized cell cultures of capsicum annuum

International Nuclear Information System (INIS)

Islek, C.

2014-01-01

The effect of different concentrations of cellulase on the production of capsaicin in freely suspended cell and immobilized cell cultures of Kahramanmara pepper seeds (Capsicum annuum L.) were studied. Calluses were obtained from in vitro germinated hypocotyl explants of pepper seedlings and cell suspensions were prepared from these calluses. Immobilized cell suspension cultures with calcium alginate and free cell suspension cultures were obtained by using cell suspensions. Elicitor such as cellulase (5-30 micro g/ml), was applied both for the free and immobilized cell suspensions and control group without elicitor was prepared. The concentration of capsaicin in freely suspended cells, immobilized cells and their filtrates were identified by HPLC after extraction with ethyl acetate. It was found that the immobilization process had an increasing effect on the capsaicin accumulation. The concentration of capsaicin in the immobilized cells for both control groups and elicitor added samples was higher than the free cells. In general, capsaicin concentration in the filtrate for free cells was higher than the immobilized cells. When all the cellulase and the sampling hours were compared, the highest capsaicin concentration for the immobilized cells was determined as 362,91 micro g/ml f.w. at the 24th hour for 30 micro g/ml cellulase applied samples. (author)

Usefulness of laser-evoked potentials and quantitative sensory testing in the diagnosis of neuropathic spinal cord injury pain: a multiple case study.

Science.gov (United States)

Landmann, G; Berger, M F; Stockinger, L; Opsommer, E

2017-06-01

A retrospective study. The aim of this study was to investigate the contribution of laser-evoked potentials (LEPs) and quantitative sensory testing (QST) to the diagnosis of neuropathic pain in patients with spinal cord injury (SCI) and inconclusive magnetic resonance imaging (MRI) findings. A multidisciplinary pain center. QST (DFNS protocol) and Tm-YAG-laser stimulation of the skin were applied within the pain site corresponding with dermatomes of altered sensation. Available MRI scans were reviewed. Thirteen individuals (50±16 years) with SCI were examined. In four cases with no detectable neural lesion on MRI, all QST but three LEP were abnormal. In four patients with poorly defined spinal lesion on MRI, all QST but three LEP only were abnormal. In four cases where pain was not matching adequately with MRI lesions, all patients had abnormal LEP and QST. In one patient showing a spinal cord atrophy, LEP was normal but QST was abnormal. Findings supported the diagnoses at-level (n=5) and below-level (n=8) SCI pain. Spinothalamic tract function assessed by LEP was normal in three cases, but QST was abnormal in all cases. As QST is a psychophysical examination depending on patient cooperation, we suggest that the combination of QST and LEP might be a valuable diagnostic tool to detect lesions of the somatosensory system in a subgroup of patients with neuropathic spinal cord injury pain and inconclusive MRI findings.

Assessment of pain sensitivity in patients with deep bite and sex- and age-matched controls

DEFF Research Database (Denmark)

Sonnesen, Ane Liselotte; Svensson, Peter

2011-01-01

AIMS: To compare pain sensitivity between deep bite patients and a sex- and age-matched control group with normal occlusion. METHODS: Pain sensitivity was assessed by injections of the excitatory amino acid glutamate into the masseter and brachioradialis muscles. Intensity of glutamate-evoked pai...... of gender-related differences in somatosensory sensitivity and for the first time indicate that subjects with deep bite may be more sensitive to glutamate-evoked pain and thermal stimuli.......AIMS: To compare pain sensitivity between deep bite patients and a sex- and age-matched control group with normal occlusion. METHODS: Pain sensitivity was assessed by injections of the excitatory amino acid glutamate into the masseter and brachioradialis muscles. Intensity of glutamate-evoked pain...

Implications of NRL/ATM solar flare observations on flare theories

International Nuclear Information System (INIS)

Cheng, C.C.; Spicer, D.S.

1975-01-01

During the Skylab mission, many solar flares were observed with the NRL XUV spectroheliogram in the wavelength region from 150 to 650 A. Because of its high spatial resolution (approximately 2ins.) the three-dimensional structures of the flare emission regions characterized by temperatures from 10 4 K to 20 x 10 6 K can be resolved. Thus the spatial relationship between the relatively cool plasma and the hot plasma components of a flare, and the associated magnetic field structure can be inferred. The implications for various flare models are discussed. (Auth.)

Premature infants display increased noxious-evoked neuronal activity in the brain compared to healthy age-matched term-born infants.

Science.gov (United States)

Slater, Rebeccah; Fabrizi, Lorenzo; Worley, Alan; Meek, Judith; Boyd, Stewart; Fitzgerald, Maria

2010-08-15

This study demonstrates that infants who are born prematurely and who have experienced at least 40days of intensive or special care have increased brain neuronal responses to noxious stimuli compared to healthy newborns at the same postmenstrual age. We have measured evoked potentials generated by noxious clinically-essential heel lances in infants born at term (8 infants; born 37-40weeks) and in infants born prematurely (7 infants; born 24-32weeks) who had reached the same postmenstrual age (mean age at time of heel lance 39.2+/-1.2weeks). These noxious-evoked potentials are clearly distinguishable from shorter latency potentials evoked by non-noxious tactile sensory stimulation. While the shorter latency touch potentials are not dependent on the age of the infant at birth, the noxious-evoked potentials are significantly larger in prematurely-born infants. This enhancement is not associated with specific brain lesions but reflects a functional change in pain processing in the brain that is likely to underlie previously reported changes in pain sensitivity in older ex-preterm children. Our ability to quantify and measure experience-dependent changes in infant cortical pain processing will allow us to develop a more rational approach to pain management in neonatal intensive care. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Differential bitterness in capsaicin, piperine, and ethanol associates with polymorphisms in multiple bitter taste receptor genes.

Science.gov (United States)

Nolden, Alissa A; McGeary, John E; Hayes, John E

2016-03-15

To date, the majority of research exploring associations with genetic variability in bitter taste receptors has understandably focused on compounds and foods that are predominantly or solely perceived as bitter. However, other chemosensory stimuli are also known to elicit bitterness as a secondary sensation. Here we investigated whether TAS2R variation explains individual differences in bitterness elicited by chemesthetic stimuli, including capsaicin, piperine and ethanol. We confirmed that capsaicin, piperine and ethanol elicit bitterness in addition to burning/stinging sensations. Variability in perceived bitterness of capsaicin and ethanol were significantly associated with TAS2R38 and TAS2R3/4/5 diplotypes. For TAS2R38, PAV homozygotes perceived greater bitterness from capsaicin and ethanol presented on circumvallate papillae, compared to heterozygotes and AVI homozygotes. For TAS2R3/4/5, CCCAGT homozygotes rated the greatest bitterness, compared to heterozygotes and TTGGAG homozygotes, for both ethanol and capsaicin when presented on circumvallate papillae. Additional work is needed to determine how these and other chemesthetic stimuli differ in bitterness perception across concentrations and presentation methods. Furthermore, it would be beneficial to determine which TAS2R receptors are activated in vitro by chemesthetic compounds. Copyright © 2016. Published by Elsevier Inc.

Antilithogenic influence of dietary capsaicin and curcumin during experimental induction of cholesterol gallstone in mice.

Science.gov (United States)

Shubha, Malenahalli C; Reddy, Raghunatha R L; Srinivasan, Krishnapura

2011-04-01

Spice bioactive compounds, capsaicin and curcumin, were both individually and in combination examined for antilithogenic potential during experimental induction of cholesterol gallstones in mice. Cholesterol gallstones were induced by feeding mice a high-cholesterol (0.5%) diet for 10 weeks. Groups of mice were maintained on a lithogenic diet that was supplemented with 0.015% capsaicin/0.2% curcumin/0.015% capsaicin + 0.2% curcumin. The lithogenic diet that contained capsaicin, curcumin, or their combination reduced the incidence of cholesterol gallstones by 50%, 66%, and 56%, respectively, compared with lithogenic control. This was accompanied by reduced biliary cholesterol and a marginal increase in phospholipid in these spice-fed groups. Increased cholesterol saturation index and cholesterol : phospholipid ratio in the bile caused by the lithogenic diet was countered by the dietary spice compounds. The antilithogenic influence of spice compounds was attributable to the cholesterol-lowering effect of these dietary spices in blood and liver, as well as a moderate increase in phospholipids. Decreased activities of hepatic glutathione reductase and glutathione-S-transferase caused by the lithogenic diet were countered by the combination of capsaicin and curcumin. The increased lipid peroxidation and the decreased concentration of ascorbic acid in the liver that was caused by the lithogenic diet was countered by the dietary spice compounds, individually or in combination. Thus, while the capsaicin and curcumin combination did not have an additive influence in reducing the incidence of cholesterol gallstones in mice, their combination nevertheless was more beneficial in enhancing the activity of hepatic antioxidant enzyme ─ glutathione reductase in the lithogenic situation. The antioxidant effects of dietary spice compounds are consistent with the observed reduction in cholesterol gallstones formed under lithogenic condition.

Statistical study of spatio-temporal distribution of precursor solar flares associated with major flares

Science.gov (United States)

Gyenge, N.; Ballai, I.; Baranyi, T.

2016-07-01

The aim of the present investigation is to study the spatio-temporal distribution of precursor flares during the 24 h interval preceding M- and X-class major flares and the evolution of follower flares. Information on associated (precursor and follower) flares is provided by Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI). Flare list, while the major flares are observed by the Geostationary Operational Environmental Satellite (GOES) system satellites between 2002 and 2014. There are distinct evolutionary differences between the spatio-temporal distributions of associated flares in about one-day period depending on the type of the main flare. The spatial distribution was characterized by the normalized frequency distribution of the quantity δ (the distance between the major flare and its precursor flare normalized by the sunspot group diameter) in four 6 h time intervals before the major event. The precursors of X-class flares have a double-peaked spatial distribution for more than half a day prior to the major flare, but it changes to a lognormal-like distribution roughly 6 h prior to the event. The precursors of M-class flares show lognormal-like distribution in each 6 h subinterval. The most frequent sites of the precursors in the active region are within a distance of about 0.1 diameter of sunspot group from the site of the major flare in each case. Our investigation shows that the build-up of energy is more effective than the release of energy because of precursors.

Alterations of autonomic nervous activity and energy metabolism by capsaicin ingestion during aerobic exercise in healthy men.

Science.gov (United States)

Shin, Ki Ok; Moritani, Toshio

2007-04-01

We investigated whether capsaicin ingestion (150 mg) enhances substrate oxidation associated with thermogenic sympathetic activity as an energy metabolic modulator without causing prolongation of the cardiac OT interval during aerobic exercise in humans. Ten healthy males [24.4 (4.3) y] volunteered for this study. The cardiac autonomic nervous activities evaluated by means of heart rate variability of power spectral analysis, energy metabolism, and ECG QT interval were continuously measured during 5-min rest and 30-min exercise at 50% of maximal ventilatory threshold (50% VT(max)) on a stationary ergometer with placebo or capsaicin oral administration chosen at random. The results indicated that there were no significant differences in heart rate during rest or exercise between the two trials. Autonomic nervous activity increased in the capsaicin tablet trial during exercise, but the difference did not reach statistical significance. Capsaicin, however, significantly induced a lower respiratory gas exchange ratio [0.92 (0.02) vs. 0.94 (0.02), means (SE), p means (SE), p < 0.05] during exercise. On the other hand, the data on the cardiac OT interval showed no significant difference, indicating that oral administration of capsaicin did not cause any adverse effect on cardiac depolarization-repolarization. In conclusion, it may be considered that capsaicin consumption 1 h before low intensity exercise (50% VT(max)) is a valuable supplement for the treatment of individuals with hyperlipidemia and/or obesity because it improves lipolysis without any adverse effects on the cardiac depolarization and repolarization process.

Flare stars in Pleiades. 6

International Nuclear Information System (INIS)

Mirzoyan, L.V.; Chavushyan, O.S.; Oganyan, G.B.; Ambaryan, V.V.; Garibdzhanyan, A.T.; Melikyan, N.D.; Natsvlishvili, R.Sh.; AN Gruzinskoj SSR, Abastumani. Abastumanskaya Astrofizicheskaya Observatoriya)

1981-01-01

The results of photographic observations of stellar flares in the Pleiades region carried out at the Byurakan and Abastumani astrophysical observatories during 1976-1979 are given. On the basis of these observations 17 new flare stars have been found. Total number of all known flare stars in the Pleiades region on 1 June 1980 reached 524, and the number of all flares-1244. The observational data on distribution of flare stars according to the observed flares is satisfactorily represented by the average frequency function introduced by V.A.Ambartsumian. The total number of the flare stars in the Pleiades is of the order of 1100. Using three telescopes, synchronous photographic observations of stellar flares in Pleiades in U, B, V, system are carried out. The colour indices U-B and B-V of stellar flares in periods including the maximum of the flare slightly differ from that of photoelectrically defined for flares of UV Ceti type stars, which testifies the physical relationship of flare stars in Pleiades and in the vicinity of the Sun [ru

Temporal and Periodic Variations of Sunspot Counts in Flaring and Non-Flaring Active Regions

Science.gov (United States)

Kilcik, A.; Yurchyshyn, V.; Donmez, B.; Obridko, V. N.; Ozguc, A.; Rozelot, J. P.

2018-04-01

We analyzed temporal and periodic variations of sunspot counts (SSCs) in flaring (C-, M-, or X-class flares), and non-flaring active regions (ARs) for nearly three solar cycles (1986 through 2016). Our main findings are as follows: i) temporal variations of monthly means of the daily total SSCs in flaring and non-flaring ARs behave differently during a solar cycle and the behavior varies from one cycle to another; during Solar Cycle 23 temporal SSC profiles of non-flaring ARs are wider than those of flaring ARs, while they are almost the same during Solar Cycle 22 and the current Cycle 24. The SSC profiles show a multi-peak structure and the second peak of flaring ARs dominates the current Cycle 24, while the difference between peaks is less pronounced during Solar Cycles 22 and 23. The first and second SSC peaks of non-flaring ARs have comparable magnitude in the current solar cycle, while the first peak is nearly absent in the case of the flaring ARs of the same cycle. ii) Periodic variations observed in the SSCs profiles of flaring and non-flaring ARs derived from the multi-taper method (MTM) spectrum and wavelet scalograms are quite different as well, and they vary from one solar cycle to another. The largest detected period in flaring ARs is 113± 1.6 days while we detected much longer periodicities (327± 13, 312 ± 11, and 256± 8 days) in the non-flaring AR profiles. No meaningful periodicities were detected in the MTM spectrum of flaring ARs exceeding 55± 0.7 days during Solar Cycles 22 and 24, while a 113± 1.3 days period was detected in flaring ARs of Solar Cycle 23. For the non-flaring ARs the largest detected period was only 31± 0.2 days for Cycle 22 and 72± 1.3 days for the current Cycle 24, while the largest measured period was 327± 13 days during Solar Cycle 23.

Influence of glutamate-evoked pain and sustained elevated muscle activity on blood oxygenation in the human masseter muscle.

Science.gov (United States)

Suzuki, Shunichi; Arima, Taro; Kitagawa, Yoshimasa; Svensson, Peter; Castrillon, Eduardo

2017-12-01

This study aimed to investigate the effect of glutamate-evoked masseter muscle pain on intramuscular oxygenation during rest and sustained elevated muscle activity (SEMA). Seventeen healthy individuals participated in two sessions in which they were injected with glutamate and saline in random order. Each session was divided into three, 10-min periods. During the first (period 1) and the last (period 3) 10-min periods, participants performed five intercalated 1-min bouts of masseter SEMA with 1-min periods of 'rest'. At onset of the second 10-min period, glutamate (0.5 ml, 1 M; Ajinomoto, Tokyo, Japan) or isotonic saline (0.5 ml; 0.9%) was injected into the masseter muscle and the participants kept the muscle relaxed in a resting position for 10 min (period 2). The hemodynamic characteristics of the masseter muscle were recorded simultaneously during the experiment by a laser blood-oxygenation monitor. The results demonstrated that glutamate injections caused significant levels of self-reported pain in the masseter muscle; however, this nociceptive input did not have robust effects on intramuscular oxygenation during rest or SEMA tasks. Interestingly, these findings suggest an uncoupling between acute nociceptive activity and hemodynamic parameters in both resting and low-level active jaw muscles. Further studies are needed to explore the pathophysiological significance of blood-flow changes for persistent jaw-muscle pain conditions. © 2017 Eur J Oral Sci.

Solar Flares: Magnetohydrodynamic Processes

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Kazunari Shibata

2011-12-01

Full Text Available This paper outlines the current understanding of solar flares, mainly focused on magnetohydrodynamic (MHD processes responsible for producing a flare. Observations show that flares are one of the most explosive phenomena in the atmosphere of the Sun, releasing a huge amount of energy up to about 10^32 erg on the timescale of hours. Flares involve the heating of plasma, mass ejection, and particle acceleration that generates high-energy particles. The key physical processes for producing a flare are: the emergence of magnetic field from the solar interior to the solar atmosphere (flux emergence, local enhancement of electric current in the corona (formation of a current sheet, and rapid dissipation of electric current (magnetic reconnection that causes shock heating, mass ejection, and particle acceleration. The evolution toward the onset of a flare is rather quasi-static when free energy is accumulated in the form of coronal electric current (field-aligned current, more precisely, while the dissipation of coronal current proceeds rapidly, producing various dynamic events that affect lower atmospheres such as the chromosphere and photosphere. Flares manifest such rapid dissipation of coronal current, and their theoretical modeling has been developed in accordance with observations, in which numerical simulations proved to be a strong tool reproducing the time-dependent, nonlinear evolution of a flare. We review the models proposed to explain the physical mechanism of flares, giving an comprehensive explanation of the key processes mentioned above. We start with basic properties of flares, then go into the details of energy build-up, release and transport in flares where magnetic reconnection works as the central engine to produce a flare.

Modulation of laser-evoked potentials and pain perception by transcutaneous electrical nerve stimulation (TENS): a placebo-controlled study in healthy volunteers.

Science.gov (United States)

Vassal, François; Créac'h, C; Convers, Ph; Laurent, B; Garcia-Larrea, L; Peyron, R

2013-09-01

To investigate the effects of transcutaneous electrical nerve stimulation (TENS) on brain nociceptive responses (laser-evoked potentials, LEPs) and pain perception. Twenty healthy subjects were included. Nociceptive CO(2)-laser pulses were sequentially delivered to the dorsum of both feet. The amplitude of LEPs and nociceptive thresholds were collected in three consecutive conditions: T1: "sham" TENS (2 Hz/low-intensity) positioned heterotopically, over the left thigh; T2: "active" TENS (120 Hz/low-intensity) applied homotopically, over the left common peroneal nerve; and T3: "sham" TENS (replication of condition T1). Compared with "sham" TENS, "active" TENS significantly decreased the LEPs amplitude. This effect was observed exclusively when "active" TENS was applied ipsilaterally to the painful stimulus. Nociceptive thresholds increased with sessions in both limbs, but the increase observed during the "active" condition of TENS (T2) exceeded significantly that observed during the condition T3 only on the foot ipsilateral to TENS. Compared with a credible placebo TENS, high-frequency TENS induced a significant attenuation of both the acute pain and LEPs induced by noxious stimuli applied on the same dermatome. This modulation of subjective and objective concomitants of pain processing reflects a real neurophysiological TENS-related effect on nociceptive transmission. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Models for stellar flares

International Nuclear Information System (INIS)

Cram, L.E.; Woods, D.T.

1982-01-01

We study the response of certain spectral signatures of stellar flares (such as Balmer line profiles and the broad-band continuum) to changes in atmospheric structure which might result from physical processes akin to those thought to occur in solar flares. While each physical process does not have a unique signature, we can show that some of the observed properties of stellar flares can be explained by a model which involves increased pressures and temperatures in the flaring stellar chromosphere. We suggest that changes in stellar flare area, both with time and with depth in the atmosphere, may play an important role in producing the observed flare spectrum

Flare stars in Pleiades. 5

International Nuclear Information System (INIS)

Mirzoyan, L.V.; Chavushyan, O.S.; Erastova, L.K.; Oganyan, G.B.; Melikyan, N.D.; Natsvlishvili, R.Sh.; Tsvetkov, M.K.

1977-01-01

The results of photographic observations of stellar flares in the Pleiades region made in the Byurakan and Abastumany astrophysical observatories in 1973-1974 are presented. The observations and revisions of the pictures taken earlier helped to detect 20 new flare stars and 62 repeated flares of flare stars known before. Two-colour photographic and UV observation of 21 flares were carried out. The observation data point to considerable differences in the mean frequency of flares of various flare stars in the Pleiades

Post-treatment pain in teeth with primary infections

OpenAIRE

Jesus Djalma Pécora; Cynthia Rodrigues de Araújo Estrela; Orlando Aguirre Guedes; Aldo Brugnera Junior; Carlos Estrela

2008-01-01

Objective: The purpose of this assay was to evaluate longitudinal studies about the pain after endodontic treatment, with primary infection, using a systematic review. Methods: A MEDLINE search strategy was developed to identify articles using the following uniterms: endodontic(s) and pulpal pain, endodontic(s) and periapical pain, endodontic(s) and symptom, endodontic(s) and flare-ups, endodontic(s) pain and post-treatment, endodontic(s) and inter-appointment/interappointment. The search inc...

Development of 68Ga-SCN-DOTA-Capsaicin as an Imaging Agent Targeting Apoptosis and Cell Cycle Arrest in Breast Cancer.

Science.gov (United States)

Lee, Jun Young; Lee, Sang-Yeun; Kim, Gun Gyun; Hur, Min Goo; Yang, Seung Dae; Park, Jeong-Hoon; Kim, Sang Wook

2017-06-01

68 Ga-labeled capsaicin using a DOTA (1,4,7,10-tetraazocyclododecane-N,N',N″,N'″-tetraacetic acid) derivative [ 68 Ga-SCN-Benzyl(Bn)-DOTA-capsaicin] was studied for the diagnosis of breast cancers, such as MCF-7 and SK-BR-3. The standard compound, 69 Ga-SCN-Bn-DOTA-capsaicin, was also prepared and characterized by spectroscopic analysis. The binding affinity of 68 Ga-SCN-Bn-DOTA-capsaicin was evaluated by using breast cancer cell lines (MCF-7, SK-BR-3) and colon cancer cell (CT-26); the biodistribution was carried out by using MCF-7-bearing nude mice, after which the positron emission tomography (PET) images were obtained at different time intervals (15-120 minutes). 68 Ga-SCN-Bn-DOTA-capsaicin showed a cellular uptake of 0.93% Injected Dose (ID) after 30 minutes of incubation, whereas 68 Ga-SCN-Bn-DOTA showed a lower uptake of 0.25% ID. The tumor-to-blood ID/g% ratios increased and were found to be 0.49, 0.22, and 0.77 for 15, 30, and 60 minutes, respectively. The small-animal PET study showed that the uptake of 68 Ga-SCN-Bn-DOTA-capsaicin was higher in the tumor regions even at 30 minutes after injection. These results suggest that 68 Ga-SCN-Bn-DOTA-capsaicin is a potential targeting agent for PET imaging of MCF-7.

Elongation of Flare Ribbons

Energy Technology Data Exchange (ETDEWEB)

Qiu, Jiong; Longcope, Dana W. [Department of Physics, Montana State University, Bozeman MT (United States); Cassak, Paul A. [Department of Physics and Astronomy, West Virginia University, Morgantown WV (United States); Priest, Eric R. [School of Mathematics and Statistics, University of St. Andrews, Fife KY16 9SS, Scotland (United Kingdom)

2017-03-20

We present an analysis of the apparent elongation motion of flare ribbons along the polarity inversion line (PIL), as well as the shear of flare loops in several two-ribbon flares. Flare ribbons and loops spread along the PIL at a speed ranging from a few to a hundred km s{sup −1}. The shear measured from conjugate footpoints is consistent with the measurement from flare loops, and both show the decrease of shear toward a potential field as a flare evolves and ribbons and loops spread along the PIL. Flares exhibiting fast bidirectional elongation appear to have a strong shear, which may indicate a large magnetic guide field relative to the reconnection field in the coronal current sheet. We discuss how the analysis of ribbon motion could help infer properties in the corona where reconnection takes place.

Design, synthesis and biological evaluation of novel hydrogen sulfide releasing capsaicin derivatives.

Science.gov (United States)

Gao, Mingxiang; Li, Jinyu; Nie, Cunbin; Song, Beibei; Yan, Lin; Qian, Hai

2018-05-15

Capsaicin (CAP), the prototypical TRPV1 agonist, is the major active component in chili peppers with health-promoting benefits. However, its use is limited by the low bioavailability and irritating quality. In this study, for improving the activity of CAP and alleviating its irritating effects, a series of H 2 S-releasing CAPs were designed and synthesized by combining capsaicin and dihydro capsaicin with various hydrogen sulfide donors. The resulting compounds were evaluated their TRPV1 agonist activity, analgesic activity, anticancer activities, H 2 S-releasing ability, and gastric mucosa irritation. Biological evaluation indicated that the most active compound B 9 , containing 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione moiety as H 2 S donor, had better analgesic activity and displayed more potent cytotoxic effects on the test cell lines than the lead compound CAP. Furthermore, the preferred compound, B 9 reduced rat gastric mucosa irritation caused by CAP. Notably, the improved properties of this derivative are associated with its H 2 S-releasing capability. Copyright © 2018 Elsevier Ltd. All rights reserved.

Flare-ups incidence and severity after using calcium hydroxide as intracanal dressing.

Science.gov (United States)

Ghoddusi, Jamileh; Javidi, Maryam; Zarrabi, Mohammad Hasan; Bagheri, Hossein

2006-01-01

Acute pain and swelling following endodontic treatment are a challenge for both the patient and the dentist. According to previous studies, the incidence of flare-ups increases after endodontic treatment of teeth with necrotic pulps. Calcium hydroxide is currently used as a multi-purpose drug in root canal therapy. The aim of this study was to evaluate the incidence and severity of flare-ups after treatment of pulpless teeth using calcium hydroxide as an intracanal dressing. Sixty patients with single-root necrotic teeth participated in this study. These patients were randomly divided into three groups of 20. The patients were treated in Group A in a single-visit approach, in group B with a two-visit approach without any intracanal dressing and group C with a two-visit approach using calcium hydroxide as an intracanal dressing for one week. All of the patients were followed for 72 hours after each treatment session. The information about the incidence and severity of pain and swelling was recorded in tables, using a modified Visual Analogue Scale for pain severity measurement and a scale with four degrees for measuring the severity of swelling. The data were analyzed by chi-square test and GENMODE procedure.

Magnetic transients in flares

International Nuclear Information System (INIS)

Zirin, H.; Tanaka, K.

1981-01-01

We present data on magnetic transients (mgtr's) observed in flares on 1980 July 1 and 5 with Big Bear videomagnetograph (VMG). The 1980 July 1 event was a white light flare in which a strong bipolar mgtr was observed, and a definite change in the sunspots occurred at the time of the flare. In the 1980 July 5 flare, a mgtr was observed in only one polarity, and, although no sunspot changes occurred simultaneous with the flare, major spot changes occurred in a period of hours

High pain sensitivity is distinct from high susceptibility to non-painful sensory input at threshold level.

Science.gov (United States)

Hummel, Thomas; Springborn, Maria; Croy, Ilona; Kaiser, Jochen; Lötsch, Jörn

2011-04-01

Individuals may differ considerably in their sensitivity towards various painful stimuli supporting the notion of a person as stoical or complaining about pain. Molecular and functional imaging research provides support that this may extend also to other sensory qualities. Whether a person can be characterized as possessing a generally high or low sensory acuity is unknown. This was therefore assessed with thresholds to painful and non-painful stimuli, with a focus on chemical stimuli that besides pain may evoke clearly non-painful sensations such as taste or smell. In 36 healthy men and 78 women (ages 18 to 52 years), pain thresholds to chemo-somatosensory (intranasal gaseous CO(2)) and electrical stimuli (cutaneous stimulation) were significantly correlated (ρ(2)=0.2268, psensory qualities, i.e., for the rose-like odor phenyl ethyl alcohol and gustatory thresholds for sour (citric acid) and salty (NaCl). Similarly, pain clusters showed no differences in thresholds to other stimuli. Moreover, no clustering was obtained for thresholds to both painful and non-painful stimuli together. Thus, individuals could not be characterized as highly sensitive (or insensitive) to all chemical stimuli no matter of evoking pain. This suggests that pain is primarily a singular sensory perception distinct from others such as olfaction or taste. Copyright © 2011 Elsevier B.V. All rights reserved.

Antibacterial effect of silver nanoparticles and capsaicin against MDR-ESBL producing Escherichia coli: An in vitro study

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Debasish Kar

2016-10-01

Full Text Available Objective: To evaluate the antibacterial property of silver nanoparticles (AgNPs and capsaicin against multidrug resistant (MDR and extended spectrum beta-lactamase (ESBL producing Escherichia coli of bovine and poultry origin. Methods: Antibacterial efficacy of AgNPs and capsaicin was measured using broth dilution method. Five MDR-ESBL producing E. coli isolates of poultry (PEC4, PEC6, PEC15 and PEC16 and cattle mastitis origin (MEC2 were taken to evaluate the antibacterial effect of AgNPs and capsaicin. Results: At 50 mmol/L AgNPs, the viability of MDR of bacterial pathogens was reduced to almost 80%–90% and at 1000 mmol/L, the viability went down to 0%–3%. The minimum inhibitory concentration (MIC50 of AgNPs against these MDR-ESBL producing isolates was found to vary between 172–218 mmol/L whereas the MIC80 varied between 450–640 mmol/L. Capsaicin showed more prominent bactericidal effect and only at 2.5 mmol/L concentration, the viability was shown to be reduced by 20%–35% whereas at 7.5 mmol/L concentration, there was approximately 60% reduction in viability. Further at 25 mmol/L concentration, the viability was reduced to 0%–8%. The MIC50 and MIC80 of capsaicin against these MDRESBL producing isolates were found to vary between 4.6–7.5 mmol/L and 10.9–16.9 mmol/L, respectively. Conclusions: The results point out that capsaicin and AgNPs could be of use in treating ESBL infection.

Role of the intraluminal contents and the continuity of intrinsic neurons in intracolonic capsaicin-induced contraction and defecation in dogs.

Science.gov (United States)

Kikuchi, Daisuke; Shibata, Chikashi; Imoto, Hirofumi; Someya, Soutoku; Miyachi, Tomohiro; Miura, Koh; Naitoh, Takeshi; Unno, Michiaki

2014-01-01

We, herein, examined the role of the intraluminal contents and continuity of colonic intrinsic neurons in intracolonic capsaicin-induced enhancement of colonic motility and defecation. Five beagle dogs were equipped with three strain gauge force transducers throughout the colon. The colonic contractile activity in response to intracolonic capsaicin was studied in intact dogs, dogs after colonic cleansing and dogs with transection/re-anastomosis (T/R) between the proximal and middle colon. The effects of intravenous yohimbine, a α2 adrenergic antagonist, on the colonic motility and defecation were also studied in the same models. In intact dogs, capsaicin (10 mg) and yohimbine (2 mg/kg) immediately induced contractions throughout the colon, with defecation occurring in all experiments. In dogs after colonic cleansing and T/R, the capsaicin (10 mg)-induced enhancement of colonic motility was decreased in the middle and distal colon, and capsaicin-induced defecation was observed in 0-20 % of experiments (p continuity of the colonic intrinsic nerves as well as the intraluminal contents appear to play an important role in the colonic motor response to intracolonic capsaicin.

Solar flares

International Nuclear Information System (INIS)

Brown, J.C.; Smith, D.F.

1980-01-01

The current observational and theoretical status of solar flares as a typical astrophysical problem is reviewed with especial reference to the intense and complex energy release in large flares. Observations and their diagnostic applications are discussed in three broad areas: thermal radiation at temperatures T 5 K; thermal radiation at T > approximately 10 5 K; and non-thermal radiation and particles. Particular emphasis is given to the most recent observational discoveries such as flare γ-rays, interplanetary Langmuir waves, and the ubiquitous association of soft x-ray loops with flares, and also the progress in particle diagnostics of hard x-ray and radio bursts. The theoretical problems of primary energy release are considered in terms of both possible magnetic configuration and in plasma instabilities and the question of achieving the necessary flash power discussed. The credibility of models for the secondary redistribution through the atmosphere of the primary magnetic energy released in terms of conduction, convection, radiation and particle transport is examined. Progress made in the flare problem in the past decade is assessed and some possible reasons why no convincing solution has yet been found are considered. 296 references. (U.K.)

Inhibitory effect of chronic oral treatment with fluoxetine on capsaicin-induced external carotid vasodilatation in anaesthetised dogs.

Science.gov (United States)

Muñoz-Islas, Enriqueta; González-Hernández, Abimael; Lozano-Cuenca, Jair; Ramírez-Rosas, Martha Beatríz; Medina-Santillán, Roberto; Centurión, David; MaassenVanDenBrink, Antoinette; Villalón, Carlos M

2015-10-01

During migraine, capsaicin-sensitive trigeminal sensory nerves release calcitonin gene-related peptide (CGRP), resulting in cranial vasodilatation and central nociception. Moreover, 5-HT is involved in the pathophysiology of migraine and depression. Interestingly, some limited lines of evidence suggest that fluoxetine may be effective in migraine prophylaxis, but the underlying mechanisms are uncertain. Hence, this study investigated the canine external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine before and after acute and chronic oral treatment with fluoxetine. Forty-eight vagosympathectomised male mongrel dogs were prepared to measure blood pressure, heart rate and external carotid blood flow. The thyroid artery was cannulated for infusions of agonists. In 16 of these dogs, a spinal cannula was inserted (C1-C3) for infusions of 5-HT. The external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine remained unaffected after intracarotid or i.v. fluoxetine. In contrast, the vasodilator responses to capsaicin, but not those to α-CGRP or acetylcholine, were inhibited after chronic oral treatment with fluoxetine (300 µg/kg; for 90 days) or intrathecal 5-HT. Chronic oral fluoxetine inhibited capsaicin-induced external carotid vasodilatation, and this inhibition could partly explain its potential prophylactic antimigraine action. © International Headache Society 2015.

Preparative separation of capsaicin and dihydrocapsaicin from Capsicum frutescens by high-speed counter-current chromatography.

Science.gov (United States)

Peng, Aihua; Ye, Haoyu; Li, Xia; Chen, Lijuan

2009-09-01

Capsaicin and dihydrocapsaicin are two main bioactive components of Capsicum frutescens and are widely used as food additives and drugs in China and India. Due to their similarity in structures, isolation of capsaicin and dihydrocapsaicin with traditional methods such as silica gel column chromatography, normal-phase thin-layer chromatography (TLC) becomes difficult. This study involves separating capsaicin and dihydrocapsaicin with sufficient purity and recovery using high-speed counter-current chromatography (HSCCC) with a solvent system composed of n-hexane-ethyl acetate-methanol-water-acetic acid (20:20:20:20:2, v/v/v/v/v). Separation parameters such as sample volume, and sample concentration were first optimized on analytical HSCCC, and then scaled up to preparative HSCCC. 0.65 g capsaicin and 0.28 g dihydrocapsaicin were obtained from 1.2 g crude extract and their purities were 98.5 and 97.8%, respectively. The recoveries of the two compounds were 86.3 and 85.4%, respectively. The purity of the isolated compounds was analyzed by high-performance liquid chromatography (HPLC) and their structures were identified by (1)H nuclear magnetic resonance (NMR) and (13)C NMR analysis.

Effects of capsaicin, green tea and CH-19 sweet pepper on appetite and energy intake in humans in negative and positive energy balance

DEFF Research Database (Denmark)

Reinbach, Helene Christine; Smeets, A.; Martinussen, Torben

2009-01-01

Summary Background & aims Bioactive ingredients have been shown to reduce appetite and energy intake. The magnitude of these effects might depend on energy balance why it was investigated how capsaicin, green tea, CH-19 sweet pepper as well as green tea and capsaicin affect appetite and energy...... intake during respectively negative and positive energy balance. Methods 27 subjects were randomized to three weeks of negative and three weeks of positive energy balance during which capsaicin, green tea, CH-19 sweet pepper, capsaicin + green tea or placebo was ingested on ten separate test days while...... the effects on appetite, energy intake, body weight and heart rate were assessed. Results CH-19 sweet pepper and a combination of capsaicin and green tea reduced energy intake during positive energy balance. Capsaicin and green tea suppressed hunger and increased satiety more during negative than during...

The Natural History of Flare-Ups in Fibrodysplasia Ossificans Progressiva (FOP): A Comprehensive Global Assessment.

Science.gov (United States)

Pignolo, Robert J; Bedford-Gay, Christopher; Liljesthröm, Moira; Durbin-Johnson, Blythe P; Shore, Eileen M; Rocke, David M; Kaplan, Frederick S

2016-03-01

Fibrodysplasia ossificans progressiva (FOP) leads to disabling heterotopic ossification (HO) from episodic flare-ups. However, the natural history of FOP flare-ups is poorly understood. A 78-question survey on FOP flare-ups, translated into 15 languages, was sent to 685 classically-affected patients in 45 countries (six continents). Five hundred patients or knowledgeable informants responded (73%; 44% males, 56% females; ages: 1 to 71 years; median: 23 years). The most common presenting symptoms of flare-ups were swelling (93%), pain (86%), or decreased mobility (79%). Seventy-one percent experienced a flare-up within the preceding 12 months (52% spontaneous; 48% trauma-related). Twenty-five percent of those who had received an intramuscular injection reported an immediate flare-up at the injection site, 84% of whom developed HO. Axial flare-ups most frequently involved the back (41.6%), neck (26.4%), or jaw (19.4%). Flare-ups occurred more frequently in the upper limbs before 8 years of age, but more frequently in the lower limbs thereafter. Appendicular flare-ups occurred more frequently at proximal than at distal sites without preferential sidedness. Seventy percent of patients reported functional loss from a flare-up. Thirty-two percent reported complete resolution of at least one flare-up and 12% without any functional loss (mostly in the head or back). The most disabling flare-ups occurred at the shoulders or hips. Surprisingly, 47% reported progression of FOP without obvious flare-ups. Worldwide, 198 treatments were reported; anti-inflammatory agents were most common. Seventy-five percent used short-term glucocorticoids as a treatment for flare-ups at appendicular sites. Fifty-five percent reported that glucocorticoids improved symptoms occasionally whereas 31% reported that they always did. Only 12% reported complete resolution of a flare-up with glucocorticoids. Forty-three percent reported rebound symptoms within 1 to 7 days after completing a course of

Capsaicin pretreatment enhanced the bioavailability of fexofenadine in rats by P-glycoprotein modulation: in vitro, in situ and in vivo evaluation.

Science.gov (United States)

Bedada, Satish Kumar; Appani, Ramgopal; Boga, Praveen Kumar

2017-06-01

Capsaicin is the main pungent principle present in chili peppers has been found to possess P-glycoprotein (P-gp) inhibition activity in vitro, which may have the potential to modulate bioavailability of P-gp substrates. Therefore, purpose of this study was to evaluate the effect of capsaicin on intestinal absorption and bioavailability of fexofenadine, a P-gp substrate in rats. The mechanistic evaluation was determined by non-everted sac and intestinal perfusion studies to explore the intestinal absorption of fexofenadine. These results were confirmed by an in vivo pharmacokinetic study of oral administered fexofenadine in rats. The intestinal transport and apparent permeability (P app ) of fexofenadine were increased significantly by 2.8 and 2.6 fold, respectively, in ileum of capsaicin treated rats when compared to control group. Similarly, absorption rate constant (K a ), fraction absorbed (F ab ) and effective permeability (P eff ) of fexofenadine were increased significantly by 2.8, 2.9 and 3.4 fold, respectively, in ileum of rats pretreated with capsaicin when compared to control group. In addition, maximum plasma concentration (C max ) and area under the concentration-time curve (AUC) were increased significantly by 2.3 and 2.4 fold, respectively, in rats pretreated with capsaicin as compared to control group. Furthermore, obtained results in rats pretreated with capsaicin were comparable to verapamil (positive control) treated rats. Capsaicin pretreatment significantly enhanced the intestinal absorption and bioavailability of fexofenadine in rats likely by inhibition of P-gp mediated cellular efflux, suggesting that the combined use of capsaicin with P-gp substrates may require close monitoring for potential drug interactions.

A study of flare-ups following single-visit root canal treatment in endodontic patients.

Science.gov (United States)

Kalhoro, Feroze Ali; Mirza, Assad Javed

2009-07-01

To determine the frequency of flare-ups in single-visit endodontic treatment and the associated factors. Observational. Baqai Dental College Hospital, Karachi, from November 2005 to May 2006. One hundred patients were assigned for single-visit root canal treatment. Patients that defaulted after the first appointment (incomplete treatment) were excluded from the study. For each tooth treated, the clinical factors and conditions existing before and after the completion of treatment were recorded. This data included patient's age, gender, type of tooth, pre-operative status of pulp and periapical tissues and recording pain and swelling (flare-ups) postoperatively after 1 day, 7 days and 1 month. The significance of results was obtained by applying paired-sample t-test and Pearson X2 test. Three of one hundred cases showed flare-ups after treated in single appointment. On the other hand, a marked number (n=97) of cases did not show flare-ups during the study period. None of the studied variables showed any statistically significant bearing on rate of flare-ups in single appointment root canal treatment. The single-visit root canal treatment was safe in terms of endodontic flare-ups as far as results of this study are concerned. It was safer in both vital and non-vital teeth, and even in teeth with periapical pathosis.

Recent big flare

International Nuclear Information System (INIS)

Moriyama, Fumio; Miyazawa, Masahide; Yamaguchi, Yoshisuke

1978-01-01

The features of three big solar flares observed at Tokyo Observatory are described in this paper. The active region, McMath 14943, caused a big flare on September 16, 1977. The flare appeared on both sides of a long dark line which runs along the boundary of the magnetic field. Two-ribbon structure was seen. The electron density of the flare observed at Norikura Corona Observatory was 3 x 10 12 /cc. Several arc lines which connect both bright regions of different magnetic polarity were seen in H-α monochrome image. The active region, McMath 15056, caused a big flare on December 10, 1977. At the beginning, several bright spots were observed in the region between two main solar spots. Then, the area and the brightness increased, and the bright spots became two ribbon-shaped bands. A solar flare was observed on April 8, 1978. At first, several bright spots were seen around the solar spot in the active region, McMath 15221. Then, these bright spots developed to a large bright region. On both sides of a dark line along the magnetic neutral line, bright regions were generated. These developed to a two-ribbon flare. The time required for growth was more than one hour. A bright arc which connects two ribbons was seen, and this arc may be a loop prominence system. (Kato, T.)

Pharmacological treatment of diabetic neuropathic pain.

Science.gov (United States)

Smith, Howard S; Argoff, Charles E

2011-03-26

Neuropathic pain continues to be a difficult and challenging clinical issue to deal with effectively. Painful diabetic polyneuropathy is a complex pain condition that occurs with reasonable frequency in the population and it may be extremely difficult for clinicians to provide patients with effective analgesia. Chronic neuropathic pain may occur in approximately one of every four diabetic patients. The pain may be described as burning or a deep-seated ache with sporadic paroxysms of lancinating painful exacerbations. The pain is often constant, moderate to severe in intensity, usually primarily involves the feet and generally tends to worsen at night. Treatment may be multimodal but largely involves pharmacological approaches. Pharmacological therapeutic options include antidepressants (tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors), α2δ ligands and topical (5%) lidocaine patch. Other agents may be different antiepileptic drugs (carbamazepine, lamotrigine, topiramate), topical capsaicin, tramadol and other opioids. Progress continues with respect to understanding various mechanisms that may contribute to painful diabetic neuropathy. Agents that may hold some promise include neurotrophic factors, growth factors, immunomodulators, gene therapy and poly (adenosine diphosphate-ribose) polymerase inhibitors. It is hoped that in the future clinicians will be able to assess patient pathophysiology, which may help them to match optimal therapeutic agents to target individual patient aberrant mechanisms.

Identifying flares in rheumatoid arthritis

DEFF Research Database (Denmark)

Bykerk, Vivian P; Bingham, Clifton O; Choy, Ernest H

2016-01-01

to flare, with escalation planned in 61%. CONCLUSIONS: Flares are common in rheumatoid arthritis (RA) and are often preceded by treatment reductions. Patient/MD/DAS agreement of flare status is highest in patients worsening from R/LDA. OMERACT RA flare questions can discriminate between patients with...... Set. METHODS: Candidate flare questions and legacy measures were administered at consecutive visits to Canadian Early Arthritis Cohort (CATCH) patients between November 2011 and November 2014. The American College of Rheumatology (ACR) core set indicators were recorded. Concordance to identify flares...

Light evokes melanopsin-dependent vocalization and neural activation associated with aversive experience in neonatal mice.

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Anton Delwig

Full Text Available Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs are the only functional photoreceptive cells in the eye of newborn mice. Through postnatal day 9, in the absence of functional rods and cones, these ipRGCs mediate a robust avoidance behavior to a light source, termed negative phototaxis. To determine whether this behavior is associated with an aversive experience in neonatal mice, we characterized light-induced vocalizations and patterns of neuronal activation in regions of the brain involved in the processing of aversive and painful stimuli. Light evoked distinct melanopsin-dependent ultrasonic vocalizations identical to those emitted under stressful conditions, such as isolation from the litter. In contrast, light did not evoke the broad-spectrum calls elicited by acute mechanical pain. Using markers of neuronal activation, we found that light induced the immediate-early gene product Fos in the posterior thalamus, a brain region associated with the enhancement of responses to mechanical stimulation of the dura by light, and thought to be the basis for migrainous photophobia. Additionally, light induced the phosphorylation of extracellular-related kinase (pERK in neurons of the central amygdala, an intracellular signal associated with the processing of the aversive aspects of pain. However, light did not activate Fos expression in the spinal trigeminal nucleus caudalis, the primary receptive field for painful stimulation to the head. We conclude that these light-evoked vocalizations and the distinct pattern of brain activation in neonatal mice are consistent with a melanopsin-dependent neural pathway involved in processing light as an aversive but not acutely painful stimulus.

Muscular heat and mechanical pain sensitivity after lengthening contractions in humans and animals.

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Queme, Fernando; Taguchi, Toru; Mizumura, Kazue; Graven-Nielsen, Thomas

2013-11-01

Mechanical sensitivity of muscle nociceptors was previously shown to increase 2 days after lengthening contractions (LC), but heat sensitivity was not different despite nerve growth factor (NGF) being upregulated in the muscle during delayed-onset muscle soreness (DOMS). The discrepancy of these results and lack of other reports drove us to assess heat sensitivity during DOMS in humans and to evaluate the effect of NGF on the heat response of muscle C-fibers. Pressure pain thresholds and pain intensity scores to intramuscular injection of isotonic saline at 48°C and capsaicin were recorded in humans after inducing DOMS. The response of single unmyelinated afferents to mechanical and heat stimulations applied to their receptive field was recorded from muscle-nerve preparations in vitro. In humans, pressure pain thresholds were reduced but heat and capsaicin pain responses were not increased during DOMS. In rats, the mechanical but not the heat sensitivity of muscle C-fibers was increased in the LC group. NGF applied to the receptive field facilitated the heat sensitivity relative to the control. The absence of facilitated heat sensitivity after LC, despite the NGF sensitization, may be explained if the NGF concentration produced after LC is not sufficient to sensitize nociceptor response to heat. This article presents new findings on the basic mechanisms underlying hyperalgesia during DOMS, which is a useful model to study myofascial pain syndrome, and the role of NGF on muscular nociception. This might be useful in the search for new pharmacologic targets and therapeutic approaches. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

Solar flare impulsivity and its relationship with white-light flares and with CMEs

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Watanabe, K.; Masuda, S.

2017-12-01

There are many types of classification in solar flares. One of them is a classification by flare duration in soft X-rays; so-called impulsive flare and long duration event (LDE). Typically, the duration of an impulsive flare is shorter than 1 hour, and that of an LDE is longer than 1 hour. These two types of flare show different characteristics. In soft X-rays, impulsive flares usually have a compact loop structure. On the other hand, LDEs show a large-scale loop, sometimes a large arcade structure. In hard X-rays (HXRs), the difference appears clear, too. The former shows a strong and short-time (10 minutes) emissions and show a large coronal source. These facts suggest that HXR observation becomes one of a good indicator to classify solar flares, especially for the study on the particle acceleration and the related phenomena. However, HXR data do not always exist due to the satellite orbit and the small sensitivity of HXR instruments. So, in this study, based on the concept of the Neupert effect (Neupert, 1968), we use soft X-ray derivative data as the proxy of HXR. From this data, we define impulsivity (IP) for each flare. Then we investigate solar flares using this new index. First we apply IP index to white-light flare (WLF) research. We investigate how WL enhancement depends on IP, then it is found that WLF tend to have large IP values. So the flare impulsivity (IP) is one of the important factors if WL enhancement appears or not in a solar flare. Next we investigate how CME itself and/or its physical parameters depend on IP index. It has been believed that most of CMEs are associated with LDEs, but we found that there is only a weak correlation between the existence of CME and IP index. Finally, we also search for the relationship between WLF and CME as a function of IP and discuss the physical condition of WLF.

Which of Kepler's Stars Flare?

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Kohler, Susanna

2017-12-01

The habitability of distant exoplanets is dependent upon many factors one of which is the activity of their host stars. To learn about which stars are most likely to flare, a recent study examines tens of thousands of stellar flares observed by Kepler.Need for a Broader SampleArtists rendering of a flaring dwarf star. [NASAs Goddard Space Flight Center/S. Wiessinger]Most of our understanding of what causes a star to flare is based on observations of the only star near enough to examine in detail the Sun. But in learning from a sample size of one, a challenge arises: we must determine which conclusions are unique to the Sun (or Sun-like stars), and which apply to other stellar types as well.Based on observations and modeling, astronomers think that stellar flares result from the reconnection of magnetic field lines in a stars outer atmosphere, the corona. The magnetic activity is thought to be driven by a dynamo caused by motions in the stars convective zone.HR diagram of the Kepler stars, with flaring main-sequence (yellow), giant (red) and A-star (green) stars in the authors sample indicated. [Van Doorsselaere et al. 2017]To test whether these ideas are true generally, we need to understand what types of stars exhibit flares, and what stellar properties correlate with flaring activity. A team of scientists led by Tom Van Doorsselaere (KU Leuven, Belgium) has now used an enormous sample of flares observed by Kepler to explore these statistics.Intriguing TrendsVan Doorsselaere and collaborators used a new automated flare detection and characterization algorithm to search through the raw light curves from Quarter 15 of the Kepler mission, building a sample of 16,850 flares on 6,662 stars. They then used these to study the dependence of the flare occurrence rate, duration, energy, and amplitude on the stellar spectral type and rotation period.This large statistical study led the authors to several interesting conclusions, including:Flare star incidence rate as a a

Pharmacological Treatment of Painful HIV-Associated Sensory Neuropathy: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

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Phillips, Tudor J. C.; Cherry, Catherine L.; Cox, Sarah; Marshall, Sarah J.; Rice, Andrew S. C.

2010-01-01

Background Significant pain from HIV-associated sensory neuropathy (HIV-SN) affects ∼40% of HIV infected individuals treated with antiretroviral therapy (ART). The prevalence of HIV-SN has increased despite the more widespread use of ART. With the global HIV prevalence estimated at 33 million, and with infected individuals gaining increased access to ART, painful HIV-SN represents a large and expanding world health problem. There is an urgent need to develop effective pain management strategies for this condition. Method and Findings Objective: To evaluate the clinical effectiveness of analgesics in treating painful HIV-SN. Design: Systematic review and meta-analysis. Data sources: Medline, Cochrane central register of controlled trials, www.clinicaltrials.gov, www.controlled-trials.com and the reference lists of retrieved articles. Selection criteria: Prospective, double-blinded, randomised controlled trials (RCTs) investigating the pharmacological treatment of painful HIV-SN with sufficient quality assessed using a modified Jadad scoring method. Review methods: Four authors assessed the eligibility of articles for inclusion. Agreement of inclusion was reached by consensus and arbitration. Two authors conducted data extraction and analysis. Dichotomous outcome measures (≥30% and ≥50% pain reduction) were sought from RCTs reporting interventions with statistically significant efficacies greater than placebo. These data were used to calculate RR and NNT values. Results Of 44 studies identified, 19 were RCTs. Of these, 14 fulfilled the inclusion criteria. Interventions demonstrating greater efficacy than placebo were smoked cannabis NNT 3.38 95%CI(1.38 to 4.10), topical capsaicin 8%, and recombinant human nerve growth factor (rhNGF). No superiority over placebo was reported in RCTs that examined amitriptyline (100mg/day), gabapentin (2.4g/day), pregabalin (1200mg/day), prosaptide (16mg/day), peptide-T (6mg/day), acetyl-L-carnitine (1g/day), mexilitine (600mg

Pharmacological treatment of painful HIV-associated sensory neuropathy: a systematic review and meta-analysis of randomised controlled trials.

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Tudor J C Phillips

Full Text Available BACKGROUND: Significant pain from HIV-associated sensory neuropathy (HIV-SN affects ∼40% of HIV infected individuals treated with antiretroviral therapy (ART. The prevalence of HIV-SN has increased despite the more widespread use of ART. With the global HIV prevalence estimated at 33 million, and with infected individuals gaining increased access to ART, painful HIV-SN represents a large and expanding world health problem. There is an urgent need to develop effective pain management strategies for this condition. METHOD AND FINDINGS: OBJECTIVE: To evaluate the clinical effectiveness of analgesics in treating painful HIV-SN. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Cochrane central register of controlled trials, www.clinicaltrials.gov, www.controlled-trials.com and the reference lists of retrieved articles. SELECTION CRITERIA: Prospective, double-blinded, randomised controlled trials (RCTs investigating the pharmacological treatment of painful HIV-SN with sufficient quality assessed using a modified Jadad scoring method. REVIEW METHODS: Four authors assessed the eligibility of articles for inclusion. Agreement of inclusion was reached by consensus and arbitration. Two authors conducted data extraction and analysis. Dichotomous outcome measures (≥ 30% and ≥ 50% pain reduction were sought from RCTs reporting interventions with statistically significant efficacies greater than placebo. These data were used to calculate RR and NNT values. RESULTS: Of 44 studies identified, 19 were RCTs. Of these, 14 fulfilled the inclusion criteria. Interventions demonstrating greater efficacy than placebo were smoked cannabis NNT 3.38 95%CI(1.38 to 4.10, topical capsaicin 8%, and recombinant human nerve growth factor (rhNGF. No superiority over placebo was reported in RCTs that examined amitriptyline (100mg/day, gabapentin (2.4 g/day, pregabalin (1200 mg/day, prosaptide (16 mg/day, peptide-T (6 mg/day, acetyl-L-carnitine (1g

Neonatal capsaicin causes compensatory adjustments to energy homeostasis in rats

NARCIS (Netherlands)

van de Wall, E. H. E. M.; Wielinga, P. Y.; Strubbe, J. H.; van Dijk, G.

2006-01-01

Several mechanisms involved in ingestive behavior and neuroendocrine activity rely on vagal afferent neuronal signaling. Seemingly contradictory to this idea are observations that vagal afferent neuronal ablation by neonatal capsaicin (CAP) treatment has relatively small effects on glucose

Estimation of capsaicin through scanning densitometry and evaluation of different varieties of capsicum in India.

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Gantait, Arunava; Maji, Amal; Barman, Tapu; Banerji, Pratim; Venkatesh, P; Mukherjee, Pulok K

2012-01-01

Capsicum annuum L. (family: Solanaceae) possesses therapeutic benefits for the treatment of rheumatism, neuropathy, psoriasis, flatulence and so on. In this study fruits of four different varieties of C. annuum from four different geographical regions in India were evaluated based on their total content of capsaicin. Ethanol extracts of the fruits were used. HPTLC plates were developed in a mobile phase containing benzene, ethyl acetate and methanol (75:20:5). Densitometric scanning was performed at a wavelength of 283 nm in the absorbance mode. The calibration curve was described by the equation Y=393.587+3.836*X with a correlation coefficient (r) of 0.99890. The content of capsaicin in Nagaland, Manipur, West Bengal and Shimla varieties was found to be 3.71%, 1.78%, 0.54% and 0.06%, respectively. The developed densitometric method was found to be specific, accurate and precise. A recovery study and precision showed low levels of %RSD values. The linearity range of the curve for capsaicin was found to be 300-900 ng per spot. The limit of detection and the limit of quantification values were determined to be 31 and 94 ng, respectively, proving the sensitivity of the method. Thus the method can be used to control the total content of capsaicin on an industrial scale.

TRPA1-dependent reversible opening of tight junction by natural compounds with an α,β-unsaturated moiety and capsaicin.

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Kanda, Yusuke; Yamasaki, Youhei; Sasaki-Yamaguchi, Yoshie; Ida-Koga, Noriko; Kamisuki, Shinji; Sugawara, Fumio; Nagumo, Yoko; Usui, Takeo

2018-02-02

The delivery of hydrophilic macromolecules runs into difficulties such as penetration of the cell membrane lipid bilayer. Our prior experiment demonstrated that capsaicin induces the reversible opening of tight junctions (TJs) and enhances the delivery of hydrophilic macromolecules through a paracellular route. Herein, we screened paracellular permeability enhancers other than capsaicin. As TJ opening by capsaicin is associated with Ca 2+ influx, we first screened the compounds that induce Ca 2+ influx in layered MDCK II cells, and then we determined the compounds' abilities to open TJs. Our results identified several natural compounds with α,β-unsaturated moiety. A structure-activity relationship (SAR) analysis and the results of pretreatment with reducing reagent DTT suggested the importance of α,β-unsaturated moiety. We also examined the underlying mechanisms, and our findings suggest that the actin reorganization seen in capsaicin treatment is important for the reversibility of TJ opening. Furthermore, our analyses revealed that TRPA1 is involved in the Ca 2+ influx and TJ permeability increase not only by an α,β-unsaturated compound but also by capsaicin. Our results indicate that the α,β-unsaturated moiety can be a potent pharmacophore for TJ opening.

Conformational analysis of capsaicin using 13C, 15N MAS NMR, GIAO DFT and GA calculations

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Siudem, Paweł; Paradowska, Katarzyna; Bukowicki, Jarosław

2017-10-01

Capsaicin produced by plants from genus Capsicum exerts multiple pharmacological effects and has found applications in food and pharmaceutical industry. The alkaloid was studied by a combined approach: solid-state NMR, GA conformational search and GIAO DFT methods. The 13C CPMAS NMR spectra were recorded using variable contact time and dipolar dephasing experiments. The results of cross-polarization (CP) kinetics, such as TCP values and long T1ρH (100-200 ms), indicated that the capsaicin molecule is fairly mobile, especially at the end of the aliphatic chain. The15N MAS NMR spectrum showed one narrow signal at -255 ppm. Genetic algorithm (GA) search with multi modal optimization was used to find low-energy conformations of capsaicin. Theoretical GIAO DFT calculations were performed using different basis sets to characterize five selected conformations. 13C CPMAS NMR was used as a validation method and the experimental chemical shifts were compared with those calculated for selected stable conformers. Conformational analysis suggests that the side chain can be bent or extended. A comparison of the experimental and the calculated chemical shifts indicates that solid capsaicin does not have the same structure as those established by PWXRD.

Healthy volunteers can be phenotyped using cutaneous sensitization pain models.

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Mads U Werner

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

Experiencing Physical Pain Leads to More Sympathetic Moral Judgments

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Xiao, Qianguo; Zhu, Yi; Luo, Wen-bo

2015-01-01

Previous studies have shown that observing another’s pain can evoke other-oriented emotions, which instigate empathic concern for another’s needs. It is not clear whether experiencing first-hand physical pain may also evoke other-oriented emotion and thus influence people’s moral judgment. Based on the embodied simulation literature and neuroimaging evidence, the present research tested the idea that participants who experienced physical pain would be more sympathetic in their moral judgments. Study 1 showed that ice-induced physical pain facilitated higher self-assessments of empathy, which motivated participants to be more sympathetic in their moral judgments. Study 2 confirmed findings in study 1 and also showed that State Perspective Taking subscale of the State Empathy Scale mediated the effects of physical pain on moral judgment. These results provide support for embodied view of morality and for the view that pain can serve a positive psychosocial function. PMID:26465603

Normative data for Aδ contact heat evoked potentials in adult population: a multicenter study.

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Granovsky, Yelena; Anand, Praveen; Nakae, Aya; Nascimento, Osvaldo; Smith, Benn; Sprecher, Elliot; Valls-Solé, Josep

2016-05-01

There has been a significant increase over recent years in the use of contact heat evoked potentials (CHEPs) for the evaluation of small nerve fiber function. Measuring CHEP amplitude and latency has clinical utility for the diagnosis and assessment of conditions with neuropathic pain. This international multicenter study aimed to provide reference values for CHEPs to stimuli at 5 commonly examined body sites. Contact heat evoked potentials were recorded from 226 subjects (114 females), distributed per age decade between 20 and 79 years. Temperature stimuli were delivered by a thermode (32°C-51°C at a rate of 70°C/s). In phase I of the study, we investigated side-to-side differences and reported the maximum normal side-to-side difference in Aδ CHEP peak latency and amplitude for leg, forearm, and face. In phase II, we obtained normative data for 3 CHEP parameters (N2P2 amplitude, N2 latency, and P2 latency), stratified for gender and age decades from face, upper and lower limbs, and overlying cervical and lumbar spine. In general, larger CHEP amplitudes were associated with higher evoked pain scores. Females had CHEPs of larger amplitude and shorter latency than males. This substantive data set of normative values will facilitate the clinical use of CHEPs as a rapid, noninvasive, and objective technique for the assessment of patients presenting with neuropathic pain.

Flare up rate related to root canal treatment of asymptomatic pulpally necrotic central incisor teeth in patients attending a military hospital.

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Al-Negrish, Abdul Rohman Salem; Habahbeh, Riyad

2006-10-01

This prospective study was conducted to determine the flare up rate related to root canal treatment of asymptomatic non vital maxillary central incisor teeth performed in one and two appointments and the relationship, if any between pain and number of treatment visits. The frequency of postobturation pain and swelling was recorded and evaluated over an observation period of 1 week in a 120 consecutive patients undergoing root canal treatment. The patients were assigned randomly into one of two groups of 60 patients each. The canals of all teeth were prepared and filled using the step-back preparation and lateral condensation filling techniques. The data were analyzed statistically using Mann-Whitney test. Eight of the 120 patients were excluded from the analysis as they failed to attend for postoperative reviews. Out of the 112 patients involved in the study 90 patients had no pain, 9 patients had slight pain, 8 patients had moderate pain, and 5 patients had severe pain after 2 days. After 7 days 104 patients had no pain, 4 patients had slight pain, 3 patients had moderate pain and 1 patient had severe pain. No statistically significant difference in the incidence and degree of postoperative pain was found between one and two visit Endodontic procedures. The rate of post obturation flare up in asymptomatic Endodontically treated non vital maxillary centarl incisors was 11.6 and 3.6% after 2 and 7 days, respectively.

Partial transformation from fast to slow muscle fibers induced by deafferentation of capsaicin-sensitive muscle afferents.

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Brunetti, O; Barazzoni, A M; Della Torre, G; Clavenzani, P; Pettorossi, V E; Bortolami, R

1997-11-01

Mechanical and histochemical characteristics of the lateral gastrocnemius (LG) muscle of the rat were examined 21 days after capsaicin injection into the LG muscle. The capsaicin caused a decrease in generation rate of twitch and tetanic tension and an increase in fatigue resistance of LG muscle. The histochemical muscle fiber profile evaluated by myosin adenosine triphosphatase and reduced nicotinamide adenine dinucleotide tetrazolium reductase methods showed an increase of type I and IIC fibers and a decrease of the type IIB in whole muscle, and a decrease of the IIA, IIX fibers in the red part accompanied by their increase in the white part. Therefore the capsaicin treatment, which selectively eliminated fibers belonging to the III and IV groups of muscle afferents, induced muscle fiber transformation from fast contracting fatiguing fibers to slowly contracting nonfatiguing ones.

Physical pain increases interpersonal trust in females.

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Wang, C; Gao, J; Ma, Y; Zhu, C; Dong, X-W

2018-01-01

People behave and interact with others differently when experiencing physical pain. Pain has dramatic effects on one's emotional responses, cognitive functions and social interaction. However, little has been known about whether and how physical pain influences interpersonal trust in social interaction. In the present study, we examined the influence of physical pain on trusting behaviour. A total of 112 healthy participants were recruited and assigned to physical pain condition (induced by Capsaicin) and control condition (with hand cream), respectively. Thirty minutes after pain induction, three decision-making tasks were conducted to measure behaviours in social interaction, including trust and trustworthiness (trust game), non-social risk-taking (risk game) and altruism (dictator game). Results showed that physical pain increased interpersonal trust among females, but not among males. Pain did not influence non-social risk-taking, altruism or trustworthiness, as evaluated by monetary transfers in those tasks. Moreover, the effect of physical pain on interpersonal trust was fully mediated by expectation of monetary profit. These findings demonstrate an effect of pain on interpersonal trust and suggest a reciprocity mechanism that the effect may be driven by self-interest rather than altruistic motivation. The pain effect on trust was evident only in females, implying distinct pain coping strategies used by both genders. The present work highlights the social component of pain and extends our understanding of mutual interactions between pain and social cognition. © 2017 European Pain Federation - EFIC®.

Expression and function of proton-sensing G-protein-coupled receptors in inflammatory pain

Directory of Open Access Journals (Sweden)

Lin Chih-Shin

2009-07-01

Full Text Available Abstract Background Chronic inflammatory pain, when not effectively treated, is a costly health problem and has a harmful effect on all aspects of health-related quality of life. Despite the availability of pharmacologic treatments, chronic inflammatory pain remains inadequately treated. Understanding the nociceptive signaling pathways of such pain is therefore important in developing long-acting treatments with limited side effects. High local proton concentrations (tissue acidosis causing direct excitation or modulation of nociceptive sensory neurons by proton-sensing receptors are responsible for pain in some inflammatory pain conditions. We previously found that all four proton-sensing G-protein-coupled receptors (GPCRs are expressed in pain-relevant loci (dorsal root ganglia, DRG, which suggests their possible involvement in nociception, but their functions in pain remain unclear. Results In this study, we first demonstrated differential change in expression of proton-sensing GPCRs in peripheral inflammation induced by the inflammatory agents capsaicin, carrageenan, and complete Freund's adjuvant (CFA. In particular, the expression of TDAG8, one proton-sensing GPCR, was increased 24 hours after CFA injection because of increased number of DRG neurons expressing TDAG8. The number of DRG neurons expressing both TDAG8 and transient receptor potential vanilloid 1 (TRPV1 was increased as well. Further studies revealed that TDAG8 activation sensitized the TRPV1 response to capsaicin, suggesting that TDAG8 could be involved in CFA-induced chronic inflammatory pain through regulation of TRPV1 function. Conclusion Each subtype of the OGR1 family was expressed differently, which may reflect differences between models in duration and magnitude of hyperalgesia. Given that TDAG8 and TRPV1 expression increased after CFA-induced inflammation and that TDAG8 activation can lead to TRPV1 sensitization, it suggests that high concentrations of protons after

Effect of Capsaicin Cream on the Secretion of the Submandibular and Parotid Gland in the General Population with Different Chilli-eating Habits.

Science.gov (United States)

Wang, Yang; Wang, Zhen; Yu, Guang Yan; Tang, Zhan Gui; Hu, Ji An

2016-06-01

To investigate the effect of capsaicin cream on the secretion of the submandibular gland (SMG) and the parotid gland (PG) in the general population, with different chilli-eating habits. In two groups with different chilli-eating habits, the salivary flow rate of the SMG and the PG was detected at statics and different times, after application of capsaicin cream. In both groups, the topical application of capsaicin cream could significantly increase the salivary secretion of SMG (P 0.05). On the other hand, although the salivary flow rate of PG also increased after stimulation, the increase had no statistical difference (P > 0.05). The application of capsaicin cream can effectively promote the secretion of the SMG and the PG, and its effect is independent of chilli-eating habits, which indicates that topical application of capsaicin cream can be considered as a potential treatment for the hypofunction of the salivary gland.

Solar Flares and Their Prediction

Science.gov (United States)

Adams, Mitzi L.

1999-01-01

Solar flares and coronal mass ejection's (CMES) can strongly affect the local environment at the Earth. A major challenge for solar physics is to understand the physical mechanisms responsible for the onset of solar flares. Flares, characterized by a sudden release of energy (approx. 10(exp 32) ergs for the largest events) within the solar atmosphere, result in the acceleration of electrons, protons, and heavier ions as well as the production of electromagnetic radiation from hard X-rays to km radio waves (wavelengths approx. = 10(exp -9) cm to 10(exp 6) cm). Observations suggest that solar flares and sunspots are strongly linked. For example, a study of data from 1956-1969, reveals that approx. 93 percent of major flares originate in active regions with spots. Furthermore, the global structure of the sunspot magnetic field can be correlated with flare activity. This talk will review what we know about flare causes and effects and will discuss techniques for quantifying parameters, which may lead to a prediction of solar flares.

How flares can be understood

International Nuclear Information System (INIS)

Severny, A.B.

1977-01-01

Specific features of the flare phenomenon which are important for understanding of flares are the following: (1) Fine structure of visible emission of flares, especially at the very beginning and in the pre-flare active region. This structure can be seen also in later stages of development as bright points, some of which exist from the flare beginning (Babin's observations at Crimea, 1972-1976). (2) Turbulent motion with velocities up to 250-300 km s -1 as can be estimated from broadening of emission lines. (3) Predominantly red asymmetry of emission lines in the explosive phase and during further development of flares. (4) 'Supersonic' velocities and supergravitational accelerations of separate moving masses of the flare plasma. (5) The appearance of flares in areas with high grad H, exceeding 0.1 G km -1 which is equivalent to regions of electric currents > approximately 10 11 A. (6) Strong variations of net magnetic flux through the active region, as it follows from Meudon, Crimean, and Sacramento Peak (Rust's) observations. (Auth.)

Solar neighbourhood flare stars - a review

International Nuclear Information System (INIS)

Kunkel, W.E.

1975-01-01

The review concentrates on 'astronomical' aspects of flare activity, such as where, and under what circumstances flare activity is found in the solar vicinity. Non-classical activity is briefly described (without regard for completeness) and the influence of detection effects on flare observations is treated. Flare stars discovered during the last four years are described and flare activity of local dMe stars is compared. The BY Draconis syndrome is discussed followed by some remarks about rotation. Pleiades flare activity is compared to that of the solar neighbourhood and evidence for the evolution of flare activity in stars is examined. (Auth.)

Flare colours and luminosities

International Nuclear Information System (INIS)

Cristaldi, S.; Rodono, M.

1975-01-01

Flare colours determined from simultaneous UBV observations made at Catania Observatory and from sequential UBV observations made at McDonald Observatory are presented. They fit fairly well with the theoretical colours computed according to the Gurzadian's (1970) non-thermal model. Only part of the observed flare colours are consistent with the solar type models by Gershberg (1967) and Kunkel (1970). From a B-band patrol of UV Cet-type stars carried out from 1967 to 1972, some quantitative estimates of flare frequencies and luminosities and their average contributions to the stellar radiation are given. The corresponding parameters for the Sun, which were estimated from 'white light' flare activity, are also given for comparison. The Sun and V 1216 Sgr can be regarded as low-activity flare stars of the type found by Kunkel (1973). (Auth.)

Deficient conditioned pain modulation after spinal cord injury correlates with clinical spontaneous pain measures.

Science.gov (United States)

Albu, Sergiu; Gómez-Soriano, Julio; Avila-Martin, Gerardo; Taylor, Julian

2015-02-01

The contribution of endogenous pain modulation dysfunction to clinical and sensory measures of neuropathic pain (NP) has not been fully explored. Habituation, temporal summation, and heterotopic noxious conditioning stimulus-induced modulation of tonic heat pain intensity were examined in healthy noninjured subjects (n = 10), and above the level of spinal cord injury (SCI) in individuals without (SCI-noNP, n = 10) and with NP (SCI-NP, n = 10). Thermoalgesic thresholds, Cz/AFz contact heat evoked potentials (CHEPs), and phasic or tonic (30 seconds) heat pain intensity were assessed within the C6 dermatome. Although habituation to tonic heat pain intensity (0-10) was reported by the noninjured (10 s: 3.5 ± 0.3 vs 30 s: 2.2 ± 0.5 numerical rating scale; P = 0.003), loss of habituation was identified in both the SCI-noNP (3.8 ± 0.3 vs 3.6 ± 0.5) and SCI-NP group (4.2 ± 0.4 vs 4.9 ± 0.8). Significant temporal summation of tonic heat pain intensity was not observed in the 3 groups. Inhibition of tonic heat pain intensity induced by heterotopic noxious conditioning stimulus was identified in the noninjured (-29.7% ± 9.7%) and SCI-noNP groups (-19.6% ± 7.0%), but not in subjects with SCI-NP (+1.1% ± 8.0%; P pain modulation response correlated positively with Cz/AFz CHEP amplitude (ρ = 0.8; P = 0.015) and evoked heat pain intensity (ρ = 0.8; P = 0.007) in the SCI-NP group. Stepwise regression analysis revealed that the mean conditioned pain modulation (R = 0.72) correlated with pain severity and pressing spontaneous pain in the SCI-NP group. Comprehensive assessment of sensory dysfunction above the level of injury with tonic thermal test and conditioning stimuli revealed less-efficient endogenous pain modulation in subjects with SCI-NP.

Flares on a Bp Star

Science.gov (United States)

Mullan, D. J.

2009-09-01

Two large X-ray flares have been reported from the direction of a magnetic B2p star (σ Ori E). Sanz-Forcada et al. have suggested that the flares did not occur on the B2p star but on a companion of late spectral type. A star which is a candidate for a late-type flare star near σ Ori E has recently been identified by Bouy et al. However, based on the properties of the flares, and based on a recent model of rotating magnetospheres, we argue that, rather than attributing the two flares to a late-type dwarf, it is a viable hypothesis that the flares were magnetic phenomena associated with the rotating magnetosphere of the B2p star itself.

FLARES ON A Bp STAR

International Nuclear Information System (INIS)

Mullan, D. J.

2009-01-01

Two large X-ray flares have been reported from the direction of a magnetic B2p star (σ Ori E). Sanz-Forcada et al. have suggested that the flares did not occur on the B2p star but on a companion of late spectral type. A star which is a candidate for a late-type flare star near σ Ori E has recently been identified by Bouy et al. However, based on the properties of the flares, and based on a recent model of rotating magnetospheres, we argue that, rather than attributing the two flares to a late-type dwarf, it is a viable hypothesis that the flares were magnetic phenomena associated with the rotating magnetosphere of the B2p star itself.

An improved behavioural assay demonstrates that ultrasound vocalizations constitute a reliable indicator of chronic cancer pain and neuropathic pain

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Selvaraj Deepitha

2010-03-01

Full Text Available Abstract Background On-going pain is one of the most debilitating symptoms associated with a variety of chronic pain disorders. An understanding of mechanisms underlying on-going pain, i.e. stimulus-independent pain has been hampered so far by a lack of behavioural parameters which enable studying it in experimental animals. Ultrasound vocalizations (USVs have been proposed to correlate with pain evoked by an acute activation of nociceptors. However, literature on the utility of USVs as an indicator of chronic pain is very controversial. A majority of these inconsistencies arise from parameters confounding behavioural experiments, which include novelty, fear and stress due to restrain, amongst others. Results We have developed an improved assay which overcomes these confounding factors and enables studying USVs in freely moving mice repetitively over several weeks. Using this improved assay, we report here that USVs increase significantly in mice with bone metastases-induced cancer pain or neuropathic pain for several weeks, in comparison to sham-treated mice. Importantly, analgesic drugs which are known to alleviate tumour pain or neuropathic pain in human patients significantly reduce USVs as well as mechanical allodynia in corresponding mouse models. Conclusions We show that studying USVs and mechanical allodynia in the same cohort of mice enables comparing the temporal progression of on-going pain (i.e. stimulus-independent pain and stimulus-evoked pain in these clinically highly-relevant forms of chronic pain.

Dietary capsaicin and antibiotics act synergistically to reduce non-alcoholic fatty liver disease induced by high fat diet in mice.

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Hu, Jingjuan; Luo, Haihua; Jiang, Yong; Chen, Peng

2017-06-13

The prevalence of non-alcoholic fatty liver disease is increasing rapidly worldwide. However, effective strategies for combating high-fat diet (HFD) induced obesity, fatty liver and metabolic disorder are still limited, and outcomes remain poor. In the present study, we evaluated the combined actions of dietary capsaicin and antibiotics on HFD-induced physiological abnormalities in mice. C57BL/6 male mice were fed with HFD (60% calories from fat) for 17 weeks, and the resultant pathophysiological effects were examined. Antibiotic treatment markedly attenuated gut inflammation and leakiness induced by HFD, whereas capsaicin showed limited effects on the gut. However, dietary capsaicin significantly increased PPAR-α expression in adipose tissue, while antibiotics had no such effect. Animals treated with a combination of capsaicin and antibiotics had the smallest body weight gain and fat pad index, as well as the lowest hepatic fat accumulation. Combination treatment also maximally improved insulin responsiveness, as indicated by insulin tolerance tests. These results suggest the co-treatment of capsaicin and antibiotics, a novel combination strategy, would play synergistically to attenuate the HFD-induced obesity, fatty liver and metabolic disorder.

Design alternatives, components key to optimum flares

International Nuclear Information System (INIS)

Cunha-Leite, O.

1992-01-01

A properly designed flare works as an emissions control system with greater than 98% combustion efficiency. The appropriate use of steam, natural gas, and air-assisted flare tips can result in smokeless combustion. Ground flare, otherwise the elevated flare is commonly chosen because it handles larger flow releases more economically. Flaring has become more complicated than just lighting up waste gas. Companies are increasingly concerned about efficiency. In addition, U.S. Occupational Safety and Health Administration (OSHA) and U.S. Environmental Protection Agency (EPA) have become more active, resulting in tighter regulations on both safety and emissions control. These regulations have resulted in higher levels of concern and involvement in safety and emissions matters, not to mention smoke, noise, glare, and odor. This first to two articles on flare design and components looks at elevated flares, flare tips, incinerator-type flares, flare pilots, and gas seals. Part 2 will examine knockout drums, liquid-seal drums, ignition systems, ground flares, vapor recovery systems, and flare noise

Search for relation between flares and photometric variability outside of flares in EV Lac

International Nuclear Information System (INIS)

Rojzman, G.Sh.

1984-01-01

The observations of the flare star EV Lac in July-September 1981 have confirmed the existence of photometric variability outside the flares during the night. It was found that, as a rule, a slow increase of brightness in U and B bands during 1-2 hours preceded the flares. It is suggested that the variability outside the flares is the result of the variability of chpomospheric emission lines and continuum that are emitted by the chromospheric preflare formations

Proton solar flares

International Nuclear Information System (INIS)

Shaposhnikova, E.F.

1979-01-01

The observations of proton solar flares have been carried out in 1950-1958 using the extrablackout coronograph of the Crimea astrophysical observatory. The experiments permit to determine two characteristic features of flares: the directed motion of plasma injection flux from the solar depths and the appearance of a shock wave moving from the place of the injection along the solar surface. The appearance of the shock wave is accompanied by some phenomena occuring both in the sunspot zone and out of it. The consistent flash of proton flares in the other groups of spots, the disappearance of fibres and the appearance of eruptive prominences is accomplished in the sunspot zone. Beyond the sunspot zone the flares occur above spots, the fibres disintegrate partially or completely and the eruptive prominences appear in the regions close to the pole

A “burning” therapy for burning mouth syndrome: preliminary results with the administration of topical capsaicin.

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Azzi, L; Croveri, F; Pasina, L; Porrini, M; Vinci, R; Manfredini, M; Tettamanti, L; Tagliabue, A; Silvestre-Rangil, J; Spadari, F

2017-01-01

Burning mouth syndrome is defined as an intraoral burning sensation for which no medical or dental cause can be found. Recently, researchers have demonstrated an altered trophism of the small nerve fibres and alterations in the numbers of TRPV-1 vanilloid receptors. Capsaicin is a molecule that is contained in hot peppers and is specifically detected by TRPV-1 vanilloid receptors that are distributed in the oral mucosae. We aimed at verifying if topical capsaicin could prove to be an effective treatment of Burning Mouth Syndrome. A group of 99 BMS patients were recruited. We subdivided the BMS patients into two groups: the collaborative patients, who expressed a predominantly neuropathic pattern of symptoms, and the non-collaborative patients, who were characterised by stronger psychogenic patterns of the syndrome. Both groups underwent topical therapy with capsaicin in the form of a mouth rinse 3 times a day for a long period. After 1 year of treatment, the final overall success rate was approximately 78%, but with a significant difference in the success rates of the two groups of patients (87% and 20% among the collaborative and non-collaborative patients, respectively; p=0.000). The use of topical capsaicin can improve the oral discomfort of BMS patients, especially during the first month of therapy, but it is more effective for those patients in which the neuropathic component of the syndrome is predominant. Our hypothesis is that chronic stimulation with capsaicin leads to decreases in burning symptoms. This phenomenon is called desensitisation and is accompanied by substantial improvements in oral symptoms.

Effect of duration of postherpetic neuralgia on efficacy analyses in a multicenter, randomized, controlled study of NGX-4010, an 8% capsaicin patch evaluated for the treatment of postherpetic neuralgia

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Rauck Richard

2010-10-01

Full Text Available Abstract Background Postherpetic neuralgia (PHN is a painful and difficult to treat complication of acute herpes zoster. Current treatment options provide only partial relief and are often limited by poor tolerability. We evaluated the safety and efficacy of a single 60-minute application of NGX-4010, an 8% capsaicin patch, in patients with PHN. Methods This multicenter, double-blind, controlled study randomized 155 patients 2:1 to receive either NGX-4010 or a 0.04% capsaicin control patch. Patients were at least 18 years old with PHN for at least 3 months, and an average Numeric Pain Rating Scale (NPRS score of 3 to 9. The primary efficacy endpoint was the percentage change in NPRS score from baseline to weeks 2-8. Results The mean percent reduction in "average pain for the past 24 hours" NPRS scores from baseline to weeks 2-8 was greater in the NGX-4010 group (36.5% compared with control (29.9% although the difference was not significant (p = 0.296. PGIC analysis demonstrated that more NGX-4010 recipients considered themselves improved (much, or very much compared with control at weeks 8 and 12, but the differences did not reach statistical significance. Post hoc analyses of patients with PHN for at least 6 months showed significantly greater reductions in "average pain for the past 24 hours" NPRS scores from baseline to weeks 2-8 in NGX-4010 patients compared to controls (37.6% versus 23.4%; p = 0.0291. PGIC analysis in this subgroup demonstrated that significantly more NGX-4010 recipients considered themselves much or very much improved compared with control at week 12 (40% versus 20%; p = 0.0403;. Conclusions Although treatment appeared to be safe and well tolerated, a single 60-minute application of NGX-4010 failed to show efficacy in this study which included patients with PHN for less than 6 months. Large reductions in pain observed among control patients with pain for less than 6 months may have been due to spontaneous resolution of PHN

Pharmacologic attenuation of cross-modal sensory augmentation within the chronic pain insula

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Harte, Steven E.; Ichesco, Eric; Hampson, Johnson P.; Peltier, Scott J.; Schmidt-Wilcke, Tobias; Clauw, Daniel J.; Harris, Richard E.

2016-01-01

Abstract Pain can be elicited through all mammalian sensory pathways yet cross-modal sensory integration, and its relationship to clinical pain, is largely unexplored. Centralized chronic pain conditions such as fibromyalgia are often associated with symptoms of multisensory hypersensitivity. In this study, female patients with fibromyalgia demonstrated cross-modal hypersensitivity to visual and pressure stimuli compared with age- and sex-matched healthy controls. Functional magnetic resonance imaging revealed that insular activity evoked by an aversive level of visual stimulation was associated with the intensity of fibromyalgia pain. Moreover, attenuation of this insular activity by the analgesic pregabalin was accompanied by concomitant reductions in clinical pain. A multivariate classification method using support vector machines (SVM) applied to visual-evoked brain activity distinguished patients with fibromyalgia from healthy controls with 82% accuracy. A separate SVM classification of treatment effects on visual-evoked activity reliably identified when patients were administered pregabalin as compared with placebo. Both SVM analyses identified significant weights within the insular cortex during aversive visual stimulation. These data suggest that abnormal integration of multisensory and pain pathways within the insula may represent a pathophysiological mechanism in some chronic pain conditions and that insular response to aversive visual stimulation may have utility as a marker for analgesic drug development. PMID:27101425

Tachycardia in response to remote capsaicin injection as a model for nociception in the ball python (Python regius).

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Williams, Catherine J A; James, Lauren E; Bertelsen, Mads F; Wang, Tobias

2016-07-01

To quantify the effect of subcutaneous (SC) capsaicin injection on heart rate (HR) in ball pythons (Python regius) and to assess the efficacy of two opioids (morphine and butorphanol) in modifying this response. Prospective, randomized, unmatched study. Eleven mixed-sex, captive-bred ball pythons. Snakes were randomly assigned to three groups (n = 6) by intramuscular premedication: 1) control: saline (0.9 mL); 2) morphine (10 mg kg(-1) ); and 3) butorphanol (10 mg kg(-1) ). Three snakes were tested twice and another two were tested three times in different treatments administered 1 month apart. Under isoflurane anaesthesia, snakes were instrumented with SC electrocardiogram (ECG) electrodes and an SC catheter for remote stimulus delivery. After recovery from anaesthesia, all snakes, in visual and audial isolation from the experimenter, received a sham stimulus of saline (0.4 mL) via the SC catheter. A nociceptive stimulus of SC capsaicin (3 mg in 0.2 mL saline with 7% Tween 80) was then applied by catheter at 7 hours after premedication. In a subset (n = 3), two sham injections (saline 0.2 mL) preceded the capsaicin treatment. HR was recorded via ECG, and changes in HR (ΔHR) from baseline were calculated for all stimulations. Capsaicin injection was associated with a significant increase in HR [peak ΔHR: saline group: 8.8 ± 7.1 beats minute(-1) ; capsaicin group: 21.1 ± 5.8 beats minute(-1) (p = 0.0055)] and integrated ΔHR as a function of time. The administration of morphine or butorphanol 7 hours prior to nociception failed to significantly reduce the peak and integrated ΔHR. Butorphanol caused marked, long-lasting sedation as assessed by muscle tone. The HR response to an SC capsaicin injection can serve as a nociceptive model in P. regius. Morphine and butorphanol administration did not reduce HR response to capsaicin stimulation but produced significantly different effects on pre-stimulation HR and sedation. © 2015 Association

Improved flare tip design

Energy Technology Data Exchange (ETDEWEB)

Gogolek, P. [Natural Resources Canada, Ottawa, ON (Canada). CANMET Energy Technology Centre

2004-07-01

This paper discusses the testing procedures and development of an improved flare tip design. Design objectives included performance equal to or better than utility flares at low wind speed; conversion efficiency; fuel slip; smoking; significant improvement at high wind speed; and no increase in trace emissions. A description of the testing facility of the flare tip was provided, with reference to the fact that the facility allowed for realistic near full scale gas flares in a single-pass flare test facility. Other details of the facility included: an adjustable ceiling; high capacity variable speed fan; sampling ports along working section in stack; windows along working section; and air cooled walls, floor, and ceiling. The fuels used in the flare tip included natural gas, propane, gasoline and inert gases. Details of wind speed, appurtenances and turbulence generating grids were presented, with reference to continuous gas emission measurements. A list of design constraints was provided. Flare performance included wind speed, turbulence and fuel composition. A chart of conversion inefficiencies with a correlation of wind speed and turbulence, fuel flow and pipe size was also presented. Several new tip designs were fabricated for testing, with screening tests for comparison to basic pipe and ranking designs. Significant improvements were found in one of the new designs, including results with 30 per cent propane in fuel. Emissions reduction from 10 to 35 per cent were noted. It was concluded that future work should focus on evaluating improved tip for stability at low wind speeds. Fuel slips are the primary source of emissions, and it was recommended that further research is necessary to improve existing flare tips. tabs, figs.

Oral treatment with methanolic extract of the root bark of Condalia buxifolia Reissek alleviates acute pain and inflammation in mice: Potential interactions with PGE2, TRPV1/ASIC and PKA signaling pathways.

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Simões, Róli Rodrigues; Dos Santos Coelho, Igor; do Espírito Santo, Caroline Cunha; Morel, Ademir Farias; Zanchet, Eliane Maria; Santos, Adair Roberto Soares

2016-06-05

The Condalia buxifolia root bark infusion is used in traditional medicine in Brazil as antipyretic, anti-inflammatory and anti-dysentery. Previous data from our group showed that methanolic extract of Condalia buxifolia (MECb) produced a marked antinociceptive effect in animal models of acute pain. The purpose of this study was to investigate the mechanisms of MECb-induced antinociception as measured by nocifensive behavior in pain induced by endogenous (prostaglandin E2) or exogenous (TRPs and ASIC agonist, and protein kinase A and C activators) chemical stimuli, and the potential role of PKA signaling and capsaicin-sensitive central C-fiber afferents. The effect of MECb administered orally (0.1-300mg/kg, i.g.) to mice on nociception induced by capsaicin (TRPV1 agonist), cinnamaldehyde (TRPA1 agonist), menthol (TRPM8 agonist), acidified saline (ASIC agonist), PMA (protein kinase C activator), PGE2 and forskolin (protein kinase A activator) was assessed. Moreover, this study also investigated the role of C-fibers desensitizing mice with a high dose of intrathecal capsaicin. Furthermore, this study performed the western blot to PKA phosphorylated on nocifensive behavior induced by forskolin. MECb was able to reduce the nociception and paw edema induced by capsaicin, acidified saline, PMA, PGE2 and forskolin, but not by cinnamaldehyde or menthol. Western blot analyses showed that MECb reduced the levels of PKA phosphorylation induced by forskolin in hind paws. Finally, ablating central afferent C-fibers abolished MECb antinociception. In accordance with its use in traditional medicine, these findings provide new evidence indicating that Condalia buxifolia reduces the acute painful behavior of animals caused by chemical stimuli. The precise mechanism of MECb antinociceptive activity is not completely understood but the results suggest involvement of PGE2, TRPV1/ASIC and PKA signaling pathways, and require integrity of the capsaicin-sensitive central C-fiber afferents

Pain increases during sympathetic arousal in patients with complex regional pain syndrome.

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Drummond, P D; Finch, P M; Skipworth, S; Blockey, P

2001-10-09

To investigate the effect of sympathetic arousal on pain and vasomotor responses in healthy control subjects and patients with complex regional pain syndrome (CRPS), and to determine whether pain increases in patients with particular symptoms. In experiments 1 and 2, capsaicin was applied to the forearm of 24 healthy subjects to induce thermal hyperalgesia. Vascular responses were monitored and subjects rated thermal hyperalgesia before and after being startled (experiment 1), and before, during, and after mental arithmetic, breath holding, forehead cooling, the Valsalva maneuver, and a cold pressor test in experiment 2. In a third experiment, sensitivity to heat, cold, and mechanical stimulation was investigated in 61 patients with CRPS. Pain ratings and vascular and electrodermal responses were recorded after patients were startled and during forehead cooling. In experiment 1, thermal hyperalgesia decreased in healthy control subjects after they were startled, and digital blood vessels constricted symmetrically. In experiment 2, thermal hyperalgesia decreased during and after other forms of sympathetic arousal. However, in experiment 3, ratings of clinical pain increased during forehead cooling or after being startled in over 70% of patients with CRPS. Pain increased most consistently during forehead cooling in patients with cold allodynia or punctate allodynia. Digital blood vessels constricted more intensely on the symptomatic than the nonsymptomatic side in patients with CRPS during sympathetic arousal. Normal inhibitory influences on pain during sympathetic arousal are compromised in the majority of patients with CRPS. The augmented vasoconstrictor response in the symptomatic limb during sympathetic arousal is consistent with adrenergic supersensitivity. An adrenergic sensitivity in nociceptive afferents might contribute to pain and hyperalgesia during sympathetic arousal in certain patients with CRPS.

[Aural Stimulation with Capsaicin Ointment Improved the Swallowing Function in Patients with Dysphagia: Evaluation by the SMRC Scale].

Science.gov (United States)

Kondo, Eiji; Jinnouchi, Osamu; Ohnishi, Hiroki; Kawata, Ikuji; Takeda, Noriaki

2015-11-01

Cough and swallowing reflexes are important airway-protective mechanisms against aspiration. Angiotensin-converting enzyme (ACE) inhibitors, one of the side effects of which is cough, have been reported to reduce the incidence of aspiration pneumonia in hypertensive patients with stroke. ACE inhibitors have also been reported to improve the swallowing function in post-stroke patients. On the other hand, stimulation of the Arnold nerve, the auricular branch of the vagus, triggers the cough reflex (Arnold's ear-cough reflex). Capsaicin, an agonist of Transient Receptor Potential Vanilloid 1 (TRPV1), has been shown to activate the peripheral sensory C-fibers. Stimulation of the sensory branches of the vagus in the laryngotracheal mucosa with capsaicin induces the cough reflex and has been reported to improve the swallowing function in patients with dysphagia. In our previous study, we showed that aural stimulation of the Arnold nerve with 0.025% capsaicin ointment improved the swallowing function, as evaluated by the endoscopic swallowing score, in 26 patients with dysphagia. In the present study, the video images of swallowing recorded in the previous study were re-evaluated using the SMRC scale by an independent otolaryngologist who was blinded to the information about the patients and the endoscopic swallowing score. The SMRC scale is used to evaluate four aspects of the swallowing function: 1) Sensory: the initiation of the swallowing reflex as assessed by the white-out timing; 2) Motion: the ability to hold blue-dyed water in the oral cavity and induce laryngeal elevation; 3) Reflex: glottal closure and the cough reflex induced by touching the epiglottis or arytenoid with the endoscope; 4) Clearance: pharyngeal clearance of the blue-dyed water after swallowing. Accordingly, we demonstrated that a single application of capsaicin ointment to the external auditory canal of patients with dysphagia significantly improved the R, but not the S, M or C scores, and this

Incidence and factors associated with flare-ups in a post graduate programme in the indian population.

Science.gov (United States)

Pamboo, Jaya; Hans, Manoj-Kumar; Kumaraswamy, Bangalore-Niranjan; Chander, Subhash; Bhaskaran, Sajeev

2014-12-01

The study had twin objectives: to assess the incidence of flare-ups (a severe problem requiring an unscheduled visit and treatment) among patients who received endodontic treatment in the Department of Conservative Dentistry and Endodontics in Vyas Dental college and hospital, Jodhpur during a period of one year, and also to examine the correlation with pre-operative and operative variables. Data was collected from 1023 teeth from 916 patients who had received endodontic treatment over a 12- month period. Information was obtained for each patient treated, including pulp and peri-radicular diagnosis for the tooth, presence of pre-operatory pain, type of medication being used, type of instrumentation technique used and number of appointments needed to complete the root canal treatment. The results showed an incidence of 2.35% for flare-ups from 1023 endodontically treated teeth. Statistical analysis was done using the chi-square test. Flare-ups were found to be affected significantly by gender of patient, presence of radiolucent lesions, patients taking pre-operative analgesic or anti-inflammatory drugs and on type of instrumentation technique. In contrast, there was no correlation between flare-ups and age, different arch/tooth groups and single or multiple visit endodontics. Key words:Anti-inflammatory, flare-ups, instrumentation, prospective.

Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX and Sirtuin1 (SIRT1

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Ming-Hung Lin

2016-06-01

Full Text Available Bladder cancer is one of the most frequent cancers among males, and its poor survival rate reflects problems with aggressiveness and chemo-resistance. Recent interest has focused on the use of chemopreventatives (nontoxic natural agents that may suppress cancer progression to induce targeted apoptosis for cancer therapy. Capsaicin, which has anti-cancer properties, is one such agent. It is known to preferentially inhibit a tumor-associated NADH oxidase (tNOX that is preferentially expressed in cancer/transformed cells. Here, we set out to elucidate the correlation between tNOX expression and the inhibitory effects of capsaicin in human bladder cancer cells. We showed that capsaicin downregulates tNOX expression and decreases bladder cancer cell growth by enhancing apoptosis. Moreover, capsaicin was found to reduce the expression levels of several proteins involved in cell cycle progression, in association with increases in the cell doubling time and enhanced cell cycle arrest. Capsaicin was also shown to inhibit the activation of ERK, thereby reducing the phosphorylation of paxillin and FAK, which leads to decreased cell migration. Finally, our results indicate that RNA interference-mediated tNOX depletion enhances spontaneous apoptosis, prolongs cell cycle progression, and reduces cell migration and the epithelial-mesenchymal transition. We also observed a downregulation of sirtuin 1 (SIRT1 in these tNOX-knockdown cells, a deacetylase that is important in multiple cellular functions. Taken together, our results indicate that capsaicin inhibits the growth of bladder cancer cells by inhibiting tNOX and SIRT1 and thereby reducing proliferation, attenuating migration, and prolonging cell cycle progression.

Mass-spectrometric identification of T-kininogen I/thiostatin as an acute-phase inflammatory protein suppressed by curcumin and capsaicin.

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Joe, Bina; Nagaraju, Anitha; Gowda, Lalitha R; Basrur, Venkatesha; Lokesh, Belur R

2014-01-01

Curcumin and capsaicin are dietary xenobiotics with well-documented anti-inflammatory properties. Previously, the beneficial effect of these spice principles in lowering chronic inflammation was demonstrated using a rat experimental model for arthritis. The extent of lowering of arthritic index by the spice principles was associated with a significant shift in macrophage function favoring the reduction of pro-inflammatory molecules such as reactive oxygen species and production and release of anti-inflammatory metabolites of arachidonic acid. Beyond the cellular effects on macrophage function, oral administration of curcumin and capsaicin caused alterations in serum protein profiles of rats injected with adjuvant to develop arthritis. Specifically, a 72 kDa acidic glycoprotein, GpA72, which was elevated in pre-arthritic rats, was significantly lowered by feeding either curcumin or capsaicin to the rats. Employing the tandem mass spectrometric approach for direct sequencing of peptides, here we report the identification of GpA72 as T-kininogen I also known as Thiostatin. Since T-kininogen I is an early acute-phase protein, we additionally tested the efficiency of curcumin and capsaicin to mediate the inflammatory response in an acute phase model. The results demonstrate that curcumin and capsaicin lower the acute-phase inflammatory response, the molecular mechanism for which is, in part, mediated by pathways associated with the lowering of T-kininogen I.

Mass-spectrometric identification of T-kininogen I/thiostatin as an acute-phase inflammatory protein suppressed by curcumin and capsaicin.

Directory of Open Access Journals (Sweden)

Bina Joe

Full Text Available Curcumin and capsaicin are dietary xenobiotics with well-documented anti-inflammatory properties. Previously, the beneficial effect of these spice principles in lowering chronic inflammation was demonstrated using a rat experimental model for arthritis. The extent of lowering of arthritic index by the spice principles was associated with a significant shift in macrophage function favoring the reduction of pro-inflammatory molecules such as reactive oxygen species and production and release of anti-inflammatory metabolites of arachidonic acid. Beyond the cellular effects on macrophage function, oral administration of curcumin and capsaicin caused alterations in serum protein profiles of rats injected with adjuvant to develop arthritis. Specifically, a 72 kDa acidic glycoprotein, GpA72, which was elevated in pre-arthritic rats, was significantly lowered by feeding either curcumin or capsaicin to the rats. Employing the tandem mass spectrometric approach for direct sequencing of peptides, here we report the identification of GpA72 as T-kininogen I also known as Thiostatin. Since T-kininogen I is an early acute-phase protein, we additionally tested the efficiency of curcumin and capsaicin to mediate the inflammatory response in an acute phase model. The results demonstrate that curcumin and capsaicin lower the acute-phase inflammatory response, the molecular mechanism for which is, in part, mediated by pathways associated with the lowering of T-kininogen I.

Transient magnetic field changes in flares

International Nuclear Information System (INIS)

Patterson, A.; Zirin, H.

1981-01-01

Magnetic changes have been detected with the videomagnetograph (VMG) at Big Bear during two large flares on 1979 November 5. Two kinds of changes were detected in both flares: a decrease in satellite field strength near the locus of the flare and the appearance of strong transient fields during the peak of the flare. We explain why we believe that the observed effects are real and not instrumental and discuss their significance for flare studies

Radio imaging of solar flares using the very large array - New insights into flare process

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Kundu, M. R.; Schmahl, E. J.; Vlahos, L.; Velusamy, T.

1982-01-01

An interpretation of VLA observations of microwave bursts is presented in an attempt to distinguish between certain models of flares. The VLA observations provide information about the pre-flare magnetic field topology and the existence of mildly relativistic electrons accelerated during flares. Examples are shown of changes in magnetic field topology in the hour before flares. In one case, new bipolar loops appear to emerge, which is an essential component of the model developed by Heyvaerts et al. (1977). In another case, a quadrupole structure, suggestive of two juxtaposed bipolar loops, appears to trigger the flare. Because of the observed diversity of magnetic field topologies in microwave bursts, it is believed that the magnetic energy must be dissipated in more than one way. The VLA observations are clearly providing means for sorting out the diverse flare models.

Modelling blazar flaring using a time-dependent fluid jet emission model - an explanation for orphan flares and radio lags

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Potter, William J.

2018-01-01

Blazar jets are renowned for their rapid violent variability and multiwavelength flares, however, the physical processes responsible for these flares are not well understood. In this paper, we develop a time-dependent inhomogeneous fluid jet emission model for blazars. We model optically thick radio flares for the first time and show that they are delayed with respect to the prompt optically thin emission by ∼months to decades, with a lag that increases with the jet power and observed wavelength. This lag is caused by a combination of the travel time of the flaring plasma to the optically thin radio emitting sections of the jet and the slow rise time of the radio flare. We predict two types of flares: symmetric flares - with the same rise and decay time, which occur for flares whose duration is shorter than both the radiative lifetime and the geometric path-length delay time-scale; extended flares - whose luminosity tracks the power of particle acceleration in the flare, which occur for flares with a duration longer than both the radiative lifetime and geometric delay. Our model naturally produces orphan X-ray and γ-ray flares. These are caused by flares that are only observable above the quiescent jet emission in a narrow band of frequencies. Our model is able to successfully fit to the observed multiwavelength flaring spectra and light curves of PKS1502+106 across all wavelengths, using a transient flaring front located within the broad-line region.

Photospheric Magnetic Field Properties of Flaring versus Flare-quiet Active Regions. II. Discriminant Analysis

Science.gov (United States)

Leka, K. D.; Barnes, G.

2003-10-01

We apply statistical tests based on discriminant analysis to the wide range of photospheric magnetic parameters described in a companion paper by Leka & Barnes, with the goal of identifying those properties that are important for the production of energetic events such as solar flares. The photospheric vector magnetic field data from the University of Hawai'i Imaging Vector Magnetograph are well sampled both temporally and spatially, and we include here data covering 24 flare-event and flare-quiet epochs taken from seven active regions. The mean value and rate of change of each magnetic parameter are treated as separate variables, thus evaluating both the parameter's state and its evolution, to determine which properties are associated with flaring. Considering single variables first, Hotelling's T2-tests show small statistical differences between flare-producing and flare-quiet epochs. Even pairs of variables considered simultaneously, which do show a statistical difference for a number of properties, have high error rates, implying a large degree of overlap of the samples. To better distinguish between flare-producing and flare-quiet populations, larger numbers of variables are simultaneously considered; lower error rates result, but no unique combination of variables is clearly the best discriminator. The sample size is too small to directly compare the predictive power of large numbers of variables simultaneously. Instead, we rank all possible four-variable permutations based on Hotelling's T2-test and look for the most frequently appearing variables in the best permutations, with the interpretation that they are most likely to be associated with flaring. These variables include an increasing kurtosis of the twist parameter and a larger standard deviation of the twist parameter, but a smaller standard deviation of the distribution of the horizontal shear angle and a horizontal field that has a smaller standard deviation but a larger kurtosis. To support the

What's an Asthma Flare-Up?

Science.gov (United States)

... Staying Safe Videos for Educators Search English Español Asthma Flare-Ups KidsHealth / For Parents / Asthma Flare-Ups ... español ¿Qué es una crisis asmática? What Are Asthma Flare-Ups? Keeping asthma under control helps kids ...

Feature Selection, Flaring Size and Time-to-Flare Prediction Using Support Vector Regression, and Automated Prediction of Flaring Behavior Based on Spatio-Temporal Measures Using Hidden Markov Models

Science.gov (United States)

Al-Ghraibah, Amani

Solar flares release stored magnetic energy in the form of radiation and can have significant detrimental effects on earth including damage to technological infrastructure. Recent work has considered methods to predict future flare activity on the basis of quantitative measures of the solar magnetic field. Accurate advanced warning of solar flare occurrence is an area of increasing concern and much research is ongoing in this area. Our previous work 111] utilized standard pattern recognition and classification techniques to determine (classify) whether a region is expected to flare within a predictive time window, using a Relevance Vector Machine (RVM) classification method. We extracted 38 features which describing the complexity of the photospheric magnetic field, the result classification metrics will provide the baseline against which we compare our new work. We find a true positive rate (TPR) of 0.8, true negative rate (TNR) of 0.7, and true skill score (TSS) of 0.49. This dissertation proposes three basic topics; the first topic is an extension to our previous work [111, where we consider a feature selection method to determine an appropriate feature subset with cross validation classification based on a histogram analysis of selected features. Classification using the top five features resulting from this analysis yield better classification accuracies across a large unbalanced dataset. In particular, the feature subsets provide better discrimination of the many regions that flare where we find a TPR of 0.85, a TNR of 0.65 sightly lower than our previous work, and a TSS of 0.5 which has an improvement comparing with our previous work. In the second topic, we study the prediction of solar flare size and time-to-flare using support vector regression (SVR). When we consider flaring regions only, we find an average error in estimating flare size of approximately half a GOES class. When we additionally consider non-flaring regions, we find an increased average

Aural stimulation with capsaicin ointment improved swallowing function in elderly patients with dysphagia: a randomized, placebo-controlled, double-blind, comparative study.

Science.gov (United States)

Kondo, Eiji; Jinnouchi, Osamu; Nakano, Seiichi; Ohnishi, Hiroki; Kawata, Ikuji; Okamoto, Hidehiko; Takeda, Noriaki

2017-01-01

The aim of this study was to assess whether aural stimulation with ointment containing capsaicin improves swallowing function in elderly patients with dysphagia. A randomized, placebo-controlled, double-blind, comparative study. Secondary hospital. Twenty elderly dysphagic patients with a history of cerebrovascular disorder or Parkinson's disease were randomly divided into two groups: 10 receiving aural stimulation with 0.025% capsaicin ointment and 10 stimulated with placebo. The ointments were applied to the external auditory canal with a cotton swab. Then, swallowing of a bolus of blue-dyed water was recorded using transnasal videoendoscopy, and the swallowing function was evaluated according to both endoscopic swallowing scoring and Sensory-Motor-Reflex-Clearance (SMRC) scale. The sum of endoscopic swallowing scores was significantly decreased 30 and 60 min after a single administration in patients treated with capsaicin, but not with placebo. Reflex score, but not Sensory, Motion and Clearance scores, of the SMRC scale was significantly increased 5, 30 and 60 min after single administration in patients treated with capsaicin, but not with placebo. No patient showed signs of adverse effects. As capsaicin is an agonist of the transient receptor potential vanilloid 1 (TRPV1), these findings suggest that improvement of the swallowing function, especially glottal closure and cough reflexes, in elderly dysphagic patients was due to TRPV1-mediated aural stimulation of vagal Arnold's nerve with capsaicin, but not with a nonspecific mechanical stimulation with a cotton swab.

Influences of misprediction costs on solar flare prediction

Science.gov (United States)

Huang, Xin; Wang, HuaNing; Dai, XingHua

2012-10-01

The mispredictive costs of flaring and non-flaring samples are different for different applications of solar flare prediction. Hence, solar flare prediction is considered a cost sensitive problem. A cost sensitive solar flare prediction model is built by modifying the basic decision tree algorithm. Inconsistency rate with the exhaustive search strategy is used to determine the optimal combination of magnetic field parameters in an active region. These selected parameters are applied as the inputs of the solar flare prediction model. The performance of the cost sensitive solar flare prediction model is evaluated for the different thresholds of solar flares. It is found that more flaring samples are correctly predicted and more non-flaring samples are wrongly predicted with the increase of the cost for wrongly predicting flaring samples as non-flaring samples, and the larger cost of wrongly predicting flaring samples as non-flaring samples is required for the higher threshold of solar flares. This can be considered as the guide line for choosing proper cost to meet the requirements in different applications.

Ablation of capsaicin sensitive afferent nerves impairs defence but not rapid repair of rat gastric mucosa.

Science.gov (United States)

Pabst, M A; Schöninkle, E; Holzer, P

1993-07-01

Capsaicin sensitive afferent neurones have previously been reported to play a part in gastric mucosal protection. The aim of this study was to investigate whether these nociceptive neurones strengthen mucosal defence against injury or promote rapid repair of the damaged mucosa, or both. This hypothesis was examined in anaesthetised rats whose stomachs were perfused with ethanol (25 or 50% in saline, wt/wt) for 30 minutes. The gastric mucosa was inspected 0 and 180 minutes after ethanol had been given at the macroscopic, light, and scanning electron microscopic level. Rapid repair of the ethanol injured gastric mucosa (reduction of deep injury, partial re-epithelialisation of the denuded surface) took place in rats anaesthetised with phenobarbital, but not in those anaesthetised with urethane. Afferent nerve ablation as a result of treating rats with a neurotoxic dose of capsaicin before the experiment significantly aggravated ethanol induced damage as shown by an increase in the area and depth of mucosal erosions. Rapid repair of the injured mucosa, however, as seen in rats anesthetised with phenobarbital 180 minutes after ethanol was given, was similar in capsaicin and vehicle pretreated animals. Ablation of capsaicin sensitive afferent neurones was verified by a depletion of calcitonin gene related peptide from the gastric corpus wall. These findings indicate that nociceptive neurones control mechanisms of defence against acute injury but are not required for rapid repair of injured mucosa.

Thermoreceptive innervation of human glabrous and hairy skin: a contact heat evoked potential analysis.

Science.gov (United States)

Granovsky, Yelena; Matre, Dagfinn; Sokolik, Alexander; Lorenz, Jürgen; Casey, Kenneth L

2005-06-01

The human palm has a lower heat detection threshold and a higher heat pain threshold than hairy skin. Neurophysiological studies of monkeys suggest that glabrous skin has fewer low threshold heat nociceptors (AMH type 2) than hairy skin. Accordingly, we used a temperature-controlled contact heat evoked potential (CHEP) stimulator to excite selectively heat receptors with C fibers or Adelta-innervated AMH type 2 receptors in humans. On the dorsal hand, 51 degrees C stimulation produced painful pinprick sensations and 41 degrees C stimuli evoked warmth. On the glabrous thenar, 41 degrees C stimulation produced mild warmth and 51 degrees C evoked strong but painless heat sensations. We used CHEP responses to estimate the conduction velocities (CV) of peripheral fibers mediating these sensations. On hairy skin, 41 degrees C stimuli evoked an ultra-late potential (mean, SD; N wave latency: 455 (118) ms) mediated by C fibers (CV by regression analysis: 1.28 m/s, N=15) whereas 51 degrees C stimuli evoked a late potential (N latency: 267 (33) ms) mediated by Adelta afferents (CV by within-subject analysis: 12.9 m/s, N=6). In contrast, thenar responses to 41 and 51 degrees C were mediated by C fibers (average N wave latencies 485 (100) and 433 (73) ms, respectively; CVs 0.95-1.35 m/s by regression analysis, N=15; average CV=1.7 (0.41) m/s calculated from distal glabrous and proximal hairy skin stimulation, N=6). The exploratory range of the human and monkey palm is enhanced by the abundance of low threshold, C-innervated heat receptors and the paucity of low threshold AMH type 2 heat nociceptors.

Flaring research update

International Nuclear Information System (INIS)

Reynen, B.A.

1999-01-01

Several studies regarding waste gas flaring have been conducted in an effort to determine the potential health and environmental impacts associated with flaring. Energy source conservation and greenhouse gas emissions reduction are other reasons for studying the issue. A brief outline for each of the following research priorities was given: (1) operating practices, (2) flare performance, focusing on improved combustion efficiency, (3) speciation, addressing the potential effects of incomplete combustion, (4) alternative technologies such as membrane technology, cryogenics and power generation to reduce flare gas volume, (5) improved liquid separation, concentrating on the removal of entrained liquids to improve performance and reduce emissions and (6) fate and transport, including plume modeling, ambient air monitoring, tracking of known toxins, primarily to address concerns of environmental groups.The expectation is that this broad and comprehensive research effort will yield substantive and credible scientific data, lead to cooperation in the research community, reduce emissions, beneficially impact on regulations and standards and gain the support of environmental organizations

Flare-up rate in pulpally necrotic molars in one-visit versus two-visit endodontic treatment.

Science.gov (United States)

Eleazer, P D; Eleazer, K R

1998-09-01

This retrospective study compared one-visit versus two-visit endodontic treatment. The same technique and materials were used before and after making the sole change to one-visit endodontic treatment in 1991. Treatment records of 402 consecutive patients with pulpally necrotic first and second molars were compared. In 201 patients, treatment was provided by debridement and instrumentation, followed by obturation at a second visit; whereas the second group received single visit therapy. Flare-ups were defined as either patient reports of pain not controlled with over-the-counter medication or as increasing swelling. Sixteen flare-ups (8%) occurred in the two-visit group versus six flare-ups (3%) for the one-visit group. This showed an advantage for one-visit treatment at a 95% confidence level. In a second comparison, one-visit patients who had previously received two-visit treatment for a different pulpally necrotic molar served as their own control. No significant differences were present in this subgroup of 17 patients.

Upstream petroleum industry flaring guide : review draft

International Nuclear Information System (INIS)

1999-03-01

The Alberta requirements and expectations for upstream petroleum flaring are presented. Flaring is associated with a wide range of energy activities including oil and gas well drilling and well completion operations. The guide incorporates the recommendations made to the Alberta Energy and Utilities Board (EUB) in June 1998 by the multi-stakeholder Clean Air Strategic Alliance (CASA) on associated or solution gas flaring. Additional requirements which address flaring issues not covered in the CASA report are also included in this guide. The Guide requires a 15 per cent reduction in solution gas flare volume by the end of year 2000 from the 1996 baseline, and a 25 per cent reduction by the end of 2001. The Guide prescribes new flare performance requirements for all flares, within three years for existing solution gas flares, five years for flares at other existing permanent facilities. It sets personal consultation and public notification requirements for new and existing solution gas batteries, and new sulphur recovery requirements for facilities not covered by existing EUB regulations. The Guide also addresses the question of conflict resolution to deal with flaring concerns, the release of flaring and venting data, the proposed reduction of flare limits, progress towards minimizing requirements for electricity generators using otherwise flared gas, annual reporting to the EUB, and management framework review in 2001

Chemical analysis of freshly prepared and stored capsaicin solutions: implications for tussigenic challenges.

Science.gov (United States)

Kopec, Scott E; DeBellis, Ronald J; Irwin, Richard S

2002-01-01

The purpose of this study was to assess the stability of stored capsaicin solutions and the actual concentrations of prepared solutions. Capsaicin solutions ranging in concentration from 0.5 to 128 microM were mixed and analyzed using high performance liquid chromatography. Samples of varying concentrations were then stored under 4 environmental conditions: 4 degrees C and protected from light, room temperature (RT) exposed to light, RT protected from light, and -20 degrees C and protected from light. The concentrations were measured every other month for 1 year. Actual concentrations of freshly prepared solutions were on average 88.3% of predicted. For solutions stored at 4 degrees C, there was a decrease only in the lower concentrations (0.5, 1, and 2 microM) after 2 months (P=0.003). Solutions stored at RT exposed to light decreased in concentration after 6 months (P=0.020), and solutions stored at RT protected from light decreased in concentration after 4 months (P=0.026). The group stored at -20 degrees C decreased in concentration after 1 year (P=0.033). We conclude that the actual concentration of capsaicin solution is less than predicted, and solutions of 4 microM or higher concentration are stable for 1 year if stored at 4 degrees C protected from light.

Jaw-motor effects of experimental jaw-muscle pain and stress in patients with deep bite and matched control subjects

DEFF Research Database (Denmark)

Sonnesen, Liselotte; Svensson, Peter

2013-01-01

clenching, during evoked pain and stress between deep bite patients and controls was investigated. DESIGN: In 30 deep bite patients and in 30 sex-/age-matched controls with neutral occlusion EMG activity was recorded bilaterally from masseter and anterior temporalis muscles before and during evoked pain......OBJECTIVE: The effect of experimental jaw-muscle pain and stress on masticatory muscle activity in TMD-patients has been discussed. Furthermore, associations between TMD and deep bite patients have been studied. Accordingly in the present study, comparison of EMG responses at rest, maximal...... and before and during a stress task. Evoked pain was induced by injections of glutamate into the masseter (local pain) and brachioradialis (remote pain) muscles and resting EMG activity was recorded before and after 1, 2, 3, 4, 5 and 10min. A precision task was used to simulate a stressful condition and EMG...

The capsaicin cough reflex in patients with symptoms elicited by odorous chemicals

DEFF Research Database (Denmark)

Holst, H.; Arendt-Nielsen, Lars; Mosbech, H.

2010-01-01

between groups in age, body mass index or pulmonary function. The median C5 were 129 micromol/L (control group), 48 micromol/L (multiple chemical sensitivity patients), 32 micromol/L (eczema patients). The reporting of lower airway symptoms from odorous chemicals was significantly (p......Patients with multiple chemical sensitivity and eczema patients with airway symptoms elicited by odorous chemicals have enhanced cough reflex to capsaicin when applying the tidal breathing method. The aims of the present study were to test whether the capsaicin induced cough reflex was enhanced...... when applying the single breath inhalation method in similar groups of patients with symptoms related to odorous chemicals e.g. other persons wearing of perfume; and to investigate to what extent the reporting of lower airway symptoms influenced the cough reflex. Sixteen patients fulfilling Cullen...

Psychophysical examination in patients with post-mastectomy pain

DEFF Research Database (Denmark)

Gottrup, Hanne; Andersen, Jørn; Arendt-Nielsen, Lars

2000-01-01

and contralateral sides in 15 women with spontaneous pain and sensory abnormalities and 11 pain-free women. Testing included the VAS score of spontaneous pain, detection and pain threshold to thermal and mechanical stimuli, temporal summation to repetitive heat and pinprick stimuli, and assessment of skin blood...... to side difference was seen in pressure pain threshold in the pain-free group. Evoked pain intensity to repetitive stimuli at 0.2 and 2.0 Hz was significantly higher on the operated side in pain patients compared to the control area while no such difference was seen in pain-free patients. Cutaneous blood...

Flare observation by the satellite 'Hinotori'

International Nuclear Information System (INIS)

Tanaka, Toshio

1981-01-01

The satellite ''Hinotori'' makes 5 rounds a day and is doing flare observation. The total observation days amounted to 94 days. Among the observed flares, the quiet mode flares were picked up from the reproduced data. The plot of the time variation of flares was obtained for four energy bands, HXM-1 (17 to 40 keV), HXM2 - 7 (over 40 keV), FLM-L (1 to 5 keV) and FLM-H (5 to 12 keV). At present, the judge of flares is made by using hard X-ray of the HXM-1 plot. False signals were completely removed. A large percentage of big flares was collected by Hinotori, eleven X-class flares were recorded. The operation status of ''Hinotori'' has been in good condition. The spin frequency has increased with a constant rate. (Kato, T.)

Personalized Pain Therapy : Is the answer in the genes?

NARCIS (Netherlands)

M. Matić (Maja)

2017-01-01

textabstractThe experience of pain is very subjective and multidimensional, displaying substantial variability between individuals even when exposed to an identical pain-evoking stimulus. Differences in gender, age, ethnicity and anxiety level are among the known factors that contribute to this

A Combined Water Extract of Frankincense and Myrrh Alleviates Neuropathic Pain in Mice via Modulation of TRPV1

Directory of Open Access Journals (Sweden)

Danyou Hu

2017-01-01

Full Text Available Frankincense and myrrh are widely used in clinics as a pair of herbs to obtain a synergistic effect for relieving pain. To illuminate the analgesia mechanism of frankincense and myrrh, we assessed its effect in a neuropathic pain mouse model. Transient receptor potential vanilloid 1 (TRPV1 plays a crucial role in neuropathic pain and influences the plasticity of neuronal connectivity. We hypothesized that the water extraction of frankincense and myrrh (WFM exerted its analgesia effect by modulating the neuronal function of TRPV1. In our study, WFM was verified by UHPLC-TQ/MS assay. In vivo study showed that nociceptive response in mouse by heat and capsaicin induced were relieved by WFM treatment. Furthermore, thermal hypersensitivity and mechanical allodynia were also alleviated by WFM treatment in a chronic constriction injury (CCI mouse model. CCI resulted in increased TRPV1 expression at both the mRNA and protein levels in predominantly small-to-medium neurons. However, after WFM treatment, TRPV1 expression was reverted in real-time PCR, Western blot, and immunofluorescence experiments. Calcium response to capsaicin was also decreased in cultured DRG neurons from CCI model mouse after WFM treatment. In conclusion, WFM alleviated CCI-induced mechanical allodynia and thermal hypersensitivity via modulating TRPV1.

Offshore production flares: a PETROBRAS review

Energy Technology Data Exchange (ETDEWEB)

Pagot, Paulo R.; Burmann, Clovis P.; Araujo, Paulo Bento de; Motomura, Tsukasa [PETROBRAS S.A., Rio de Janeiro, RJ (Brazil)

2008-07-01

The purpose of the present work is to briefly present the offshore flare system technological evolution and the main design criteria for flare and its supporting structure. In order to perform the aimed task, this work was divided into two parts: the first part presents the technological evolution of the offshore production flares and the second one discusses the flare system designing criteria. The evolution of the technology associated to the offshore production flares is organized by the authors just dividing the history in four chronological phases. Each phase is defined by the predominant use of the, by the time, most up-to-date technological alternative and it will be described with the help of sketches, drawings, photographs, data and information about the platforms where such technologies were applied. The second part of the present work discusses the dimensional criteria, interesting aspects and flaws of the offshore flare systems in two different fields, which are: definition of the flare system capacity; and flow and thermal design of the flare system. (author)

Fast electrons in small solar flares

International Nuclear Information System (INIS)

Lin, R.P.

1975-01-01

Because approximately 5-100 keV electrons are frequently accelerated and emitted by the Sun in small flares, it is possible to define a detailed characteristic physical picture of these events. The review summarizes both the direct spacecraft observations of non-relativistic solar electrons, and observations of the X-ray and radio emission generated by these particles at the Sun and in the interplanetary medium. These observations bear on the basic astrophysical process of particle acceleration in tenuous plasmas. It is found that in many small solar flares the approximately 5-100 keV electrons accelerated during flash phase constitute the bulk of the total flare energy. Thus the basic flare mechanism in these flares essentially converts the available flare energy into fast electrons. These electrons may produce the other flare electromagnetic emissions through their interactions with the solar atmosphere. In large proton flares these electrons may provide the energy to eject material from the Sun and to create a shock wave which could then accelerate nuclei and electrons to much higher energies. (Auth.)

Parameterization of solar flare dose

International Nuclear Information System (INIS)

Lamarche, A.H.; Poston, J.W.

1996-01-01

A critical aspect of missions to the moon or Mars will be the safety and health of the crew. Radiation in space is a hazard for astronauts, especially high-energy radiation following certain types of solar flares. A solar flare event can be very dangerous if astronauts are not adequately shielded because flares can deliver a very high dose in a short period of time. The goal of this research was to parameterize solar flare dose as a function of time to see if it was possible to predict solar flare occurrence, thus providing a warning time. This would allow astronauts to take corrective action and avoid receiving a dose greater than the recommended limit set by the National Council on Radiation Protection and Measurements (NCRP)

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

Institute of Scientific and Technical Information of China (English)

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

2006-01-01

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

Persistent idiopathic facial pain

DEFF Research Database (Denmark)

Maarbjerg, Stine; Wolfram, Frauke; Heinskou, Tone Bruvik

2017-01-01

Introduction: Persistent idiopathic facial pain (PIFP) is a poorly understood chronic orofacial pain disorder and a differential diagnosis to trigeminal neuralgia. To address the lack of systematic studies in PIFP we here report clinical characteristics and neuroimaging findings in PIFP. Methods...... pain 7 (13%), hypoesthesia 23 (48%), depression 16 (30%) and other chronic pain conditions 17 (32%) and a low prevalence of stabbing pain 21 (40%), touch-evoked pain 14 (26%) and remission periods 10 (19%). The odds ratio between neurovascular contact and the painful side was 1.4 (95% Cl 0.4–4.4, p = 0.......565) and the odds ratio between neurovascular contact with displacement of the trigeminal nerve and the painful side was 0.2 (95% Cl 0.0–2.1, p = 0.195). Conclusion: PIFP is separated from trigeminal neuralgia both with respect to the clinical characteristics and neuroimaging findings, as NVC was not associated...

The thermal phase of solar flares

International Nuclear Information System (INIS)

Hirayama, Tadashi

1979-01-01

This paper is described on the observation of the flares, and then the numerical simulation on the structural change in the corona and the chromosphere during the flare is briefly discussed. Most of the flares occur on the active region where the density and the electron temperature are higher than those in the quiet region. The temperature and density increase after the flare started. The temperature of the pre-flare chromosphere is about 6000 K, and it rises during the flare. The temperature of the transition region is about 10 5 K, and the gas pressure increases more than one order of magnitude during the flare. Sometimes, the flaring in the photosphere is observed. Large amount of mass ejected at the time of the flare is observed. Most probable energy source of the flare is the magnetic energy contained in the form of electric current. Liberation of this energy into the corona is discussed in this paper. It is assumed that a column of unit area is standing vertically in the corona, the top being closed. A hydrostatic model of the corona-chromosphere is constructed, in which the heat source is assumed to be in the corona. As the results of calculation, it can be said that the temperature of the flaring corona does not depend upon the liberated energy, the density in the corona increases proportionally to the energy, and particles are supplied from the chromosphere with the upward velocity of about 100 km/s. The gas pressure of the transition region can become up to three orders of magnitude larger. All these are consistent with the observation. Extension of this calculation is also performed. (Kato, T.)

Negative body image associated with changes in the visual body appearance increases pain perception.

Directory of Open Access Journals (Sweden)

Michihiro Osumi

Full Text Available Changing the visual body appearance by use of as virtual reality system, funny mirror, or binocular glasses has been reported to be helpful in rehabilitation of pain. However, there are interindividual differences in the analgesic effect of changing the visual body image. We hypothesized that a negative body image associated with changing the visual body appearance causes interindividual differences in the analgesic effect although the relationship between the visual body appearance and analgesic effect has not been clarified. We investigated whether a negative body image associated with changes in the visual body appearance increased pain. Twenty-five healthy individuals participated in this study. To evoke a negative body image, we applied the method of rubber hand illusion. We created an "injured rubber hand" to evoke unpleasantness associated with pain, a "hairy rubber hand" to evoke unpleasantness associated with embarrassment, and a "twisted rubber hand" to evoke unpleasantness associated with deviation from the concept of normality. We also created a "normal rubber hand" as a control. The pain threshold was measured while the participant observed the rubber hand using a device that measured pain caused by thermal stimuli. Body ownership experiences were elicited by observation of the injured rubber hand and hairy rubber hand as well as the normal rubber hand. Participants felt more unpleasantness by observing the injured rubber hand and hairy rubber hand than the normal rubber hand and twisted rubber hand (p<0.001. The pain threshold was lower under the injured rubber hand condition than with the other conditions (p<0.001. We conclude that a negative body appearance associated with pain can increase pain sensitivity.

A comprehensive Fabry-related pain questionnaire for adult patients.

Science.gov (United States)

Üçeyler, Nurcan; Magg, Barbara; Thomas, Phillip; Wiedmann, Silke; Heuschmann, Peter; Sommer, Claudia

2014-11-01

Pain may be the earliest symptom in Fabry disease and presents with a distinct phenotype including triggerable pain attacks, evoked pain, pain crises, and chronic pain. Current pain questionnaires do not reflect the special phenotype of Fabry disease-associated pain, which hampers its systematic evaluation as the basis of correct diagnosis and effective treatment. A questionnaire specifically designed to assess Fabry disease-associated pain is thus urgently needed. At the Würzburg Fabry Center for Interdisciplinary Therapy (FAZIT), Germany, we developed and validated the first face-to-face Fabry Pain Questionnaire (FPQ) for adult patients. The initial version of the FPQ was tested in a pilot study with 20 consecutive Fabry disease patients. The performance of the revised FPQ was assessed in a first (n=56) and second (n=20) validation phase in consecutive Fabry disease patients. For this, patients were interviewed at baseline and 2 weeks later. We determined the test-retest reliability and validity of the FPQ in comparison to data obtained with the Neuropathic Pain Symptom Inventory. The FPQ contains 15 questions on the 4 pain phenotypes of Fabry disease (pain attacks, pain crises, evoked pain, chronic pain) in childhood and adulthood, on pain development during life with and without enzyme replacement therapy, and on everyday life impairment due to pain. This first disease-specific questionnaire is a valuable tool for baseline and follow-up assessment of pain in Fabry disease patients and may guide treatment in this distinct pain phenotype. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

The Effects of Dietary Iron and Capsaicin on Hemoglobin, Blood Glucose, Insulin Tolerance, Cholesterol, and Triglycerides, in Healthy and Diabetic Wistar Rats.

Science.gov (United States)

Márquez-Ibarra, Adriana; Huerta, Miguel; Villalpando-Hernández, Salvador; Ríos-Silva, Mónica; Díaz-Reval, María I; Cruzblanca, Humberto; Mancilla, Evelyn; Trujillo, Xóchitl

2016-01-01

Our aim was to assess the effects of dietary iron, and the compound capsaicin, on hemoglobin as well as metabolic indicators including blood glucose, cholesterol, triglycerides, insulin, and glucose tolerance. Our animal model was the Wistar rat, fed a chow diet, with or without experimentally induced diabetes. Diabetic males were fed control, low, or high-iron diets, the latter, with or without capsaicin. Healthy rats were fed identical diets, but without the capsaicin supplement. We then measured the parameters listed above, using the Student t-test and ANOVA, to compare groups. Healthy rats fed a low-iron diet exhibited significantly reduced total cholesterol and triglyceride levels, compared with rats fed a control diet. Significantly reduced blood lipid was also provoked by low dietary iron in diabetic rats, compared with those fed a control diet. Insulin, and glucose tolerance was only improved in healthy rats fed the low-iron diet. Significant increases in total cholesterol were found in diabetic rats fed a high-iron diet, compared with healthy rats fed the same diet, although no statistical differences were found for triglycerides. Hemoglobin levels, which were not statistically different in diabetic versus healthy rats fed the high-iron diet, fell when capsaicin was added. Capsaicin also provoked a fall in the level of cholesterol and triglycerides in diabetic animals, versus diabetics fed with the high iron diet alone. In conclusion, low levels of dietary iron reduced levels of serum triglycerides, hemoglobin, and cholesterol, and significantly improved insulin, and glucose tolerance in healthy rats. In contrast, a high-iron diet increased cholesterol significantly, with no significant changes to triglyceride concentrations. The addition of capsaicin to the high-iron diet (for diabetic rats) further reduced levels of hemoglobin, cholesterol, and triglycerides. These results suggest that capsaicin, may be suitable for the treatment of elevated hemoglobin

AUTONOMIC NERVOUS ACTIVITY AND LIPID OXIDATION POSTEXERCISE WITH CAPSAICIN IN THE HUMANS

Directory of Open Access Journals (Sweden)

Ki Ok Shin

2010-06-01

Full Text Available This study evaluated the synergistic effects of acute exercise with capsaicin (200mg upon the restoration of cardiac autonomic functions and depolarization- repolarization interval as well as substrate oxidation. Nine healthy males [21.9(0.8 yrs] volunteered for this study. Cardiac autonomic activity, metabolic responses, and the ECG QT intervals were continuously measured during 5 min at rest and postexercise recovery after 30 min exercise at 50% VO2max on a stationary ergometer with placebo (ECON or capsaicin intake (ECAP, and no exercise control (NCON were randomized. Results indicated that the HF power reflecting parasympathetic activity significantly returned to the baseline much faster during ECAP than ECON trial during postexercise [122.1 (23.2 vs. 60.2 (11.7 %, p < 0.05]. The ECAP trial significantly decreased RQ [0.79(0.02 vs. 0.85 (0.03, p < 0.05] with significantly greater fat oxidation [69.3 (6.0 vs. 49.4 (10.8 %, p < 0.05] in comparison to NCON trial during 120 min postexercise recovery without any adverse effects on cardiac electrical stability as determined by trigger-averaged ECG QT interval analyses. We suggest that capsaicin before the exercise may contribute to the improvement of cardio-protective functions and metabolic responses as one of the beneficial supplements accelerating faster restoration of autonomic activity and enhanced lipolysis during postexercise recovery without any adverse effects on cardiac electrical stability

SLIPPING MAGNETIC RECONNECTIONS WITH MULTIPLE FLARE RIBBONS DURING AN X-CLASS SOLAR FLARE

International Nuclear Information System (INIS)

Zheng, Ruisheng; Chen, Yao; Wang, Bing

2016-01-01

With the observations of the Solar Dynamics Observatory , we present the slipping magnetic reconnections with multiple flare ribbons (FRs) during an X1.2 eruptive flare on 2014 January 7. A center negative polarity was surrounded by several positive ones, and three FRs appeared. The three FRs showed apparent slipping motions, and hook structures formed at their ends. Due to the moving footpoints of the erupting structures, one tight semi-circular hook disappeared after the slippage along its inner and outer edges, and coronal dimmings formed within the hook. The east hook also faded as a result of the magnetic reconnection between the arcades of a remote filament and a hot loop that was impulsively heated by the under flare loops. Our results are accordant with the slipping magnetic reconnection regime in three-dimensional standard model for eruptive flares. We suggest that the complex structures of the flare are likely a consequence of the more complex flux distribution in the photosphere, and the eruption involves at least two magnetic reconnections.

Solar flares through electric current interaction

International Nuclear Information System (INIS)

De Jager, C.

1988-01-01

The fundamental hypothesis by Alfven and Carlqvist (1967) that solar flares are related to electrical currents in the solar chromosphere and low corona is investigated in the light of modern observations. The authors confirm the important role of currents in solar flares. There must be tens of such current loops (flux threads) in any flare, and this explains the hierarchy of bursts in flares. The authors summarize quantitative data on energies, numbers of particles involved and characteristic times. A special case is the high-energy flare: this one may originate in the same way as less energetic ones, but it occurs in regions with higher magnetic field strength. Because of the high particle energies involved their emission seats live only very briefly; hence the area of emission coincides virtually with the seat of the instability. These flares are therefore the best examples for studying the primary instability leading to the flare. Finally, the authors compare the merits of the original Alfven-Carlqvist idea (that flares originate by current interruption) with the one that they are due to interaction (reconnection) between two or more fluxthreads. The authors conclude that a final decision cannot yet by made, although the observed extremely short time constants of flare bursts seem to demand a reconnection-type instability rather than interruption of a circuit

Identification of Gene-Specific Polymorphisms and Association with Capsaicin Pathway Metabolites in Capsicum annuum L. Collections

Science.gov (United States)

Abburi, Venkata L.; Alaparthi, Suresh Babu; Unselt, Desiree; Hankins, Gerald; Park, Minkyu; Choi, Doil

2014-01-01

Pepper (Capsicum annuum L.) is an economically important crop with added nutritional value. Production of capsaicin is an important quantitative trait with high environmental variance, so the development of markers regulating capsaicinoid accumulation is important for pepper breeding programs. In this study, we performed association mapping at the gene level to identify single nucleotide polymorphisms (SNPs) associated with capsaicin pathway metabolites in a diverse Capsicum annuum collection during two seasons. The genes Pun1, CCR, KAS and HCT were sequenced and matched with the whole-genome sequence draft of pepper to identify SNP locations and for further characterization. The identified SNPs for each gene underwent candidate gene association mapping. Association mapping results revealed Pun1 as a key regulator of major metabolites in the capsaicin pathway mainly affecting capsaicinoids and precursors for acyl moieties of capsaicinoids. Six different SNPs in the promoter sequence of Pun1 were found associated with capsaicin in plants from both seasons. Our results support that CCR is an important control point for the flux of p-coumaric acid to specific biosynthesis pathways. KAS was found to regulate the major precursors for acyl moieties of capsaicinoids and may play a key role in capsaicinoid production. Candidate gene association mapping of Pun1 suggested that the accumulation of capsaicinoids depends on the expression of Pun1, as revealed by the most important associated SNPs found in the promoter region of Pun1. PMID:24475113

An oral TRPV1 antagonist attenuates laser radiant-heat-evoked potentials and pain ratings from UV(B)-inflamed and normal skin.

Science.gov (United States)

Schaffler, Klaus; Reeh, Peter; Duan, W Rachel; Best, Andrea E; Othman, Ahmed A; Faltynek, Connie R; Locke, Charles; Nothaft, Wolfram

2013-02-01

Laser (radiant-heat) evoked potentials (LEPs) from vertex-EEG peak-to-peak (PtP) amplitude were used to determine acute antinociceptive/antihyperalgesic efficacy of ABT-102, a novel TRPV1 antagonist efficacious in preclinical pain models, compared with active controls and placebo in normal and UV(B)-inflamed skin. This was a randomized, placebo- and active-controlled, double-blind, intra-individual, crossover trial. Twenty-four healthy subjects received six sequences of single doses of ABT-102 (0.5, 2, 6 mg), etoricoxib 90 mg, tramadol 100 mg and placebo. Painful stimuli were induced by CO(2) -laser on normal and UV(B) -inflamed skin. LEPs and visual analogue scale (VAS-pain) ratings were taken at baseline and hourly up to 8 h post-dose from both skin types. Compared with placebo, significant mean decreases in the primary variable of LEP PtP-amplitude from UV(B)-inflamed skin were observed with ABT-102 6 mg (P < 0.001), ABT-102 2 mg (P = 0.002), tramadol 100 mg (P < 0.001), and etoricoxib 90 mg (P = 0.001) over the 8 h period; ABT-102 0.5 mg was similar to placebo. ABT-102 6 mg was superior to active controls over the 8 h period (P < 0.05) whereas ABT-102 2 mg was comparable. Improvements in VAS scores compared with placebo were observed with ABT-102 6 mg (P < 0.001) and ABT-102 2 mg (P = 0.002). ABT-102 average plasma concentrations were 1.3, 4.4 and 9.4 ng ml(-1) for the 0.5, 2 and 6 mg doses, respectively. There were no clinically significant safety findings. TRPV-1 antagonism appears promising in the management of clinical pain, but requires further investigation. © 2012 Abbott. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Dwarf Star Erupts in Giant Flare

Science.gov (United States)

2005-01-01

This movie taken by NASA'S Galaxy Evolution Explorer shows one of the largest flares, or star eruptions, ever recorded at ultraviolet wavelengths. The star, called GJ 3685A, just happened to be in the Galaxy Evolution Explorer's field of view while the telescope was busy observing galaxies. As the movie demonstrates, the seemingly serene star suddenly exploded once, then even more intensely a second time, pouring out in total about one million times more energy than a typical flare from our Sun. The second blast of light constituted an increase in brightness by a factor of at least 10,000. Flares are huge explosions of energy stemming from a single location on a star's surface. They are caused by the brief destruction of a star's magnetic fields. Many types of stars experience them, though old, small, rapidly rotating 'red dwarfs' like GJ 3685A tend to flare more frequently and dramatically. These stars, called flare stars, can experience powerful eruptions as often as every few hours. Younger stars, in general, also erupt more often. One of the reasons astronomers study flare stars is to gain a better picture and history of flare events taking place on the Sun. A preliminary analysis of the GJ 3685A flare shows that the mechanisms underlying stellar eruptions may be more complex than previously believed. Evidence for the two most popular flare theories was found. Though this movie has been sped up (the actual flare lasted about 20 minutes), time-resolved data exist for each one-hundredth of a second. These observations were taken at 2 p.m. Pacific time, April 24, 2004. In the still image, the time sequence starts in the upper left panel, continues in the upper right, then moves to the lower left and ends in the lower right. The circular and linear features that appear below and to the right of GJ 3685A during the flare event are detector artifacts caused by the extreme brightness of the flare.

Sun and solar flares

Energy Technology Data Exchange (ETDEWEB)

McKenna-Lawlor, S. (Saint Patrick' s Coll., Maynooth (Ireland))

1982-07-01

The subject is discussed under the headings: the sun's core (thermonuclear reactions, energy transfer from core through radiation zone, convection zone, photosphere, chromosphere and corona); the photosphere (convection, granulation, sunspots, magnetic fields, solar cycle, rotation of the sun); solar variability and paleoclimatic records (correlation of low solar activity with increased /sup 14/C production in atmosphere); the chromosphere and corona (turbulence, temperature, coronal streamers, energy transfer); solar flares (cosmic rays, aurorae, spectra, velocity of flares, prominences, mechanisms of flares); the solar wind.

Mechanisms underlying ectopic persistent tooth-pulp pain following pulpal inflammation.

Directory of Open Access Journals (Sweden)

Shingo Matsuura

Full Text Available In order to clarify the peripheral mechanisms of ectopic persistent pain in a tooth pulp following pulpal inflammation of an adjacent tooth, masseter muscle activity, phosphorylated extracellular signal-regulated protein kinase (pERK and TRPV1 immunohistochemistries and satellite cell activation using glial fibrillary acidic protein (GFAP immunohistochemistry in the trigeminal ganglion (TG were studied in the rats with molar tooth-pulp inflammation. And, Fluorogold (FG and DiI were also used in a neuronal tracing study to analyze if some TG neurons innervate more than one tooth pulp. Complete Freund's adjuvant (CFA or saline was applied into the upper first molar tooth pulp (M1 in pentobarbital-anesthetized rats, and capsaicin was applied into the upper second molar tooth pulp (M2 on day 3 after the CFA or saline application. Mean EMG activity elicited in the masseter muscle by capsaicin application to M2 was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats. The mean number of pERK-immunoreactive (IR TG cells was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats. Application of the satellite cell inhibitor fluorocitrate (FC into TG caused a significant depression of capsaicin-induced masseter muscle activity and a significant reduction of satellite cell activation. The number of TRPV1-IR TG cells innervating M2 was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats, and that was decreased following FC injection into TG. Furthermore, 6% of TG neurons innervating M1 and/or M2 innervated both M1 and M2. These findings suggest that satellite cell activation following tooth pulp inflammation and innervation of multiple tooth pulps by single TG neurons may be involved in the enhancement of the activity of TG neurons innervating adjacent non-inflamed teeth that also show enhancement of TRPV1 expression in TG neurons, resulting in the ectopic persistent tooth

Flare Characteristics from X-ray Light Curves

Science.gov (United States)

Gryciuk, M.; Siarkowski, M.; Sylwester, J.; Gburek, S.; Podgorski, P.; Kepa, A.; Sylwester, B.; Mrozek, T.

2017-06-01

A new methodology is given to determine basic parameters of flares from their X-ray light curves. Algorithms are developed from the analysis of small X-ray flares occurring during the deep solar minimum of 2009, between Solar Cycles 23 and 24, observed by the Polish Solar Photometer in X-rays (SphinX) on the Complex Orbital Observations Near-Earth of Activity of the Sun-Photon (CORONAS- Photon) spacecraft. One is a semi-automatic flare detection procedure that gives start, peak, and end times for single ("elementary") flare events under the assumption that the light curve is a simple convolution of a Gaussian and exponential decay functions. More complex flares with multiple peaks can generally be described by a sum of such elementary flares. Flare time profiles in the two energy ranges of SphinX (1.16 - 1.51 keV, 1.51 - 15 keV) are used to derive temperature and emission measure as a function of time during each flare. The result is a comprehensive catalogue - the SphinX Flare Catalogue - which contains 1600 flares or flare-like events and is made available for general use. The methods described here can be applied to observations made by Geosynchronous Operational Environmental Satellites (GOES), the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) and other broad-band spectrometers.

Statistical investigation of flare stars. III. Flare stars in the general galactic star field

International Nuclear Information System (INIS)

Mirzoyan, L.V.; Ambaryan, V.V.; Garibdzhanyan, A.T.; Mirzoyan, A.L.

1989-01-01

Some questions relating to the existence of a large number of flare stars in the general star field of the Galaxy are discussed. It is shown that only a small proportion of them can be found by photographic observations, and the fraction of field flare stars among such stars found in the regions of star clusters and associations does not exceed 10%. The ratio of the numbers of flare stars of the foreground and the background for a particular system depends on its distance, reaching zero at a distance of about 500 pc. The spatial density of flare stars in the Pleiades is at least two orders of magnitude greater than in the general galactic field. A lower limit for the number of flare stars in the Galaxy is estimated at 4.2 ·10 9 , and the number of nonflare red dwarfs at 2.1·10 10 . There are grounds for believing that they were all formed in star clusters and associations

Technical and economic analysis use of flare gas into alternative energy as a breakthrough in achieving zero routine flaring

Science.gov (United States)

Petri, Y.; Juliza, H.; Humala, N.

2018-03-01

The activity of exploring natural oil and gas will produce gas flare 0.584 MMSCFD. A gas flare is the combustion of gas remaining to avoid poisonous gas like H2S and CO which is very dangerous for human and environmental health. The combustion can bring about environmental pollution and losses because it still contains valuable energy. It needs the policy to encourage the use of flare gas with Zero Routine Flaring and green productivity to reduce waste and pollution. The objective of the research was to determine the use of gas flare so that it will have economic value and can achieve Zero Routine Flaring. It was started by analysing based on volume or rate and composition gas flare was used to determine technical feasibility, and the estimation of the gas reserves as the determination of the economy of a gas well. The results showed that the use of flare gas as fuel for power generation feasible to be implemented technically and economically with Internal Rate of Return (IRR) 19.32% and the Payback Period (PP) 5 year. Thus, it can increase gas flare value economically and can achieve a breakthrough in Zero Routine Flaring.

Flare Seismology from SDO Observations

Science.gov (United States)

Lindsey, Charles; Martinez Oliveros, Juan Carlos; Hudson, Hugh

2011-10-01

Some flares release intense seismic transients into the solar interior. These transients are the sole instance we know of in which the Sun's corona exerts a conspicuous influence on the solar interior through flares. The desire to understand this phenomenon has led to ambitious efforts to model the mechanisms by which energy stored in coronal magnetic fields drives acoustic waves that penetrate deep into the Sun's interior. These mechanisms potentially involve the hydrodynamic response of the chromosphere to thick-target heating by high-energy particles, radiative exchange in the chromosphere and photosphere, and Lorentz-force transients to account for acoustic energies estimated up to at 5X10^27 erg and momenta of order 6X10^19 dyne sec. An understanding of these components of flare mechanics promises more than a powerful diagnostic for local helioseismology. It could give us fundamental new insight into flare mechanics themselves. The key is appropriate observations to match the models. Helioseismic observations have identified the compact sources of transient seismic emission at the foot points of flares. The Solar Dynamics Observatory is now giving us high quality continuum-brightness and Doppler observations of acoustically active flares from HMI concurrent with high-resolution EUV observations from AIA. Supported by HXR observations from RHESSI and a broad variety of other observational resources, the SDO promises a leading role in flare research in solar cycle 24.

Scent-evoked nostalgia.

Science.gov (United States)

Reid, Chelsea A; Green, Jeffrey D; Wildschut, Tim; Sedikides, Constantine

2015-01-01

Can scents evoke nostalgia; what might be the psychological implications of such an evocation? Participants sampled 12 scents and rated the extent to which each scent was familiar, arousing and autobiographically relevant, as well as the extent to which each scent elicited nostalgia. Participants who were high (compared to low) in nostalgia proneness reported more scent-evoked nostalgia, and scents elicited greater nostalgia to the extent that they were arousing, familiar and autobiographically relevant. Scent-evoked nostalgia predicted higher levels of positive affect, self-esteem, self-continuity, optimism, social connectedness and meaning in life. In addition, scent-evoked nostalgia was characterised by more positive emotions than either non-nostalgic autobiographical memories or non-nostalgic non-autobiographical memories. Finally, scent-evoked nostalgia predicted in-the-moment feelings of personal (general or object-specific) nostalgia. The findings represent a foray into understanding the triggers and affective signature of scent-evoked nostalgia.

Effect of hypnotic pain modulation on brain activity in patients with temporomandibular disorder pain

DEFF Research Database (Denmark)

Abrahamsen, Randi; Dietz, Martin; Lodahl, Sanne

2010-01-01

hyperalgesia. Direct contrasts between control and hypnotic hypoalgesia conditions demonstrated significant decreases in right posterior insula and BA21, as well as left BA40 during hypoalgesia. These findings are the first to describe hypnotic modulation of brain activity associated with nociceptive......Hypnosis modulates pain perception but the associated brain mechanisms in chronic pain conditions are poorly understood. Brain activity evoked by painful repetitive pin-prick stimulation of the left mental nerve region was investigated with use of fMRI in 19 patients with painful temporomandibular...... condition and significantly higher in the hypnotic hyperalgesia condition. In the control condition, painful stimulation caused significant activation of right posterior insula, primary somatosensory cortex (SI), BA21, and BA6, and left BA40 and BA4. Painful stimulation during hypnotic hyperalgesia...

Feasibility of flare gas reformation to practical energy in Farashband gas refinery: no gas flaring.

Science.gov (United States)

Rahimpour, Mohammad Reaza; Jokar, Seyyed Mohammad

2012-03-30

A suggested method for controlling the level of hazardous materials in the atmosphere is prevention of combustion in flare. In this work, three methods are proposed to recover flare gas instead of conventional gas-burning in flare at the Farashband gas refinery. These methods aim to minimize environmental and economical disadvantages of burning flare gas. The proposed methods are: (1) gas to liquid (GTL) production, (2) electricity generation with a gas turbine and, (3) compression and injection into the refinery pipelines. To find the most suitable method, the refinery units that send gas to the flare as well as the required equipment for the three aforementioned methods are simulated. These simulations determine the amount of flare gas, the number of GTL barrels, the power generated by the gas turbine and the required compression horsepower. The results of simulation show that 563 barrels/day of valuable GTL products is produced by the first method. The second method provides 25 MW electricity and the third method provides a compressed natural gas with 129 bar pressure for injection to the refinery pipelines. In addition, the economics of flare gas recovery methods are studied and compared. The results show that for the 4.176MMSCFD of gas flared from the Farashband gas refinery, the electricity production gives the highest rate of return (ROR), the lowest payback period, the highest annual profit and mild capital investment. Therefore, the electricity production is the superior method economically. Copyright © 2012 Elsevier B.V. All rights reserved.

Interaction between Mu and Delta Opioid Receptor Agonists in an Assay of Capsaicin-Induced Thermal Allodynia in Rhesus Monkeys