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Muscle and bone pressure pain threshold and pain tolerance in fibromyalgia patients and controls.  


Pressure pain thresholds and pressure pain tolerances on non-trigger-point muscle and bone were measured with a dolorimeter in 46 female patients with primary fibromyalgia and in 50 healthy women of the same age. The pressure pain thresholds and the pressure pain tolerances on both muscle and bone were lower in the fibromyalgia patients than in the healthy controls. All the differences were statistically highly significant, though there was a certain degree of overlapping between the patients and the controls. It is concluded that patients with primary fibromyalgia have a generalized amplification of pain sensitivity, a sign that might be useful in the diagnosis of fibromyalgia. PMID:1514890

Mikkelsson, M; Latikka, P; Kautiainen, H; Isomeri, R; Isomäki, H



Effects of stress on pain threshold and tolerance in children with recurrent abdominal pain.  


Models of stress-induced hyperalgesia state that exposure to stress can exaggerate subsequent pain experiences. Studies using both animal and human subjects have shown evidence for hyperalgesia as a function of stress [e.g., Jorum E. Analgesia or hyperalgesia following stress correlates with emotional behavior in rats. Pain 1988;32:341-48; Peckerman A, Hurwitz BE, Saab PG, Llabre MM, McCabe PM, Schneiderman N. Stimulus dimensions of the cold pressor test and the associated patterns of cardiovascular response. Psychophysiology 1994;31:282-90; Gameiro et al. Nociception and anxiety-like behavior in rats submitted to different periods of restraint stress. Physiol. Behav. 2006;87:643-49; Lucas et al. Visceral pain and public speaking stress: neuroendocrine and immune cell responses in healthy subjects. Brain Behav. Immun. 2006;20:49-56]. However, the role of stress in pediatric pain is not well understood. This study examined stress reactivity and pain tolerance and sensitivity in a population of children with Recurrent abdominal pain (RAP). Forty-nine children meeting criteria for RAP (28 female; mean age 13years; range 9-17years) were randomly assigned to either a condition in which they completed an experimental stressor paradigm (stress interview, serial subtraction task) followed by a pain task (cold pressor) or a condition in which they received the pain task prior to the stress tasks. Children who underwent the stress tasks before the pain task exhibited lower levels of pain tolerance than those who received the pain task first (p<.01); no differences were found between the two groups in pain threshold or pain intensity ratings. Further, pain tolerance was not related to individual differences in physiological reactivity (heart rate change) to the stressor. The present research demonstrates the first evidence of the occurrence of stress-induced hyperalgesia in a pediatric pain population. PMID:17716818

Dufton, Lynette M; Konik, Brian; Colletti, Richard; Stanger, Catherine; Boyer, Margaret; Morrow, Sara; Compas, Bruce E



Reliability of pain tolerance threshold testing by applying an electrical current stimulus to the alveolar ridge.  


The purpose of this study was to assess the reliability of testing pain tolerance threshold (PTT) by applying an electrical current stimulus to the alveolar ridge. Twenty volunteers studying or working at the Nihon University School of Dentistry at Matsudo participated in this study. Participants were seated comfortably on a dental chair in a quiet room during testing. A single operator obtained mucosal PTT measurements around the right greater palatine foramen using a Neurometer CPT/C(®) device (Neurotron Inc., Baltimore, MD, USA) to deliver electrical stimulation at frequencies of 5, 250 and 2000 Hz. The participant released a button to automatically discontinue the stimulus when it could no longer be tolerated. Two types of factors were confirmed: the consistency of repeated measurements and a potential carry-over effect on PTTs. The consistency and carry-over effects of pain with regard to PTT measurements were analysed via Cronbach's coefficient ?. The Cronbach's coefficient ? of PTTs calculated more than 6 days of PTT testing at 5, 250 and 2000 Hz was 0·97, 0·95 and 0·97, respectively, suggesting that the consistency of the measurements was excellent. The Cronbach's coefficient ? calculated when the three frequencies of 5, 250 and 2000 Hz were applied in different orders was 0·91, 0·87 and 0·90, respectively, suggesting no carry-over effect. In conclusion, the measurement of PTTs at the alveolar ridge as assessed by applying an electrical current stimulus with an electro-diagnostic device exhibited excellent reliability, and thus, it constitutes a widely available option for PTT measurement in the clinical setting. PMID:24814257

Nakashima, Y; Kimoto, S; Kawai, Y



The effects of total sleep deprivation, selective sleep interruption and sleep recovery on pain tolerance thresholds in healthy subjects.  


The aim of this study was to compare the effects of total sleep deprivation (TSD), rapid eye movement (REM) sleep and slow wave sleep (SWS) interruption and sleep recovery on mechanical and thermal pain sensitivity in healthy adults. Nine healthy male volunteers (age 26--43 years) were randomly assigned in this double blind and crossover study to undergo either REM sleep or SWS interruption. Periods of 6 consecutive laboratory nights separated by at least 2 weeks were designed as follows: N1 Adaptation night; N2 Baseline night; N3 Total sleep deprivation (40 h); N4 and N5 SWS or REM sleep interruption; N6 Recovery. Sleep was recorded and scored using standard methods. Tolerance thresholds to mechanical and thermal pain were assessed using an electronic pressure dolorimeter and a thermode operating on a Peltier principle. Relative to baseline levels, TSD decreased significantly mechanical pain thresholds (-8%). Both REM sleep and SWS interruption tended to decrease mechanical pain thresholds. Recovery sleep, after SWS interruption produced a significant increase in mechanical pain thresholds (+ 15%). Recovery sleep after REM sleep interruption did not significantly increase mechanical pain thresholds. No significant differences in thermal pain thresholds were detected between and within periods. In conclusion this experimental study in healthy adult volunteers has demonstrated an hyperalgesic effect related to 40 h TSD and an analgesic effect related to SWS recovery. The analgesic effect of SWS recovery is apparently greater than the analgesia induced by level I (World Health Organization) analgesic compounds in mechanical pain experiments in healthy volunteers. PMID:11285053

Onen, S H; Alloui, A; Gross, A; Eschallier, A; Dubray, C



Tactile threshold and pressure pain threshold during treatment of orofacial pain: an explorative study  

Microsoft Academic Search

The aim of the present study was to evaluate the pressure pain threshold (PPT), tactile threshold (TT) and pain intensity as measured on a Visual Analogue Scale (VAS) in patients with pain in the orofacial region. Twenty-six patients with myogenous pain (7 ss), myogenous and capsular pain (11 ss) or neuropathic pain (8 ss) participated in the study. At baseline,

Wojciech Drobek; Antoon De Laat; Joseph Schoenaers



Systemic Inflammation Decreases Pain Threshold in Humans In Vivo  

PubMed Central

Background Hyperalgesia is a well recognized hallmark of disease. Pro-inflammatory cytokines have been suggested to be mainly responsible, but human data are scarce. Changes in pain threshold during systemic inflammation evoked by human endotoxemia, were evaluated with three quantitative sensory testing methods. Methods and Results Pressure pain thresholds, electrical pain thresholds and tolerance to the cold pressor test were measured before and 2 hours after the intravenous administration of 2 ng/kg purified E. coli endotoxin in 27 healthy volunteers. Another 20 subjects not exposed to endotoxemia served as controls. Endotoxemia led to a rise in body temperature and inflammatory symptom scores and a rise in plasma TNF-?, IL-6, IL-10 and IL-1RA. During endotoxemia, pressure pain thresholds and electrical pain thresholds were reduced with 20±4 % and 13±3 %, respectively. In controls only a minor decrease in pressure pain thresholds (7±3 %) and no change in electrical pain thresholds occurred. Endotoxin-treated subjects experienced more pain during the cold pressor test, and fewer subjects were able to complete the cold pressor test measurement, while in controls the cold pressor test results were not altered. Peak levels and area under curves of each individual cytokine did not correlate to a change in pain threshold measured by one of the applied quantitative sensory testing techniques. Conclusions and Significance In conclusion, this study shows that systemic inflammation elicited by the administration of endotoxin to humans, results in lowering of the pain threshold measured by 3 quantitative sensory testing techniques. The current work provides additional evidence that systemic inflammation is accompanied by changes in pain perception.

de Goeij, Moniek; van Eijk, Lucas T.; Vanelderen, Pascal; Wilder-Smith, Oliver H.; Vissers, Kris C.; van der Hoeven, Johannes G.; Kox, Matthijs; Scheffer, Gert Jan; Pickkers, Peter



Assessment of pressure-pain thresholds and central sensitization of pain in lateral epicondylalgia.  


OBJECTIVE.: To assess pain sensitivity and spreading hyperalgesia in lateral epicondylalgia (LE). SUBJECTS.: Twenty-two women with LE, and 38 controls were included. OUTCOME MEASURES.: Computerized cuff pressure algometry was used for assessment of pressure-pain threshold and tolerance. The stimulus was applied using a single (stimulation-area: 241?cm(2) ) or double-chambered (stimulation-area: 482?cm(2) ) tourniquet on the arm and leg. Spatial summation was expressed as the ratio between pressure-pain thresholds to single and double cuff-chamber stimulation. During 10-minute constant pressure stimulation at intensity relative to the individual pain threshold, the pain intensity was continuously recorded using an electronic visual analogue scale (VAS), and from this the degree of temporal summation was estimated. For LE, a Doppler ultrasound examination of the elbow was made to identify inflammation. RESULTS.: In LE compared with controls the pressure-pain threshold and tolerance were on average reduced by respectively 31% (nonsignificant) and 18% (nonsignificant) on the lower arm and by 32% (P?pain thresholds were on average reduced by 20% (P?pain tolerance by 10% (nonsignificant) on the painful compared with the asymptomatic side. Spatial summation (P?pain hypersensitivity and Doppler ultrasound into clinically meaningful subgroups with varying duration of symptoms and different degrees of central sensitization. These groups may require different pain management strategies. PMID:23279601

Jespersen, Anders; Amris, Kirstine; Graven-Nielsen, Thomas; Arendt-Nielsen, Lars; Bartels, Else Marie; Torp-Pedersen, Søren; Bliddal, Henning; Danneskiold-Samsoe, Bente



Auricular electrical stimulation and dental pain threshold.  

PubMed Central

A modified double-blind evaluation of naloxone reversibility of dental analgesia produced by auricular electrical stimulation (AES) was examined in 40 subjects assigned randomly to one of four groups: AES followed by saline (AS), AES followed by naloxone (AN), placebo AES followed by saline (PS), and placebo AES followed by naloxone (PN). Dental pain threshold was tested using a hand-held dental pulp tester. A second investigator administered the true or placebo AES using an electrical stimulator. A third investigator injected intravenously saline or naloxone. The subjects and investigators 1 and 3 were blind to all treatment conditions. A repeated measures analysis of variance revealed a significant difference among the four groups. The AES groups exhibited a statistically significant 18% elevation of pain threshold, whereas the two placebo stimulation groups (PS and PN) remained essentially unchanged. The mean pain threshold increased to more than 23% for group AS, but fell to less than 12% for the subjects in group AN, who were given naloxone. These findings indicate a small but significant elevation of pain threshold by AES, an effect partially blocked by naloxone, suggesting an endogenous opioid system as one mechanism for AES analgesia. Images Figure 1 Figure 2

Simmons, M. S.; Oleson, T. D.



Dopamine Transporter Genotype Dependent Effects of Apomorphine on Cold Pain Tolerance in Healthy Volunteers  

PubMed Central

The aims of this study were to assess the effects of the dopamine agonist apomorphine on experimental pain models in healthy subjects and to explore the possible association between these effects and a common polymorphism within the dopamine transporter gene. Healthy volunteers (n?=?105) participated in this randomized double-blind, placebo-controlled, cross-over trial. Heat pain threshold and intensity, cold pain threshold, and the response to tonic cold pain (latency, intensity, and tolerance) were evaluated before and for up to 120 min after the administration of 1.5 mg apomorphine/placebo. A polymorphism (3?-UTR 40-bp VNTR) within the dopamine transporter gene (SLC6A3) was investigated. Apomorphine had an effect only on tolerance to cold pain, which consisted of an initial decrease and a subsequent increase in tolerance. An association was found between the enhancing effect of apomorphine on pain tolerance (120 min after its administration) and the DAT-1 polymorphism. Subjects with two copies of the 10-allele demonstrated significantly greater tolerance prolongation than the 9-allele homozygote carriers and the heterozygote carriers (p?=?0.007 and p?=?0.003 in comparison to the placebo, respectively). In conclusion, apomorphine administration produced a decrease followed by a genetically associated increase in cold pain tolerance.

Treister, Roi; Pud, Dorit; Ebstein, Richard P.; Eisenberg, Elon



Aesthetic value of paintings affects pain thresholds.  


Pain is modulated by cognitive factors, including attention and emotions. In this study we evaluated the distractive effect of aesthetic appreciation on subjectively rated pain (visual analogue scale;VAS) and multi-channel evoked potentials induced by CO(2) laser stimulation of the left hand in twelve healthy volunteers. Subjects were stimulated by laser in the absence of other external stimulation (baseline condition) and while looking at different paintings they had previously rated as beautiful, neutral or ugly. The view of paintings previously appreciated as beautiful produced lower pain scores and a clear inhibition of the P2 wave amplitude, localized in the anterior cingulate cortex; the inhibition of P2 wave amplitude was lesser or not significant during the presentation of the ugly or neutral paintings, respectively. Dipole source localization analysis of the LEP peaks showed significant changes during different conditions, with a shift from the posterior to the anterior right cingulated cortex while looking at paintings previously rated as beautiful. Our results provide evidence that pain may be modulated at cortical level by the aesthetic content of the distracting stimuli. PMID:18762434

de Tommaso, Marina; Sardaro, Michele; Livrea, Paolo



Validity of pressure pain thresholds in female workers with and without recurrent low back pain  

Microsoft Academic Search

Recurrent low back pain (LBP) is a common pain condition in elderly workers in a variety of occupations, but little is known\\u000a about its origin and the mechanisms leading to an often disabling sensation of pain that may be persistent or intermittent.\\u000a In the present study we evaluated the pressure pain thresholds (PPTs) in subjects suffering from recurrent LBP, as

Peter Schenk; Thomas Laeubli; Andreas Klipstein



Silica Nanoconstruct Cellular Toleration Threshold In Vitro  

PubMed Central

The influence of geometry of silica nanomaterials on cellular uptake and toxicity on epithelial and phagocytic cells was studied. Three types of amine-terminated silica nanomaterials were prepared and characterized via the modified Stober method, namely spheres (178±27 nm), worms (232±22 nm × 1348±314 nm) and cylinders (214±29 nm × 428±66 nm). The findings of the study suggest that in this size range and for the cell types studied, geometry does not play a dominant role in the modes of toxicity and uptake of these particles. Rather, a concentration threshold and cell type dependent toxicity of all particle types was observed. This correlated with confocal microscopy observations, as all nanomaterials were observed to be taken up in both cell types, with a greater extent in phagocytic cells. It must be noted that there appears to be a concentration threshold at ~100 µg/mL, below which there is limited to no impact of the nanoparticles on membrane integrity, mitochondrial function, phagocytosis or cell death. Analysis of cell morphology by transmission electron microscopy, colocalization experiments with intracellular markers and Western Blot results provide evidence of potential involvement of lysosomal escape, autophagic like activity, compartmental fusion and recycling in response to intracellular nanoparticle accumulation. These processes could be involved in cellular coping or defense mechanisms. The manipulation of physicochemical properties to enhance or reduce toxicity paves the way for the safe design of silica-based nanoparticles for use in nanomedicine.

Herd, Heather L.; Malugin, Alexander; Ghandehari, Hamidreza



Modification of Electrical Pain Threshold by Voluntary Breathing-Controlled Electrical Stimulation (BreEStim) in Healthy Subjects  

PubMed Central

Background Pain has a distinct sensory and affective (i.e., unpleasantness) component. BreEStim, during which electrical stimulation is delivered during voluntary breathing, has been shown to selectively reduce the affective component of post-amputation phantom pain. The objective was to examine whether BreEStim increases pain threshold such that subjects could have improved tolerance of sensation of painful stimuli. Methods Eleven pain-free healthy subjects (7 males, 4 females) participated in the study. All subjects received BreEStim (100 stimuli) and conventional electrical stimulation (EStim, 100 stimuli) to two acupuncture points (Neiguan and Weiguan) of the dominant hand in a random order. The two different treatments were provided at least three days apart. Painful, but tolerable electrical stimuli were delivered randomly during EStim, but were triggered by effortful inhalation during BreEStim. Measurements of tactile sensation threshold, electrical sensation and electrical pain thresholds, thermal (cold sensation, warm sensation, cold pain and heat pain) thresholds were recorded from the thenar eminence of both hands. These measurements were taken pre-intervention and 10?min post-intervention. Results There was no difference in the pre-intervention baseline measurement of all thresholds between BreEStim and EStim. The electrical pain threshold significantly increased after BreEStim (27.5±6.7% for the dominant hand and 28.5±10.8% for the non-dominant hand, respectively). The electrical pain threshold significantly decreased after EStim (9.1±2.8% for the dominant hand and 10.2±4.6% for the non–dominant hand, respectively) (F[1, 10]?=?30.992, p?=?.00024). There was no statistically significant change in other thresholds after BreEStim and EStim. The intensity of electrical stimuli was progressively increased, but no difference was found between BreEStim and EStim. Conclusion Voluntary breathing controlled electrical stimulation selectively increases electrical pain threshold, while conventional electrical stimulation selectively decreases electrical pain threshold. This may translate into improved pain control.

Li, Shengai; Berliner, Jeffrey C.; Melton, Danielle H.; Li, Sheng



Effect of manipulated state aggression on pain tolerance.  


Swearing produces a pain lessening (hypoalgesic) effect for many people; an emotional response may be the underlying mechanism. In this paper, the role of manipulated state aggression on pain tolerance and pain perception is assessed. In a repeated-measures design, pain outcomes were assessed in participants asked to play for 10 minutes a first-person shooter video game vs a golf video game. Sex differences were explored. After playing the first-person shooter video game, aggressive cognitions, aggressive affect, heart rate, and cold pressor latency were increased, and pain perception was decreased. These data indicate that people become more pain tolerant with raised state aggression and support our theory that raised pain tolerance from swearing occurs via an emotional response. PMID:23045874

Stephens, Richard; Allsop, Claire



A rise in pain threshold during labor: A prospective clinical trial  

Microsoft Academic Search

To evaluate changes in pain threshold before, during and after labor in a prospective clinical trial. Forty pregnant women at term were included. Pain threshold in 18 specific pressure points was evaluated using a dolorimeter. Woman underwent pain threshold assessment at term before labor, during the active phase of labor and postpartum. Subjective pain intensity was assessed by the parturient

Iris Ohel; Asnat Walfisch; Dorit Shitenberg; Eyal Sheiner; Mordechai Hallak



Effects of mechanical stimulation in measurement of thermal pain threshold.  


The improved thermal dolorimeter developed by Fukumoto has made it easy to measure thermal pain thresholds, but mechanical stimulations may be included as the probe is pressed into the skin. In order to evaluate these effects of mechanical stimulation on the improved thermal dolorimeter, the pain threshold temperatures were measured by a probe pressed to the human skin surface with weighting loads from 0.5 to 2.5 kgf. The loads of 2.0-2.5 kgf felt invasive to 8 of the 12 subjects, i.e., they experienced pain and numbness. The threshold temperature of one of these subjects, who developed water blisters around load-added area on the skin after the experiments, exceeded 50 degrees C. The result that no significant difference could be found among the thresholds at the loads of over 2.0 kgf suggests the load of less than 2.0 kgf should be kept to execute proper experiments. In order to investigate other effects on thermal property by compressing, the blood flow was measured when the skin was compressed and three dimensional heat transfer simulations were conducted. The results of the simulations demonstrated that the temperatures of the heat source which were measurable in practice differed approximately 1 to 2 degrees C from the true thresholds. The velocity of heating is also increased and subjects will be given stronger feelings of heating. PMID:9431705

Satoh, T; Fukumoto, I



Pain Tolerance, Arousal, and Personality Relationships of Athletes and Nonathletes  

ERIC Educational Resources Information Center

In this study, college athletes and nonathletes performed a muscular endurance task to determine pain tolerance, during which galvanic skin-response measures of arousal were obtained. The Bernreuter Personality Inventory was administered after this treatment. (JS)

Ellison, Kerry; Freischlag, Jerry



[Pharmacological correction of pain sensitivity threshold in magnesium deficiency].  


The purpose of this study was to compare effect of: Mg L-aspartate and MgCl2 alone and in combination with pyridoxine (B6) on hyperalgesia in rats fed with Mg-deficient diet. To induce hypomagnesemia, two hundred rats were placed on a Mg-deficient diet (MP Biomedicals Inc., OH) and demineralized water. To evaluate pain sensitivity, motor and vocalization threshold in response to a mechanical stimulus (Randall-Selitto paw pressure test) and tail withdrawal, simple and brief vocalization threshold in response to an electrical stimulation (algesimetry by electrical stimulation of the tail through intracutaneous needles) were assessed. In our study Mg deficiency results in reduced vocalization threshold by 42% in response to a mechanical stimulus. Thresholds of motor tail response, simple vocalization and brief vocalization after discharge in response to an electrical stimulation were decreased by 32.5%, 20.5% and 23.8%. Oral magnesium salts led to normalization of thresholds of pain sensitivity with a return to pre-deficient levels. Magnesium salts in combinations with pyridoxine tended to be significantly more effective in Randall-Selitto paw pressure test as compared with salts without pyridoxine. The effect of studied salts was comparable with those observed in Magne B6 treatment and significantly higher than in magnesium sulfate treatment. PMID:20731120

Spasiov, A A; Iezhitsa, I N; Kharitonova, M V; Kravchenko, M S



Pain threshold and pain recovery after experimental stimulation in patients with burning mouth syndrome.  


The aim of the present study was to examine pain threshold and pain recovery in patients with burning mouth syndrome (BMS) and matched no-pain controls. Twenty female patients diagnosed with BMS without organic gross changes were enrolled in the study. Twenty control subjects were chosen from age-matched healthy female volunteers. We compared the thermal pain threshold using heat beam dolorimeter on the finger and tongue between patients and controls. Warm (at 50 degrees C for 5 s), cold (at 0 degrees C for 30 s) and mechanical (stimulation by electric tooth brush for 15 s) stimulation was applied to the tongue for both groups. Participants were asked to rate the subjective pain using a visual analogue scale (VAS). Although there was no significant differences between patients and controls in terms of the threshold on the finger, the threshold on the tongue was significantly higher in patients than in controls. We suggest there were peripheral dysfunction at the tongue, and/or central dysfunction in patients with BMS. Among the three types of stimulation, the patients perceived significantly the highest pain from the mechanical stimulation for the first 5 min after the stimulation. Furthermore, when patients with BMS perceived some pain, they continued to complain of the pain longer and more intricately than the controls. This indicates that the pain of the patients is strongly affected not only at a sensory component but also at an affective/motivational component than the controls. However, we should be cautious of simply advancing psychogenic theory in this etiology. PMID:11952919

Ito, Mikiko; Kurita, Kenichi; Ito, Takako; Arao, Munetaka



Medial tibial pain pressure threshold algometry in runners.  


PURPOSE: Pressure algometry (PA) may provide an objective and standardised tool in assessing palpation pain over the tibia. The purpose of this study was to analyse the intra-rater repeatability of PA and to determine whether tibial tenderness in healthy runners differ from runners with medial tibial stress syndrome (MTSS). METHODS: Pressure algometry was performed on 20 asymptomatic runners (40 legs) and 9 MTSS patients (14 symptomatic legs) at standardised locations along the medial border of the tibia. Intra-rater reliability was assessed in 10 randomly selected asymptomatic runners through repeated measurements 2 weeks later. RESULTS: Intra-rater reliability was moderate to excellent (ICC 0.53-0.90) in asymptomatic runners. Pain pressure threshold (PPT) was significantly reduced at 2/9-5/9 of the distance from the medial malleolus to the medial tibial condyle (p = 0.002-0.022). There was evidence of a statistically significant association between both height and weight, and PPT from the 3/9 (r = 0.416, p = 0.008) to 7/9 (r = 0.334, p = 0.035) and 3/9 (r = 0.448, p = 0.004) to 6/9 (r = 0.337, p = 0.034) area, respectively. In both MTSS patients and healthy runners, there was evidence of lower PPT in females compared to males (p = 0.0001-0.049) and a negative association between age and PPT (p = 0.001-0.033). MTSS patients had significantly lower PPT at the 3/9 site (p = 0.048) compared to asymptomatic runners. CONCLUSION: Pain pressure threshold algometry can be incorporated into MTSS clinical assessment to objectively assess pain and monitor progress. The presence of reduced medial tibial PPT in asymptomatic runners suggests that clinicians may not need to await resolution of medial tibia tenderness before allowing return to sport in MTSS patients. LEVEL OF EVIDENCE: III. PMID:23740326

Aweid, Osama; Gallie, Rosa; Morrissey, Dylan; Crisp, Tom; Maffulli, Nicola; Malliaras, Peter; Padhiar, Nat



Insular Cortex Mediates Increased Pain Tolerance in Yoga Practitioners.  


Yoga, an increasingly popular discipline among Westerners, is frequently used to improve painful conditions. We investigated possible neuroanatomical underpinnings of the beneficial effects of yoga using sensory testing and magnetic resonance imaging techniques. North American yogis tolerated pain more than twice as long as individually matched controls and had more gray matter (GM) in multiple brain regions. Across subjects, insular GM uniquely correlated with pain tolerance. Insular GM volume in yogis positively correlated with yoga experience, suggesting a causal relationship between yoga and insular size. Yogis also had increased left intrainsular white matter integrity, consistent with a strengthened insular integration of nociceptive input and parasympathetic autonomic regulation. Yogis, as opposed to controls, used cognitive strategies involving parasympathetic activation and interoceptive awareness to tolerate pain, which could have led to use-dependent hypertrophy of insular cortex. Together, these findings suggest that regular and long-term yoga practice improves pain tolerance in typical North Americans by teaching different ways to deal with sensory inputs and the potential emotional reactions attached to those inputs leading to a change in insular brain anatomy and connectivity. PMID:23696275

Villemure, Chantal; Ceko, Marta; Cotton, Valerie A; Bushnell, M Catherine



Pain ratings, sensory thresholds, and psychosocial functioning in women with provoked vestibulodynia.  


Psychosocial and psychophysical functioning in 25 women with and 25 without provoked vestibulodynia (PVD) were examined. Participants underwent quantitative sensory testing and completed psychosocial measures. Women with PVD displayed lower pain thresholds, higher pain ratings, lower sexual functioning and sexual self-efficacy, and higher levels of somatization and catastrophization than controls. Lower psychosocial functioning correlated with decreased vulvar pressure-pain threshold and increased cotton-swab test pain ratings. For PVD women, decreased sexual function and sexual self-efficacy were associated with higher vulvar pressure-pain ratings. Findings suggest that women with PVD would benefit from treatment that addresses pain-focused and psychosocial components. PMID:19466666

Sutton, Katherine S; Pukall, Caroline F; Chamberlain, Susan



Correlations between Brain Cortical Thickness and Cutaneous Pain Thresholds Are Atypical in Adults with Migraine  

PubMed Central

Background/Objective Migraineurs have atypical pain processing, increased expectations for pain, and hypervigilance for pain. Recent studies identified correlations between brain structure and pain sensation in healthy adults. The objective of this study was to compare cortical thickness-to-pain threshold correlations in migraineurs to healthy controls. We hypothesized that migraineurs would have aberrant relationships between the anatomical neurocorrelates of pain processing and pain thresholds. Methods Pain thresholds to cutaneously applied heat were determined for 31 adult migraineurs and 32 healthy controls. Cortical thickness was determined from magnetic resonance imaging T1-weighted sequences. Regional cortical thickness-to-pain threshold correlations were determined for migraineurs and controls separately using a general linear model whole brain vertex-wise analysis. A pain threshold-by-group interaction analysis was then conducted to estimate regions where migraineurs show alterations in the pain threshold-to-cortical thickness correlations relative to healthy controls. Results Controls had negative correlations (p<0.01 uncorrected) between pain thresholds and cortical thickness in left posterior cingulate/precuneus, right superior temporal, right inferior parietal, and left inferior temporal regions, and a negative correlation (p<0.01 Monte Carlo corrected) with a left superior temporal/inferior parietal region. Migraineurs had positive correlations (p<0.01 uncorrected) between pain thresholds and cortical thickness in left superior temporal/inferior parietal, right precuneus, right superior temporal/inferior parietal, and left inferior parietal regions. Cortical thickness-to-pain threshold correlations differed between migraine and control groups (p<0.01 uncorrected) for right superior temporal/inferior parietal, right precentral, left posterior cingulate/precuneus, and right inferior parietal regions and (p<0.01 Monte Carlo corrected) for a left superior temporal/inferior parietal region. Conclusions Unlike healthy control subjects who have a significant negative correlation between cortical thickness in a superior temporal/inferior parietal region with pain thresholds, migraineurs have a non-significant positive correlation between cortical thickness in a superior temporal/inferior parietal region with pain thresholds. Since this region participates in orienting and attention to painful stimuli, absence of the normal correlation might represent a migraineurs inability to inhibit pain sensation via shifting attention away from the painful stimulus.

Schwedt, Todd J.; Chong, Catherine D.



Quantitative sensory testing and pain tolerance in patients with mild to moderate Alzheimer disease compared to healthy control subjects.  


Patients with Alzheimer disease (AD) report pain less frequently than their cognitively intact peers. It has been hypothesized that pain processing is altered in AD. The aim of this study was to investigate agreement and reliability of 3 pain sensitivity tests and to examine pain threshold and tolerance in patients with AD. We examined 29 patients with mild to moderate AD and 29 age- and gender-matched healthy control subjects with quantitative sensory testing, ie, assessments of detection threshold (warmth detection threshold [WDT]) and pain threshold (heat pain threshold [HPT], pressure algometry, cold pressor test), and assessments of tolerance (pressure algometry, cold pressor test). All procedures were done twice on day 1, 1hour apart, and repeated on day 2. We found no difference between groups for WDT (patient vs control subjects: mean [95% confidence interval]: 35.5°C [33.4°C to 37.6°C] vs 35.4°C [34.3°C to 36.5°C], P=.8) or HPT (41.2°C [40.0°C to 42.4°C] vs 42.3°C [41.1°C to 43.5°C], P=.24). We observed comparable thresholds for pressure algometry (median [25% to 75% interquartile range]: 120kPa [100 to 142kPa] vs 131kPa [113 to 192kPa], P=.10), but significantly lower tolerance in AD patients (213kPa [188 to 306kPa] vs 289kPa [262 to 360kPa], P=.008). No differences were found for the cold pressor test. The study demonstrated good replicability of the sensory testing data with comparable data variability, for both groups, which supports the use of these methods in studies of patients with mild to moderate AD. Contrary to previous studies, we observed a reduced pain tolerance in patients with mild to moderate AD, which suggests that the reduced report of pain cannot be explained by reduced processing of painful stimuli. PMID:24412285

Jensen-Dahm, Christina; Werner, Mads U; Dahl, Jørgen B; Jensen, Troels Staehelin; Ballegaard, Martin; Hejl, Anne-Mette; Waldemar, Gunhild



Testing different biphasic waveforms and capacitances: Effect on atrial defibrillation threshold and pain perception  

Microsoft Academic Search

Objectives. The goal of this study was to compare the effect of different tilts and capacitances for biphasic shocks on atrial defibrillation efficacy and pain threshold.Background. Although biphasic shocks have been shown to be superior to monophasic shocks, the effect of tilt and capacitance on atrial defibrillation success and pain perception has not been studied in patients.Methods. Atrial defibrillation threshold

Gery Tomassoni; Keith H. Newby; Margaret M. Kearney; Mary Joan Brandon; Helen Barold; Andrea Natale



Effects of Sensory Behavioral Tasks on Pain Threshold and Cortical Excitability  

PubMed Central

Background/Objective Transcutaneous electrical stimulation has been proven to modulate nervous system activity, leading to changes in pain perception, via the peripheral sensory system, in a bottom up approach. We tested whether different sensory behavioral tasks induce significant effects in pain processing and whether these changes correlate with cortical plasticity. Methodology/Principal Findings This randomized parallel designed experiment included forty healthy right-handed males. Three different somatosensory tasks, including learning tasks with and without visual feedback and simple somatosensory input, were tested on pressure pain threshold and motor cortex excitability using transcranial magnetic stimulation (TMS). Sensory tasks induced hand-specific pain modulation effects. They increased pain thresholds of the left hand (which was the target to the sensory tasks) and decreased them in the right hand. TMS showed that somatosensory input decreased cortical excitability, as indexed by reduced MEP amplitudes and increased SICI. Although somatosensory tasks similarly altered pain thresholds and cortical excitability, there was no significant correlation between these variables and only the visual feedback task showed significant somatosensory learning. Conclusions/Significance Lack of correlation between cortical excitability and pain thresholds and lack of differential effects across tasks, but significant changes in pain thresholds suggest that analgesic effects of somatosensory tasks are not primarily associated with motor cortical neural mechanisms, thus, suggesting that subcortical neural circuits and/or spinal cord are involved with the observed effects. Identifying the neural mechanisms of somatosensory stimulation on pain may open novel possibilities for combining different targeted therapies for pain control.

Volz, Magdalena Sarah; Pinheiro, Fernando Santos; Merabet, Lotfi B.; Fregni, Felipe



Reliability and Usefulness of the Pressure Pain Threshold Measurement in Patients with Myofascial Pain  

PubMed Central

Objective To assess the usefulness of a pressure algometer to measure pressure pain threshold (PPT) for diagnosis of myofascial pain syndrome (MPS) in the upper extremity and trunk muscles. Method A group of 221 desk workers complaining of upper body pain participated in this study. Five physiatrists made the diagnosis of MPS using physical examination and PPT measurements. PPT measurements were determined for several muscles in the back and upper extremities. Mean PPT data for gender, side, and dominant hand groups were analyzed. Sensitivity and specificity of Fischer's standard method were evaluated. PPT cut-off values for each muscle group were determined using an ROC curve. Results Cronbach's alpha for each muscle was very high. The PPT in men was higher than in females, and the PPT in the left side was higher than in the right side for all muscles tested (p<0.05). There was no significant difference in PPT for all muscles between dominant and non-dominant hand groups. Diagnosis of MPS based on Fischer's standard showed relatively high specificity and poor sensitivity. Conclusion The digital pressure algometer showed high reliability. PPT might be a useful parameter for assessing a treatment's effect, but not for use in diagnosis or even as a screening method.

Park, Giburm; Kim, Chan Woo; Park, Si Bog; Kim, Mi Jung



Validity of pressure pain thresholds in female workers with and without recurrent low back pain  

PubMed Central

Recurrent low back pain (LBP) is a common pain condition in elderly workers in a variety of occupations, but little is known about its origin and the mechanisms leading to an often disabling sensation of pain that may be persistent or intermittent. In the present study we evaluated the pressure pain thresholds (PPTs) in subjects suffering from recurrent LBP, as well as in healthy controls, to investigate if recurrent LBP is associated with an increased sensitivity of the muscular and ligamentous structures located on the lower back. One hundred and six female workers, aged between 45 and 62 years and working either in administrative or nursing professions were examined. The subjects were classified into LBP cases and controls based on the Nordic questionnaire. Subjects indicating 8–30 or more days with LBP during the past 12 months were graded as cases. PPTs were measured on 12 points (six on each side of the body) expected to be relevant for LBP (paravertebral muscles, musculus quadratus lumborum, os ilium, iliolumbar ligament, musculus piriformis and greater trochanter), as well as on a reference point (middle of the forehead) using a digital dolorimeter. The PPTs on all points on the lower back highly correlated with each other and a high internal consistency was found with a Cronbach alpha coefficient > 0.95. There was a moderate and significant correlation of the PPT on the forehead with the PPT on the lower back with correlation coefficients ranging from 0.36 to 0.49. In LBP cases from administrative professions, the PPT on the forehead was significantly decreased (P < 0.05). The PPT on the lower back did not significantly differ between the four groups studied, namely nurses and administrative workers with and without recurrent LBP. These results give evidence that recurrent LBP is not associated with an altered sensitivity of the muscular and myofascial tissues in the lumbar region. Furthermore, they raise questions about the value of reference point measurements in recurrent LBP.

Laeubli, Thomas; Klipstein, Andreas



Validity of pressure pain thresholds in female workers with and without recurrent low back pain.  


Recurrent low back pain (LBP) is a common pain condition in elderly workers in a variety of occupations, but little is known about its origin and the mechanisms leading to an often disabling sensation of pain that may be persistent or intermittent. In the present study we evaluated the pressure pain thresholds (PPTs) in subjects suffering from recurrent LBP, as well as in healthy controls, to investigate if recurrent LBP is associated with an increased sensitivity of the muscular and ligamentous structures located on the lower back. One hundred and six female workers, aged between 45 and 62 years and working either in administrative or nursing professions were examined. The subjects were classified into LBP cases and controls based on the Nordic questionnaire. Subjects indicating 8-30 or more days with LBP during the past 12 months were graded as cases. PPTs were measured on 12 points (six on each side of the body) expected to be relevant for LBP (paravertebral muscles, musculus quadratus lumborum, os ilium, iliolumbar ligament, musculus piriformis and greater trochanter), as well as on a reference point (middle of the forehead) using a digital dolorimeter. The PPTs on all points on the lower back highly correlated with each other and a high internal consistency was found with a Cronbach alpha coefficient > 0.95. There was a moderate and significant correlation of the PPT on the forehead with the PPT on the lower back with correlation coefficients ranging from 0.36 to 0.49. In LBP cases from administrative professions, the PPT on the forehead was significantly decreased (P < 0.05). The PPT on the lower back did not significantly differ between the four groups studied, namely nurses and administrative workers with and without recurrent LBP. These results give evidence that recurrent LBP is not associated with an altered sensitivity of the muscular and myofascial tissues in the lumbar region. Furthermore, they raise questions about the value of reference point measurements in recurrent LBP. PMID:16680447

Schenk, Peter; Laeubli, Thomas; Klipstein, Andreas



The effect of soft tissue deloading tape on thoracic spine pressure pain thresholds in asymptomatic subjects.  


The application of tape to deload soft tissue is used in the management of thoracic spine pain. A reported clinical feature of this treatment is reduced tenderness of the spine during postero-anterior mobilizations. A randomized, single blind, placebo controlled, repeated measures design study was employed to investigate the effects of deloading tape on pressure pain threshold measurements at the level of the T7 spinous process in an asymptomatic group of 24 subjects. Pressure pain thresholds were assessed prior to and following the application of deloading tape, placebo sham tape and no-tape control conditions. All subjects received all three conditions in a randomized order on three separate days. Differences between the pre- and post-measurements were used as indicators of change in a subject's pressure pain threshold. No significant change in pressure pain threshold measurements was found between conditions. In summary, this study demonstrated that deloading tape applied to the level of the T7 spinous process did not significantly change pressure pain threshold measurements in asymptomatic subjects, raising the possibility that any pain relieving effect may well be conditional upon pain being present. PMID:12372311

O' Leary, S; Carroll, M; Mellor, R; Scott, A; Vicenzino, B



76 FR 67315 - Supplemental Nutrition Assistance Program: Quality Control Error Tolerance Threshold  

Federal Register 2010, 2011, 2012, 2013

...DEPARTMENT OF AGRICULTURE Food and Nutrition Service 7 CFR Part 275 [FNS-2011-0060] RIN 0584-AE24 Supplemental Nutrition Assistance Program: Quality Control...Tolerance Threshold AGENCY: Food and Nutrition Service, USDA. ACTION:...



Perception for ischemic pain shows similarities in adjustment disorder and major depression  

Microsoft Academic Search

We recently described an increase of pain thresholds and tolerances for thermal and electrical pain in patients suffering from adjustment disorder (AD). Furthermore, we presented evidence that pain perception in major depressive disorder (MDD) depends on pain modality, with thresholds for ischemic pain being decreased compared to increased thermal and electrical pain thresholds.Here, we investigated perception of experimentally induced ischemic

M. K. Boettger; K. J. Bär



Catastrophizing is related to pain ratings, but not nociceptive flexion reflex threshold  

PubMed Central

Catastrophizing is reliably associated with increased reports of clinical and experimental pain. To test the hypothesis that catastrophizing may heighten pain experience by increasing nociceptive transmission through spinal gating mechanisms, the present study examined catastrophizing as a predictor of pain ratings and nociceptive flexion reflex (NFR) thresholds in 88 young adult men (n = 47) and women (n = 41). The NFR threshold was defined as the intensity of electrocutaneous sural nerve stimulation required to elicit a withdrawal response from the biceps femoris muscle of the ipsilateral leg. Participants completed an assessment of their NFR threshold and then provided pain ratings using both a numerical rating scale (NRS) and the short-form McGill pain questionnaire (SF-MPQ). Pain catastrophizing was assessed using the catastrophizing subscale of the coping strategies questionnaire (CSQ). Although catastrophizing was positively related to both NRS and SF-MPQ pain ratings, catastrophizing was not significantly related to NFR threshold. These findings suggest that differential modulation of spinal nociceptive input may not account for the relationship between catastrophizing and increased pain.

France, Christopher R.; France, Janis L.; al'Absi, Mustafa; Ring, Christopher; McIntyre, David



Pressure pain thresholds of tender point sites in patients with fibromyalgia and in healthy controls  

Microsoft Academic Search

Pressure pain threshold (PPT) is defined as the minimum force applied which induces pain. This measure has proven to be commonly useful in evaluating tenderness symptom. Our aim was to study the intra-examiner reproducibility of PPT measurement, define cutoffs in normal groups, and compare these results with patients with fibromyalgia (FM). Fifty healthy females, 50 healthy males, and 20 patients

Didier Maquet; Jean-Louis Croisier; Christophe Demoulin; Jean-Michel Crielaard



Determinants of pressure pain threshold in adult twins: evidence that shared environmental influences predominate  

Microsoft Academic Search

The objective of this study was to examine the relative contribution of genetic and environmental factors in determining pain perception in a classical twin study. Dolorimeter measurements of pressure pain threshold (PPT) were recorded in 609 healthy female-female twin pairs of whom 269 pairs were monozygotic (MZ) and 340 were dizygotic (DZ). There was a strong correlation (R) in PPT

Alexander J. MacGregor; Gareth O. Griffiths; Juliet Baker; Timothy D. Spector



Transcutaneous electrical nerve stimulation produces variable changes in somatosensory evoked potentials, sensory perception and pain threshold: clinical implications for pain relief.  

PubMed Central

Transcutaneous electrical nerve stimulation decreased early and late somatosensory evoked potential amplitudes and stimulus intensity ratings, and elevated sensory detection threshold, in normal subjects. Effects on pain threshold depended on pre-treatment threshold. These findings are relevant to treatment of clinical pain by transcutaneous electrical nerve stimulation.

Golding, J F; Ashton, H; Marsh, R; Thompson, J W



Pressure Pain Threshold Changes After Repeated Mechano-Nociceptive Stimulation of the Trapezius Muscle: Possible Influence of Previous Pain Experience  

Microsoft Academic Search

We examined the relation between repeated noxious pressure over the trapezius muscle and changes in pressure pain thresholds (PPTs) in a before-after trial design. A conditioning series of 30 mechano-nociceptive stimuli was applied manually with a handheld algometer probe, and PPTs were measured over 1 trapezius muscle (skin anaesthetized) in 27 healthy women before and after the intervention. With a

Bengt H. Sjölund; Ann L. Persson


Social comparison performance standards, threat, and tolerance for experimentally-induced pain.  


Social modelling experiments have illustrated how upward social comparisons (i.e., observing pain tolerant role models) can facilitate tolerance relative to downward social comparison (i.e., observing pain intolerant alternatives). However, because clinical studies suggest that people prefer to make downward social comparisons with less fortunate others when they are threatened or overwhelmed with pain or illness, it seems plausible that upward social comparisons confer fewer benefits when pain is appraised as threatening. To address this issue, we assessed effects of verbally-presented upward and downward social comparison standards on tolerance for cold pressor pain among 124 Australian adults (44 men, 80 women) primed with either more or less threatening orienting information about task-related pain sensations. As predicted, participants exposed to the lower threat orienting prime and upward comparison performance standard were significantly more pain tolerant than peers in all other conditions. Conversely, the average tolerance time for participants presented with the higher threat orienting prime and upward comparison standard did not differ from that of either downward comparison group. The research highlighted powerful situational influences on tolerance for experimental pain and identified conditions under which verbally-presented upward social comparison standards may facilitate and hinder the capacity to bear pain. PMID:21600818

Jackson, Todd; Phillips, Heath



Altered esophageal pain threshold in irritable bowel syndrome  

Microsoft Academic Search

Gut motility disorders and altered pain perception were reported in patients with irritable bowel syndrome (IBS). To verify foregut involvement in IBS, we studied 30 patients using esophageal manometry and 24-hr pH monitoring of the distal esophagus. Two subgroups of patients underwent esophageal provocative tests (bethanechol 50 µg\\/kg subcutaneously and esophageal balloon distension test). Twelve healthy volunteers formed a control

Mario Costantini; Giacomo Carlo Sturniolo; Giovanni Zaninotto; Renata D'Incà; Rita Polo; Remo Naccarato; Ermanno Ancona



Vestibular tactile and pain thresholds in women with vulvar vestibulitis syndrome  

Microsoft Academic Search

Vulvar vestibulitis syndrome (VVS) is a common cause of dyspareunia in pre-menopausal women. Little is known about sensory function in the vulvar vestibule, despite Kinsey's assertion that it is important for sexual sensation. We examined punctate tactile and pain thresholds to modified von Frey filaments in the genital region of women with VVS and age- and contraceptive-matched pain-free controls. Women

Caroline F Pukall; Yitzchak M Binik; Samir Khalifé; Rhonda Amsel; Frances V Abbott



Changes in Pressure Pain Threshold of the Upper Trapezius, Levator Scapular and Rhomboid Muscles during Continuous Computer Work.  


[Purpose] This study investigated the changes in pressure pain threshold of the upper trapezius, levator scapular, and rhomboid muscles during continuous computer work. [Subjects] Fourteen males and females aged 26-32?years, were recruited. [Methods] A dolorimeter pressure algometer was used to measure the pressure pain threshold of the upper trapezius, levator scapular, and rhomboid muscles, respectively, before computer work and after 15?min, 30?min, and 60?min of computer work. [Results] The pressure pain threshold of the upper trapezius was significantly decreased after 15?min or more of computer work. The pressure pain threshold of the levator scapular was significantly decreased after computer work for 30?min and 60?min. The pressure pain threshold of the rhomboid muscle was significantly decreased after 60?min of computer work. [Conclusion] Continuous computer work could produce much more pain in the levator scapular and rhomboid muscle than the upper trapezius. PMID:24259907

Yoo, Won-Gyu



Measurement of pain threshold in patients with rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and healthy controls  

Microsoft Academic Search

Summary Pain threshold was measured using a pressure algometer in 126 subjects, of whom 54 were females and 72 males. These subjects included 18 males and 18 females with rheumatoid arthritis, 18 males and 18 females with osteoarthritis, 18 males with ankylosing spondylitis, and 18 male and 18 female healthy control volunteers. Six points were studied on each side of

E. M. Gerecz-Simon; E. R. Tunks; J.-A. Heale; W. F. Kean; W. W. Buchanan



Fifteen minutes of left prefrontal repetitive transcranial magnetic stimulation acutely increases thermal pain thresholds in healthy adults  

PubMed Central

BACKGROUND: Transcranial magnetic stimulation (TMS) of the motor cortex appears to alter pain perception in healthy adults and in patients with chronic neuropathic pain. There is, however, emerging brain imaging evidence that the left prefrontal cortex is involved in pain inhibition in humans. OBJECTIVE: Because the prefrontal cortex may be involved in descending pain inhibitory systems, the present pilot study was conducted to investigate whether stimulation of the left prefrontal cortex via TMS might affect pain perception in healthy adults. METHODS: Twenty healthy adults with no history of depression or chronic pain conditions volunteered to participate in a pilot laboratory study in which thermal pain thresholds were assessed before and after 15 min of repetitive TMS (rTMS) over the left prefrontal cortex (10 Hz, 100% resting motor threshold, 2 s on, 60 s off, 300 pulses total). Subjects were randomly assigned to receive either real or sham rTMS and were blind to condition. RESULTS: Subjects who received real rTMS demonstrated a significant increase in thermal pain thresholds following TMS. Subjects receiving sham TMS experienced no change in pain threshold. CONCLUSIONS: rTMS over the left prefrontal cortex increases thermal pain thresholds in healthy adults. Results from the present study support the idea that the left prefrontal cortex may be a promising TMS cortical target for the management of pain. More research is needed to establish the reliability of these findings, maximize the effect, determine the length of effect and elucidate possible mechanisms of action.

Borckardt, Jeffrey J; Smith, Arthur R; Reeves, Scott T; Weinstein, Mitchell; Kozel, F Andrew; Nahas, Ziad; Shelley, Neal; Branham, R Kyle; Thomas, K Jackson; George, Mark S



Decreased pain threshold and enhanced synaptic transmission in the anterior cingulate cortex of experimental hypothyroidism mice  

PubMed Central

Background Thyroid hormones are essential for the maturation and functions of the central nervous system. Pain sensitivity is related to the thyroid status. However, information on how thyroid hormones affect pain processing and synaptic transmission in the anterior cingulate cortex (ACC) is limited. Nociceptive threshold and synaptic transmission in the ACC were detected in the experimental hypothyroidism (HT) mice. Results HT was induced by methimazole and potassium perchlorate in distilled drinking water for 4 weeks. The threshold of pain perception to hot insults, but not mechanical ones, decreased in hypothyroid mice. After treatment with tri-iodothyronine (T3) or thyroxine (T4) for 2 weeks, thermal pain threshold recovered. Electrophysiological recordings revealed enhanced glutamatergic synaptic transmission and reduced GABAergic synaptic transmission in the ACC. Supplementation with T3 or T4 significantly rescued this synaptic transmission imbalance. In the same model, HT caused the up-regulation of the GluR1 subunit of the ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor and NR2B-containing N-methyl-D-aspartate receptors, but it down-regulated ?-aminobutyric acid A receptors in the ACC. Supplementation with T3 or T4 notably recovered the levels of above proteins. Conclusions These results suggest that HT promotes hypersensitivity to noxious thermal, and that supplementation with T3 or T4 rescues the imbalance between excitatory and inhibitory transmission in the ACC.



Sensory, motor, and pain thresholds for stimulation with medium frequency alternating current  

Microsoft Academic Search

Objectives: To investigate the effect of frequency of alternating current on the sensory, motor, and pain thresholds in normal subjects, and to establish the optimal frequency for motor stimulation with minimal subject discomfort.Design: A repeated measures design using two groups of 11 subjects.Setting: A laboratory setting was used.Participants: Participants were volunteers who met the inclusion criteria.Interventions: Alternating current with 20

Alex R. Ward; Valma J. Robertson



The reliability and validity of pain threshold measurements in osteoarthritis of the knee.  


The purpose of this study was to examine the reliability and validity of measuring pain threshold (PT) of persons with osteoarthritis (OA) of the knee. The PTs of women with and without OA of the knee were measured on 3 occasions at 6 sites at the knee with a pressure dolorimeter. Subjects with OA also recorded their pain on a visual analogue scale (VAS) and on the McGill Pain Questionnaire (MPQ). The reliability coefficients for repeated measures of PT varied from 0.61 to 0.91 in the OA group and from 0.71 to 0.90 in the control group. PT was lower in the OA group at all sites. Only the control group demonstrated significant differences between sites. The correlations between PT and measures of pain intensity were poor. It is concluded that the measurement of PT at the knee distinguishes OA from healthy controls, and that it has moderate reliability. However, it cannot substitute for a measure of pain intensity. PMID:7481589

Wessel, J



The analgesic effect of codeine as compared to imipramine in different human experimental pain models.  


The hypoalgesic effect of single oral doses of 100 mg imipramine and 125 mg codeine was evaluated in a randomised, placebo-controlled, double-blind, 3-way cross-over experiment including 18 healthy volunteers. Pain tests were performed before and 90, 180, 270, 360 and 450 min after medication. The tests included determination of pain tolerance thresholds to pressure, pain detection/tolerance thresholds to single electrical sural nerve stimulation and pain summation at tolerance threshold to repetitive electrical sural nerve stimulation (temporal summation) and pain experienced during the cold pressor test, rated as peak pain intensity, pain average intensity and discomfort. Compared to placebo, imipramine significantly increased pressure pain tolerance threshold (P = 0.03) and increased pain tolerance threshold (P = 0.05) and pain summation threshold (P = 0.03), but not pain detection threshold to electrical stimulation. Imipramine did not cause significant changes in pain perception during the cold pressor test. Codeine significantly increased pressure pain tolerance threshold (P = 0.02), pain detection (P = 0.04) and pain tolerance threshold (P = 0.01) and pain summation threshold (P = 0.02) to electrical stimulation. In addition, codeine reduced the pain experienced during the cold pressor test (P = 0.04-0.003). It is concluded that both imipramine and codeine inhibit temporal pain summation, whereas only codeine reduces cold pressor pain. Pain summation may be a key mechanism in neuropathic pain. Imipramine has a documented effect on such pain conditions on temporal summation. The present study showed that codeine also inhibits temporal summation, which is in line with the clinical observations indicating that opioids relieve neuropathic pain. PMID:11323149

Enggaard, T P; Poulsen, L; Arendt-Nielsen, L; Hansen, S H; Bjørnsdottir, I; Gram, L F; Sindrup, S H



Shared Mechanisms for Opioid Tolerance and a Transition to Chronic Pain  

PubMed Central

Clinical pain conditions may remain responsive to opiate analgesics for extended periods, but such persistent acute pain can undergo a transition to an opiate-resistant chronic pain state that becomes a much more serious clinical problem. To test the hypothesis that cellular mechanisms of chronic pain in the primary afferent also contribute to the development of opiate resistance, we employed a recently developed model of the transition of from acute to chronic pain, hyperalgesic priming. Repeated intradermal administration of the potent and highly selective ?-opioid agonist, DAMGO, to produce tolerance for its inhibition of prostaglandin E2 (PGE2) hyperalgesia, simultaneously produced hyperalgesic priming. Conversely, injection of an inflammogen, carrageenan, used to produce priming produced DAMGO tolerance. Both effects were prevented by inhibition of protein kinase C? (PKC?). Carrageenan also induced opioid dependence, manifest as ?-opioid receptor antagonist (CTOP)-induced hyperalgesia that, like priming, was PKC?- and Gi-dependent. These findings suggest that the transition from acute to chronic pain, and development of ?-opioid receptor tolerance and dependence may be linked by common cellular mechanisms in the primary afferent.

Joseph, Elizabeth K.; Reichling, David B.; Levine, Jon D.



A preliminary report on adjuvant analgesic efficacy of HANS in opioid tolerant patients with cancer pain  

PubMed Central

Objective To observe the adjuvant analgesic efficacy of Han’s Acupoint Nerve Stimulator (HANS) in opioid tolerant patients with cancer pain. Methods A prospective non-controlled study was conducted. Opioid tolerant patients with cancer pain were enrolled and treated with both routinely analgesics and adjuvant HANS (2/100 Hz for 30 min/d, 5 d on and 2 d off for two weeks). Cancer pain, quality of life (QOL), anxiety and depression were assessed before enrollment and on d 8 and d 15 with the BPI-C, EORTC QLQ-C30, and self-rating anxiety scale (SAS)/self-rating depression scale (SDS), respectively; the therapeutic frequency of breakthrough pain (BP) and daily opioid dose were also recorded. Results Totally 47 patients meeting the inclusion criteria participated in this study; 43 patients completed the two-week treatment and assessment. The mean scores of patient’s “worst” and “least” pain intensity assessed with BPI-C decreased significantly on d 8 and d 15; the therapeutic frequency of BP also significantly decreased; but the average daily dose of opioids did not change significantly. For the nine symptoms in EORTC QLQ-C30 assessment, the mean scores of pain, fatigue, constipation and insomnia were significantly lower on d 8 and d 15 compared with baseline; the mean scores of the overall health status, nausea/vomiting and the incidence rates of both anxiety and depression also decreased significantly on d 15. Conclusions To opioid tolerant patients with cancer pain, adjuvant treatment with HANS could improve pain release and patients’ QOL by decreasing the severity of pain, fatigue, constipation, insomnia and other concomitant symptoms; it could also decrease the incidence rates of anxiety and depression.

Li, Xiaomei; Zhu, Jianhua; Li, Pingping; Zhu, Guangqing; Wu, Xiaoming; Chen, Huoming; Zhao, Huixia; Wang, Wei; Zhang, Ying; Liu, Duanqi



Sedation and analgesia for colonoscopy: patient tolerance, pain, and cardiorespiratory parameters  

Microsoft Academic Search

Background: Colonoscopy is generally performed with the patient sedated and receiving analgesics. However, the benefit of the most often used combination of intravenous midazolam and pethidine on patient tolerance and pain and its cardiorespiratory risk have not been fully defined. Methods: In this double-blind prospective study, 150 outpatients undergoing routine colonoscopy were randomly assigned to receive either (1) low-dose midazolam

Florian Froehlich; Joël Thorens; Werner Schwizer; Martin Preisig; Manfred Köhler; Ron D. Hays; Michael Fried; Jean-Jacques Gonvers



The Effect of Traditional Cupping on Pain and Mechanical Thresholds in Patients with Chronic Nonspecific Neck Pain: A Randomised Controlled Pilot Study  

PubMed Central

Introduction. Cupping has been used since antiquity in the treatment of pain conditions. In this pilot study, we investigated the effect of traditional cupping therapy on chronic nonspecific neck pain (CNP) and mechanical sensory thresholds. Methods. Fifty CNP patients were randomly assigned to treatment (TG, n = 25) or waiting list control group (WL, n = 25). TG received a single cupping treatment. Pain at rest (PR), pain related to movement (PM), quality of life (SF-36), Neck Disability Index (NDI), mechanical detection (MDT), vibration detection (MDT), and pressure pain thresholds (PPT) were measured before and three days after a single cupping treatment. Patients also kept a pain and medication diary (PaDi, MeDi) during the study. Results. Baseline characteristics were similar in the two groups. After cupping TG reported significantly less pain (PR: ?17.9?mm VAS, 95%CI ?29.2 to ?6.6; PM: ?19.7, 95%CI ?32.2 to ?7.2; PaDi: ?1.5 points on NRS, 95%CI ?2.5 to ?0.4; all P < 0.05) and higher quality of life than WL (SF-36, Physical Functioning: 7.5, 95%CI 1.4 to 13.5; Bodily Pain: 14.9, 95%CI 4.4 to 25.4; Physical Component Score: 5.0, 95%CI 1.4 to 8.5; all P < 0.05). No significant effect was found for NDI, MDT, or VDT, but TG showed significantly higher PPT at pain-areas than WL (in lg(kPa); pain-maximum: 0.088, 95%CI 0.029 to 0.148, pain-adjacent: 0.118, 95%CI 0.038 to 0.199; both P < 0.01). Conclusion. A single application of traditional cupping might be an effective treatment for improving pain, quality of life, and hyperalgesia in CNP.

Lauche, Romy; Cramer, Holger; Hohmann, Claudia; Choi, Kyung-Eun; Rampp, Thomas; Saha, Felix Joyonto; Musial, Frauke; Langhorst, Jost; Dobos, Gustav



Upper bounds on fault tolerance thresholds of noisy Clifford-based quantum computers  

NASA Astrophysics Data System (ADS)

We consider the possibility of adding noise to a quantum circuit to make it efficiently simulatable classically. In previous works, this approach has been used to derive upper bounds to fault tolerance thresholds—usually by identifying a privileged resource, such as an entangling gate or a non-Clifford operation, and then deriving the noise levels required to make it 'unprivileged'. In this work, we consider extensions of this approach where noise is added to Clifford gates too and then 'commuted' around until it concentrates on attacking the non-Clifford resource. While commuting noise around is not always straightforward, we find that easy instances can be identified in popular fault tolerance proposals, thereby enabling sharper upper bounds to be derived in these cases. For instance we find that if we take Knill's (2005 Nature 434 39) fault tolerance proposal together with the ability to prepare any possible state in the XY plane of the Bloch sphere, then not more than 3.69% error-per-gate noise is sufficient to make it classical, and 13.71% of Knill's ? noise model is sufficient. These bounds have been derived without noise being added to the decoding parts of the circuits. Introducing such noise in a toy example suggests that the present approach can be optimized further to yield tighter bounds.

Plenio, M. B.; Virmani, S.



Determinants of pressure pain threshold in adult twins: evidence that shared environmental influences predominate.  


The objective of this study was to examine the relative contribution of genetic and environmental factors in determining pain perception in a classical twin study. Dolorimeter measurements of pressure pain threshold (PPT) were recorded in 609 healthy female-female twin pairs of whom 269 pairs were monozygotic (MZ) and 340 were dizygotic (DZ). There was a strong correlation (R) in PPT in both MZ and DZ pairs (R(MZ) = 0.57, 95% confidence interval (CI): [0.49, 0.65]; R(DZ) = 0.51, 95% CI: [0.42, 0.59]). The slight excess in intraclass correlation observed in MZ when compared with DZ twins corresponds to a heritability for PPT of only 10% and is not statistically significant. Neither estimate of intraclass correlation was substantially altered after adjusting for a range of potential confounding variables including age, current tobacco and alcohol use, current analgesic use, psychological status assessed by the general health questionnaire, and social class. The dolorimeter measurements were shown to be reliable (between observer agreement R = 0.66; within observer agreement R = 0.70-0.76) and stable over time. In conclusion, these data suggest that there is no significant genetic contribution to the strong correlation in PPT that is observed in twin pairs. These findings reinforce the view that learned patterns of behaviour within families are an important determinant of perceived sensitivity to pain. PMID:9415513

MacGregor, A J; Griffiths, G O; Baker, J; Spector, T D



Cortex glial cells activation, associated with lowered mechanical thresholds and motor dysfunction, persists into adulthood after neonatal pain.  


We investigated if changes in glial activity in cortical areas that process nociceptive stimuli persisted in adult rats after neonatal injury. Neonatal pain was induced by repetitive needle prickling on the right paw, twice per day for 15 days starting at birth. Wistar rats received either neonatal pain or tactile stimulation and were tested behaviorally for mechanical withdrawal thresholds of the paws and gait alterations, after 15 (P15) or 180 (P180) days of life. Brains from rats on P15 and P180 were immunostained for glial markers (GFAP, MCP-1, OX-42) and the following cortical areas were analyzed for immunoreactivity density: prefrontal, anterior insular, anterior cingulated, somatosensory and motor cortices. Withdrawal thresholds of the stimulated paw remained decreased on P180 after neonatal pain when compared to controls. Neonatal pain animals showed increased density for both GFAP and MCP-1 staining, but not for OX-42, in all investigated cortical areas on both experimental times (P15 and P180). Painful stimuli in the neonatal period produced pain behaviors immediately after injury that persisted in adult life, and was accompanied by increase in the glial markers density in cortical areas that process and interpret pain. Thus, long-lasting changes in cortical glial activity could be, at least in part, responsible for the persistent hyperalgesia in adult rats that suffered from neonatal pain. PMID:24667146

Sanada, Luciana Sayuri; Sato, Karina Laurenti; Machado, Nathalia Leilane Berto; Carmo, Elisabete de Cássia do; Sluka, Kathleen A; Fazan, Valeria Paula Sassoli



Superconducting quantum circuits at the surface code threshold for fault tolerance  

NASA Astrophysics Data System (ADS)

A quantum computer can solve hard problems, such as prime factoring, database searching and quantum simulation, at the cost of needing to protect fragile quantum states from error. Quantum error correction provides this protection by distributing a logical state among many physical quantum bits (qubits) by means of quantum entanglement. Superconductivity is a useful phenomenon in this regard, because it allows the construction of large quantum circuits and is compatible with microfabrication. For superconducting qubits, the surface code approach to quantum computing is a natural choice for error correction, because it uses only nearest-neighbour coupling and rapidly cycled entangling gates. The gate fidelity requirements are modest: the per-step fidelity threshold is only about 99 per cent. Here we demonstrate a universal set of logic gates in a superconducting multi-qubit processor, achieving an average single-qubit gate fidelity of 99.92 per cent and a two-qubit gate fidelity of up to 99.4 per cent. This places Josephson quantum computing at the fault-tolerance threshold for surface code error correction. Our quantum processor is a first step towards the surface code, using five qubits arranged in a linear array with nearest-neighbour coupling. As a further demonstration, we construct a five-qubit Greenberger-Horne-Zeilinger state using the complete circuit and full set of gates. The results demonstrate that Josephson quantum computing is a high-fidelity technology, with a clear path to scaling up to large-scale, fault-tolerant quantum circuits.

Barends, R.; Kelly, J.; Megrant, A.; Veitia, A.; Sank, D.; Jeffrey, E.; White, T. C.; Mutus, J.; Fowler, A. G.; Campbell, B.; Chen, Y.; Chen, Z.; Chiaro, B.; Dunsworth, A.; Neill, C.; O'Malley, P.; Roushan, P.; Vainsencher, A.; Wenner, J.; Korotkov, A. N.; Cleland, A. N.; Martinis, John M.



Superconducting quantum circuits at the surface code threshold for fault tolerance.  


A quantum computer can solve hard problems, such as prime factoring, database searching and quantum simulation, at the cost of needing to protect fragile quantum states from error. Quantum error correction provides this protection by distributing a logical state among many physical quantum bits (qubits) by means of quantum entanglement. Superconductivity is a useful phenomenon in this regard, because it allows the construction of large quantum circuits and is compatible with microfabrication. For superconducting qubits, the surface code approach to quantum computing is a natural choice for error correction, because it uses only nearest-neighbour coupling and rapidly cycled entangling gates. The gate fidelity requirements are modest: the per-step fidelity threshold is only about 99 per cent. Here we demonstrate a universal set of logic gates in a superconducting multi-qubit processor, achieving an average single-qubit gate fidelity of 99.92 per cent and a two-qubit gate fidelity of up to 99.4 per cent. This places Josephson quantum computing at the fault-tolerance threshold for surface code error correction. Our quantum processor is a first step towards the surface code, using five qubits arranged in a linear array with nearest-neighbour coupling. As a further demonstration, we construct a five-qubit Greenberger-Horne-Zeilinger state using the complete circuit and full set of gates. The results demonstrate that Josephson quantum computing is a high-fidelity technology, with a clear path to scaling up to large-scale, fault-tolerant quantum circuits. PMID:24759412

Barends, R; Kelly, J; Megrant, A; Veitia, A; Sank, D; Jeffrey, E; White, T C; Mutus, J; Fowler, A G; Campbell, B; Chen, Y; Chen, Z; Chiaro, B; Dunsworth, A; Neill, C; O'Malley, P; Roushan, P; Vainsencher, A; Wenner, J; Korotkov, A N; Cleland, A N; Martinis, John M



Threshold temperatures mediate the impact of reduced snow cover on overwintering freeze-tolerant caterpillars  

NASA Astrophysics Data System (ADS)

Decreases in snow cover due to climate change could alter the energetics and physiology of ectothermic animals that overwinter beneath snow, yet how snow cover interacts with physiological thresholds is unknown. We applied numerical simulation of overwintering metabolic rates coupled with field validation to determine the importance of snow cover and freezing to the overwintering lipid consumption of the freeze-tolerant Arctiid caterpillar Pyrrharctia isabella. Caterpillars that overwintered above the snow experienced mean temperatures 1.3°C lower than those below snow and consumed 18.36 mg less lipid of a total 68.97-mg reserve. Simulations showed that linear temperature effects on metabolic rate accounted for only 30% of the difference in lipid consumption. When metabolic suppression by freezing was included, 93% of the difference between animals that overwintered above and below snow was explained. Our results were robust to differences in temperature sensitivity of metabolic rate, changes in freezing point, and the magnitude of metabolic suppression by freezing. The majority of the energy savings was caused by the non-continuous reduction in metabolic rate due to freezing, the first example of the importance of temperature thresholds in the lipid use of overwintering insects.

Marshall, Katie E.; Sinclair, Brent J.



Pressure pain thresholds of tender point sites in patients with fibromyalgia and in healthy controls.  


Pressure pain threshold (PPT) is defined as the minimum force applied which induces pain. This measure has proven to be commonly useful in evaluating tenderness symptom. Our aim was to study the intra-examiner reproducibility of PPT measurement, define cutoffs in normal groups, and compare these results with patients with fibromyalgia (FM). Fifty healthy females, 50 healthy males, and 20 patients with FM participated in the study. PPTs were assessed for 18 specific tender point sites by a dolorimeter. The intra-individual coefficient of variation determined by a test-retest PPT measurement procedure with 3-days interval reached, respectively, 17% and 13% in healthy females and males, versus 24% in patients with FM. PPTs were significantly lower in healthy females than in healthy males (p<0.01). Statistical analysis failed to show any differences between the dominant and nondominant side for both normal groups. PPTs were lower over all examined areas in patients with FM than those obtained in healthy females (p<0.000). Lower cutoff levels were calculated from normal values for all specific tender point sites. On average, 14 tender point sites in patients with FM were under the established lower cutoffs. In conclusion, pressure pain sensitivity was influenced by the anatomical localization of tender point and gender differences. Lowest PPTs were localized in trapezius, occiput, anterior cervical, and second rib. The reduction of total tender point score in patients with FM averaged 60% comparatively with normal values. PPT reproducibility and discrimination between the two groups were optimal for the gluteal and knee sites. PMID:14987620

Maquet, Didier; Croisier, Jean-Louis; Demoulin, Christophe; Crielaard, Jean-Michel



Self-reported somatosensory symptoms of neuropathic pain in fibromyalgia and chronic widespread pain correlate with tender point count and pressure-pain thresholds  

Microsoft Academic Search

Widespread pain and pain hypersensitivity are the hallmark of fibromyalgia, a complex pain condition linked to central sensitization. In this study the painDETECT questionnaire (PDQ), validated to identify neuropathic pain and based on pain quality items, was applied in a cross-sectional sample of patients with chronic widespread pain (CWP). The aims of the study were to assess the patient-reported sensory

Kirstine Amris; Anders Jespersen; Henning Bliddal



Pressure Pain Thresholds Increase after Preconditioning 1 Hz Repetitive Transcranial Magnetic Stimulation with Transcranial Direct Current Stimulation  

PubMed Central

Background The primary motor cortex (M1) is an effective target of non-invasive cortical stimulation (NICS) for pain threshold modulation. It has been suggested that the initial level of cortical excitability of M1 plays a key role in the plastic effects of NICS. Objective Here we investigate whether transcranial direct current stimulation (tDCS) primed 1 Hz repetitive transcranial magnetic stimulation (rTMS) modulates experimental pressure pain thresholds and if this is related to observed alterations in cortical excitability. Method 15 healthy, male participants received 10 min 1 mA anodal, cathodal and sham tDCS to the left M1 before 15 min 1 Hz rTMS in separate sessions over a period of 3 weeks. Motor cortical excitability was recorded at baseline, post-tDCS priming and post-rTMS through recording motor evoked potentials (MEPs) from right FDI muscle. Pressure pain thresholds were determined by quantitative sensory testing (QST) through a computerized algometer, on the palmar thenar of the right hand pre- and post-stimulation. Results Cathodal tDCS-primed 1 Hz-rTMS was found to reverse the expected suppressive effect of 1 Hz rTMS on cortical excitability; leading to an overall increase in activity (p<0.001) with a parallel increase in pressure pain thresholds (p<0.01). In contrast, anodal tDCS-primed 1 Hz-rTMS resulted in a corresponding decrease in cortical excitability (p<0.05), with no significant effect on pressure pain. Conclusion This study demonstrates that priming the M1 before stimulation of 1 Hz-rTMS modulates experimental pressure pain thresholds in a safe and controlled manner, producing a form of analgesia.

Moloney, Tonya M.; Witney, Alice G.



Chronic pain has a small influence and mood has no influence on vibrotactile perception thresholds among working women.  


In chronic diffuse upper limb pain physical abnormalities are usually absent. The aims of our study were to investigate: (1) the function of somatosensory pathways and (2) the influence of mood on vibration perception. Measurements were made of: (i) vibrotactile perception thresholds (VPTs) and nerve conduction in working women with (n = 35) and without (n = 65) chronic diffuse upper limb pain, and (ii) perceived stress and energy using a two-dimensional mood adjective checklist. The groups did not differ in any nerve conduction measurements. Women with chronic pain had raised VPTs in the radial and ulnar nerve areas, but not in the median nerve area. Neither perceived stress nor energy appeared to influence the VPT. Increases of VPTs in chronic diffuse upper limb pain may be due to peripheral nerve affliction, but our findings support the idea that they may also be secondary to pain and may be related to a central nervous mechanism. PMID:20564595

Sandén, Helena; Wallin, B Gunnar; Hagberg, Mats



Chronic pain has a small influence and mood has no influence on vibrotactile perception thresholds among working women  

PubMed Central

In chronic diffuse upper limb pain physical abnormalities are usually absent. The aims of our study were to investigate: (1) the function of somatosensory pathways and (2) the influence of mood on vibration perception. Measurements were made of: (i) vibrotactile perception thresholds (VPTs) and nerve conduction in working women with (n = 35) and without (n = 65) chronic diffuse upper limb pain, and (ii) perceived stress and energy using a two-dimensional mood adjective checklist. The groups did not differ in any nerve conduction measurements. Women with chronic pain had raised VPTs in the radial and ulnar nerve areas, but not in the median nerve area. Neither perceived stress nor energy appeared to influence the VPT. Increases of VPTs in chronic diffuse upper limb pain may be due to peripheral nerve affliction, but our findings support the idea that they may also be secondary to pain and may be related to a central nervous mechanism. Muscle Nerve, 2010

Sanden, Helena; Wallin, B Gunnar; Hagberg, Mats



Is experimentally induced pain associated with socioeconomic status? Do poor people hurt more?  

PubMed Central

Background The association of pain and socioeconomic status is widely reported, yet much less clearly understood. The aim of this study was to investigate the association of experimentally induced pain threshold and tolerance with socioeconomic status. Material/Methods The study sample consisted of 319 adult subjects from the population of the island of Vis, Croatia, which was previously shown to have a high level of social homogeneity. A manual dolorimeter was used to measure mechanical pressure pain threshold (least stimulus intensity) and pain tolerance (maximum tolerance stimulus intensity) on both hands. Pain tolerance interval was defined as the difference between pain tolerance and threshold. Years of schooling and material status were used as socioeconomic estimates. Results Both of the socioeconomic estimates were significantly correlated with pain threshold, tolerance, and tolerance interval (P<0.001). The mixed modeling analysis, controlled for the effects of age, gender, and 4 psychological variables, indicated that education was not a significant predictor in any of the 3 models. However, lower material status was significantly associated with lower pain tolerance (P=0.038) and narrower pain tolerance interval (P=0.032), but not with pain threshold (P=0.506). The overall percentages of explained variance were lower in the tolerance interval model (20.2%) than in pain tolerance (23.1%) and threshold (33.1%), suggesting the increasing share of other confounding variables in pain tolerance and even more so in tolerance interval model. Conclusions These results suggest a significant association between experimentally induced pain tolerance and tolerance interval with material status, suggesting that poor people indeed do hurt more.

Miljkovic, Ana; Stipcic, Ana; Bras, Marijana; ?or?evic, Veljko; Brajkovic, Lovorka; Hayward, Caroline; Pavic, Arsen; Kolcic, Ivana; Polasek, Ozren



Is experimentally induced pain associated with socioeconomic status? Do poor people hurt more?  


Background The association of pain and socioeconomic status is widely reported, yet much less clearly understood. The aim of this study was to investigate the association of experimentally induced pain threshold and tolerance with socioeconomic status. Material and Methods The study sample consisted of 319 adult subjects from the population of the island of Vis, Croatia, which was previously shown to have a high level of social homogeneity. A manual dolorimeter was used to measure mechanical pressure pain threshold (least stimulus intensity) and pain tolerance (maximum tolerance stimulus intensity) on both hands. Pain tolerance interval was defined as the difference between pain tolerance and threshold. Years of schooling and material status were used as socioeconomic estimates. Results Both of the socioeconomic estimates were significantly correlated with pain threshold, tolerance, and tolerance interval (P<0.001). The mixed modeling analysis, controlled for the effects of age, gender, and 4 psychological variables, indicated that education was not a significant predictor in any of the 3 models. However, lower material status was significantly associated with lower pain tolerance (P=0.038) and narrower pain tolerance interval (P=0.032), but not with pain threshold (P=0.506). The overall percentages of explained variance were lower in the tolerance interval model (20.2%) than in pain tolerance (23.1%) and threshold (33.1%), suggesting the increasing share of other confounding variables in pain tolerance and even more so in tolerance interval model. Conclusions These results suggest a significant association between experimentally induced pain tolerance and tolerance interval with material status, suggesting that poor people indeed do hurt more. PMID:25029965

Miljkovi?, Ana; Stip?i?, Ana; Braš, Marijana; Dor?evi?, Veljko; Brajkovi?, Lovorka; Hayward, Caroline; Pavi?, Arsen; Kol?i?, Ivana; Polašek, Ozren



Evaluation of sensitivity, motor and pain thresholds across the menstrual cycle through medium-frequency transcutaneous electrical nerve stimulation  

PubMed Central

OBJECTIVES: The aim of this study was to identify variations in nervous thresholds in different phases of the menstrual cycle in eumenorrheic women and users of oral contraceptives. METHOD: An observational study was performed including 56 volunteers, consisting of 30 eumenorrheic women who were non-users of oral contraceptives and 26 users of oral contraceptives. An electrical stimulator was employed to assess their nervous thresholds, with pulses applied at a fixed frequency of 2,500 Hz, modulated at 50 Hz, with phase variances of 20 ?s, 50 ?s and 100 ?s. Sensitivity, motor and pain thresholds were evaluated during five menstrual cycle phases: phase 1 - menstrual, phase 2 - follicular, phase 3 - ovulatory, phase 4 - luteal and phase 5 - premenstrual. RESULTS: The results indicated low sensitivity thresholds of 100 ?s for non-users of oral contraceptives and 50 ?s for oral contraceptive users in phase 5. Low motor thresholds of 20 ?s, 50 ?s and 100 ?s were observed for non-users of oral contraceptives in phase 5, while that of oral contraceptive users was 100 ?s. Finally, a low pain threshold of 100 ?s was observed in phase 5, but only in the oral contraceptive group. CONCLUSION: Nervous thresholds vary systematically across the phases of the menstrual cycle, with or without the use of oral contraceptives. These variations should be taken into account during research performed in women.

de Brito Barbosa, Mariana; de Oliveira Guirro, Elaine Caldeira; Nunes, Fabiana Roberta



Rectal distention testing in patients with irritable bowel syndrome: Sensitivity, specificity, and predictive values of pain sensory thresholds  

Microsoft Academic Search

Background & Aims: Visceral hypersensitivity was detected in patients with functional gastrointestinal disorders and has been proposed as a biological marker of irritable bowel syndrome (IBS). The purpose of this study was to assess the sensitivity, specificity, and the predictive values of pain thresholds evaluated by rectal distention using an electronic barostat in patients with or without IBS and in

Mickael Bouin; Victor Plourde; Michel Boivin; Monique Riberdy; France Lupien; Marie Laganière; Pierre Verrier; Pierre Poitras



Simultaneous electric activities of pain-excitation and pain-inhibition neurons in nucleus parafascicularis of thalamus in rats during acute morphine tolerance.  


When acute morphine-tolerated rat was administered by ip morphine (10 mg/kg) which was effective before the acute tolerance to morphine, both the inhibitory effect of morphine on the electric discharges of pain-excitation neurons (PEN) in nucleus parafascicularis (PF) and the excitatory effect of morphine on the electric activities of pain-inhibition neurons (PIN) were simultaneously weakened, or even vanished. If a large dose of morphine (20 mg) was given ip, the modulating action of morphine on simultaneous electric discharges of PEN and PIN reappeared. It is obvious that the phenomenon of acute morphine tolerance and the antagonism to morphine tolerance can be explicitly expressed on the level of central neurons. PMID:2087992

Xu, M Y; Sun, M Z; Yang, L Z; Zhang, L M; Han, J S



Answer to comment on "sleep quality, arousal and pain thresholds in migraineurs: a blinded controlled polysomnographic study"  

PubMed Central

We discuss the comments on our article “Sleep quality, arousal and pain thresholds in migraineurs. A blinded controlled polysomnographic study” published in JHP 2013 Feb 14;14(1):12. We hypothesize that migraineurs need more sleep than healthy controls and more sleep than they manage to achieve. Some migraineurs probably have a decreased ability to process incoming stimuli. Increased spontaneous pain may follow either sleep restriction or sleep disturbance. A comparison of migraineurs with attack onset related to sleep, migraineurs with attack onset not related to sleep and controls will be reported in another paper.



Interferential therapy effect on mechanical pain threshold and isometric torque after delayed onset muscle soreness induction in human hamstrings  

Microsoft Academic Search

This study was undertaken to examine the acute effect of interferential current on mechanical pain threshold and isometric peak torque after delayed onset muscle soreness induction in human hamstrings. Forty-one physically active healthy male volunteers aged 18?33 years were randomly assigned to one of two experimental groups: interferential current group (n = 21) or placebo group (n = 20). Both groups performed a bout

Clarice S. Rocha; Fábio J. Lanferdini; Carolina Kolberg; Marcelo F. Silva; Marco A. VAZ; Wania A. Partata; Milton A. Zaro



Efficacy and Tolerability of Intramuscular Dexketoprofen in Postoperative Pain Management following Hernia Repair Surgery  

PubMed Central

Objective. To evaluate the safety and efficacy of intramuscular dexketoprofen for postoperative pain in patients undergoing hernia surgery. Methodology. Total 202 patients received single intramuscular injection of dexketoprofen 50?mg or diclofenac 50?mg postoperatively. The pain intensity (PI) was self-evaluated by patients on VAS at baseline 1, 2, 4, 6, and 8 hours. The efficacy parameters were number of responders, difference in PI (PID) at 8?hours, sum of analogue of pain intensity differences (SAPID), and onset and duration of analgesia. Tolerability assessment was done by global evaluation and adverse events in each group. Results. Dexketoprofen showed superior efficacy in terms of number of responders (P = .007), PID at 8?hours (P = .02), and SAPID 0–8 hours (P < .0001). It also showed faster onset of action (42 minutes) and longer duration of action (6.5 hours). The adverse events were comparable in both groups. Conclusion. Single dose of dexketoprofen trometamol 50?mg given intramuscularly provided faster, better, and longer duration of analgesia in postoperative patients of hernia repair surgery than diclofenac 50?mg, with comparable safety.

Jamdade, P. T.; Porwal, A.; Shinde, J. V.; Erram, S. S.; Kamat, V. V.; Karmarkar, P. S.; Bhagtani, K.; Dhorepatil, S.; Irpatgire, R.; Bhagat, H.; Kolte, S. S.; Shirure, P. A.



Efficacy and Tolerability of Intramuscular Dexketoprofen in Postoperative Pain Management following Hernia Repair Surgery.  


Objective. To evaluate the safety and efficacy of intramuscular dexketoprofen for postoperative pain in patients undergoing hernia surgery. Methodology. Total 202 patients received single intramuscular injection of dexketoprofen 50?mg or diclofenac 50?mg postoperatively. The pain intensity (PI) was self-evaluated by patients on VAS at baseline 1, 2, 4, 6, and 8 hours. The efficacy parameters were number of responders, difference in PI (PID) at 8?hours, sum of analogue of pain intensity differences (SAPID), and onset and duration of analgesia. Tolerability assessment was done by global evaluation and adverse events in each group. Results. Dexketoprofen showed superior efficacy in terms of number of responders (P = .007), PID at 8?hours (P = .02), and SAPID( 0-8 hours ) (P < .0001). It also showed faster onset of action (42 minutes) and longer duration of action (6.5 hours). The adverse events were comparable in both groups. Conclusion. Single dose of dexketoprofen trometamol 50?mg given intramuscularly provided faster, better, and longer duration of analgesia in postoperative patients of hernia repair surgery than diclofenac 50?mg, with comparable safety. PMID:21716733

Jamdade, P T; Porwal, A; Shinde, J V; Erram, S S; Kamat, V V; Karmarkar, P S; Bhagtani, K; Dhorepatil, S; Irpatgire, R; Bhagat, H; Kolte, S S; Shirure, P A



High-power pain threshold ultrasound technique in the treatment of active myofascial trigger points: a randomized, double-blind, case-control study  

Microsoft Academic Search

Majlesi J, Ünalan H. High-power pain threshold ultrasound technique in the treatment of active myofascial trigger points: a randomized, double-blind, case-control study. Arch Phys Med Rehabil 2004;85:833-6.

Javid Majlesi; Halil Ünalan



The Fine Tuning of Pain Thresholds: A Sophisticated Double Alarm System  

Microsoft Academic Search

Two distinctive features characterize the way in which sensations including pain, are evoked by heat: (1) a thermal stimulus is always progressive; (2) a painful stimulus activates two different types of nociceptors, connected to peripheral afferent fibers with medium and slow conduction velocities, namely A?- and C-fibers. In the light of a recent study in the rat, our objective was

Léon Plaghki; Céline Decruynaere; Paul Van Dooren; Daniel Le Bars



Tolerance to non-opioid analgesics in PAG involves unresponsiveness of medullary pain-modulating neurons in male rats.  


Opiate analgesia can be hampered by a reduction in pharmacological effectiveness (tolerance), and this crucially depends on the periaqueductal gray matter (PAG). Non-opioids like metamizol (dipyrone) or aspirin also induce PAG-dependent analgesia and tolerance, but the neuronal bases of this tolerance are unknown. Metamizol is a pyrazolon derivative and cyclooxygenase inhibitor with widespread use as an analgesic in Europe and Latin America. Metamizol was microinjected into the PAG of awake male rats, and antinociception was assessed by the tail flick (TF) and hot plate (HP) tests. Microinjection twice daily for 2.5 days caused tolerance to metamizol. The rats were then anesthetized and recordings from pain-facilitating on-cells and pain-inhibiting off-cells of the rostral ventromedial medulla (RVM) were performed. PAG microinjection of morphine or metamizol depresses on-cells, activates off-cells and thus inhibits nociception, including TF and HP. In metamizol-tolerant rats, however, PAG microinjection of metamizol failed to affect on- or off-cells, and this is interpreted as the reason for tolerance. In metamizol-tolerant rats morphine microinjection into PAG also failed to affect RVM neurons or nociception (cross-tolerance). In naïve, non-tolerant rats the antinociceptive effect of PAG-microinjected metamizol or morphine was blocked when CTOP, a mu-opioid antagonist, was previously microinjected into the same PAG site. These results emphasize a close relationship between opioid and non-opioid analgesic mechanisms in the PAG and show that, like morphine, tolerance to metamizol involves a failure of on- and off-cells to, respectively, disfacilitate and inhibit nociception. Cross-tolerance between non-opioid and opioid analgesics should be important in the clinical setting. PMID:19302154

Tortorici, Victor; Aponte, Yexica; Acevedo, Humberto; Nogueira, Lourdes; Vanegas, Horacio



Ranking of parameters of pain hypersensitivity according to their discriminative ability in chronic low back pain.  


Low back pain is associated with plasticity changes and central hypersensitivity in a subset of patients. We performed a case-control study to explore the discriminative ability of different quantitative sensory tests in distinguishing between 40 cases with chronic low back pain and 300 pain-free controls, and to rank these tests according to the extent of their association with chronic pain. Gender, age, height, weight, body mass index, and psychological measures were recorded as potential confounders. We used 26 quantitative sensory tests, including different modalities of pressure, heat, cold, and electrical stimulation. As measures of discrimination, we estimated receiver operating characteristics (ROC) and likelihood ratios. Six tests seemed useful (in order of their discriminative ability): (1) pressure pain detection threshold at the site of most severe pain (fitted area under the ROC, 0.87), (2) single electrical stimulation pain detection threshold (0.87), (3) single electrical stimulation reflex threshold (0.83), (4) pressure pain tolerance threshold at the site of most severe pain (0.81), (5) pressure pain detection threshold at suprascapular region (0.80), and (6) temporal summation pain threshold (0.80). Pressure and electrical pain modalities seemed most promising and may be used for diagnosis of pain hypersensitivity and potentially for identifying individuals at risk of developing chronic low back pain over time. PMID:22846347

Neziri, Alban Y; Curatolo, Michele; Limacher, Andreas; Nüesch, Eveline; Radanov, Bogdan; Andersen, Ole K; Arendt-Nielsen, Lars; Jüni, Peter



Olea Europea-derived phenolic products attenuate antinociceptive morphine tolerance: an innovative strategic approach to treat cancer pain.  


Morphine and related opioid drugs are currently the major drugs for severe pain. Their clinical utility is limited in the management of severe cancer pain due to the rapid development of tolerance. Restoring opioid efficacy is therefore of great clinical importance. A great body of evidence suggests the key role of free radicals and posttranslational modulation in the development of tolerance to the analgesic activity of morphine. Epidemiological studies have shown a relationship between the Mediterranean diet and a reduced incidence of pathologies such as coronary heart disease and cancer. A central hallmark of this diet is the high consumption of virgin olive oil as the main source of fat which contains antioxidant components in the non-saponifiable fraction, including phenolic compounds absent in seed oils. Here, we show that in a rodent model of opiate tolerance, removal of the free radicals with phenolic compounds of olive oil such as hydroxytyrosol and oleuropein reinstates the analgesic action of morphine. Chronic injection of morphine in mice led to the development of tolerance and this was associated with increased nitrotyrosin and malondialdehyde (MDA) formation together with nitration and deactivation of MnSOD in the spinal cord. Removal of free radicals by hydroxytyrosol and oleuropein blocked morphine tolerance by inhibiting nitration and MDA formation and replacing the MnSOD activity. The phenolic fraction of virgin olive oil exerts antioxidant activities in vivo and free radicals generation occurring during chronic morphine administration play a crucial role in the development of opioid tolerance. Our data suggest novel therapeutic approach in the management of chronic cancer pain, in particular for those patients who require long-term opioid treatment for pain relief without development of tolerance. PMID:24750796

Muscoli, C; Lauro, F; D'Agostino, C; Ilari, S; Giancotti, L A; Gliozzi, M; Costa, N; Carresi, C; Musolino, V; Casale, F; Ventrice, D; Oliverio, E; Palma, E; Nistico', S; Procopio, A; Mollace, V



The effect of dry needling on pain, pressure pain threshold and disability in patients with a myofascial trigger point in the upper trapezius muscle.  


Dry needling (DN) has been used recently by physical therapists as a therapy of choice for patients with myofascial trigger points (TrP). The purpose of this randomized controlled trial was to investigate the effect of DN in the treatment of TrPs in the upper trapezius (UT) muscle. A sample of convenience of 33 patients with TrP in the UT muscle participated in this study. Patients were randomly assigned to a standard (N = 17) or experimental group (N = 16). The treatment protocol for the standard group consisted of trigger point compression technique (TCT) on MTP, while the patients in the experimental group received DN. Pain intensity and pressure pain thresholds were assessed for both groups before and after the treatment sessions. In addition, the Disability of Arm, Hand, and Shoulder (DASH) was administered. Statistical analysis (paired t-test) revealed a significant improvement in pain, PPT and DASH scores after treatment in the experimental (DN) and standard (TCT) group compared with before treatment (P < 0.05). The ANCOVA revealed significant differences between the DN and TCT groups on the post-measurement VAS score (P = 0.01). There was, however, no significant difference between the two groups on the post-measurement score of the PPT (P = 0.08) and DASH (P = 0.34). DN produces an improvement in pain intensity, PPT and DASH and may be prescribed for subjects with TrP in UT muscles especially when pain relief is the goal of the treatment. PMID:24725800

Ziaeifar, Maryam; Arab, Amir Massoud; Karimi, Noureddin; Nourbakhsh, Mohammad Reza



Ferulic acid increases pain threshold and ameliorates depression-like behaviors in reserpine-treated mice: behavioral and neurobiological analyses.  


Depression-pain dyad involves a series of pathological changes including the dysfunction of neuroendocrine and immune networks. Depression and pain influence each other, but the mechanisms are still obscure. The present study aimed to investigate the effect of ferulic acid (FA) on reserpine-induced pain and depression-like behaviors in mice. The results showed that reserpine (1 mg/kg for 3 days, i.p.) led to a significant decrease in nociceptive threshold in thermal hyperalgesia and mechanical allodynia, as well as a significant increase in the immobility time in mouse models of despair test. The neurochemical assays suggested the decreased neurotransmitters (dopamine, norepinephrine and serotonin) along with the increased oxidative stress, inflammatory cytokines, and apoptotic parameters in the frontal cortex and hippocampus of the reserpinised mice. Treatment with FA (40 or 80 mg/kg, p.o.) reversed the behavioral abnormalities and decreased norepinephrine, serotonin and dopamine levels in the hippocampus and frontal cortex induced by reserpine. The higher dose of FA effectively antagonized the oxidative and nitrosative stress and inflammation as evidenced by down-regulated nitrite, LPO, IL-1?, TNF-?, and up-regulated GSH and SOD. Furthermore, FA produced a dose dependent decrease in substance P, NF-?? p65 and caspase-3 levels in the frontal cortex and hippocampus of reserpinised mice. The findings suggest that FA exerts the effects on reserpine-induced pain and depression-like behaviors through regulating monoaminergic system, oxidative/antioxidant defense, inflammatory and apoptotic signaling pathways. Understanding the mechanism by which FA ameliorates depression and pain as a multi-targeted compound could open new avenues for the development of innovative treatments for depression coupled with pain. PMID:23584961

Xu, Ying; Zhang, Lu; Shao, Tuo; Ruan, Lina; Wang, Lin; Sun, Jiao; Li, Jianxin; Zhu, Xinbo; O'Donnell, James M; Pan, Jianchun



Decreased sensitivity to experimental pain in adjustment disorder  

Microsoft Academic Search

An altered perception of pain has been described for several psychiatric disorders. To date the influence of adjustment disorders (AD) on pain perception has not been described.Here, we investigated perception of experimentally induced pain in 15 patients suffering from AD (subtype with depressive symptoms) and controls matched for age and sex. Thresholds and tolerances were assessed for thermal and electrical

Karl-Jürgen Bär; Stanislaw Brehm; Michael Karl Boettger; Gerd Wagner; Silke Boettger; Heinrich Sauer



[Effect of intraventricular injection of somatostatin on pain threshold, and contents of the monoamines, xanthine, hypoxanthine in rats brain].  


Using HPLC with electrochemical detection, we found that icv somatostatin (Som) 5 or 10 micrograms increased rat's pain threshold and contents of 5-HT and 5-HIAA in hippocampus, hypothalamus and brainstem, except the 5-HIAA content of brainstem in Som 5 micrograms group. However, the changes of NE among above three areas of brain were different, the NE contents of hypothalamus and brainstem significantly increased while that of hippocampus markedly decreased. After icv Som 20 micrograms, hypoxanthine and xanthine in hippocampus and hypothalamus decreased significantly, but encephaledema occurred. Som 40 micrograms icv caused necrotic changes of neurons in brain. PMID:1688090

Li, X C; Li, H D; Zhao, B Y; Huan, H Z



Differential effect of brain-derived neurotrophic factor on high-threshold mechanosensitivity in a rat neuropathic pain model.  


We investigated the effect of the systemic infusion of brain derived neurotrophic factor (BDNF) on the behavioral response in a rat neuropathic pain model. One microgram per hour infusion of BDNF significantly attenuated mechanical hyperalgesia tested by the pin-prick test, however, 20 microg/h-BDNF infusion, on the contrary, enhanced the response. Neither 0.5 nor 10 microg/h-BDNF infusion influenced the mechanical hyperalgesia. Mechanical allodynia and thermal hyperalgesia, tested using a von Frey filament (23.0 mN) and the plantar test, were not influenced by BDNF treatment. These data suggest that systemic BDNF treatment can specifically alter high-threshold mechanosensitivity. PMID:10643807

Miki, K; Fukuoka, T; Tokunaga, A; Kondo, E; Dai, Y; Noguchi, K



The analgesic effect of codeine as compared to imipramine in different human experimental pain models  

Microsoft Academic Search

The hypoalgesic effect of single oral doses of 100 mg imipramine and 125 mg codeine was evaluated in a randomised, placebo-controlled, double-blind, 3-way cross-over experiment including 18 healthy volunteers. Pain tests were performed before and 90, 180, 270, 360 and 450 min after medication. The tests included determination of pain tolerance thresholds to pressure, pain detection\\/tolerance thresholds to single electrical

Thomas P Enggaard; Lars Poulsen; Lars Arendt-Nielsen; Steen Honoré Hansen; Inga Bjørnsdottir; Lars F Gram; Søren H Sindrup



Ketamine as an Adjunct to Postoperative Pain Management in Opioid Tolerant Patients After Spinal Fusions: A Prospective Randomized Trial  

PubMed Central

Management of acute postoperative pain is challenging, particularly in patients with preexisting narcotic dependency. Ketamine has been used at subanesthetic doses as a N-methyl d-aspartate (NMDA) receptor antagonist to block the processing of nociceptive input in chronic pain syndromes. This prospective randomized study was designed to assess the use of ketamine as an adjunct to acute pain management in narcotic tolerant patients after spinal fusions. Twenty-six patients for 1–2 level posterior lumbar fusions with segmental instrumentation were randomly assigned to receive ketamine or act as a control. Patients in the ketamine group received 0.2 mg/kg on induction of general anesthesia and then 2 mcg kg?1 hour?1 for the next 24 hours. Patients were extubated in the operating room and within 15 minutes of arriving in the Post Anesthesia Care Unit (PACU) were started on intravenous patient-controlled analgesia (PCA) hydromorphone without a basal infusion. Patients were assessed for pain (numerical rating scale [NRS]), narcotic use, level of sedation, delirium, and physical therapy milestones until discharge. The ketamine group had significantly less pain during their first postoperative hour in the PACU (NRS 4.8 vs 8.7) and continued to have less pain during the first postoperative day at rest (3.6 vs 5.5) and with physical therapy (5.6 vs 8.0). Three patients in the control group failed PCA pain management and were converted to intravenous ketamine infusions when their pain scores improved. Patients in the ketamine group required less hydromorphone than the control group, but the differences were not significant. Subanesthetic doses of ketamine reduced postoperative pain in narcotic tolerant patients undergoing posterior spine fusions.

Ya Deau, Jacques T.; Wukovits, Barbara; Lipnitsky, Jane Y.



Determination of a pressure pain threshold cut-off value for the diagnosis of temporomandibular joint arthralgia.  


Temporomandibular joint (TMJ) disorders are divided by the American Academy of Orofacial Pain into five categories. The most common ones are joint pain, as arthralgia and joint disorders, as disc displacements. An important clinical presentation of arthralgia is the painful tenderness to manual palpation or decreased pressure pain threshold (PPT). The authors conducted a study to determine the appropriate PPT value to discriminate asymptomatic TMJ individuals from those with moderate to severe arthralgia. Forty-nine individuals was evaluated and divided into groups: TMJ arthralgia, asymptomatic disc displacement and control group. Magnetic resonance images were obtained for all the groups, and algometry was performed on the TMJ lateral pole. Patients with arthralgia filled out a visual analogue scale (VAS). anova test with 1% of significance analysed the data. Specificity, sensitivity and ROC curve were also determined. Arthralgia group had significant lower PPT (mean of 1·07 kgf cm(-2) ) than the others. Asymptomatic disc displacement group (mean of 1·64 kgf cm(-2) ) has shown significant lower PPT than the control (mean of 2·35 kgf cm(-2) ). 89·66% of specificity and 70% of sensitivity were obtained when 1·36 kgf cm(-2) was applied to the TMJ (ROC area = 0·90). This value was considered to be the most appropriate to detected moderate to severe TMJ arthralgia. Indeed, the presence of disc displacement seems to significantly decrease PPT levels in asymptomatic subjects. The PPT value of 1·36 kgf cm(-2) can be used in the calibration procedures of the professionals involved with temporomandibular disorders and orofacial pain. PMID:24612404

Cunha, C O; Pinto-Fiamengui, L M S; Castro, A C P C; Lauris, J R P; Conti, P C R



A Threshold for Central T Cell Tolerance to an Inducible Serum Protein1  

Microsoft Academic Search

We report an inducible system of self Ag expression that examines the relationship between serum protein levels and central T cell tolerance. This transgenic approach is based on tetracycline-regulated expression of a secreted form of hen egg lysozyme, tagged with a murine hemoglobin (Hb) epitope. In the absence of the tetracycline-regulated transactivator, serum levels of the chimeric protein are extremely

Dipica Haribhai; Deborah Engle; Michelle Meyer; David Donermeyer; J. Michael White; Calvin B. Williams


Subgroups based on thermal and pressure pain thresholds in women with chronic whiplash display differences in clinical presentation - an explorative study  

PubMed Central

Purpose To investigate the presence of subgroups in chronic whiplash-associated disorders (WAD) based on pain thresholds for pressure (PPT), cold (CPT), and heat (HPT) and to compare these subgroups with respect to symptomatology, disability, and health aspects. Methods Two groups of female subjects – patients with chronic WAD (n = 28) and healthy controls (CON; n = 29) – were investigated. Quantitative sensory testing (QST) for thermal thresholds and algometry for PPT at four sites in the body (over the trapezius and tibialis anterior bilaterally) were determined. Habitual pain intensities, psychological strain, disability, and health aspects were registered using a questionnaire. Results A cluster analysis based on PPT, CPT, and HPT identified two subgroups of chronic WAD: one sensitive subgroup (s-WAD; n = 21), and one less sensitive subgroup (ls-WAD; n = 6). S-WAD displayed widespread hyperalgesia, whereas ls-WAD had localized hyperalgesia in the neck area, with tendencies to supernormal values in remote areas of the body. Generally, s-WAD had a significantly worse situation than the CON with respect to symptomatology, disability, and health aspects. The ls-WAD group was intermediary between s-WAD and CON in these aspects. Conclusion Different explanations, eg, severity of the pain condition per se, etiological factors, and pre-trauma differences in pain sensitivity, may exist for the differences in pain thresholds between the two subgroups. Future research should investigate the role of pain thresholds in the chronic stage to determine the efficacy of treatment interventions.

Borsbo, Bjorn; Liedberg, Gunilla M; Wallin, Mia; Gerdle, Bjorn



Comparison of Pressure Pain Threshold, Grip Strength, Dexterity and Touch Pressure of Dominant and Non-Dominant Hands within and Between Right- and Left-Handed Subjects  

PubMed Central

This study was done to evaluate differences in pressure pain threshold, grip strength, manual dexterity and touch pressure threshold in the dominant and non-dominant hands of right- and left-handed subjects, and to compare findings within and between these groups. Thirty-nine right-handed and twenty-one left-handed subjects participated in the study. Pressure pain threshold was assessed using a dolorimeter, grip strength was assessed with a hand-grip dynamometer, manual dexterity was evaluated using the VALPAR Component Work Sample-4 system, and touch pressure threshold was determined using Semmes Weinstein monofilaments. Results for the dominant and non-dominant hands were compared within and between the groups. In the right-handed subjects, the dominant hand was significantly faster with the VALPAR Component Work Sample-4, showed significantly greater grip strength, and had a significantly higher pressure pain threshold than the non-dominant hand. The corresponding results for the two hands were similar in the left-handed subjects. The study revealed asymmetrical manual performance in grip strength, manual dexterity and pressure pain threshold in right-handed subjects, but no such asymme-tries in left-handed subjects.

Tulum, Zeliha; P?nar, Lamia; Baskurt, Ferdi



Upper Bounds on the Noise Threshold for Fault-Tolerant Quantum Computing  

Microsoft Academic Search

We prove new upper bounds on the tolerable level of noise in a quantum circuit. We consider circuits consisting of unitary k-qubit gates each of whose input wires is subject to depolarizing noise of strength p, as well as arbitrary one-qubit gates that are essentially noise-free. We assume that the output of the circuit is the result of measuring some

Julia Kempe; Oded Regev; Falk Unger; Ronald De Wolf; L. Aceto



Heat-Related Deaths in Hot Cities: Estimates of Human Tolerance to High Temperature Thresholds  

PubMed Central

In this study we characterized the relationship between temperature and mortality in central Arizona desert cities that have an extremely hot climate. Relationships between daily maximum apparent temperature (ATmax) and mortality for eight condition-specific causes and all-cause deaths were modeled for all residents and separately for males and females ages <65 and ?65 during the months May–October for years 2000–2008. The most robust relationship was between ATmax on day of death and mortality from direct exposure to high environmental heat. For this condition-specific cause of death, the heat thresholds in all gender and age groups (ATmax = 90–97 °F; 32.2?36.1 °C) were below local median seasonal temperatures in the study period (ATmax = 99.5 °F; 37.5 °C). Heat threshold was defined as ATmax at which the mortality ratio begins an exponential upward trend. Thresholds were identified in younger and older females for cardiac disease/stroke mortality (ATmax = 106 and 108 °F; 41.1 and 42.2 °C) with a one-day lag. Thresholds were also identified for mortality from respiratory diseases in older people (ATmax = 109 °F; 42.8 °C) and for all-cause mortality in females (ATmax = 107 °F; 41.7 °C) and males <65 years (ATmax = 102 °F; 38.9 °C). Heat-related mortality in a region that has already made some adaptations to predictable periods of extremely high temperatures suggests that more extensive and targeted heat-adaptation plans for climate change are needed in cities worldwide.

Harlan, Sharon L.; Chowell, Gerardo; Yang, Shuo; Petitti, Diana B.; Morales Butler, Emmanuel J.; Ruddell, Benjamin L.; Ruddell, Darren M.



Evaluation of thermal, pain, and vibration sensation thresholds in newly diagnosed type 1 diabetic patients  

Microsoft Academic Search

Small and large fibre function was studied in 40 non-ketotic, newly diagnosed Type 1 diabetic patients and 48 age-matched controls, using 12 quantitative tests for assessment of cutaneous sensation. Patients were aged 10-39 years and had been treated with insulin for 4-31 days. Thermal discrimination (foot), warm and cold thermal perception (thenar eminence and foot), and heat and cold pain

D Ziegler; P Mayer; F A Gries



Blockade of Toll-Like Receptor 4 Attenuates Morphine Tolerance and Facilitates the Pain Relieving Properties of Morphine  

PubMed Central

The ventrolateral periaqueductal gray (vlPAG) is an integral locus for morphine action. Although it is clear that glia contribute to the development of morphine tolerance, to date, the investigation of their role has been limited to spinal and medullary loci. Opioids induce a neuroinflammatory response that opposes acute and long-term analgesia, thereby limiting their efficacy as therapeutic agents. Recent data suggest that the innate immune receptor Toll-like receptor 4 (TLR4), along with its coreceptor myeloid differentiation factor-2 (MD-2), mediates these effects. To date, the brain loci through which TLR4 modulates morphine tolerance have not been identified. We have previously demonstrated that chronic subcutaneous morphine results in tolerance that is accompanied by increases in vlPAG glial cell activity. Using in vivo pharmacological manipulations of vlPAG glia and TLR4 in the adult male rat, we show that intra-vlPAG administration of the general glial cell metabolic inhibitor propentofylline or the astrocyte activity inhibitor fluorocitrate attenuate tolerance to morphine. Characterization of MD-2 expression within the PAG revealed dense MD-2 expression throughout the vlPAG. Further, antagonizing vlPAG TLR4 dose dependently prevented the development of morphine tolerance, and vlPAG microinjections of TLR4 agonists dose dependently produced a “naive” tolerance to subsequent challenge doses of morphine. Finally, using a model of persistent inflammatory pain and pharmacological manipulation of TLR4 we demonstrate that systemic antagonism of TLR4 potentiated acute morphine antihyperalgesia. These results, together, indicate that vlPAG glia regulate morphine tolerance development via TLR4 signaling, and implicate TLR4 as a potential therapeutic target for the treatment of pain.

Eidson, Lori N.



Efficacy and tolerability of celecoxib versus hydrocodone\\/acetaminophen in the treatment of pain after ambulatory orthopedic surgery in adults  

Microsoft Academic Search

Background: Current outpatient management of postoperative pain includes the use of oral opioid analgesics or nonsteroidal anti-inflammatory drugs; however, both types of medications are associated with side effects that can limit their usefulness in the outpatient setting.Objective: Two studies with identical protocols assessed the single- and multiple-dose analgesic efficacy and tolerability of celecoxib, a specific cyclooxygenase-2 inhibitor, in the treatment

Joseph S. Gimbel; Andrew Brugger; William Zhao; Kenneth M. Verburg; G. Steven Geis



Identifying a temporal threshold of tolerance for silent gaps after requests.  


This study addresses whether there is a threshold, some particular length of silent gap between two speakers' turns, at which negative social attributions emerge. The effect of such inter-turn silence was tested by constructing dialogues where responses to requests were identical and affirmative so that study participants' (n = 380) ratings about "willingness" would be colored by lag time, not semantics. 100 ms intervals between 200 and 1200 ms were tested in a between groups design. There was a notable drop-off in ratings at 600 ms and a statistically significant difference in ratings between 700 and 800 ms. PMID:23742442

Roberts, Felicia; Francis, Alexander L



A Novel Magnetic Stimulator Increases Experimental Pain Tolerance in Healthy Volunteers - A Double-Blind Sham-Controlled Crossover Study  

PubMed Central

The ‘complex neural pulse’TM (CNP) is a neuromodulation protocol employing weak pulsed electromagnetic fields (PEMF). A pioneering paper reported an analgesic effect in healthy humans after 30 minutes of CNP-stimulation using three nested whole head coils. We aimed to devise and validate a stimulator with a novel design entailing a multitude of small coils at known anatomical positions on a head cap, to improve applicability. The main hypothesis was that CNP delivery with this novel device would also increase heat pain thresholds. Twenty healthy volunteers were enrolled in this double-blind, sham-controlled, crossover study. Thirty minutes of PEMF (CNP) or sham was applied to the head. After one week the other treatment was given. Before and after each treatment, primary and secondary outcomes were measured. Primary outcome was heat pain threshold (HPT) measured with thermal quantitative sensory testing. Other outcomes were warmth detection threshold, and aspects of cognition, emotion and motor performance. As hypothesized heat pain threshold was significantly increased after the PEMF stimulation. All other outcomes were unaltered by the PEMF but there was a trend level reduction of cognitive performance after PEMF stimulation as measured by the digit-symbol substitution task. Results from this pilot study suggest that our device is able to stimulate the brain and to modulate its function. This is in agreement with previous studies that used similar magnetic field strengths to stimulate the brain. Specifically, pain control may be achieved with PEMF and for this analgesic effect, coil design does not appear to play a dominant role. In addition, the flexible configuration with small coils on a head cap improves clinical applicability. Trial Registration Dutch Cochrane Centre NTR1093

Kortekaas, Rudie; Konopka, Karl-Heinz; Harbers, Marten; van der Hoeven, Johannes H.; van Wijhe, Marten; Aleman, Andre; Maurits, Natasha M.



Changes in G proteins genes expression in rat lumbar spinal cord support the inhibitory effect of chronic pain on the development of tolerance to morphine analgesia.  


There are some reports regarding the inhibitory effect of pain on tolerance development to analgesic effect of opioids. The present study was designed to investigate whether the chronic formalin induced pain is able to reverse analgesic tolerance to morphine and to evaluate the expression of G(alpha i/o) and G(beta) subunits of G proteins in the context of chronic pain, development of morphine tolerance and their combination. Morphine tolerance was induced by chronic systemic (intraperitoneally, i.p.) or spinal (intrathecally, i.t.) administration of morphine to male Wistar rats weighing 200-240 g and analgesia was assessed using tail flick test. Chronic pain was induced by 4 daily intraplantar injections of 50 microl of 5% formalin. Lumbar spinal tissues were assayed for the expression of G(alpha i/o) and G(beta) proteins using "semiquantitative PCR" normalized to beta-actin gene expression. Results showed that chronic formalin induced pain could reduce and reverse the development of tolerance in rats that had received chronic (i.p. or i.t.) administration of morphine. Chronic administration of morphine did not change G(alpha i/o) gene expression, while chronic pain significantly increased its expression. The expression of G(beta), however, was increased after the chronic administration of morphine, but did not change after the induction of chronic pain. None of these increases were observed when morphine and formalin were administered at the same time. Due to synchronous development of morphine tolerance and changes in expression of G(beta), it may be concluded that the development of tolerance to analgesic effect of morphine is partially mediated by increase in G(beta) gene expression. The increase in G(alpha i/o) genes expression produced by chronic pain may facilitate the opioid signaling pathway and compensate for morphine-induced tolerance. PMID:16055216

Javan, Mohammad; Ahmadiani, Abolhassan; Motamadi, Fereshteh; Kazemi, Bahram





... of Orthropaedic and Sports Physical Therapy) [ PDF] Chronic Pain Management (Anesthesiology) [699KB PDF] Diagnosis and Treatment of Low- ... Journal of the American Osteopathic Association) [340KB PDF] Pain Management Task Force Final Report (Office of The Army ...


Influence of Geometry, Porosity and Surface Characteristics of Silica Nanoparticles on Acute Toxicity: Their Vasculature Effect and Tolerance Threshold  

PubMed Central

Silica nanoparticles (SiO2) are widely used in biomedical applications such as drug delivery, cell tracking and gene transfection. The capability to control the geometry, porosity, and surface characteristics of SiO2 further provides new opportunities for their applications in nanomedicine. Concerns however remain about the potential toxic effects of SiO2 upon exposure to biological systems. In the present study, the acute toxicity of SiO2 of systematically varied geometry, porosity and surface characteristics was evaluated in immune-competent mice when administered intravenously. Results suggest that in vivo toxicity of SiO2 was mainly influenced by nanoparticle porosity and surface characteristics. The maximum tolerated dose (MTD) increased in the following order: Mesoporous SiO2 (aspect ratio 1, 2, 8) at 30 – 65 mg/kg < amine-modified mesoporous SiO2 (aspect ratio 1, 2, 8) at 100 – 150 mg/kg < unmodified or amine-modified nonporous SiO2 at 450 mg/kg. The adverse reactions above MTDs were primarily caused by the mechanical obstruction of SiO2 in the vasculature that led to congestion in multiple vital organs and subsequent organ failure. It was revealed that hydrodynamic sizes of SiO2 post protein exposure had an important implication in relating SiO2 physicochemical properties with their vasculature impact and resultant tolerance threshold, as the larger the hydrodynamic size in the presence of serum protein, the lower the MTD. This study sheds light on the rational design of SiO2 to minimize in vivo toxicity and provides a critical guideline in selecting SiO2 as the appropriate system for nanomedicine applications.

Yu, Tian; Greish, Khaled; McGill, Lawrence D.; Ray, Abhijit; Ghandehari, Hamidreza



Efficacy and tolerability of carbamazepine for the treatment of painful diabetic neuropathy in adults: a 12-week, open-label, multicenter study  

PubMed Central

Objective Anticonvulsants are increasingly being used in the symptomatic management of several neuropathic pain disorders. The present observational study was designed to evaluate the efficacy, tolerability, and quality of life (QoL) of carbamazepine use for 12 weeks in patients with painful diabetic neuropathy, in Pakistan. Methods This was a 12-week, multicenter, open-label, uncontrolled trial in adult type 2 diabetic patients (aged 18–65 years) suffering from clinically confirmed neuropathic pain (Douleur Neuropathique en 4 [DN4] score ?4). Change in neuropathic pain at week 12 compared with baseline was assessed using the Brief Pain Inventory Scale–Short Form (pain severity score and pain interference score). QoL was determined by the American Chronic Pain Association QoL scale. Safety was assessed based on patient reported adverse events (AEs) and serious AEs. Results Of the total 500 screened patients, 452 enrolled and completed the study. The mean (± standard deviation [SD]) pain interference score decreased from 4.5±2.0 at baseline to 3.1±1.9 at week 12 (P<0.001). The mean (± SD) pain severity score decreased from 5.8±2.0 at baseline to 3.6±2.2 at week 12 (P<0.001). There was a decrease of ?30% in the pain severity score between visits. The mean (± SD) QoL scale score improved from 5.9±1.6 at baseline to 8.0±1.7 at week 12. A total of ten (2.2%) patients reported AEs during the study period. No patient discontinued the study due to AEs. Conclusion In this real-life experience study, carbamazepine, when prescribed for 12 weeks to adult diabetic patients suffering from neuropathic pain, showed pain-relief effect, with reduced mean pain severity and mean pain interference scores and with improved QoL and good tolerability profile.

Saeed, Tariq; Nasrullah, Muhammad; Ghafoor, Adnan; Shahid, Riaz; Islam, Nadeem; Khattak, Mohammad Usman; Maheshwary, Neeta; Siddiqi, Ahson; Khan, Muhammad Athar



Opiate tolerance to daily heroin administration: an apparent phenomenon associated with enhanced pain sensitivity  

Microsoft Academic Search

From a classical viewpoint, tolerance to analgesic effects of opiates refers to the decreased effectiveness of a given opiate following its repeated use.[11]Despite much research, it has not been conclusively demonstrated in vivo that functional changes observed at the opioid receptor level in the responsiveness to opiates account for development of tolerance.[2, 9, 10, 36]An alternative hypothesis is that opioid

J. P Laulin; E Célèrier; A Larcher; M Le Moal; G Simonnet



Effectiveness and gastrointestinal tolerability during conversion and titration with once-daily OROS(R) hydromorphone extended release in opioid-tolerant patients with chronic low back pain  

PubMed Central

Purpose To describe the efficacy and safety of hydromorphone extended-release tablets (OROS hydromorphone ER) during dose conversion and titration. Patients and methods A total of 459 opioid-tolerant adults with chronic moderate to severe low back pain participated in an open-label, 2- to 4-week conversion/titration phase of a double-blind, placebo-controlled, randomized withdrawal trial, conducted at 70 centers in the United States. Patients were converted to once-daily OROS hydromorphone ER at 75% of the equianalgesic dose of their prior total daily opioid dose (5:1 conversion ratio), and titrated as frequently as every 3 days to a maximum dose of 64 mg/day. The primary outcome measure was change in pain intensity numeric rating scale; additional assessments included the Patient Global Assessment and the Roland–Morris Disability Questionnaire scores. Safety assessments were performed at each visit and consisted of recording and monitoring all adverse events (AEs) and serious AEs. Results Mean (standard deviation) final daily dose of OROS hydromorphone ER was 37.5 (17.8) mg. Mean (standard error of the mean [SEM]) numeric rating scale scores decreased from 6.6 (0.1) at screening to 4.3 (0.1) at the final titration visit (mean [SEM] change, ?2.3 [0.1], representing a 34.8% reduction). Mean (SEM) change in Patient Global Assessment was ?0.6 (0.1), and mean change (SEM) in the Roland–Morris Disability Questionnaire was ?2.8 (0.3). Patients achieving a stable dose showed greater improvement than patients who discontinued during titration for each of these measures (P < 0.001). Almost 80% of patients achieving a stable dose (213/268) had a ?30% reduction in pain. Commonly reported AEs were constipation (15.4%), nausea (11.9%), somnolence (8.7%), headache (7.8%), and vomiting (6.5%); 13.0% discontinued from the study due to AEs. Conclusion The majority of opioid-tolerant patients with chronic low back pain were successfully converted to effective doses of OROS hydromorphone ER within 2 to 4 weeks.

Hale, Martin E; Nalamachu, Srinivas R; Khan, Arif; Kutch, Michael



Red clover Trifolium pratense (Linn.) isoflavones extract on the pain threshold of normal and ovariectomized rats--a long-term study.  


Depletion of estrogens occurs in women during menopause, while in experimental animals, oophorectomy is a common method to deplete the animals of their gonadal hormones. Recently, phytoestrogens derived from plants have been tried as estrogen substitutes during menopause. In the present study an isoflavones methanol extract from red clover Trifolium pratense (Linn.) was administered orally (500?mg/kg of body weight) to ovariectomized (OVX) and normal (controls) rats for 90 and 180 days. Their pain threshold was monitored using tail flicking and formalin test methods. Observations showed that the OVX rat pain threshold was reduced due to estrogen deprivation, whereas the pain threshold levels in OVX rats treated with isoflavones extract was similar to the control animals. The present study demonstrated the influence of phytoestrogen on long-term OVX rats in pain perception in the absence of ovarian estrogen and without toxic side effects. However, the actions of gonadal hormones on nociceptive axis are myriad and complex, so further studies on the exact physiological mechanism of the phytoestrogen action on nociceptive axis is warranted. PMID:20623592

Vishali, Nagarajan; Kamakshi, Krishnaswamy; Suresh, Sekar; Prakash, Seppan





... or pain in at least 11 of 18 “tender points,” specific spots on the neck, shoul- ders, ... other symptoms: • fatigue • trouble sleeping • morning stiffness Fibromyalgia Tender Points Treatment • • • • • Pregabalin (pre-gaB-uh-lin) and ...


The MERITO Study: a multicentre trial of the analgesic effect and tolerability of normal-release oral morphine during 'titration phase' in patients with cancer pain.  


Adequate and rapid pain control is one of the main goals of cancer pain treatment. The objective of this study was to assess the effect and tolerability of oral normal-release morphine during the initial phase of treatment in patients with moderate-to-severe cancer pain. Consecutive patients naïve to strong opioids received normal-release morphine 5 or 10 mg every 4 h during the titration phase (first 5 days), depending on previous analgesic therapy. Pain intensity was assessed using an 11-point Numerical Rating Scale (0-10), and data were recorded in a patient-compiled diary. The primary endpoint was the proportion of time with pain control (a reduction of at least 50% with respect to the baseline pain score) during the titration phase. A total of 159 consecutive patients (102 men; mean age 65 years) with cancer-related pain were enrolled. Pain control was observed for 75% (95% CI 70-80) of the follow-up period in the intent-to-treat population. Overall, 50% and 75% of patients achieved pain control within 8 and 24 h after starting normal-release morphine therapy respectively. The mean pain score was 7.63 points at baseline, and decreased to 2.43 and 1.67 points (both P<0.001) at days 3 and 5 respectively. The most commonly reported adverse events were somnolence (24% of patients), constipation (22%), vomiting (13%), nausea (10%) and confusion (7%). Normal-release morphine results in rapid and satisfactory pain control, and is well tolerated, during the strong-opioid titration phase in patients with moderate-to-severe cancer pain. PMID:18477715

De Conno, F; Ripamonti, C; Fagnoni, E; Brunelli, C; Luzzani, M; Maltoni, M; Arcuri, E; Bertetto, O



Higher serum S100B and BDNF levels are correlated with a lower pressure-pain threshold in fibromyalgia  

PubMed Central

Background Fibromyalgia (FM) is conceptualized as a central sensitization (CS) condition, that presents high serum brain-derived neurotrophic factor (BDNF) and neuroglia activation. Although the S100B protein regulates neuroglia functions, it has been traditionally used as a proxy of central nervous system damage. However, neither BDNF nor S100B association with the clinical picture of FM has been elucidated. To explore their association with the pressure-pain threshold (PPT) in FM, we performed a cross-sectional study, including 56 females with confirmed FM aged 18–65 years. Linear regression models were used to adjust for potential confounding factors between serum BDNF, S100B and PPT. Results Serum BDNF and S100B were correlated (Spearman’s Rho?=?0.29). Serum BDNF (log) and S100B (log) were correlated with the PPT (log) (Partial ?2?=?0.129, P?=?0.012 for the BDNF (log), and Partial ?2?=?0.105, P?=?0.025 for the S100B (log)). Serum BDNF (log) was inversely associated with PPT (log) (??=?-1.01, SE?=?0.41), age (??=?-0.02, SE?=?0.15) and obsessive compulsive disorder (??=?-0.36, SE?=?0.15), while serum S100B (log) was inversely associated with PPT (log) (??=?-1.38, SE?=?0.50), only. Conclusions Both neuroglia key mediators in the CS process were inversely correlated with the PPT. Serum assessment of BDNF and S100B deserve further study to determine its potential as a proxy for the CS spectrum in FM.



Structural Health Monitoring: Leveraging Pain in the Human Body  

NASA Astrophysics Data System (ADS)

Tissue damage, or the perception thereof, is managed through pain experience. The neurobiological process of pain triggers most effective defense mechanisms for our safety. Structural health monitoring (SHM) is also a very similar function, albeit in engineering systems. SHM technology can leverage many aspects of pain mechanisms to progress in several critical areas. Discrimination between features from the undamaged and damaged structures can follow the threshold gate mechanism of the pain perception. Furthermore, the sensing mechanisms can be adaptive to changes by adjusting the threshold as does the pain perception. A distributed sensor network, often advanced by SHM, can be made fault-tolerant and robust by following the perception way of self-organization and redundancy. Data handling in real life is a huge challenge for large-scale SHM. As sensory data of pain is first cleaned, the threshold is then processed through experiential information gathering and use.

Nayak, Subhadarshi



Efficacy and Tolerability of Nonprescription Ibuprofen versus Celecoxib for Dental Pain  

Microsoft Academic Search

Many clinicians appear confused about the purported clinical advantages of the new generation COX-2 inhibitors compared to both over-the-counter and prescription nonsteroidal anti-inflammatory analgesic agents (NSAIDs). In fact, there is a paucity of published information comparing the safety and efficacy of these two classes of drugs when used to treat acute pain. This study was designed to compare the safety

Geraldine Doyle; Shyamalie Jayawardena; Elizabeth Ashraf; Stephen A. Cooper



Structural damage alarming using auto-associative neural network technique: Exploration of environment-tolerant capacity and setup of alarming threshold  

NASA Astrophysics Data System (ADS)

With the intention of avoiding false-positive and false-negative alarms in structural damage alarming using the auto-associative neural network (AANN) technique, two issues pertaining to this technique are addressed in this study. The first issue explored is the environment-tolerant capacity of the AANN. Efforts have been made to seek a generalization technique to enhance the environment-tolerant capacity. First, a baseline AANN model is formulated using the conventional training algorithm. Generalization techniques including AIC and FPE, early stopping, and Bayesian regularization are then investigated, resulting in three new AANN models. Their environment-tolerant capacity is evaluated as per their capability to avoid false-positive and false-negative alarms. The other issue addressed is the setup of alarming threshold, with intent to reduce the uncertainty in AANN-based structural damage alarming. A procedure based on the probability analysis of the novelty index is proposed for this purpose. First, the novelty index characterizing the intact structure is analyzed by the Kolmogorov-Smirnov goodness-of-fit test to obtain its best-fit continuous probability distribution. A confidence interval is then defined in consideration of the compromise between type I and type II errors. The alarming threshold of the novelty index is consequently set at the upper limit of the confidence interval. The above explorations are examined by using the long-term monitoring data on modal properties of the cable-stayed Ting Kau Bridge. The capability to eliminate false-positive alarm is verified by using unseen testing data which were not used in formulating the AANN models, while the capability to alleviate false-negative alarm is examined by using simulated data from the 'damaged' bridge with the help of a precise finite element model. The study indicates that the early stopping technique performs best in improving the environment-tolerant capacity of the AANN, and the alarming threshold set by the proposed procedure helps to reduce the uncertainty in AANN-based structural damage alarming.

Zhou, H. F.; Ni, Y. Q.; Ko, J. M.



Sexual pain.  


Sexual pain is an underrecognized and poorly treated constellation of disorders that significantly impact affected women and their partners. Recognized as a form of chronic pain, sexual pain disorders are heterogeneous and include dyspareunia (superficial and deep), vaginismus, vulvodynia, vestibulitis, and noncoital sexual pain disorder. Women too often tolerate pain in the belief that this will meet their partners' needs. This article provides a review of the terminology and definition of the condition, theories on the pathophysiology, diagnostic considerations, and recommendations on the management of female sexual pain. PMID:20393420

Boardman, Lori A; Stockdale, Colleen K



Comparison of pressure pain threshold, grip strength,dexterity and touch pressure of dominant and non-dominant hands within and between right-and left-handed subjects.  


This study was done to evaluate differences in pressure pain threshold, grip strength, manual dexterity and touch pressure threshold in the dominant and non-dominant hands of right- and left-handed subjects, and to compare findings within and between these groups. Thirty-nine right-handed and twenty-one left-handed subjects participated in the study. Pressure pain threshold was assessed using a dolorimeter, grip strength was assessed with a hand-grip dynamometer, manual dexterity was evaluated using the VALPAR Component Work Sample-4 system, and touch pressure threshold was determined using Semmes Weinstein monofilaments. Results for the dominant and non-dominant hands were compared within and between the groups. In the right-handed subjects, the dominant hand was significantly faster with the VALPAR Component Work Sample-4, showed significantly greater grip strength, and had a significantly higher pressure pain threshold than the non-dominant hand. The corresponding results for the two hands were similar in the left-handed subjects. The study revealed asymmetrical manual performance in grip strength, manual dexterity and pressure pain threshold in right-handed subjects, but no such asymmetries in left-handed subjects. PMID:15608401

Ozcan, Ayse; Tulum, Zeliha; Pinar, Lamia; Ba?kurt, Ferdi



A double-blind, multicentre, randomised clinical trial comparing the efficacy and tolerability of aceclofenac with diclofenac resinate in patients with acute low back pain  

Microsoft Academic Search

The efficacy and tolerability of aceclofenac was compared with diclofenac resinate in a double-blind, multicentre randomised\\u000a study in patients with acute low back pain suffering from degenerative spinal disorders. The study included 227 patients randomised\\u000a to receive either aceclofenac 2 ? 100 mg daily or diclofenac resinate 2 ? 75 mg daily for up to 10 days. The primary objective

M. Schattenkirchner; K. A. Milachowski



Gender, variation in opioid receptor genes and sensitivity to experimental pain  

PubMed Central

Background Pain tolerance is subject to considerable inter-individual variation, which may be influenced by a number of genetic and non-genetic factors. The mu, delta and kappa opioid receptors play a role in pain perception and are thought to mediate different pain modalities. The aim of this study was to explore associations between pain thresholds and gender and genetic variants in the three opioid receptor genes (OPRM, OPRD and OPRK). Experimental multi-modal pain data from previously published studies carried out in healthy Caucasian volunteers were used in order to limit the number of confounders to the study outcome. Data on thermal skin pain (n=36), muscle pressure pain (n=31) and mechanical visceral pain (n=50)) tolerance thresholds were included. Results Nineteen genetic polymorphisms were included in linear regression modeling. Males were found to tolerate higher thermal and muscle pressure pain than females (p=0.003 and 0.02). Thirty four percent of variability in thermal skin pain was accounted for by a model consisting of OPRK rs6473799 and gender. This finding was just outside significance when correction for multiple testing was applied. Variability in muscle pressure pain tolerance was associated with OPRK rs7016778 and rs7824175. These SNPs accounted for 43% of variability in muscle pressure pain sensitivity and these findings remained significant after adjustment for multiple testing. No association was found with mechanical visceral pain. Conclusion This is a preliminary and hypothesis generating study due to the relatively small study size. However, significant association between the opioid receptor genes and experimental pain sensitivity supports the influence of genetic variability in pain perception. These findings may be used to generate hypotheses for testing in larger clinical trials of patients with painful conditions.



Nociceptive Flexion Reflex and Pain Rating Responses During Endogenous Opiate Blockade with Naltrexone in Healthy Young Adults  

PubMed Central

The effect of opioid blockade on nociceptive flexion reflex (NFR) activity and subjective pain ratings was examined in 151 healthy young men and women. Using a within-subjects design, NFR threshold was assessed on two days after administration of either placebo or a 50 mg dose of naltrexone. Electrocutaneous pain threshold and tolerance levels were measured after NFR threshold assessment on each day. Results indicated that administration of naltrexone was consistently associated with hypoalgesic responding. Specifically, participants exhibited lower levels of NFR activity and reported lower pain ratings for electrocutaneous stimulation delivered at pain threshold and tolerance levels following administration of naltrexone as compared to placebo. These findings indicate that opiate blockade using the current standard dose may elicit hypoalgesia. A potential moderating effect of dose of opiate blockade medication and level of endogenous opioid activation should be carefully examined in future research.

France, Christopher R.; al'Absi, Mustafa; Ring, Christopher; France, Janis L.; Harju, Angie; Wittmers, Lorentz E.



Dopamine D2 receptor binding in the human brain is associated with the response to painful stimulation and pain modulatory capacity.  


The pain modulatory role of dopamine D2 receptors of the human forebrain was studied by determining the association between dopamine D2 receptor binding potential and the response to experimental pain. Nineteen healthy male volunteers participated in a dopamine D2 receptor positron emission tomography study. The extrastriatal regions of interest studied with [11C]FLB 457 as radioligand (n = 11) were the anterior cingulum, the medial and lateral thalamus, the medial and lateral frontal cortex, and the medial and lateral temporal cortex. The striatal regions of interest studied with [11C]raclopride (n = 8) were the caudate nucleus and the putamen. The latency to the ice water-induced cold pain threshold and tolerance were determined in a separate psychophysical test session. Moreover, the cutaneous heat pain threshold and its elevation by concurrent cold pain in the contralateral hand were determined in each subject. Cold pain threshold was inversely correlated with D2 binding potential in the right putamen and the cold pain tolerance was inversely correlated with D2 binding potential in the right medial temporal cortex. The magnitude of heat pain threshold elevation induced by concurrent cold pain was directly correlated with D2 binding potential in the left putamen. Other correlations of D2 binding potentials in varying brain regions with sensory responses were not significant. A psychophysical control study (n = 10) showed that cold pain responses were identical in the right and left hand. The results indicate that dopamine D2 receptor binding potential in the human forebrain, particularly in the striatum, may be an important parameter in determining the individual cold pain response and the potential for central pain modulation. Accordingly, an individual with only few available D2 receptors in the forebrain is likely to have a high tonic level of pain suppression, combined with a low capacity to recruit more (dopaminergic) central pain inhibition by noxious conditioning stimulation. PMID:12237205

Hagelberg, Nora; Martikainen, Ilkka K; Mansikka, Heikki; Hinkka, Susanna; Någren, Kjell; Hietala, Jarmo; Scheinin, Harry; Pertovaara, Antti



Dexamethasone mimics the inhibitory effect of chronic pain on the development of tolerance to morphine analgesia and compensates for morphine induced changes in G proteins gene expression.  


It is previously reported that the HPA axis plays role in the inhibitory effect of pain on tolerance development to analgesic effect of opioids. The present study was designed to investigate whether the chronic co-administration of dexamethasone as a glucocorticoid is also able to prevent or reverse analgesic tolerance to morphine and to compare the expression of G(alphai/o) and G(beta) subunits of G proteins in the context of chronic dexamethasone, development of morphine tolerance and their combination. Analgesic tolerance to morphine was induced by chronic intraperitoneally (i.p.) administration of morphine 20 mg/kg to male Wistar rats weighing 200-240 g within 4 consecutive days and analgesia was assessed using tail-flick test. Chronic dexamethasone was applied using 4 daily i.p. injections. Lumbar spinal tissues were assayed for the expression of G(alphai/o) and G(beta) proteins using "semiquantitative PCR" normalized to beta-actin gene expression. Results showed that chronic administration of dexamethasone could reduce and reverse the development of tolerance in rats that received chronic i.p. injections of morphine. Chronic administration of dexamethasone significantly increased the expression of G(alphai/o), while chronic administration of morphine did not change its expression. The expression of G(beta), however, was increased after the chronic administration of morphine, but did not change after the administration of chronic dexamethasone. None of these increases were observed when morphine and dexamethasone were co-administered. We conclude that the development of tolerance to analgesic effect of morphine could be prevented and reversed by dexamethasone co-administration. The increase in G(alphai/o) genes expression produced by chronic dexamethasone may facilitate the opioid signaling pathway and compensate for morphine-induced tolerance. PMID:16828064

Javan, Mohammad; Kazemi, Bahram; Ahmadiani, Abolhassan; Motamedi, Fereshteh



Adult attachment and reports of pain in experimentally-induced pain.  


Attachment theory has been proposed as a framework for understanding the development of chronic pain, with evidence supporting the overrepresentation of insecure attachment styles in chronic pain populations and links between insecure attachment and factors known to impact one's ability to cope with pain. The present study sought to extend two earlier studies exploring the relationships between adult attachment and communication of an acute pain experience, in anticipation of providing insight into individual differences in vulnerability in development of chronic pain. It was hypothesised that: (a) fearful attachment would be associated with perceptions of the pain as less intense, and (b) anxious attachment would be associated with lower pain thresholds. A convenience sample of 82 healthy adults completed self-report measures of attachment, neuroticism, and negative affect prior to taking part in a coldpressor pain inducement task. Results demonstrated that fearful attachment was associated with lower levels of pain intensity throughout the coldpressor task. In addition, dismissing attachment was also associated with less intense pain, as well as increased coldpressor endurance (tolerance) in the presence of a known assessor. These associations were retained after controlling for measures of neuroticism, negative affect, age, and social desirability. The results of this study are consistent with the proposition that fearful and dismissing individuals tend to mask their underlying distress caused by the pain experience, potentially leading to difficulties coping with pain over time. PMID:21095633

Andrews, Nicole Emma; Meredith, Pamela Joy; Strong, Jenny



Pharmacological pain management in the elderly patient  

PubMed Central

With the increasing number of elderly patients the issue of pain management for older people is of increasing relevance. The alterations with aging of the neurobiology of pain have impacts of pain threshold, tolerance and treatment. In this review the available evidence from animal and human experimentation is discussed to highlight the differences between young and older subjects along with consideration of how these changes have practical effect on drug treatment of pain. Cognitive impairment, physical disability and social isolation can also impact on the accessibility of treatment and have to be considered along with the biological changes with ageing. Conventional pain therapies, while verified in younger adults cannot be automatically applied to the elderly without consideration of all these factors and in no other group of patients is a holistic approach to treatment more important.

McCleane, Gary



Chronic inflammatory pain does not attenuate the development of tolerance to chronic morphine in adult male rats  

Microsoft Academic Search

The overall impact of chronic pain on the response to opioids is ambiguous in the literature, and comparisons between human and animal studies are complicated by vast differences between the manner and dosage of opioids given to humans treated for pain in comparison to rodents as well as a lack of healthy participant studies examining the impact of chronic opioids.

Megan L. Uhelski; Jessica A. Boyette-Davis; Perry N. Fuchs



Experimental mononeuropathy reduces the antinociceptive effects of morphine: implications for common intracellular mechanisms involved in morphine tolerance and neuropathic pain  

Microsoft Academic Search

Recent evidence suggests that hyperalgesia and morphine tolerance, two seemingly unrelated phenomena, have in common certain neural substrates such as activation of the N-methyl-d-aspartate (NMDA) receptor and the subsequent intracellular activation of protein kinase C and nitric oxide. Should common cellular elements be involved in hyperalgesia and morphine tolerance, these cellular and intracellular commonalities might be expected to result in

Jianren Mao; Donald D. Price; David J. Mayer



Elevated Pain Sensitivity in Chronic Pain Patients at Risk for Opioid Misuse  

PubMed Central

This study employed quantitative sensory testing (QST) to evaluate pain responses in chronic spinal pain patients at low risk and high risk for opioid misuse, with risk classification based on scores on the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R). Patients were further sub-grouped according to current use of prescription opioids. Of the 276 chronic pain patients tested, approximately 65% were taking opioids; a median split was used to further categorize these patients as being on lower or higher doses of opioids. The highrisk group (n= 161) reported higher levels of clinical pain, had lower pressure and thermal pain thresholds at multiple body sites, had lower heat pain tolerance, and rated repetitive mechanical stimuli as more painful relative to the low-risk group (n= 115; p’s< .01). In contrast, QST measures did not differ across opioid groups. Multiple linear regression analysis suggested that indices of pain-related distress (i.e., anxiety and catastrophizing about pain) were also predictive of hyperalgesia, particularly in patients taking opioids. Collectively, regardless of opioid status, the high-risk group was hyperalgesic relative to the low-risk group; future opioid treatment studies may benefit from the classification of opioid risk, and the examination of pain sensitivity and other factors that differentiate high- and low-risk groups.

Edwards, Robert R.; Wasan, Ajay D.; Michna, Ed; Greenbaum, Seth; Ross, Ed; Jamison, Robert N.



Assessment of sensory thresholds and nociceptive fiber growth after sciatic nerve injury reveals the differential contribution of collateral reinnervation and nerve regeneration to neuropathic pain.  


Following traumatic peripheral nerve injury reinnervation of denervated targets may be achieved by regeneration of injured axons and by collateral sprouting of neighbor undamaged axons. Experimental models commonly use sciatic nerve injuries to assess nerve regeneration and neuropathic pain, but behavioral tests for evaluating sensory recovery often disregard the pattern of hindpaw innervation. This may lead to confounding attribution of recovery of sensory responses to improvement in sciatic nerve regeneration instead of collateral reinnervation by the undamaged saphenous nerve. We used a standardized methodology to assess the separate contribution of collateral and regenerative skin reinnervation on sensory responses. Section and suture of the sciatic nerve induced loss of sensibility in the lateral and central areas of the injured paw, but nociceptive responses rapidly recovered by expansion of the intact saphenous innervation territory. We used electronic Von Frey and Plantar test devices to measure mechanical and thermal withdrawal thresholds in specific sites of the injured paw: lateral site innervated by the sciatic nerve, medial site that remained innervated by the saphenous nerve, and central site originally innervated by the sciatic nerve but affected by saphenous sprouting. After sciatic section, signs of early hyperalgesia developed in medial and central paw areas due to saphenous sprouting and expansion. The regenerating sciatic nerve fibers reached the paw at 3-4weeks and a late mechanical hyperalgesia was observed at the lateral site. Immunohistochemical staining of sensory fibers innervating the medial and lateral areas revealed a different pattern of skin reinnervation. Hypersensitivity in the intact saphenous nerve area was paralleled by early fiber sprout growth in the subepidermal plexus, but not entering the epidermis. On the other side, late sciatic hyperalgesia was accompanied by gradual skin reinnervation after 4weeks. The standardization of algesimetry testing in sciatic nerve injury models, as proposed in this study, provides a suitable model for studying in parallel neuropathic pain and sensory nerve regeneration processes. Our results also indicate that collateral sprouting and axonal regeneration contribute differently in the initiation and maintenance of neuropathic pain. PMID:24552688

Cobianchi, Stefano; de Cruz, Julia; Navarro, Xavier



The Measurement of Suprathreshold Pain.  

National Technical Information Service (NTIS)

The study of both subjective and physiological responses to painful stimulation is fraught with a number of difficulties, one of which is the difference in functional relationships between the threshold and suprathreshold of pain, such as surgical pain. B...

J. Voevodsky L. M. Cooper A. H. Morgan E. R. Hilgard



Evaluation of a Low-Threshold/High-Tolerance Methadone Maintenance Treatment Clinic in Saint John, New Brunswick, Canada: One Year Retention Rate and Illicit Drug Use  

PubMed Central

Objective. To report the one-year retention rate and the prevalence of illicit opioid use and cocaine use in the Low-Threshold/High-Tolerance (LTHT) methadone maintenance treatment (MMT) clinic located in Saint John, New Brunswick, Canada. Methods. A description of the LTHT MMT clinic is provided. The one-year retention rate was determined by collecting data on patients who enrolled in the LTHT MMT clinic between August 04, 2009 and August 04, 2010. The prevalence of illicit drug use was determined using a randomly selected retrospective cohort of 84 participants. For each participant the results of six consecutive urine tests for the most recent three months were compared to the results of the first six consecutive urine tests after program entry. Results. The one-year retention rate was 95%, 67% of the cohort achieved abstinence from illicit opioids and an additional 13% abstained from cocaine use. Conclusion. The novel feature of the LTHT MMT clinic is that patients are not denied methadone because of lack of ancillary services. Traditional comprehensive MMT programs invest the majority of financial resources in ancillary services that support the biopsychosocial model, whereas the LTHT approach utilizes a medical model and directs resources at medical management.

Christie, Timothy K. S.; Murugesan, Alli; Manzer, Dana; O'Shaughnessey, Michael V.; Webster, Duncan



Effects of thai traditional massage on pressure pain threshold and headache intensity in patients with chronic tension-type and migraine headaches.  


Abstract Objective: To investigate the effects of Thai traditional massage (TTM) on pressure pain threshold (PPT) and headache intensity in patients with chronic tension-type and migraine headaches. Design: Randomized controlled trial of TTM compared with the sham ultrasound (nine sessions each) during a 3-week period. Participants: Seventy-two participants who had had a headache diagnosis for at least 3 months before the experiment was recruited. Results: After the treatment and at 3 and 9 weeks of follow-up, the TTM group showed a significant increase in PPT (p<0.01) compared with the sham ultrasound group. PPT values at baseline, after 3 weeks of treatment, and at 3- and 9-week follow-up for the TTM group were 2.71±1.22, 3.57±1.41, 3.72±1.46, and 3.42±1.46 pounds/cm(2), respectively; values in the sham ultrasound group were 2.85±1.20, 2.62±1.07, 2.58±1.05 and 2.63±0.94 pounds/cm(2). In both groups, headache intensity decreased significantly (p<0.05) at every end point of the outcome measures, and there were no differences between the groups (p>0.05). Conclusions: TTM could increase PPT and reduce headache intensity, suggesting that this is a possible alternative treatment for chronic headaches. PMID:24738648

Chatchawan, Uraiwan; Eungpinichpong, Wichai; Sooktho, Suparat; Tiamkao, Somsak; Yamauchi, Junichiro



Glutamate-evoked jaw muscle pain as a model of persistent myofascial TMD pain?  

PubMed Central

Objective Compare pain-related measures and psychosocial variables between glutamate-evoked jaw muscle pain in healthy subjects (HS) and patients with persistent myofascial temporomandibular disorder (TMD) pain. Design 47 female HS and 10 female patients with persistent myofascial TMD pain participated. The HS received an injection of glutamate into the masseter muscle to model persistent myofascial TMD pain. Participants filled out a coping strategies questionnaire (CSQ), the symptom checklist 90 (SCL-90) and McGill Pain Questionnaire (MPQ). Pain intensity was assessed on an electronic visual analog scale (VAS). Pain-drawing areas, Numerical Rating Scale (NRS) scores of unpleasantness, pressure pain thresholds (PPT) and tolerance (PPTOL) were measured. Unpaired t-tests and correlation tests were used for analyses. Results The groups were significantly different when comparing the CSQ scores of control, decrease, diverting attention, increase of behavioral activities and somatization. The peak VAS pain, NRS of unpleasantness and MPQ scores were not significantly different between groups, but PPT and PPTOL were significantly lower in the TMD patients. Significant positive correlations were found in the TMD patients between peak VAS pain and CSQ catastrophizing score and SCL-90 somatization. The scores of PPTs and PPTOLs, in patients showed positive correlations with CSQ reinterpreting pain sensations scores and PPTs correlated with CSQ praying/hoping scores. Conclusions Glutamate-evoked pain responses in HS and persistent myofascial TMD pain have similar sensory-discriminative and affective-unpleasantness components but differ in psycho-social features. This study suggests that experimental designs based on glutamate injection into muscle can provide an appropriate model for elucidating persistent myofascial pain conditions.

Castrillon, Eduardo E.; Cairns, Brian E.; Ernberg, Malin; Wang, Kelun; Sessle, Barry; Arendt-Nielsen, Lars; Svensson, Peter



Injection-associated pain in femoral arteriography: A European multicenter study comparing safety, tolerability, and efficacy of iodixanol and iopromide  

SciTech Connect

Purpose. To evaluate injection-associated pain, safety, and efficacy with the isotonic contrast medium iodixanol (Visipaque 270 mg I/ml) compared with iopromide (Ultravist 300 mg I/ml) in femoral arteriography. Methods. A multicenter, double-blind, randomized, parallel-group clinical investigation was carried out in 54 hospitals in Europe. Of the patients evaluated, 1225 received iodixanol and 1227 iopromide in conventional and/or digital subtraction angiography. Results. The iodixanol group reported statistically significantly less injection-associated pain (0.9%) than the iopromide group (9.5%) (p<0.001). Further, 4.1% in the iodixanol group experienced pain and/or severe heat sensation vs 19.8% in the iopromide group (p<0.001). In the iodixanol group, 1.8% of the patients experienced contrast-related adverse events vs 2.4% in the iopromide group (p=NS). Overall diagnostic information was optimal for 94.1% in the iodixanol group and 95.3% in the iopromide group (p=NS). Conclusions. Iodixanol 270 mg I/ml causes significantly less injection-associated pain during femoral arteriography and is as safe and efficatious as iopromide 300 mg I/ml.

Justesen, Per [Odense University Hospital, Department of Radiology (Denmark); Downes, Mark [Kent and Canterbury Hospital, Department of Diagnostic Radiology (United Kingdom); Grynne, Birthe Hougens; Lang, Hanne; Rasch, Wenche; Seim, Eva [Nycomed Imaging AS, Clinical R and D (Norway)



Defining clinical issues around tolerance, hyperalgesia, and addiction: a quantitative and qualitative outcome study of long-term opioid dosing in a chronic pain practice.  


Treatment with opioid medications has grown over the past decades, but has been surrounded by some ongoing controversy and debate to whether it is causing more harm than good for patients. To this end, the field of pain management has suffered from a lack of clarity about some basic definitions on concepts such as tolerance and hyperalgesia. Some characterize these issues as inevitable parts of opioid therapy while other schools of thought look at these issues as relatively rare occurrences. Unfortunately, most of the rhetoric around these topics has occurred with very little in the realm of real world data. To this end, the authors have reviewed the charts of 197 patients treated by a pain specialist for at least 1 year to better illustrate whether notions of tolerance and hyperalgesia are common occurrences and, more importantly, whether they occur within any type of specified timeframe. A total of 197 patient charts were reviewed. The sample had an average age of 49.39 years (range = 19-87 years; standard deviation [SD] = 12.48) and comprised 66 men (33.5 percent) and 131 women (66.5 percent). The patients were seen in the pain practice for an average of 56.52 months (range = 12-155 months; SD = 31.26). On average, the patients maintained an average daily dose of 180 mg morphine equivalents for a period of 35.1 months (range = 3-101 months; SD = 21.3). Looking at the pattern of medication usage change over time, 34.5 percent experienced dose stabilization after the initial titration, 13.2 percent had early dose stabilization within one dose change, and an additional 14.7 percent actually had dose decreases after surgeries or other interventional procedures. Only 6.6 percent of the sample had to be discharged or weaned from controlled substances over time in the clinic. Thus, it appears that tolerance and hyperalgesia are not foregone conclusions when considering placing a patient on long-term opioid therapy. PMID:21268999

Schneider, Jennifer P; Kirsh, Kenneth L



Modulation of Remifentanil-Induced Analgesia, Hyperalgesia, and Tolerance by Small-Dose Ketamine in Humans  

Microsoft Academic Search

Adding a small dose of ketamine to opioids may increase the analgesic effect and prevent opioid-induced hyperal- gesia and acute tolerance to opioids. In this randomized, double-blinded, placebo-controlled crossover study, we investigated the effect of remifentanil combined with small concentrations of ketamine on different experimen- tal pain models. Pain detection thresholds to single and repeated IM electrical stimulation and to

Andrea Gerber; Thomas W. Schnider; Steen Petersen-Felix; Lars Arendt-Nielsen; Michele Curatolo



Restricted environmental stimulation and the enhancement of hypnotizability: Pain, EEG alpha, skin conductance and temperature responses  

Microsoft Academic Search

Restricted environmental stimulation procedures were used with 10 Ss. The Stanford Hypnotic Clinical Scale: Adult (SHCS) of Morgan and J. R. Hilgard (1975), modified to include a posthypnotic suggestion for an analgesic reaction, and pain threshold and tolerance tests were administered prior to restricted environmental stimulation technique (REST), immediately after REST, and 10–14 days later. Occipital EEG alpha, skin conductance,

Arreed F. Barabasz



Anti-opioid efficacy of Neuropeptide FF in morphine-tolerant mice  

Microsoft Academic Search

The modulatory effects of 1DMe (d-Tyr-Leu-(NMe)Phe-Gln-Pro-Gln-Arg-Phe-NH2), an agonist of Neuropeptide FF (NPFF) receptors, on opioid antinociceptive activity have been compared in naive and tolerant mice in the tail-flick and the hot-plate tests. In naive mice, 1DMe alone had no effect on pain threshold but decreased dose-dependently (3–22 nmol) the analgesic activity of morphine in both tests. In tolerant mice, injections

Agathe Gelot; Bernard Francés; Anne Roussin; Jean-Philippe Latapie; Jean-Marie Zajac



Corticotropin-releasing hormone reduces pressure pain sensitivity in humans without involvement of beta-endorphin(1-31), but does not reduce heat pain sensitivity.  


In the present study the effects of intravenously administered corticotropin-releasing hormone (CRH) on the release of proopiomelanocortin (POMC) derivatives such as adrenocorticotropic hormone (ACTH), beta-lipotropin (beta-LPH) and beta-endorphin (beta-END) as well as direct effects of CRH on pain sensitivity were examined. In 16 healthy volunteers we studied the effects of 100 microg intravenously administered CRH in absence or presence of 12 mg naloxone on heat or pressure pain sensitivity, using a double-blind, cross-over and placebo-controlled design. To evaluate analgesic effects of CRH via release of POMC derivatives, we determined plasma concentrations of beta-END-immunoreactive material (IRM), authentic beta-END (beta-END(1-31)) and beta-LPH IRM, in parallel with heat and pressure pain tolerance thresholds before and 15 and 30 min after treatment with CRH (or placebo), and 5 min after naloxone (or placebo) administration which was administered 40 min after CRH (or placebo) injection. CRH increased levels of beta-END IRM, beta-END(1-31) and beta-LPH IRM. As compared to beta-END IRM levels measured by a commercial RIA kit, the beta-END(1-31) levels determined by a highly specific two-site RIA, proved to be remarkably small. Furthermore, CRH did not induce increases of heat pain tolerance thresholds, but of pressure pain tolerance thresholds, which, however, were not reversible by naloxone. Neither beta-END nor beta-LPH IRM nor beta-END(1-31) levels correlated with heat or pressure pain tolerance thresholds. We conclude that CRH does not modulate heat, but pressure pain; POMC derivatives like beta-END IRM, beta-END(1-31) or beta-LPH do not mediate this effect. PMID:16534240

Matejec, Reginald; Uhlich, Holger; Hotz, Christina; Mühling, Jörg; Harbach, Heinz-W; Bödeker, Rolf-H; Hempelmann, Gunter; Teschemacher, Hansjörg



Comparison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study  

PubMed Central

Objective To compare the analgesic efficacy and side effects of the synthetic cannabinoid nabilone with those of the weak opioid dihydrocodeine for chronic neuropathic pain. Design Randomised, double blind, crossover trial of 14 weeks’ duration comparing dihydrocodeine and nabilone. Setting Outpatient units of three hospitals in the United Kingdom. Participants 96 patients with chronic neuropathic pain, aged 23-84 years. Main outcome measures The primary outcome was difference between nabilone and dihydrocodeine in pain, as measured by the mean visual analogue score computed over the last 2 weeks of each treatment period. Secondary outcomes were changes in mood, quality of life, sleep, and psychometric function. Side effects were measured by a questionnaire. Intervention Patients received a maximum daily dose of 240 mg dihydrocodeine or 2 mg nabilone at the end of each escalating treatment period of 6 weeks. Treatment periods were separated by a 2 week washout period. Results Mean baseline visual analogue score was 69.6 mm (range 29.4-95.2) on a 0-100 mm scale. 73 patients were included in the available case analysis and 64 patients in the per protocol analysis. The mean score was 6.0 mm longer for nabilone than for dihydrocodeine (95% confidence interval 1.4 to 10.5) in the available case analysis and 5.6 mm (10.3 to 0.8) in the per protocol analysis. Side effects were more frequent with nabilone. Conclusion Dihydrocodeine provided better pain relief than the synthetic cannabinoid nabilone and had slightly fewer side effects, although no major adverse events occurred for either drug. Trial registration Current Controlled Trials ISRCTN15330757.



Safety, tolerability, pharmacokinetics, and effects on human experimental pain of the selective ionotropic glutamate receptor 5 (iGluR5) antagonist LY545694 in healthy volunteers.  


The objective of this study was to establish in healthy volunteers the maximally tolerated multiple dose (MTMD) of the ionotropic glutamate receptor 5 antagonist LY545694 (part A), and to investigate whether that dose had analgesic or antihyperalgesic effects in the brief thermal stimulation (BTS) pain model (Part B). Part A was a double-blind, placebo-controlled study in 3 groups of 10 healthy men. To simulate an extended-release formulation, study drug was administered orally over 6hours (12 equally divided aliquots at 30-minute intervals). Part B was a double-blind, placebo-controlled, double-dummy, 3-way crossover study in 27 healthy men. At each of the 3 study periods, subjects received either LY545694 (MTMD; as determined during part A) as a simulated, twice daily extended-release formulation for 4 doses over 3days, gabapentin (600mg 8hours apart; 6 doses over 3days; positive control), or matching placebo. The BTS model was induced twice with a 1-hour interval on each of the 2 study days, before drug administration and at the time of expected peak analgesia of LY545694. Plasma exposure for LY545694 was approximately linear over the 25- to 75-mg dose range. The MTMD of LY545694 was 25mg twice daily. Areas of secondary hyperalgesia were significantly smaller after administration of LY545694 and gabapentin compared with placebo (P<.0001 and P=.0004, respectively), but there was no difference between areas after administration of gabapentin and LY545694 (P=.400). Neither gabapentin nor LY545694 reduced the painfulness of skin heating during BTS model induction. The most common treatment-emergent adverse event was dizziness. The results of this study suggest that LY545694 should be explored further as a potential treatment for chronic pain involving neuronal sensitization. PMID:24486883

Petersen, Karin L; Iyengar, Smriti; Chappell, Amy S; Lobo, Evelyn D; Reda, Haatem; Prucka, William R; Verfaille, Steven J



Gender expression, sexual orientation and pain sensitivity in women  

PubMed Central

BACKGROUND: Despite a growing body of literature investigating sex differences with regard to pain, surprisingly little research has been conducted on the influence of various aspects of self-identity, including gender expression and sexual orientation, on pain sensitivity within each sex, particularly among women. In men, dispositional femininity is linked to greater clinical pain and trait masculinity is associated with higher pain thresholds. OBJECTIVES: To examine whether gender expression and sexual orientation are associated with within-sex differences in ischemic pain sensitivity in healthy young women. METHODS: A convenience sample of 172 females (mean age 21.4 years; range 18 to 30 years of age; 56.0% white, 89% heterosexual) performed an ischemic pain task in counterbalanced order. Desired levels of dispositional femininity for a preferred romantic partner and self-described levels of personal dispositional femininity were measured. RESULTS: Compared with heterosexual women, lesbian and bisexual women reported lower pain intensity ratings early in the discomfort task. Irrespective of sexual orientation, attraction to more feminine romantic partners and dispositional masculinity were correlated with lower pain intensity, and with higher pain thresholds and tolerance levels. DISCUSSION: These preliminary findings suggest that within-sex differences in sexual orientation and other aspects of identity, irrespective of biological sex, may be important to consider when examining experimental pain performance and clinical pain experiences. CONCLUSION: Larger investigations of the psychophysiological relationships among sexual orientation, gender expression and pain sensitivity are warranted. These findings may have implications for differences in clinical pain sensitivity of lesbian and bisexual women compared with heterosexual women.

Vigil, Jacob M; Rowell, Lauren N; Lutz, Charlotte



Patients with chronic pain.  


Preoperative evaluation of patients with chronic pain is important because it may lead to multidisciplinary preoperative treatment of patients' pain and a multimodal analgesia plan for effective pain control. Preoperative multidisciplinary management of chronic pain and comorbid conditions, such as depression, anxiety, deconditioning, and opioid tolerance, can improve patient satisfaction and surgical recovery. Multimodal analgesia using pharmacologic and nonpharmacologic strategies shifts the burden of analgesia away from simply increasing opioid dosing. In more complicated chronic pain patients, multidisciplinary treatment, including pain psychology, physical therapy, judicious medication management, and minimally invasive interventions by pain specialists, can improve patients' satisfaction and surgical outcome. PMID:24182727

Salama-Hanna, Joseph; Chen, Grace



Hypoalgesia Related to Elevated Resting Blood Pressure is Absent in Adolescents and Young Adults with a History of Functional Abdominal Pain  

PubMed Central

Elevated resting blood pressure (BP) is hypoalgesic in healthy individuals, but this effect is absent in adults with chronic somatic pain. This study tested whether BP-related hypoalgesia is similarly altered in individuals with a history of chronic visceral pain in childhood. Resting BP was assessed in 94 adolescents and young adults with a known history of childhood functional abdominal pain (FAP) and 55 comparable healthy controls. Responses to an acute heat pain stimulus were then evaluated following exposure to two laboratory stressors. A significant Participant Type X Systolic BP (SBP) interaction (p<.005) revealed that elevated resting SBP was associated with significantly higher heat pain threshold (p<.001) in healthy controls, but was unrelated to pain threshold in the FAP group. A similar pattern was observed for heat pain tolerance, with elevated SBP linked to significantly higher pain tolerance (p<.05) in healthy controls, but unrelated to tolerance in the FAP group. Dysfunction in BP-related hypoalgesia associated with FAP was evident regardless of whether childhood FAP had resolved or still persisted at the time of laboratory testing. Subgroup analyses indicated that BP-related hypoalgesia (in healthy controls) and FAP-linked absence of this hypoalgesia was observed only among females. Result suggest that childhood visceral chronic pain may be associated with relatively long-lasting dysfunction in overlapping systems modulating pain and BP that persists even after FAP resolves. Potential implications for later hypertension risk are discussed.

Bruehl, Stephen; Dengler-Crish, Christine M.; Smith, Craig A.; Walker, Lynn S.



Increased Sensitivity to Thermal Pain and Reduced Subcutaneous Lidocaine Efficacy in Redheads  

PubMed Central

Background: Anesthetic requirement in redheads is exaggerated, suggesting that redheads may be especially sensitive to pain. We therefore tested the hypotheses that women with natural red hair are more sensitive to pain, and that redheads are resistant to topical and subcutaneous lidocaine. Methods: We evaluated pain sensitivity in red-haired (n=30) or dark-haired (n=30) women by determining the electrical current perception threshold, pain perception, and maximum pain tolerance with a Neurometer CPT/C (Neurotron, Inc., Baltimore, MD). We evaluated the analogous warm and cold temperature thresholds with the TSA-II Neurosensory Analyzer (Medoc Ltd., Minneapolis, MN). Volunteers were tested with both devices at baseline and with the Neurometer after 1-hour exposure to 4% liposomal lidocaine and after subcutaneous injection of 1% lidocaine. Data are presented as medians [interquartile ranges]. Results: Current perception, pain perception, and pain tolerance thresholds were similar in the red-haired and dark-haired women at 2000, 250, and 5 Hz. In contrast, redheads were more sensitive to cold pain perception (22.6°C [15.1, 26.1] vs. 12.6°C [0, 20], P=0.004), cold pain tolerance (6.0°C [0, 9.7] vs. 0.0°C [0.0, 2.0], P=0.001), and heat pain (46.3°C [45.7, 47.5] vs. 47.7°C [46.6, 48.7], P=0.009). Subcutaneous, lidocaine was significantly less effective in redheads, e.g., pain tolerance threshold at 2000 Hz stimulation in redheads was 11.0 mA [8.5, 16.5] vs. >20.0 mA [14.5, >20] in others, P=0.005). Conclusion: Red hair is the phenotype for mutations of the melanocortin 1 receptor. Our results indicate that redheads are more sensitive to thermal pain and are resistant to the analgesic effects of subcutaneous lidocaine. Mutations of the melanocortin 1 receptor, or a consequence thereof, thus modulate pain sensitivity.

Liem, Edwin B.; Joiner, Teresa V.; Tsueda, Kentaro; Sessler, Daniel I.



Effects of Videogame Distraction using a Virtual Reality Type Head-Mounted Display Helmet on Cold Pressor Pain in Children  

PubMed Central

Objective?To test whether a head-mounted display helmet enhances the effectiveness of videogame distraction for children experiencing cold pressor pain.?Method?Forty-one children, aged 6–14 years, underwent one or two baseline cold pressor trials followed by two distraction trials in which they played the same videogame with and without the helmet in counterbalanced order. Pain threshold (elapsed time until the child reported pain) and pain tolerance (total time the child kept the hand submerged in the cold water) were measured for each cold pressor trial.?Results?Both distraction conditions resulted in improved pain tolerance relative to baseline. Older children appeared to experience additional benefits from using the helmet, whereas younger children benefited equally from both conditions. The findings suggest that virtual reality technology can enhance the effects of distraction for some children. Research is needed to identify the characteristics of children for whom this technology is best suited.

Weiss, Karen E.; Dillinger Clendaniel, Lindsay; Law, Emily F.; Ackerman, Claire Sonntag; McKenna, Kristine D.



Variable-Threshold Threshold Elements.  

National Technical Information Service (NTIS)

A threshold element is a mathematical model of certain types of logic gates and of a biological neuron. Much work has been done on the subject of threshold elements with fixed thresholds; this study concerns itself with elements in which the threshold may...

W. S. Meisel



A comparison of the effect of attention training and relaxation on responses to pain.  


This study aimed to investigate the efficacy of an attention training technique (ATT) on pain ratings, threshold and tolerance during the cold pressor task. One hundred and three undergraduate students were randomly assigned to receive either threat-alleviating or threat-inducing information about the task. Participants were then re-randomized to receive either ATT or progressive muscle relaxation (PMR). Hence, the present study had a 2 (threat expectancy: high vs. low)x2 (training: ATT vs. PMR) design. Analyses confirmed that the threat manipulation was effective in increasing the harm associated with the task. ATT resulted in a relative reduction in hypervigilance to sensory pain words compared to PMR. ATT was also associated with a lower degree of focus on internal sensations, but not mindfulness or difficulty disengaging from pain words. Results showed that, relative to relaxation training, those receiving ATT reported pain less quickly than those receiving relaxation, although there were no differences between the training groups for tolerance or pain ratings. These results show that ATT changes the cognitive processes of internal/external focus and hypervigilance towards sensory pain words, but not difficulty disengaging or mindfulness. Although ATT changed threshold, the fact that neither pain ratings nor tolerance was affected suggests that a single, brief session of ATT may not be sufficient to affect broader change. Nonetheless, this study shows that ATT can change cognitive processes thought to be associated with heightened perception of pain and that this changes how quickly pain is registered and is therefore worthy of further investigation. PMID:20619540

Sharpe, L; Nicholson Perry, K; Rogers, P; Dear, B F; Nicholas, M K; Refshauge, K



Post hoc analyses of data from a 90-day clinical trial evaluating the tolerability and efficacy of tapentadol immediate release and oxycodone immediate release for the relief of moderate to severe pain in elderly and nonelderly patients  

PubMed Central

OBJECTIVE: To evaluate the tolerability and efficacy of tapentadol immediate release (IR) and oxycodone IR for relief of moderate to severe pain in elderly and nonelderly patients. METHODS: Post hoc data analyses were conducted on a 90-day randomized, phase 3, double-blind, flexible-dose study ( NCT00364546) of adults with moderate to severe lower back pain or osteoarthritis pain who received tapentadol IR 50 mg or 100 mg, or oxycodone HCl IR 10 mg or 15 mg every 4 h to 6 h as needed for pain relief. Treatment-emergent adverse events and study discontinuations were recorded. RESULTS: Data from 849 patients randomly assigned (4:1 ratio) to treatment with a study drug (tapentadol IR [n=679] or oxycodone IR [n=170]) were analyzed according to age (younger than 65 years of age [nonelderly], or 65 years of age or older [elderly]) and treatment group. Among elderly patients, incidences of constipation (19.0% versus 35.6%) and nausea or vomiting (30.4% versus 51.1%) were significantly lower with tapentadol IR versus oxycodone IR (all P<0.05). Initial onsets of nausea and constipation occurred significantly later with tapentadol IR versus oxycodone IR (both P?0.031). Tapentadol IR-treated elderly patients had a lower percentage of days with constipation than oxycodone IR-treated patients (P=0.020). For tapentadol IR- and oxycodone IR-treated elderly patients, respectively, incidences of study discontinuation due to gastrointestinal treatment-emergent adverse events were 15.8% and 24.4% (P=0.190). Tapentadol IR and oxycodone IR provided similar pain relief, with no overall age-dependent efficacy differences (mean pain scores [11-point numerical rating scale] decreased from 7.0 and 7.2 at baseline, to 4.9 and 5.2 at end point, respectively). CONCLUSIONS: Tapentadol IR was safe and effective for the relief of lower back pain and osteoarthritis pain in elderly patients, and was associated with a better gastrointestinal tolerability profile than oxycodone IR.

Vorsanger, Gary; Xiang, Jim; Biondi, David; Upmalis, David; Delfgaauw, Jacqueline; Allard, Rene; Moskovitz, Bruce



Evidence for threshold effects of 25-hydroxyvitamin D on glucose tolerance and insulin resistance in black and white obese postmenopausal women.  


We identified normal vs. abnormal 25-hydroxyvitamin D [25(OH)D] concentrations by examining the relation of 25(OH)D to non-bone-related measures (plasma glucose, insulin resistance, lipids, blood pressure, fitness, obesity, and regional adiposity) and asking whether there is a 25(OH)D concentration above and below which the relation between 25(OH)D and outcome changes. We examined the relation between 25(OH)D and outcome by race to see whether race-specific normal ranges are needed, and we examined the role of insulin-like growth factor-1 (IGF-1) in modulating the relation between 25(OH)D and outcome. In a cross-sectional study of 239 overweight and obese, sedentary postmenopausal women without diabetes (83 black, 156 white), outcome measures included plasma lipids, glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), IGF-1, parathyroid hormone (PTH), aerobic fitness, body composition, subcutaneous abdominal and visceral fat, and blood pressure. We identified threshold effects in the association between 25(OH)D and these variables using piecewise linear regressions. We found that 25(OH)D was inversely related to fasting glucose, fasting and 2-h insulin, HOMA-IR, visceral abdominal fat, percentage fat, PTH, and triglycerides. Evidence for a threshold effect of 25(OH)D was found for 2-h glucose, 2-h insulin, fasting insulin, and HOMA-IR. There was no evidence suggesting the need for race-specific normal 25(OH)D concentrations. IGF-1 modulated the relation between 25(OH)D and outcome but only below, and not above, a threshold 25(OH)D concentration. Our findings suggest a threshold effect of 25(OH)D on glucose-insulin metabolism such that 25(OH)D ? ?26 ?g/L (65.0 pmol/L) supports normal glucose homeostasis and that the same cut point defining normal 25(OH)D concentration can be used in black and white women. This study was registered at as NCT01798030. PMID:24717362

Sorkin, John D; Vasaitis, Tadas Sean; Streeten, Elizabeth; Ryan, Alice S; Goldberg, Andrew P



Alterations in endogenous pain modulation in endurance athletes: an experimental study using quantitative sensory testing and the cold-pressor task.  


There is evidence for long-term alterations in pain tolerance among athletes compared with normally active controls. However, scientific data on pain thresholds in this population are inconsistent, and the underlying mechanisms for the differences remain unclear. Therefore, we assessed differences and similarities in pain perception and conditioned pain modulation (CPM) at rest in endurance athletes and normally active controls. The standardised quantitative sensory testing protocol (QST) of the 'German-Research-Network-on-Neuropathic-Pain' was used to obtain comprehensive profiles on somatosensory functions. The protocol consisted of thermal and mechanical detection as well as pain thresholds, vibration thresholds, and pain sensitivity to sharp and blunt mechanical stimuli. CPM (the diffuse-noxious-inhibitory-control-like effect) was measured using 2 tonic heat pain test stimuli (at the temperature exceeding a subjective pain rating of 50/100) separated by a 2-min cold-pressor task (CPM-TASK; conditioning stimulus). Pain ratings were measured with a numerical rating scale. Endurance capacity was validated by assessment of maximum oxygen uptake (VO2max). Participants included 25 pain-free male endurance athletes (VO2max>60mL/min?kg) and 26 pain-free normally active controls (VO2max<45mL/min?kg) matched based on age and body mass index. Athletes were significantly less sensitive to mechanical pain but showed higher sensitivity to vibration (P<0.05). In athletes, CPM was significantly less activated by the conditioning stimuli (P<0.05) when compared with normally active controls. Our data show that somatosensory processing in athletes differs in comparison with controls, and suggest that the endogenous pain inhibitory system may be less responsive. This finding may explain the paradoxical propensity of athletes to develop chronic widespread pain. PMID:23657118

Tesarz, Jonas; Gerhardt, Andreas; Schommer, Kai; Treede, Rolf-Detlef; Eich, Wolfgang



Modulation of learning, pain thresholds, and thermoregulation in the rat by preparations of free purified alpha-linolenic and linoleic acids: determination of the optimal omega 3-to-omega 6 ratio.  

PubMed Central

Ingested polyunsaturated fatty acids are postulated to lead to changes in central nervous system activity, presumably by altering the lipid composition of neuronal membranes. In support of this hypothesis, we and other investigators have previously demonstrated cognitive effects in rats fed oils that contain both alpha-linolenic acid (18:3 omega 3) and linoleic acid (18:2 omega 6), with the relative content of alpha-linolenic acid being seen as the critical variable. The present study in rats examined the effects of preparations containing different ratios of highly purified free alpha-linolenic acid to linoleic acid (about 25 mg/kg of body weight daily) on learning performance (Morris water tank), pain thresholds (heated plate), and thermoregulatory control of d-amphetamine-induced hypothermia during 4 weeks of treatment. Preparations with omega 3-to-omega 6 ratios ranging from 1:3.5 to 1:5 (specifically a ratio of 1:4) produced significant favorable effects on all of these variables. Although the specific mode of action remains to be elucidated, these results suggest that such preparations of free fatty acids should be evaluated in the treatment of memory disorders and pain conditions.

Yehuda, S; Carasso, R L



Cholecystokinin receptors mediate tolerance to the analgesic effect of TENS in arthritic rats ?  

PubMed Central

Transcutaneous electrical nerve stimulation (TENS) is a treatment for pain that involves placement of electrical stimulation through the skin for pain relief. Previous work from our laboratory shows that repeated application of TENS produces analgesic tolerance by the fourth day and a concomitant cross-tolerance at spinal opioid receptors. Prior pharmacological studies show that blockade of cholecystokinin (CCK) receptors systemically and spinally prevents the development of analgesic tolerance to repeated doses of opioid agonists. We therefore hypothesized that systemic and intrathecal blockade of CCK receptors would prevent the development of analgesic tolerance to TENS, and cross-tolerance at spinal opioid receptors. In animals with knee joint inflammation (3% kaolin/carrageenan), high (100 Hz) or low frequency (4 Hz) TENS was applied daily and the mechanical withdrawal thresholds of the muscle and paw were examined. We tested thresholds before and after inflammation, and before and after TENS. Animals treated systemically, prior to TENS, with the CCK antagonist, proglumide, did not develop tolerance to repeated application of TENS on the fourth day. Spinal blockade of CCK-A or CCK-B receptors blocked the development of tolerance to high and low frequency TENS, respectively. In the same animals we show that spinal blockade of CCK-A receptors prevents cross-tolerance at spinal delta-opioid receptors that normally occurs with high frequency TENS; and blockade of CCK-B receptors prevents cross-tolerance at spinal mu-opioid receptors that normally occurs with low frequency TENS. Thus, we conclude that blockade of CCK receptors prevents the development of analgesic tolerance to repeated application of TENS in a frequency-dependent manner.

DeSantana, Josimari M.; da Silva, Luis Felipe S.; Sluka, Kathleen A.



A comparison of the effect of attention training and relaxation on responses to pain  

Microsoft Academic Search

This study aimed to investigate the efficacy of an attention training technique (ATT) on pain ratings, threshold and tolerance during the cold pressor task. One hundred and three undergraduate students were randomly assigned to receive either threat-alleviating or threat-inducing information about the task. Participants were then re-randomized to receive either ATT or progressive muscle relaxation (PMR). Hence, the present study

L. Sharpe; K. Nicholson Perry; P. Rogers; B. F. Dear; M. K. Nicholas; K. Refshauge



Reliability and validity of verbal descriptor scales of painfulness.  


Previous studies have provided information about the reliability and validity of verbal descriptor scales of sensory intensity and unpleasantness and have shown that these two dimensions can be differentially affected by pharmacological manipulations. Since the relation between these dimensions and the general term 'pain' is not known, two experiments developed a verbal descriptor scale of painfulness and compared the sensitivity of this scale to pharmacological manipulations used previously with scales of sensory intensity and unpleasantness. In exp. I, 20 subjects used cross-modality matching to both handgrip force and tone duration to quantify the amount of pain implied by verbal descriptor phrases such as 'slightly painful,' 'somewhat painful' and 'very painful.' Ratio scales of relative magnitude for each individual were highly correlated within subjects (mean r = 0.92) and between a scale from each individual and a combined scale from others in the group (mean r = 0.93). These correlations indicate agreement between individual scales; an individual's scale values were predicted equally well by that individual or by a group of similar persons. In exp. II, 4 groups of 10 subjects rated the magnitude of painful tooth pulp sensations by choosing pain descriptors from randomized lists. Seven electrical stimuli spaced between individually determined pain threshold and tolerance values were delivered in random sequence 6 times before and after double-blind intravenous infusions of placebo, 0.11 mg/kg diazepam, 0.66 microgram/kg fentanyl or a combination of the diazepam and fentanyl doses. Mean responses were reduced significantly after all active drugs but not after placebo. These results suggest that the term pain does not represent a simple combination of sensory intensity and/or unpleasantness and shows that the sensitivity to an inert placebo, an active placebo, and an analgesic can vary with the type of pain assessment procedure. PMID:3614956

Gracely, R H; Dubner, R



Pain Management in Dutch Nursing Homes Leaves Much to Be Desired  

Microsoft Academic Search

This cross-sectional multicenter study describes several aspects of pain, pain intensity, and pain treatment in a Dutch nursing home population. A standardized pain questionnaire, including the Numeric Rating Scale (NRS), was used to measure aspects of pain and intensity of present pain, pain experienced in the previous week, and tolerable pain. The eligible sample comprised 320 residents (median age 79

Rhodee van Herk; Anneke A. Boerlage; Monique van Dijk; Frans P. M. Baar; Dick Tibboel; Rianne de Wit



Infrared sauna in patients with rheumatoid arthritis and ankylosing spondylitis. A pilot study showing good tolerance, short-term improvement of pain and stiffness, and a trend towards long-term beneficial effects.  


To study the effects of infrared (IR) Sauna, a form of total-body hyperthermia in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients were treated for a 4-week period with a series of eight IR treatments. Seventeen RA patients and 17 AS patients were studied. IR was well tolerated, and no adverse effects were reported, no exacerbation of disease. Pain and stiffness decreased clinically, and improvements were statistically significant (p < 0.05 and p < 0.001 in RA and AS patients, respectively) during an IR session. Fatigue also decreased. Both RA and AS patients felt comfortable on average during and especially after treatment. In the RA and AS patients, pain, stiffness, and fatigue also showed clinical improvements during the 4-week treatment period, but these did not reach statistical significance. No relevant changes in disease activity scores were found, indicating no exacerbation of disease activity. In conclusion, infrared treatment has statistically significant short-term beneficial effects and clinically relevant period effects during treatment in RA and AS patients without enhancing disease activity. IR has good tolerability and no adverse effects. PMID:18685882

Oosterveld, Fredrikus G J; Rasker, Johannes J; Floors, Mark; Landkroon, Robert; van Rennes, Bob; Zwijnenberg, Jan; van de Laar, Mart A F J; Koel, Gerard J



Groin pain  


Pain - groin; Lower abdominal pain; Genital pain; Perineal pain ... Common causes of groin pain include: Pulled muscle, tendon, or ligaments in the leg. This problem often occurs in people who play sports such as ...


Efficacy and Tolerability of Conventional Nimesulide Versus Beta-Cyclodextrin Nimesulide in Patients with Pain After Surgical Dental Extraction: A Multicenter, Prospective, Randomized, Double-Blind, Double-Dummy Study?  

PubMed Central

Background: Pain following extraction of an impacted third molar is widely used to assess analgesic efficacy, especially that of a single dose of a drug. The analgesic activity of conventional nimesulide (CN) has been documented in a variety of types of acute and chronic pain. Beta-cyclodextrin nimesulide (BN) is a new formulation in which nimesulide is included in a cyclodextrin molecule, which increases its solubility in water and its dilution rate, allowing extended, rapid absorption of the drug. Objective: The aim of this study was to assess the efficacy and tolerability of a single dose of BN compared with CN in patients with pain following extraction of an impacted third molar. Methods: This was a prospective, randomized, double-blind, double-dummy study conducted at 3 dentistry centers in Venezuela. The patients were randomized to 1 of 2 groups. One group received a single dose of BN (400-mg tablet, equivalent to 100 mg of nimesulide); the other group received a single dose of CN (100-mg tablet). Both groups also received a placebo. The efficacy variables were (1) pain intensity (PI), assessed on a visual analog scale (VAS) at the following times: 0, 5, 10, 15, 30, and 45 minutes and 1, 2, 4, 6, 8, 10, and 12 hours after drug administration; (2) time to first measurable difference in PI from baseline (PID) (PID ?1 cm on the VAS; ie, the beginning of analgesic action); (3) maximum PID (max PID); (4) sum of PIDs in the 12-hour observation period; (5) pain relief (PR), as rated on a 5-point scale; (6) maximum PR; and (7) sum of the PR scores in the 12-hour observation period (ie, total PR). For the tolerability analysis, all adverse events (AEs) were to be recorded, and the investigators were to assess whether each AE was drug related. Results: Seventy-two patients were enrolled in the study. Of these, 62 patients (40 women, 22 men; mean [SD] age, 20.1 [5.9] years) were assessed; 35 were treated with BN and 27 with CN. PI reduction was more rapid and greater in the BN group. The first measurable change in PI (PID ?1 on the VAS) was reached within 5 minutes by 39% and 15% of the patients in the BN and CN groups, respectively, and within 10 minutes by 52% and 30% of the patients in the BN and CN groups, respectively. The max PID was reached <1 hour in 32% and 15% of patients in the BN and CN groups, respectively. No AEs were reported. Conclusions: In this study population, both BN and CN were similarly effective in relieving pain after extraction of an impacted third molar, and both drugs were well tolerated. PI changes were statistically significantly more rapid and greater with BN than CN.

Bocanegra, Mildred; Seijas, Alberto; Yibirin, Maria Gonzalez



Do genetic predictors of pain sensitivity associate with persistent widespread pain?  

Microsoft Academic Search

Genetic risk factors for pain sensitivity may also play a role in susceptibility to chronic pain disorders, in which subjects have low pain thresholds. The aim of this study was to determine if proposed functional single nucleotide polymorphisms (SNPs) in the GTP cyclohydrolase (GCH1) and ? opioid receptor (OPRM1) genes previously associated with pain sensitivity affect susceptibility to chronic widespread

Kate L Holliday; Barbara I Nicholl; Gary J Macfarlane; Wendy Thomson; Kelly A Davies; John McBeth



The neuropathic pain triad: neurons, immune cells and glia  

Microsoft Academic Search

Nociceptive pain results from the detection of intense or noxious stimuli by specialized high-threshold sensory neurons (nociceptors), a transfer of action potentials to the spinal cord, and onward transmission of the warning signal to the brain. In contrast, clinical pain such as pain after nerve injury (neuropathic pain) is characterized by pain in the absence of a stimulus and reduced

Clifford J Woolf; Joachim Scholz



Flank pain  


Pain - side; Side pain ... Flank pain can be a sign of a kidney problem. However, since many organs are in this area, other causes are possible. If you have flank pain and fever , chills, blood in the urine, or ...


Adaptability to pain is associated with potency of local pain inhibition, but not conditioned pain modulation: a healthy human study.  


This study investigated the relationship between pain sensitivity, adaptability, and potency of endogenous pain inhibition, including conditioned pain modulation (CPM) and local pain inhibition. Forty-one healthy volunteers (20 male, 21 female) received conditioning stimulation (CS) over 2 sessions in a random order: tonic heat pain (46 °C) on the right leg for 7 minutes and cold pressor pain (1 °C to 4 °C) on the left hand for 5 minutes. Participants rated the intensity of pain continuously using a 0 to 10 electronic visual analogue scale. The primary outcome measures were pressure pain thresholds (PPT) measured at the heterotopic and homotopic location to the CS sites before, during, and 20 minutes after CS. Two groups of participants, pain adaptive and pain nonadaptive, were identified based on their response to pain in the cold pressor test. Pain-adaptive participants showed a pain reduction between peak pain and pain at end of the test by at least 2 of 10 (n=16); whereas the pain-nonadaptive participants reported unchanged peak pain during 5-minute CS (n=25). Heterotopic PPTs during the CS did not differ between the 2 groups. However, increased homotopic PPTs measured 20 minutes after CS correlated with the amount of pain reduction during CS. These results suggest that individual sensitivity and adaptability to pain does not correlate with the potency of CPM. Adaptability to pain is associated with longer-lasting local pain inhibition. PMID:24502842

Zheng, Zhen; Wang, Kelun; Yao, Dongyuan; Xue, Charlie C L; Arendt-Nielsen, Lars



Genes May Help Determine Your Pain Threshold  


... and a member of the American Academy of Neurology, said in an academy news release. "Identifying whether ... on April 30 at the American Academy of Neurology's annual meeting in Philadelphia. Research presented at medical ...


A Phase 3, Randomized, Double-Blind Comparison of Analgesic Efficacy and Tolerability of Q8003 vs Oxycodone or Morphine for Moderate-to-Severe Postoperative Pain Following Bunionectomy Surgery  

PubMed Central

Objective Compare the efficacy and tolerability of the dual-opioid, Q8003® (morphine/oxycodone combination) 12 mg/8 mg to morphine 12 mg or oxycodone 8 mg in subjects following bunionectomy surgery. Design This was a randomized, double-blind study. Setting Hospitalized patients. Patients Healthy men or women aged ?18 years with moderate or severe pain (score ?2 on a 4-point Likert scale) and ?4 on the 11-point numerical pain rating scale following surgery. Interventions Study medication was initiated after surgery and was given for 48 hours. Outcomes The primary efficacy variable was mean sum of the pain intensity difference (SPID) scores from the postsurgical baseline. Results Five hundred twenty-two subjects were randomized; 31 (5.9%) discontinued, including 19 (3.6%) for adverse events. The mean total morphine equivalent dose (MED) was 182.7 mg from Q8003 12 mg/8 mg, 92.4 mg for morphine 12 mg, and 92.1 mg for oxycodone 8 mg. SPID from baseline over 24 hours and SPID from baseline over 48 hours were significantly (P < 0.02) higher for Q8003 12 mg/8 mg vs morphine 12 mg or oxycodone 8 mg. Significantly (P < 0.015) fewer subjects in the Q8003 group required ibuprofen rescue medication, used lower doses of rescue medication, and had a longer median time to first use of rescue medication. Oxygen desaturation <90% occurred in 5.3% with Q8003, 2.8% with morphine 12 mg, and 2.3% with oxycodone 8 mg, and the cumulative median dose at first desaturation was twofold greater with Q8003. Conclusion Q8003 provided superior efficacy to its individual components at twice the MED with only a modest increase in the incidence of adverse events.

Richards, Patricia; Riff, Dennis; Kelen, Robin; Stern, Warren



Cancer pain  

Microsoft Academic Search

This book contains 13 chapters. Some of the chapter titles are: Importance of the Problem; Neurophysiology and Biochemistry of Pain; Assessment of Pain in Patients with Cancer; Drug Therapy; Chemotherapy and Radiotherapy for Cancer Pain; Sympton Control as it Relates to Pain Control; and Palliative Surgery in Cancer Pain Treatment.

M. Swerdlow; V. Ventafridda



Emerging therapies for neuropathic pain.  


Neuropathic pain develops as a result of damage to either the peripheral or central nervous system. It is characterised by spontaneous burning pain and/or ongoing pain with accompanying hyperalgesia and allodynia. Neuropathic pain is difficult to treat as it is often refractory to conventional analgesic treatments, with most patients obtaining only partial relief. At present, there are four major medication categories that are considered first-line treatment for neuropathic pain: antidepressants, anticonvulsants, local anaesthetic/topical agents and opioids. The efficacy of these treatments in neuropathic pain, excepting opioids, has been discovered serendipitously. However, responder rates and overall efficacy is poor with these agents and tolerability or side effects are often limiting. This update will review existing treatment options for neuropathic pain, and highlight more recent advances in the development of novel analgesics to treat this chronic disorder. PMID:15757406

Collins, Susanne D; Chessell, Iain P



Duloxetine in patients with central neuropathic pain caused by spinal cord injury or stroke: a randomized, double-blind, placebo-controlled trial.  


The mechanisms underlying central neuropathic pain are poorly understood. Pain inhibitory mechanisms including sertononergic and norepinephrine systems may be dysfunctional. In this randomized, double-blinded, placebo-controlled trial we evaluated the effects of duloxetine on pain relief (spontaneous pain and evoked pain), tolerability, health status, and quality of life in patients with central pain related to cerebrovascular lesions or spinal cord lesions. At baseline and eight weeks following start of treatment subjects were evaluated with standard measures of efficacy: pain intensity (primary efficacy variable), quantitative sensory testing, health status and quality of life (secondary efficacy variables). Forty-eight patients received escalating doses of either duloxetine (60 and 120mg/day) or matching placebo capsules. In both groups, patients started with 1 capsule per day. If pain relief was insufficient, patients were titrated to a higher dose. A trend towards a decrease in mean pain score after eight weeks was observed for duloxetine treatment (p=0.056). Duloxetine alleviated dynamic (p=0.035) and cold allodynia (p<0.001) significantly better than placebo. Tactile pain and pressure pain thresholds did not improve significantly. The duloxetine group showed a significant improvement for the bodily pain domain of the SF36 (p=0.035). No significant differences were observed in the other domains of the SF36, the Pain Disability Index, and the EQ-5D. While this trial showed no significant effect on pain intensity, duloxetine revealed a biologic effect. It would be worthwhile to suspend our judgement and to perform more studies to evaluate the role of duloxetine in modulation of the symptoms of central neuropathic pain. PMID:21078545

Vranken, J H; Hollmann, M W; van der Vegt, M H; Kruis, M R; Heesen, M; Vos, K; Pijl, A J; Dijkgraaf, M G W



Heel pain  


Pain - heel ... Heel pain is most often the result of overuse. Rarely, it may be caused by an injury. Your heel ... awkwardly on the heel Conditions related to heel pain include: Achilles tendinitis, inflammation of the large tendon ...


Belly Pain  


... is one of the most common reasons for abdominal pain. If you haven't had a bowel movement ( ... disease , or inflammatory bowel disease also can cause abdominal pain. Food. Some kids get abdominal pain because they ...


Pain Relievers  


Pain relievers are medicines that reduce or relieve headaches, sore muscles, arthritis, or other aches and pains. There ... also have a slightly different response to a pain reliever. Over-the-counter (OTC) medicines are good for ...


Knee pain  


... by: Anterior knee pain Arthritis -- including rheumatoid arthritis, osteoarthritis, and gout Baker's cyst -- a fluid-filled swelling ... This may reduce swelling and provide support. Take acetaminophen for pain or ibuprofen for pain and swelling. ...


Mechanisms of pain relief by vibration and movement.  

PubMed Central

Mechanisms of pain relief induced by vibration and movement were investigated. A CO2 laser beam, which is useful for pure nociceptive stimulation, was used for recording pain-related somatosensory evoked potentials (pain SEPs) and for measuring pain threshold and reaction time (RT). Concurrently applied vibratory stimuli to and active movements of the fingers significantly reduced and prolonged pain SEPs, increased pain threshold, and prolonged RT, indicating that an increase in the inhibitory mechanisms of painful feeling was induced by the concurrently adopted sensory inputs mediated by large myelinated fibres. In contrast, continuous cooling enhanced pain SEPs and decreased pain threshold, probably due to the spatial summation of two kinds of nociceptive impulses mediated by the same pathways. The results of this investigation throw light on the mechanisms of the alleviation of pain by vibration and movement.

Kakigi, R; Shibasaki, H



Practical quantum fault tolerance  

NASA Astrophysics Data System (ADS)

The standard approach to quantum fault tolerance is to calculate error thresholds on basic gates in the limit of arbitrarily many concatenation levels. In contrast this paper takes the number of qubits and the target implementation accuracy as given, and provides a framework for engineering the constrained quantum system to the required tolerance. The approach requires solving the full dynamics of the quantum system for an arbitrary admixture (biased or unbiased) of Pauli errors. The inaccuracy between ideal and implemented quantum systems is captured by the supremum of the Schatten k-norm of the difference between the ideal and implemented density matrices taken over all density matrices. This is a more complete analysis than the standard approach, where an intricate combination of worst case assumptions and combinatorial analysis is used to analyze the special case of equiprobable errors. Conditions for fault tolerance are now expressed in terms of error regions rather than a single number (the standard error threshold). In the important special case of a stochastic noise model and a single logical qubit, an optimization over all 2×2 density matrices is required to obtain the full dynamics. The complexity of this calculation is greatly simplified through reduction to an optimization over only three projectors. Error regions are calculated for the standard 5- and 7-qubit codes. Knowledge of the full dynamics makes it possible to design sophisticated concatenation strategies that go beyond repeatedly using the same code, and these strategies can achieve target fault tolerance thresholds with fewer qubits.

Gilbert, G.; Weinstein, Y. S.; Aggarwal, V.; Calderbank, A. R.



Dopamine and Pain Sensitivity: Neither Sulpiride nor Acute Phenylalanine and Tyrosine Depletion Have Effects on Thermal Pain Sensations in Healthy Volunteers  

PubMed Central

Based on animal studies and some indirect clinical evidence, dopamine has been suggested to have anti-nociceptive effects. Here, we investigated directly the effects of increased and decreased availability of extracellular dopamine on pain perception in healthy volunteers. In Study 1, participants ingested, in separate sessions, a placebo and a low dose of the centrally acting D2-receptor antagonist sulpiride, intended to increase synaptic dopamine via predominant pre-synaptic blockade. No effects were seen on thermal pain thresholds, tolerance, or temporal summation. Study 2 used the acute phenylalanine and tyrosine depletion (APTD) method to transiently decrease dopamine availability. In one session participants ingested a mixture that depletes the dopamine amino acid precursors, phenylalanine and tyrosine. In the other session they ingested a nutritionally balanced control mixture. APTD led to a small mood-lowering response following aversive thermal stimulation, but had no effects on the perception of cold, warm, or pain stimuli. In both studies the experimental manipulation of dopaminergic neurotransmission was successful as indicated by manipulation checks. The results contradict proposals that dopamine has direct anti-nociceptive effects in acute experimental pain. Based on dopamine’s well-known role in reward processing, we hypothesize that also in the context of pain, dopamine acts on stimulus salience and might play a role in the initiation of avoidance behavior rather than having direct antinociceptive effects in acute experimental pain.

Becker, Susanne; Ceko, Marta; Louis-Foster, Mytsumi; Elfassy, Nathaniel M.; Leyton, Marco; Shir, Yoram; Schweinhardt, Petra



Back Pain  


... are not usually advisable for acute back pain. Chronic Back Pain Treatment for chronic back pain falls into two basic categories: the ... some of the more commonly used treatments for chronic back pain. Nonsurgical Treatments Hot or cold: Hot or cold packs—or ...


Preoperative pain sensitivity and its correlation with postoperative pain and analgesic consumption: a qualitative systematic review.  


Pain perception to minor physical stimuli has been hypothesized to be related to subsequent pain ratings after surgery. The objective of this systematic review was to evaluate the correlation between preoperative pain sensitivity and postoperative pain intensity. After a literature search of MEDLINE, EMBASE, and meeting abstracts, we identified 15 studies (n = 948 patients) with univariate and/or multivariate analysis on the topic. In these studies, three types of pain stimuli were applied: thermal, pressure, and electrical pain. The intensity of suprathreshold heat pain (i.e., pain beyond patient threshold) was most consistently shown to correlate with postoperative pain. The most common limitation of the included studies was the method of statistical analysis and lack of multivariate analysis. More research is required to establish the correlation of other pain sensitivity variables with postoperative pain outcomes. PMID:21245740

Abrishami, Amir; Chan, Joshua; Chung, Frances; Wong, Jean



Algometry with a clothes peg compared to an electronic pressure algometer: a randomized cross-sectional study in pain patients  

PubMed Central

Background Hypersensitivity of the central nervous system is widely present in pain patients and recognized as one of the determinants of chronic pain and disability. Electronic pressure algometry is often used to explore aspects of central hypersensitivity. We hypothesized that a simple pain provocation test with a clothes peg provides information on pain sensitivity that compares meaningfully to that obtained by a well-established electronic pressure algometer. "Clinically meaningful" was defined as a medium (r = 0.3-0.5) or high (r > 0.5) correlation coefficient according to Cohen's conventions. Methods We tested 157 in-patients with different pain types. A calibrated clothes peg was applied for 10 seconds and patients rated the pain intensity on a 0 to 10 numerical rating scale. Pressure pain detection threshold (PPdt) and pressure pain tolerance threshold (PPtt) were measured with a standard electronic algometer. Both methods were performed on both middle fingers and ear lobes. In a subgroup of 47 patients repeatability (test-retest reliability) was calculated. Results Clothes peg values correlated with PPdt values for finger testing with r = -0.54 and for earlobe testing with r = -0.55 (all p-values < 0.001). Clothes peg values also correlated with PPtt values for finger testing with r = -0.55 (p < 0.001). Test-retest reliability (repeatability) showed equally stable results for clothes peg algometry and the electronic algometer (all r-values > 0.89, all p-values < 0.001). Conclusions Information on pain sensitivity provided by a calibrated clothes peg and an established algometer correlate at a clinically meaningful level.



NGX-4010, a high-concentration capsaicin dermal patch for lasting relief of peripheral neuropathic pain.  


NeurogesX Inc is developing NGX-4010, a rapid-delivery dermal patch application system that contains high-concentration trans-capsaicin, for the treatment of peripheral neuropathic pain. Capsaicin evokes a lasting and reversible refractory state in primary sensory neurons involved in the generation and maintenance of neuropathic pain. NGX-4010 can be applied to the painful skin area up to a total surface area of 1120 cm2. In phase I clinical trials, NGX-4010 increased the threshold for warmth detection, reduced epidermal sensory nerve fiber density and was well tolerated. In phase II trials, NGX-4010 was effective in reducing pain in patients with post-herpetic neuralgia (PHN), HIV-associated distal sensory neuropathy (HIV-DSP) and painful diabetic neuropathy (PDN). Data from phase III trials in patients with PHN demonstrated that significantly more pain relief was achieved by NGX-4010 (30 to 32% reduction from baseline) compared with a low-concentration capsaicin active control (20 to 24% reduction); however, only one of two studies involving patients with HIV-DSP met the primary endpoint. NGX-4010 appears to have the potential to be an effective adjunctive or a stand-alone therapy for PHN, as well as potentially for HIV-DSP and PDN. NGX-4010 has been granted approval by the European Commission and an NDA has been accepted for filing by the FDA. PMID:19579176

Noto, Christopher; Pappagallo, Marco; Szallasi, Arpad



Voluntary and forced exercises prevent the development of tolerance to analgesic effects of morphine in rats  

PubMed Central

Objective(s): Morphine is widely used to treat chronic pain. However, its utility is hindered by the development of tolerance to its analgesic effects. Despite the renowned beneficial effects of physical exercise on cognitive functions and signs of morphine withdrawal in morphine-dependent rats, little is known about the roles of voluntary and forced exercises in tolerance to analgesic effect of morphine in rats. Materials and Methods: In this study, rats were injected with 10 mg/kg of morphine, once daily, SC over a period of 8 days of either voluntary or treadmill exercise. Following these injections, the percent of maximum possible effect (%MPE) of morphine was measured on the 1st, 4th, and 8th days by hot plate test. Results: Both voluntary and forced exercises significantly increased pain threshold compared to the sedentary group (P<0.05). Voluntary and forced exercises also significantly increased potency of morphine compared to sedentary morphine group (P<0.05). Thus, we concluded that voluntary and forced exercises blocked the development of tolerance during 8 daily simultaneously treatments. When exercising rats were returned to sedentary conditions, sensitivity to the analgesic effects of morphine increased significantly and persisted during sedentary period in the exercising rats. In other words, %MPE of the exercising morphine-group increased significantly compared to saline group (P<0.05). Conclusion: Our results showed that voluntary and forced exercises may be possible methods for treating the development of tolerance to analgesic effect of morphine in rats.

Shokraviyan, Monireh; Miladi-Gorji, Hossein; Vaezi, Gholam Hassan



Capsaicin did not evoke pain from human hand vein segments but did so after injections into the paravascular tissue.  

PubMed Central

1. To see if pain from veins is mediated by C fibre endings, the C fibre stimulant capsaicin was applied intravenously, and, for comparison, paravenously and intracutaneously. 2. Capsaicin, dissolved in the fat emulsion Intralipid, was applied intravenously by continuous perfusion of vascularly isolated hand vein segments as well as by injections into occluded finger veins. Using the latter approach chemicals reach the paravascular space. 3. Pain intensities were recorded continuously with an electronically controlled visual analogue scale for deriving capsaicin concentration-pain intensity relations and the time course of pain (latencies, pain durations). 4. Capsaicin always evoked pain upon injection into skin and paravenous tissue (0.3-6.5 microM) and into occluded finger veins (3.3-33 microM), whereas it had no effect whatsoever when perfused through hand vein segments even at a concentration of 650 microM. 5. Pain intensity increased with concentration and usually reached the tolerance maximum at the fivefold threshold concentration, so that the concentration-pain intensity relations were congruent for the various routes of drug application. 6. The latencies and pain durations were independent of the capsaicin concentration, but were substantially longer with injections into occluded finger veins (latency 10-30 s, pain duration 60-120 s) than with intradermal or paravenous injections (2-9 s, 10-28 s). 7. These observations show for the first time a functional similarity between the nociceptive C fibre system of the skin and the paravascular tissues, and by inference, they dismiss the possibility that C fibre endings mediate pain in cutaneous veins.

Arndt, J O; Kindgen-Milles, D; Klement, W



Pain Management  


... taking, including over-the-counter medications, supplements and herbal remedies. Sometimes there can be serious interactions. Your ... or call our Information Specialists for a copy. Side Effects of Pain Medication Some pain medications have ...


Pain Management  

Microsoft Academic Search

\\u000a \\u000a \\u000a \\u000a \\u000a  \\u000a \\u000a Patients suffering with chronic diffuse pain who lack objective clinical and laboratory findings (e.g., fibromyalgia) frequently\\u000a are dismissed as not having real pain, which only perpetuates their illness.\\u000a \\u000a \\u000a \\u000a \\u000a  \\u000a \\u000a There are four principal categories of pain: nociceptive pain, neuropathic pain, chronic pain of complex etiology, and psychogenic\\u000a pain.\\u000a \\u000a \\u000a \\u000a \\u000a  \\u000a \\u000a Pain assessment should include attention to possible psychological and sociocultural

John B. Winfield


Painful swallowing  


... ulcers Something stuck in the throat (for example, fish or chicken bones) Tooth infection or abscess ... with the painful swallowing, including: Abdominal pain Chills Cough Fever Heartburn Nausea or vomiting Sour taste in ...


Pelvic Pain  


... ACOG practice bulletin no. 51. Chronic pelvic pain. Obstetrics & Gynecology, 103 ,589–605. [top] UCSF Medical Center. ( ... profile of women with chronic pelvic pain. Clinical Obstetrics and Gynecology, 33 ,130–136 [top] What are ...


Neck Pain  


... over-the counter medicine, such as acetaminophen or ibuprofen, to relieve pain, and apply heat to the ... an injury. Use anti-inflammatory medicines, such as ibuprofen and aspirin, to relieve pain and discomfort, and ...


[Spontaneous pain attacks: neuralgic pain].  


Paroxysmal orofacial pains can cause diagnostic problems, especially when different clinical pictures occur simultaneously. Pain due to pulpitis, for example, may show the same characteristics as pain due to trigeminal neuralgia would. Moreover, the trigger point of trigeminal neuralgia can either be located in a healthy tooth or in the temporomandibular joint. Neuralgic pain is distinguished into trigeminal neuralgia, glossopharyngeal neuralgia, Horton's neuralgia, cluster headache and paroxysmal hemicrania. In 2 cases trigeminal neuralgia is successfully managed with a neurosurgical microvascular decompression procedure according to Jannetta. Characteristic pain attacks resembling neuralgic pain result from well understood pathophysiological mechanisms. Consequently, adequate therapy, such as a Janetta procedure and specific pharmacological therapy, is available. PMID:17147031

de Bont, L G M



Joint pain  

Microsoft Academic Search

Joint pain may result from traumas or repeated microtraumas, as in sports injuries. Pain in osteoarthritis starts before any\\u000a objective finding. It has been demonstrated that in the first stages of this disease, pain is due to intraosseous venous engorgement\\u000a for the earlier thickening of the cortical bone under the articular cartilage. The mechanisms of inflammatory pain are more\\u000a complex

Massimo Zoppi; Elisabetta Beneforti



Neck pain  


Pain - neck; Neck stiffness ... this as having a stiff neck. If neck pain involves nerves, you may feel numbness, tingling, or ... A common cause of neck pain is muscle strain or tension. Usually, ... Such activities include: Bending over a desk for hours Poor ...


Psychophysical examination in patients with post-mastectomy pain.  


Chronic pain, lymphoedema, post-irradiation neuropathy and other symptoms are reported in as many as 75% of women following breast cancer treatment. This study examined pain and sensory abnormalities in women following breast cancer surgery. Sensory tests were carried out on operated 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 flow during repetitive brush and pinprick stimulation. Sensory threshold to pinprick and thermal stimuli was significantly higher on the operated side in both groups while pressure pain threshold was significantly lower in pain patients on the operated side compared to the contralateral side. No side 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 flow measured by laser Doppler (flux) was significantly higher when the skin was tapped at 2.0 Hz on the operated side compared to contralaterally in pain patients, while no side to side difference was seen in pain-free patients. Pinprick-evoked pain was correlated to spontaneous pain but not to flux. Spontaneous pain was not correlated to flux. Sensitization seems to be a feature in breast cancer-operated women with pain, but not in pain-free women. PMID:10963907

Gottrup, H; Andersen, J; Arendt-Nielsen, L; Jensen, T S



The pain of painful bladder  

PubMed Central

Bladder pain can have a number of different etiologies. This brief summary provides an overview of bladder pain syndrome, including current evidence-based recommendations for diagnosis and management.

Payne, Christopher



Repressive coping style and suppression of pain-related thoughts: Effects on responses to acute pain induction  

Microsoft Academic Search

Repressors have shown short-term tolerance of acute pain but long-term sensitivity to chronic pain. To reconcile this discrepancy, we hypothesised that repressors routinely suppress pain-related thoughts during acute pain, and thus paradoxically incur rebound effects (increased accessibility of the to-be-suppressed material) afterwards. Healthy individuals (n=222) were assigned to suppress or not suppress pain-related thoughts during a cold pressor. Recovery and

Erin Elfant; John W. Burns; Amos Zeichner



Opioids Switching with Transdermal Systems in Chronic Cancer Pain  

Microsoft Academic Search

BACKGROUND: Due to tolerance development and adverse side effects, chronic pain patients frequently need to be switched to alternative opioid therapy OBJECTIVE: To assess the efficacy and tolerability of an alternative transdermally applied (TDS) opioid in patients with chronic cancer pain receiving insufficient analgesia using their present treatment. METHODS: A total of 32 patients received alternative opioid therapy, 16 were

C Aurilio; MC Pace; V Pota; P Sansone; M Barbarisi; E Grella; MB Passavanti



Threshold Logic Drempellogica.  

National Technical Information Service (NTIS)

The theory is discussed of presently available threshold logic circuits, and an analysis of threshold functions is presented. An operational threshold gate adding circuit in TTL technology is described, and the difficulty of improving logic in complex cir...

C. Vader J. W. M. Wasser



Pain in Parkinson's Disease.  


Pain is reported by nearly 50% of patients with Parkinson's disease. In some patients, it can be more debilitating than the motor deficits. In order to identify the appropriate treatment strategy for each patient, it is useful to categorize pain syndromes as follows: 1) low DOPA (end of dose wearing off, diphasic, or early morning) painful states are associated with inadequate levels of dopamine receptor stimulation; 2) high DOPA (peak dose) painful states occur at times of maximum levodopa efficacy; and 3) many patients report pain that has no obvious relation to dopaminergic medications or may even be caused by other conditions. Low DOPA painful states are best treated by trying to provide more continuous dopaminergic stimulation and thereby reduce or prevent the number and duration of "off" periods. Adding or increasing the dose of direct-acting dopamine receptor agonists or of catechol-o-methyl transferase inhibitors is the best first-line strategy. Other approaches include increasing the frequency of immediate-release levodopa preparations or using controlled-release preparations. More invasive approaches should be considered only when simpler methods fail. These include deep brain stimulation to the pallidum or the subthalamic nucleus, or direct duodenal continuous infusion of levodopa in patients who are unable to undergo surgery. Pain associated with excessive dopaminergic stimulation usually is a result of dystonia or severe chorea. Reduction of levodopa is the first step in attempting to diminish high DOPA states, followed by reduction or cessation of other dopaminergic agents such as selegiline, catechol-o-methyl transferase inhibitors, or direct-acting dopamine receptor agonists. Adding amantadine can reduce chorea significantly and it should be tried if the potential and actual side effects are tolerable to the patient. Deep brain stimulation is a good final option if medication adjustments are ineffective. Nonspecific pains of Parkinson's disease can be difficult to treat. The effective use of central pain suppressant or analgesics is anecdotal and difficult to verify. In untreated early disease, generalized pain or pain related to joint or muscle immobility may be reduced by effective treatment of the underlying Parkinson's disease. PMID:15043802

Sage, Jacob I.



Tolerant B Lymphocytes Acquire Resistance to Fas-mediated Apoptosis after Treatment with Interleukin 4 but Not after Treatment with Specific Antigen Unless a Surface Immunoglobulin Threshold Is Exceeded  

Microsoft Academic Search

Summary Susceptibility to Fas-mediated apoptosis in nontolerant B cells is regulated in a receptor-specific fashion. To explore the regulation of Fas killing in tolerant, autoreactive B cells, mice doubly transgenic for hen egg lysozyme (HEL)-specific B cell receptors and soluble HEL were exam- ined. Engagement of CD40 led to enhanced Fas expression and acquisition of sensitivity to Fas-mediated apoptosis in

Linda C. Foote; Ann Marshak-Rothstein; Thomas L. Rothstein


Resveratrol attenuates morphine antinociceptive tolerance via SIRT1 regulation in the rat spinal cord.  


In recent years, researchers have begun to pay more attention to the role of Sirtuin 1 (SIRT1, a class III histone deacetylase) in pain. However, little research has been conducted examining the involvement of SIRT1 in chronic morphine tolerance. The aim of this study was to investigate the role of spinal SIRT1 and acetyl-histone H3(Ac-H3) in chronic morphine tolerance in rats. Chronic morphine tolerance was induced by twice-daily intrathecal (i.t.) injections of morphine (10?g) for 6 days. Control rats received normal saline (NS). Resveratrol (Res, a SIRT1 stimulant, 30?g i.t.) or dimethyl sulfoxide (DMSO, 10?l i.t.) was then injected on days 7-13. The thermal paw withdrawal threshold was assessed to determine the analgesic effects of morphine (10?g). qRT-PCR, western blotting and immunohistochemistry were used to detect the expression of SIRT1 and global Ac-H3. Administration of morphine for 6 days induced a stabilized antinociceptive tolerance, down-regulated SIRT1 expression and up-regulated Ac-H3 expression in the spinal dorsal horn. Resveratrol treatment from day 7 to 13 increased SIRT1 expression, suppressed global Ac-H3 expression compared to the morphine tolerance (MT) group, and significantly reversed morphine antinociceptive tolerance. These results suggest that resveratrol reversed morphine tolerance by upregulating the expression of SIRT1 in the spinal dorsal horn. SIRT1 and global Ac-H3 in the spinal cord may play an important role in the mechanisms of chronic morphine tolerance. PMID:24561089

He, Xin; Ou, Peng; Wu, Kemin; Huang, Changsheng; Wang, Yichun; Yu, Zou; Guo, Qulian



Neuropathic Pain  

PubMed Central

Neuropathic pain is triggered by lesions to the somatosensory nervous system that alter its structure and function so that pain occurs spontaneously and responses to noxious and innocuous stimuli are pathologically amplified. The pain is an expression of maladaptive plasticity within the nociceptive system, a series of changes that constitute a neural disease state. Multiple alterations distributed widely across the nervous system contribute to complex pain phenotypes. These alterations include ectopic generation of action potentials, facilitation and disinhibition of synaptic transmission, loss of synaptic connectivity and formation of new synaptic circuits, and neuroimmune interactions. Although neural lesions are necessary, they are not sufficient to generate neuropathic pain; genetic polymorphisms, gender, and age all influence the risk of developing persistent pain. Treatment needs to move from merely suppressing symptoms to a disease-modifying strategy aimed at both preventing maladaptive plasticity and reducing intrinsic risk.

Costigan, Michael; Scholz, Joachim; Woolf, Clifford J.



Pain following hysterectomy: epidemiological and clinical aspects.  


It is well known that different surgical procedures like amputation, thoracotomy, inguinal herniotomy, and mastectomy are associated with a risk of developing chronic postsurgical pain. Hysterectomy is the most frequent gynecological procedure with an annual frequency of 5000 hysterectomies for a benign indication in Denmark, but is has not previously been documented in detail to what extent this procedure leads to chronic pain. The aim of this PhD thesis was therefore to describe the epidemiology, type of pain, risk factors, and predictive factors associated with chronic pain after hysterectomy for a benign indication. The thesis includes four papers, of which one is based on a questionnaire study, two are based on a prospective clinical study, and one is a review of chronic pain after hysterectomy. The questionnaire paper included 1135 women one year after hysterectomy. A postal questionnaire about pain before and after hysterectomy was combined with data from the Danish Hysterectomy Database. Chronic postoperative pain was described by 32%, and the identified risk factors were preoperative pelvic pain, previous cesarean section, other pain problems and pain as an indication for hysterectomy. Spinal anesthesia was associated with a decreased risk of having pain after one year. The type of surgery (i.e. abdominal or vaginal hysterectomy) did not influence chronic pain. The prospective paper included 90 women referred for a hysterectomy on benign indication. The tests were performed before, on day 1, and 4 months after surgery and included questionnaires about pain, coping, and quality of life together with quantitative sensory testing of pain thresholds. Seventeen percent had pain after 4 months, and the risk factors were preoperative pain problems elsewhere and a high intensity of acute postoperative pain. Type of surgery was not a risk factor. Preoperative brush-evoked allodynia, pinprick hyperalgesia, and vaginal pain threshold were associated with a high intensity of acute postoperative pain, and preoperative brush-evoked allodynia was also associated with pelvic pain after 4 months. This PhD thesis shows that chronic postoperative pain is present after hysterectomy in 17-32% of women. The identified main risk factors are described above. The findings indicate that it is not the nerve injury itself, but more likely the underlying individual susceptibility to pain that is important for the development of chronic pain after hysterectomy. PMID:22239844

Brandsborg, Birgitte



Pain Genes  

Microsoft Academic Search

Pain, which afflicts up to 20% of the population at any time, provides both a massive therapeutic challenge and a route to understanding mechanisms in the nervous system. Specialised sensory neurons (nociceptors) signal the existence of tissue damage to the central nervous system (CNS), where pain is represented in a complex matrix involving many CNS structures. Genetic approaches to investigating

Tom Foulkes; John N. Wood



Pain without nociception?  


We describe a young woman with complete cervical spinal cord transsection, who developed significant abdominal pain, triggered by gastric distension and deep abdominal palpation. On the basis of the nature of her spinal cord injury, her brain-gut axis was limited to vagal pathways. Studies in mammalian models of human visceral sensation consistently showed that the subdiaphragmatic vagus contains a homogeneous population of afferents that are activated by low-intensity stimuli, which are generally believed to be important in regulating autonomic function and perhaps contributing to visceral sensory experiences triggered by such low-intensity stimuli (e.g. fullness, nausea), but not pain, although many fibers encode stimuli well into the noxious range. In contrast, spinal afferent pathways include fibers with high-activation thresholds that are thought to represent specialized nociceptors. This illustrative case argues against an exclusive role of specialized nociceptive pathways in visceral pain, but supports a concept of intensity coding with the composite of vagal and spinal input contributing to conscious perception and pain. PMID:22266836

Levinthal, David J; Bielefeldt, Klaus



Threshold quantum cryptography  

SciTech Connect

We present the concept of threshold collaborative unitary transformation or threshold quantum cryptography, which is a kind of quantum version of threshold cryptography. Threshold quantum cryptography states that classical shared secrets are distributed to several parties and a subset of them, whose number is greater than a threshold, collaborates to compute a quantum cryptographic function, while keeping each share secretly inside each party. The shared secrets are reusable if no cheating is detected. As a concrete example of this concept, we show a distributed protocol (with threshold) of conjugate coding.

Tokunaga, Yuuki [NTT Information Sharing Platform Laboratories, NTT Corporation, 1-1 Hikari-no-oka, Yokosuka, Kanagawa 239-0847 (Japan); Division of Materials Physics, Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka 560-8531 (Japan); Okamoto, Tatsuaki [NTT Information Sharing Platform Laboratories, NTT Corporation, 1-1 Hikari-no-oka, Yokosuka, Kanagawa 239-0847 (Japan); Imoto, Nobuyuki [Division of Materials Physics, Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka 560-8531 (Japan)



Intraoperative use of remifentanil and opioid induced hyperalgesia/acute opioid tolerance: systematic review  

PubMed Central

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

Kim, Sang Hun; Stoicea, Nicoleta; Soghomonyan, Suren; Bergese, Sergio D.



Physiopathology of pain in rheumatology.  


Pain is the main manifestation of many rheumatic diseases (be they overtly inflammatory such as rheumatoid arthritis or dysfunctional such as fibromyalgia) but, at least initially, the mechanisms involved in the genesis, amplification and chronicisation of the persistent pain characterising the various conditions can be very different. The main peripheral mechanism underlying acute nociceptive pain is a change in the activity of the nociceptors located in the affected anatomical structures (joints, tendons and ligaments), which makes them more sensitive to normally painful stimuli (hyperalgesia) or normally non-painful stimuli (allodynia). This physiopathological mechanism of peripheral sensitisation plays a primary role in rheumatic diseases characterised by acute inflammation, such as the arthritides due to microcrystals. In the case of chronic rheumatic diseases that do not regress spontaneously, functional and structural central nervous system changes cause a generalised reduction in the pain threshold that is not limited to the anatomical structures involved, thus leading to the appearance of hyperalgesia and allodynia in many, if not all body districts. This is the physiopathological basis of chronic, widespread musculoskeletal pain. PMID:24938190

Cazzola, M; Atzeni, F; Boccassini, L; Cassisi, G; Sarzi-Puttini, P



Threshold Concepts in Biochemistry  

ERIC Educational Resources Information Center

Threshold concepts can be identified for any discipline and provide a framework for linking student learning to curricular design. Threshold concepts represent a transformed understanding of a discipline, without which the learner cannot progress and are therefore pivotal in learning in a discipline. Although threshold concepts have been…

Loertscher, Jennifer



HRS Threshold Adjustment Test  

NASA Astrophysics Data System (ADS)

This test will determine the optimal, non-standard discriminator thresholds for the few anomalous channels on each HRS detector. A 15 second flat field observation followed by a 210 second dark count is performed at each of 10 discriminator threshold values for each detector. The result of the test will be the optimal threshold values to be entered into the PDB.

Troeltzsch, John



Automatic Threshold Circuit.  

National Technical Information Service (NTIS)

An automatic threshold circuit to establish a threshold that is a specified number of db above the input's rms frequency weighted noise value is described. The input is compared with the feedback threshold value, the result of which is coupled to a limite...

J. H. Bumgardner



An attempt to attenuate experimental pain in humans by dextromethorphan, an NMDA receptor antagonist  

Microsoft Academic Search

Dextromethorphan (100 mg, orally), an NMDA receptor antagonist, did not significantly attenuate pain intensity or unpleasantness induced by experimental ischemia or by topical capsaicin in healthy human subjects, nor did it increase the threshold for heat pain or mechanical pain. A dose of 200 mg produced marked side effects. Thus, systemically administered dextromethorphan does not attenuate pain at clinically applicable

Timo Kauppila; Mari Grönroos; Antti Pertovaara



Shoulder pain  


... or damaged. This condition is called rotator cuff tendinitis . Shoulder pain may also be caused by: Arthritis ... recommend such exercises. If you are recovering from tendinitis, continue to do range-of-motion exercises to ...


Abdominal Pain  


... simple and inexpensive, and works for some kids. Peppermint oil enteric-coated capsules often decrease pain in ... effective than adding fiber alone [6] . Enteric-coated peppermint oil While this study found that fiber and ...


Neuropathic Pain  


... damaged, dysfunctional, or injured. These damaged nerve fibers send incorrect signals to other pain centers. The impact ... this short relaxation experience, you may want to send for the longer audio version, available in our ...


Wrist pain  


... illness. Other common causes of wrist pain include: Gout -- this occurs when you produce too much uric ... care provider thinks that you have an infection, gout, or pseudogout, fluid may be removed from the ...


Feeling pain  

MedlinePLUS Videos and Cool Tools

... protective mechanism, alerting it to potential or actual damage to the body’s tissues. In the example of ... the pain receptors in the skin detect tissue damage from the bee sting. Then, the peripheral nerves ...


Chronic pain - resources  


Pain - resources; Resources - chronic pain ... The following organizations are good resources for information on chronic pain: American Chronic Pain Association - National Fibromyalgia and Chronic Pain Association - ...


More optimism, less pain! The influence of generalized and pain-specific expectations on experienced cold-pressor pain.  


Accumulating evidence suggests that dispositional optimism might be a protective factor against experiencing pain. The current paper presents two studies investigating the association between dispositional optimism and experimental pain. Moreover, the influence of pain-specific expectations on this association is investigated. In Study 1, mediation of pain-specific expectations in the relation between dispositional optimism and pain was hypothesized. Expected and experienced pain ratings were obtained from 66 healthy participants undergoing a cold pressor tolerance task. In Study 2, the moderating effect of dispositional optimism on the association between induced pain expectations and pain reports was studied in 60 healthy participants undergoing a 1-min cold pressor task. Both studies controlled for individual differences in fear of pain. Significant associations between dispositional optimism and pain ratings were found in both studies, although the exact time point of these associations differed. Subscale analyses revealed that only the pessimism subscale contributed significantly to these findings. We found no evidence for hypothesized mediation and moderation effects. Alternative explanations for the optimism-pain association are discussed. PMID:23239369

Hanssen, Marjolein M; Vancleef, Linda M G; Vlaeyen, Johan W S; Peters, Madelon L



Evaluation of the threshold trimming method for micro inertial fluidic switch based on electrowetting technology  

NASA Astrophysics Data System (ADS)

The switch based on electrowetting technology has the advantages of no moving part, low contact resistance, long life and adjustable acceleration threshold. The acceleration threshold of switch can be fine-tuned by adjusting the applied voltage. This paper is focused on the electrowetting properties of switch and the influence of microchannel structural parameters, applied voltage and droplet volume on acceleration threshold. In the presence of process errors of micro inertial fluidic switch and measuring errors of droplet volume, there is a deviation between test acceleration threshold and target acceleration threshold. Considering the process errors and measuring errors, worst-case analysis is used to analyze the influence of parameter tolerance on the acceleration threshold. Under worst-case condition the total acceleration threshold tolerance caused by various errors is 9.95%. The target acceleration threshold can be achieved by fine-tuning the applied voltage. The acceleration threshold trimming method of micro inertial fluidic switch is verified.

Liu, Tingting; Su, Wei; Yang, Tao; Han, Bin



Distortion tolerant correlation filter design.  


This paper introduces a computationally efficient algorithm for synthesis of a distortion tolerant correlation filter and associated threshold, denoted collectively as the enhanced matched filter (EMF). Application areas of EMF include imagery based automatic target detection and recognition and biometrics. The EMF is synthesized from a set of training images characterizing the target of interest within the expected distortion range. A distinguishing feature of EMF is the ascribed threshold, which is a byproduct of the filter computation process and does not rely on nontarget trainers. The EMF performance is compared to that of the synthetic discriminant function using realistic test scenarios. PMID:23669663

Heidary, Kaveh



Mechanical and Heat Hyperalgesia Highly Predict Clinical Pain Intensity in Patients With Chronic Musculoskeletal Pain Syndromes  

PubMed Central

Multiple abnormalities in pain processing have been reported in patients with chronic musculoskeletal pain syndromes. These changes include mechanical and thermal hyperalgesia, decreased thresholds to mechanical and thermal stimuli (allodynia), and central sensitization, all of which are fundamental to the generation of clinical pain. Therefore, we hypothesized that quantitative sensory tests may provide useful predictors of clinical pain intensity of such patients. Our previous studies of fibromyalgia (FM) patients have shown statistically significant correlations of quantitative sensory test results with clinical pain intensity, including mechanical spatial summation, number of pain areas, wind-up, and wind-up aftersensations. Although these tests predicted up to 59% of the variance in FM clinical pain intensity, their expense and technical complexities limited widespread use in clinical practice and trials. Thus, we developed practical tests of primary (mechanical) and secondary (heat) hyperalgesia that also strongly predict clinical pain intensity in patients with chronic musculoskeletal pain disorders. Thirty-six individuals with FM, 24 with local musculoskeletal pain, and 23 normal controls underwent testing of mechanical and heat hyperalgesia at the shoulders and hands. All subjects rated experimental pains using an electronic visual analog scale. Using either heat or pressure pain ratings as well as tender point counts and negative affect as predictors, up to 49.4% of the patients' variance of clinical pain intensity could be estimated. Results of this study emphasize the important contributions of peripheral and central factors to both local and widespread chronic pain. Overall, measures of mechanical and heat hyperalgesia in combination with tender point and negative affect provided powerful predictors of clinical pain intensity in chronic musculoskeletal pain patients that can be readily used in clinical practice and trials. Perspective Simple tests of mechanical and heat hyperalgesia can predict large proportions of the variance in clinical pain intensity of chronic musculoskeletal pain patients and thus are feasible to be included in clinical practice and clinical trials.

Staud, Roland; Weyl, Elizabeth E.; Price, Donald D.; Robinson, Michael E.



Pharmacological management of neuropathic pain.  


In health, the nervous system exists in a balance between inhibitory and excitatory influences. This balance may be upset if neural tissue is damaged or irritated and may give rise to neuropathic pain. Such neuropathic pain does not respond consistently to opioid analgesics or NSAIDs and it may therefore be necessary to utilise other therapeutic agents with known activity on either the excitatory or inhibitory components of the pain pathway. These other agents are traditionally considered with reference to their original uses; we still refer to tricyclic antidepressants (TCAs) and anticonvulsant drugs when a consideration of their modes of action may allow more rational use. For example, carbamazepine is related to the TCAs by virtue of its chemical structure and proposed mode of action and yet is still classified as an anticonvulsant drug. With respect to the opioids, increasing evidence points to an analgesic effect in neuropathic pain, although concerns regarding tolerance and dependence still prevent more widespread use. The anticonvulsants comprise a group of compounds possessing anticonvulsant and analgesic properties, but each possesses differing modes of action and so several members of the class should be tried before a conclusion is reached that they, as a whole, are ineffective. TCAs may also have a role in the treatment of neuropathic pain. As with all drugs, if their use is not associated with pain relief in a defined period of time, their use should be terminated. Topical TCAs may also have a role where the area of neuropathic pain is small. Other options, such as SSRIs, membrane stabilisers, capsaicin, baclofen and clonidine may have potential in treating neuropathic pain. The available evidence regarding the efficacy of currently available agents for the treatment of neuropathic pain is sparse. With the knowledge of achieving analgesia, according to the modes of actions of various agents it is hoped that the treatment of this difficult condition may be more logical and successful. PMID:14594443

McCleane, Gary



Reflex receptive fields are enlarged in patients with musculoskeletal low back and neck pain.  


Pain hypersensitivity has been consistently detected in chronic pain conditions, but the underlying mechanisms are difficult to investigate in humans and thus poorly understood. Patients with endometriosis pain display enlarged reflex receptive fields (RRF), providing a new perspective in the identification of possible mechanisms behind hypersensitivity states in humans. The primary hypothesis of this study was that RRF are enlarged in patients with musculoskeletal pain. Secondary study end points were subjective pain thresholds and nociceptive withdrawal reflex (NWR) thresholds after single and repeated (temporal summation) electrical stimulation. Forty chronic neck pain patients, 40 chronic low back pain patients, and 24 acute low back pain patients were tested. Electrical stimuli were applied to 10 sites on the sole of the foot to quantify the RRF, defined as the area of the foot from where a reflex was evoked. For the secondary end points, electrical stimuli were applied to the cutaneous innervation area of the sural nerve. All patient groups presented enlarged RRF areas compared to pain-free volunteers (P<.001). Moreover, they also displayed lower NWR and pain thresholds to single and repeated electrical stimulation (P<.001). These results demonstrate that musculoskeletal pain conditions are characterized by enlarged RRF, lowered NWR and pain thresholds, and facilitated temporal summation, most likely caused by widespread spinal hyperexcitability. This study contributes to a better understanding of the mechanisms underlying these pain conditions, and it supports the use of the RRF and NWR as objective biomarkers for pain hypersensitivity in clinical and experimental pain research. PMID:23707309

Biurrun Manresa, José A; Neziri, Alban Y; Curatolo, Michele; Arendt-Nielsen, Lars; Andersen, Ole K



Sustained antinociceptive effect of cannabinoid receptor agonist WIN 55,212-2 over time in rat model of neuropathic spinal cord injury pain  

PubMed Central

A significant complaint associated with spinal cord injury (SCI) is chronic pain, which includes symptoms such as cutaneous hypersensitivity and spontaneous unevoked pain and is difficult to treat with currently available drugs. One complication with current analgesics is tolerance, a decrease in efficacy with repeated treatment over time. One promising class of pharmacological treatment is cannabinoid (CB) receptor agonists. The current study assessed the efficacy of the CB receptor agonist WIN 55,212-2 (WIN) in a rat model of neuropathic SCI pain. Brief spinal compression leads to significant hindpaw hypersensitivity to tactile stimulation. WIN dose-dependently increased withdrawal thresholds and continued to demonstrate efficacy over a twice-daily 7-day treatment regimen. By contrast, the efficacy of morphine in SCI rats decreased over the same treatment period. Similarly, the antinociceptive efficacy of WIN to acute noxious heat in uninjured rats diminished over time. These data suggest that the sustained efficacy of a CB receptor agonist for pain could depend on the pain state. Such agonists may hold promise for long-term use in alleviating chronic SCI pain.

Hama, Aldric; Sagen, Jacqueline



Altered experimental pain perception after cerebellar infarction.  


Animal studies have suggested that the cerebellum, in addition to its motor functions, also has a role in pain processing and modulation, possibly because of its extensive connections with the prefrontal cortex and with brainstem regions involved in descending pain control. Consistently, human imaging studies have shown cerebellar activation in response to painful stimulation. However, it is presently not clear whether cerebellar lesions affect pain perception in humans. In the present study, we used experimental pain testing to compare acute pain perception and endogenous pain inhibition in 30 patients 1 to 11years after cerebellar infarction and in 30 sex- and age-matched healthy control subjects. Compared to controls, patients exhibited a significantly increased pain perception in response to acute heat stimuli (44°C-48°C, average pain intensity rating for patients 3.4±2.8 and for controls 1.5±1.7 [on a numeric rating scale of 0-10], P<.01) and to repeated 256mN pinprick stimuli (1.3±1.9 vs 0.6±1.0 [0-10], P<.05). Heat hyperalgesia in patients was more pronounced on the body side ipsilateral to the infarction. In addition, patients showed reduced offset analgesia (change in pain intensity rating: 0.0%±15.8% vs -16.9%±36.3%, P<.05) and reduced placebo analgesia (change in pain intensity rating: -1.0±1.1 vs -1.8±1.3 [0-10], P<.05) compared to controls. In contrast, heat and pressure pain thresholds were not significantly different between groups. These results show that, after cerebellar infarction, patients perceive heat and repeated mechanical stimuli as more painful than do healthy control subjects and have deficient activation of endogenous pain inhibitory mechanisms (offset and placebo analgesia). This suggests that the cerebellum has a previously underestimated role in human pain perception and modulation. PMID:24721690

Ruscheweyh, Ruth; Kühnel, Maria; Filippopulos, Filipp; Blum, Bernhard; Eggert, Thomas; Straube, Andreas



Gelsemine, a principal alkaloid from Gelsemium sempervirens Ait., exhibits potent and specific antinociception in chronic pain by acting at spinal ?3 glycine receptors.  


The present study examined the antinociceptive effects of gelsemine, the principal alkaloid in Gelsemium sempervirens Ait. A single intrathecal injection of gelsemine produced potent and specific antinociception in formalin-induced tonic pain, bone cancer-induced mechanical allodynia, and spinal nerve ligation-induced painful neuropathy. The antinociception was dose-dependent, with maximal inhibition of 50% to 60% and ED50 values of 0.5 to 0.6 ?g. Multiple daily intrathecal injections of gelsemine for 7 days induced no tolerance to antinociception in the rat model of bone cancer pain. Spinal gelsemine was not effective in altering contralateral paw withdrawal thresholds, and had only a slight inhibitory effect on formalin-induced acute nociception. The specific antinociception of gelsemine in chronic pain was blocked dose-dependently by the glycine receptor (GlyR) antagonist strychnine with an apparent ID50 value of 3.8 ?g. Gelsemine concentration-dependently displaced H(3)-strychnine binding to the membrane fraction of rat spinal cord homogenates, with a 100% displacement and a Ki of 21.9?M. Gene ablation of the GlyR ?3 subunit (?3 GlyR) but not ?1 GlyR, by a 7-day intrathecal injection of small interfering RNA (siRNA) targeting ?3 GlyR or ?1 GlyR, nearly completely prevented gelsemine-induced antinociception in neuropathic pain. Our results demonstrate that gelsemine produces potent and specific antinociception in chronic pain states without induction of apparent tolerance. The results also suggest that gelsemine produces antinociception by activation of spinal ?3 glycine receptors, and support the notion that spinal ?3 glycine receptors are a potential therapeutic target molecule for the management of chronic pain. PMID:23886522

Zhang, Jing-Yang; Gong, Nian; Huang, Jin-Lu; Guo, Ling-Chen; Wang, Yong-Xiang



Changes in Pain Perception in Women During and Following an Exhaustive Incremental Cycling Exercise  

PubMed Central

Exercise has been found to alter pain sensitivity with a hypoalgesic response (i.e., diminished sensitivity to pain) typically reported during and/or following high intensity exercise. Most of this research, however, has involved the testing of men. Thus, the purpose of the following investigation was to examine changes in pain perception in women during and following exercise. Seventeen healthy female subjects (age 20.47±.87; VO2 peak 36.77± 4.95) volunteered to undergo pain assessment prior to, during, and after a graded exhaustive VO2 peak cycling challenge. Heart Rate (HR) and Oxygen Uptake (VO2) were monitored along with electro-diagnostic assessments of Pain Threshold (PT) and Pain Tolerance (PTOL) at: 1) baseline (B), 2) during exercise (i.e., 120 Watts), 3) at exhaustive intensity (VO2 peak), and 4) 10 minutes into recovery (R). Data were analyzed using repeated measures ANOVA to determine differences across trials. Significant differences in PT and PTOL were found across trials (PT, p = 0.0043; PTOL p = 0.0001). Post hoc analyses revealed that PT were significantly elevated at VO2 peak in comparison to B (p = 0.007), 120 Watts (p = 0.0178) and R (p = 0.0072). PTOL were found to be significantly elevated at 120 Watts (p = 0.0247), VO2 peak (p < 0.001), and R (p = 0.0001) in comparison to B. In addition, PTOL were found to be significantly elevated at VO2 peak in comparison to 120 Watts (p = 0.0045). It is concluded that exercise-induced hypoalgesia occurs in women during and following exercise, with the hypoalgesic response being most pronounced following exhaustive exercise. Key Points Exercise-induced hypoalgesia (i.e., elevated PT and PTOL) was found to occur in women during and following exercise, with the hypoalgesic response being most pronounced during exhaustive exercise.

Drury, Daniel G.; Greenwood, Katelyn; Stuempfle, Kristin J.; Koltyn, Kelli F.



The reinfection threshold.  


Thresholds in transmission are responsible for critical changes in infectious disease epidemiology. The epidemic threshold indicates whether infection invades a totally susceptible population. The reinfection threshold indicates whether self-sustained transmission occurs in a population that has developed a degree of partial immunity to the pathogen (by previous infection or vaccination). In models that combine susceptible and partially immune individuals, the reinfection threshold is technically not a bifurcation of equilibria as correctly pointed out by Breban and Blower. However, we show that a branch of equilibria to a reinfection submodel bifurcates from the disease-free equilibrium as transmission crosses this threshold. Consequently, the full model indicates that levels of infection increase by two orders of magnitude and the effect of mass vaccination becomes negligible as transmission increases across the reinfection threshold. PMID:15967188

Gomes, M Gabriela M; White, Lisa J; Medley, Graham F



Shoulder pain.  


Shoulder pain is a frequent complaint encountered in the emergency setting. A brief review of shoulder anatomy and physical examination sets the foundation for evaluation of shoulder pain. Considerations of patient's age are helpful to predict injuries. Fractured clavicles are often seen in traumatic injuries in children and young adults, whereas fractures of the humeral head are more often seen in the elderly from traumatic injuries. Shoulder dislocations are more common in teens to fourth decade. This article reviews specific acute injuries, chronic conditions, and radiologic considerations of patients with shoulder complaints encountered in emergency settings. PMID:21543907

Ramponi, Denise R



Religious Tolerance.  

ERIC Educational Resources Information Center

This theme issue looks at three issues of religious tolerance. The first article examines a case recently decided by the United States Supreme Court on student-led prayers at school events. The second article explores the persecution suffered by members of the Mormon religion during the 19th century. The final article looks at Martin Luther and…

Martz, Carlton



Gluten tolerance; potential challenges in treatment strategies  

PubMed Central

Tolerable gluten thresholds in gluten free products have long been debated together with issues of cross contamination of gluten free cereals during the milling process. It is well established that a totally gluten free diet is virtually impossible owing to the presence of traces of gluten. It is estimated that daily consumption of gluten from contaminated gluten free foods is in the range of 5 to 50 mg. We believe evidence is mounting that it may be possible for some coeliac patients to tolerate gluten above the limits considered permissible at threshold levels. Conversely, it seems there is evidence that some patients might have a much lower threshold for gluten. Whatever would be the individual threshold, GFD may be of benefit to any symptomatic patients even those with milder enteropathy like microscopic enteritis.

Bold, Justine



HRS Threshold Adjustment Test  

NASA Astrophysics Data System (ADS)

This test will determine the optimal, non-standard discriminator thresholds for the few anomalous channels on each HRS detector. A 15 second flat field observation followed by a 210 second dark count is performed at each of 10 discriminator threshold values for each detector. The result of the test will be the optimal threshold values to be entered into the PDB. Edited 4/30/91 to add comments to disable/re-enable cross-talk tables.

Skapik, Joe



Acidic Buffer Induced Muscle Pain Evokes Referred Pain and Mechanical Hyperalgesia in Humans  

PubMed Central

While tissue acidosis causes local deep-tissue pain, its effect on referred pain and mechanical muscle hyperalgesia is unknown. The aim of this study was to investigate a human experimental acidic muscle pain model using a randomized, controlled, single-blinded study design. 72 subjects (36 female) participated in three visits, each involving one 15 min intramuscular infusion into the anterior tibialis muscle: acidic phosphate buffer (5.2 pH) at 40 ml/hr (N=69) or 20 ml/hr (N=54), normal phosphate buffer (7.3 pH) at 40 ml/hr (N=70), or isotonic saline at 40 ml/hr (N=19). Pain ratings and pressure sensitivity of superficial and deep tissues were assessed before, during, and 20 min after infusion. Acidic buffer produced light to moderate, rate-dependent, muscle pain (not sex-dependent) compared to the control infusions, that referred pain to the ankle in 80% of women and 40% of men. Pain did not vary across selfreported menstrual phases. Pressure pain thresholds (PPTs) were reduced over the infused muscle with acidic infusion, defined as primary mechanical hyperalgesia. PPTs decreased at the ankle in those with referred pain in response to acidic buffer, i.e. referred mechanical hyperalgesia, but not at the foot. No pain or changes in PPTs occurred in the contralateral leg. These results demonstrate muscle acidosis can lead to local and referred pain and hyperalgesia, with significant sex differences in development of referred pain.

Laura A, Frey Law; Kathleen A, Sluka; Tara, McMullen; Jennifer, Lee; Lars, Arendt-Nielsen; Thomas, Graven-Nielsen



Pain as a reward: changing the meaning of pain from negative to positive co-activates opioid and cannabinoid systems.  


Pain is a negative emotional experience that is modulated by a variety of psychological factors through different inhibitory systems. For example, endogenous opioids and cannabinoids have been found to be involved in stress and placebo analgesia. Here we show that when the meaning of the pain experience is changed from negative to positive through verbal suggestions, the opioid and cannabinoid systems are co-activated and these, in turn, increase pain tolerance. We induced ischemic arm pain in healthy volunteers, who had to tolerate the pain as long as possible. One group was informed about the aversive nature of the task, as done in any pain study. Conversely, a second group was told that the ischemia would be beneficial to the muscles, thus emphasizing the usefulness of the pain endurance task. We found that in the second group pain tolerance was significantly higher compared to the first one, and that this effect was partially blocked by the opioid antagonist naltrexone alone and by the cannabinoid antagonist rimonabant alone. However, the combined administration of naltrexone and rimonabant antagonized the increased tolerance completely. Our results indicate that a positive approach to pain reduces the global pain experience through the co-activation of the opioid and cannabinoid systems. These findings may have a profound impact on clinical practice. For example, postoperative pain, which means healing, can be perceived as less unpleasant than cancer pain, which means death. Therefore, the behavioral and/or pharmacological manipulation of the meaning of pain can represent an effective approach to pain management. PMID:23265686

Benedetti, Fabrizio; Thoen, Wilma; Blanchard, Catherine; Vighetti, Sergio; Arduino, Claudia



Oral tolerance.  


Multiple mechanisms of tolerance are induced by oral antigen. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral antigen induces T-helper 2 [interleukin (IL)-4/IL-10] and Th3 [transforming growth factor (TGF)-beta] T cells plus CD4+CD25+ regulatory cells and latency-associated peptide+ T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-beta, cholera toxin B subunit, Flt-3 ligand, and anti-CD40 ligand. Oral (and nasal) antigen administration suppresses animal models of autoimmune diseases including experimental autoimmune encephalitis, uveitis, thyroiditis, myasthenia, arthritis, and diabetes in the non-obese diabetic (NOD) mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, graft rejection, allergy, colitis, stroke, and models of Alzheimer's disease. Oral tolerance has been tested in human autoimmune diseases including multiple sclerosis (MS), arthritis, uveitis, and diabetes and in allergy, contact sensitivity to dinitrochlorobenzene (DNCB), and nickel allergy. Although positive results have been observed in phase II trials, no effect was observed in phase III trials of CII in rheumatoid arthritis or oral myelin and glatiramer acetate (GA) in MS. Large placebo effects were observed, and new trials of oral GA are underway. Oral insulin has recently been shown to delay onset of diabetes in at-risk populations, and confirmatory trials of oral insulin are being planned. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time, and antigen-specific mechanisms of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral), formulation, mucosal adjuvants, combination therapy, and early therapy. PMID:16048553

Faria, Ana M C; Weiner, Howard L



Oral Tolerance  

PubMed Central

Summary The gut-associated lymphoid tissue (GALT) is the largest immune organ in the body and is the primary route by which we are exposed to antigens. Tolerance induction is the default immune pathway in the gut, and the type of tolerance induced relates to the dose of antigen fed: anergy/deletion (high dose) or regulatory T-cell (Treg) induction (low dose). Conditioning of gut dendritic cells by gut epithelial cells and the gut flora, which itself has a major influence on gut immunity, induces a CD103+ retinoic acid-dependent dendritic cell that induces Tregs. A number of Tregs are induced at mucosal surfaces. Th3 type Tregs are transforming growth factor-? (TGF-?) dependent and express latency-associated peptide (LAP) on their surface and were discovered in the context of oral tolerance. Tr1 type Tregs (interleukin-10 dependent) are induced by nasal antigen and Foxp3 iTregs are induced by oral antigen and by oral administration of aryl hydrocarbon receptor ligands. Oral or nasal antigen ameliorates autoimmune and inflammatory diseases in animal models by inducing Tregs. Furthermore, anti-CD3 monoclonal antibody is active at mucosal surfaces and oral or nasal anti-CD3 monoclonal antibody induces a LAP+ Tregs that suppresses animal models (experimental autoimmune encephalitis, type 1 and type 2 diabetes, lupus, arthritis, atherosclerosis) and is being tested in humans. Although there is a large literature on treatment of animal models by mucosal tolerance and some positive results in humans, this approach has yet to be translated to the clinic. The successful translation will require defining responsive patient populations, validating biomarkers to measure immunologic effects, and using combination therapy and immune adjuvants to enhance Treg induction. A major avenue being investigated for the treatment of autoimmunity is the induction of Tregs and mucosal tolerance represents a non-toxic, physiologic approach to reach this goal.

Weiner, Howard L.; Cunha, Andre Pires da; Quintana, Francisco; Wu, Henry



Back pain during growth.  


It is wrong to believe that back pain only burdens adults: the yearly incidence during growth ranges from 10-20%, continuously increasing from childhood to adolescence. Rapid growth-related muscular dysbalance and insufficiency, poor physical condition in an increasingly sedentary adolescent community or - vice versa - high level sports activities, account for the most prevalent functional pain syndromes. In contrast to adults the correlation of radiographic findings with pain is high: the younger the patient, the higher the probability to establish a rare morphologic cause such as benign or malignant tumours, congenital malformations and infections. In children younger than 5 years old, the likelihood is more than 50%. The following red flags should lower the threshold for a quick in-depth analysis of the problem: Age of the patient <5 years, acute trauma, functional limitation for daily activities, irradiating pain, loss of weight, duration >4 weeks, history of tumour, exposition to tuberculosis, night pain and fever. High level sport equals a biomechanical field test which reveals the biologic individual response of the growing spine to the sports-related forces. Symptomatic or asymptomatic inhibitory or stimulatory growth disturbances like Scheuermann disease, scoliosis or fatigue fractures represent the most frequent pathomorphologies. They usually occur at the disk-growth plate compound: intraspongious disk herniation, diminuition of anterior growth with vertebral wedging and apophyseal ring fractures often occur when the biomechanical impacts exceed the mechanical resistance of the cartilaginous endplates. Spondylolysis is a benign condition which rarely becomes symptomatic and responds well to conservative measures. Associated slippage of L5 on S1 is frequent but rarely progresses. The pubertal spinal growth spurt is the main risk factor for further slippage, whereas sports activity - even at a high level - is not. Therefore, the athlete should only be precluded from training if pain persists or in case of high grade slips. Perturbance of the sagittal profile with increase of lumbar lordosis, flattening of the thoracic spine and retroflexion of the pelvis with hamstrings contractures are strong signs for a grade IV olisthesis or spondyloptosis with subsequent lumbosacral kyphosis. Idiopathic scoliosis is not related to pain unless it is a marked (thoraco-) lumbar curve or if there is an underlying spinal cord pathology. Chronic back pain is an under recognised entity characterised by its duration (>3 months or recurrence within 3 months) and its social impacts such as isolation and absence from school or work. It represents an independent disease, uncoupled from any initial trigger. Multimodal therapeutic strategies are more successful than isolated, somatising orthopaedic treatment. Primary and secondary preventive active measures for the physically passive adolescents, regular sports medical check-up's for the young high level athletes, the awareness for the rare but potentially disastrous pathologies and the recognition of chronic pain syndromes are the cornerstones for successful treatment of back pain during growth. PMID:23299906

Hasler, Carol C



The effects of mindful attention on cold pressor pain in children  

PubMed Central

BACKGROUND: Typical interventions for acute pain in children attempt to reduce pain by directing attention away from pain. Conversely, mindfulness involves devoting attention to one’s experience in an accepting and nonjudgmental way. However, the effect that instructing children to mindfully devote attention to acute pain has on pain outcomes is unknown. OBJECTIVES: To examine whether mindful attention can help children attend to pain without increasing pain intensity or decreasing pain tolerance; to compare the effects of mindful attention with a well-established intervention designed to take attention away from pain (guided imagery); and to test whether baseline coping style or trait mindfulness alter the effects of these interventions. METHODS: A total of 82 children (10 to 14 years of age) completed measures of coping style and trait mindfulness. Participants then received either mindful attention or guided imagery instructions designed to direct attention toward or away from pain, respectively, before participating in a cold pressor task. RESULTS: The mindful attention group reported more awareness of the physical sensations of pain and thoughts about those sensations. Overall, there were no between-group differences in measures of pain intensity or pain tolerance during the cold pressor task, and no evidence of an interaction between baseline characteristics of the child and experimental condition. CONCLUSIONS: Mindful attention was successful in helping children focus attention on experimental pain without increasing pain intensity or decreasing tolerance compared with a well-established intervention for acute pain reduction.

Petter, Mark; Chambers, Christine T; Chorney, Jill MacLaren



Achilles Pain.  

ERIC Educational Resources Information Center

Five ailments which can cause pain in the achilles tendon area are: (1) muscular strain, involving the stretching or tearing of muscle or tendon fibers; (2) a contusion, inflammation or infection called tenosynovitis; (3) tendonitis, the inflammation of the tendon; (4) calcaneal bursitis, the inflammation of the bursa between the achilles tendon…

Connors, G. Patrick


Managing Pain  


... itching to the hospice nurse. Often such side effects can be treated and may stop after taking the medication for a few days. • Other things that might make the pain better are: - Relaxing activities - Distracting activities such as watching TV, listening to music or playing a game - Heat (such as a ...


[Social pain].  


This chapter focuses on what social pain is and how it should be managed. In order to understand social pain in a cancer patient, it is necessary to recognize the change in the patient's daily life after the diagnosis of cancer. Because the degree of suffering and the relationships with family members and the people he or she worked with differ from patient to patient, it is important to note that the context of social pain is different in each patient. Five points shown below are essential in managing social pain. 1. Economical suffering may be alleviated by utilization of the social security system while taking into account each patient's standard of living. 2. Burdens on family members should be lessened, such as by not having them stay at the patient's bedside every day and letting them go home occasionally. 3. The normal patterns of communication, support, and conflict in the family should be identified, and the extent to which they have been disrupted by the illness should be assessed. 4. It is important to understand the ethnic, cultural, and religious background of the patient and the potential impact of their influence on the individual and the illness. 5. Practical or emotional unfinished business that the patient has needs to be identified, and efforts should be made to support fulfillment. PMID:21950034

Shimoyama, Naohito; Shimoyama, Megumi



Tolerance to the mydriatic effect of buprenorphine, butorphanol, nalbuphine, and cyclorphan, and cross-tolerance to morphine in mice.  


An increase in the use of opioid derivatives in the treatment of pain syndrome in clinical practice, and especially in the treatment of cancer, has added impetus to the search for an agent which does not induce tolerance and cross-tolerance to other opiodis. The mydriatic effect of opioids in mice, the correlation between analgesia and mydriasis, and tolerance to the analgesic effect of morphine in mice were evaluated previously. In the present work, tolerance to the mydriatic effect of four agonist-antagonists and cross-tolerance to morphine were examined. Measurement of the pupillary diameter was performed using a binocular operating microscope. Tolerance and cross-tolerance to morphine were developed following a chronic use of buprenorphine, nalbuphine, and cyclorphan. After chronic injection of butorphanol, no tolerance or cross-tolerance to morphine was observed. PMID:23568116

Kaadan, M; Stav, A; Rabinowitz, R; Shavit, S; Korczyn, A D



Central pain: clinical and physiological characteristics.  

PubMed Central

OBJECTIVES--To study the clinical and pathophysiological features of central pain due to damage to the CNS. METHODS--156 patients (mostly with ischaemic strokes, some with infarct after subarachnoid haemorrhage and other cerebral conditions; one with bulbar and others with spinal pathology) with central pain have been investigated clinically and varying numbers instrumentally with respect to quantitative somatosensory perception thresholds and autonomic function. RESULTS--Pain onset was immediate in a minority; and from a week or two up to six years in > 60%. For those with supraspinal ischaemic lesions, the median age of onset was 59; dominant and non-dominant sides were equally affected. Two thirds of the patients had allodynia, including a previously undescribed movement allodynia apparently triggered from group I afferents. Most patients exhibited autonomic instability in that their pain was increased by physical and emotional stress and alleviated by relaxation; cutaneous blood flow and sweating may also be affected. Pain occurred within a larger area of differential sensory deficit. The critical deficit seems to be for thermal and pinprick sensations, which were more pronounced in areas of greatest than in areas of least pain; whereas low threshold mechanoceptive functions, if affected, did not vary between areas of greatest and least pain. Skinfold pinch (tissue damage) pain thresholds were only slightly affected in supraspinal cases, but greatly increased in patients with spinal lesions; thermal (heat) pain did not show this dissociation. CONCLUSION--The pathogenetic hypothesis which seems best to fit the findings is that there is up regulation or down regulation of receptors for transmitters, possibly mainly noradrenergic, over time.

Bowsher, D



Patient's comfort with and tolerability of thyroid core needle biopsy.  


Recently, the core needle biopsy (CNB) has been proposed as a complementary test for thyroid nodules with inconclusive cytology by fine-needle aspiration (FNA). However, there have been no reports regarding patient comfort during and after CNB or tolerability of this procedure. Here we aimed to investigate and compare comfort with and tolerability of the CNB and FNA procedures. A 21 gauge needle was used for collection in CNB procedures, and a 23 gauge needle was used for collection in FNA procedures. Sixty-one consecutive patients underwent both biopsies and were asked to evaluate their comfort during and after these procedures by a structured questionnaire. A total of 58 (95 %) patients reported local pain during both biopsies. Two patients reported pain only during CNB, and one reported no pain. Mild pain was reported in 87 % of CNB cases. Local pain after biopsy was reported in 29 % of FNA and 45 % of CNB. The occurrence of pain in the first minutes following CNB was significantly higher than FNA (p = 0.008), while there was not a significant difference in pain at later time points after the procedures. Finally, patients were asked to evaluate the degree of tolerability of the two sampling techniques, and FNA and CNB were reported as tolerable in 82 and 83 %, respectively. The results from a questionnaire evaluating patients' comfort level showed no significant difference between the tolerability of CNB and FNA. This finding suggests that CNB may be performed with a reasonable level of patient comfort. PMID:23673868

Nasrollah, Naim; Trimboli, Pierpaolo; Rossi, Fabio; Amendola, Stefano; Guidobaldi, Leo; Ventura, Claudio; Maglio, Riccardo; Nigri, Giuseppe; Romanelli, Francesco; Valabrega, Stefano; Crescenzi, Anna



Threshold Selection, 4.  

National Technical Information Service (NTIS)

If a picture contains dark objects on a light background, or vice versa, the objects can be separated from the background by thresholding the picture. A good place to choose the threshold is at the average gray level of those picture points where the valu...

J. S. Weszka A. Rosenfeld



Bayesian Threshold Estimation  

ERIC Educational Resources Information Center

Bayesian estimation of a threshold time (hereafter simply threshold) for the receipt of impulse signals is accomplished given the following: 1) data, consisting of the number of impulses received in a time interval from zero to one and the time of the largest time impulse; 2) a model, consisting of a uniform probability density of impulse time…

Gustafson, S. C.; Costello, C. S.; Like, E. C.; Pierce, S. J.; Shenoy, K. N.



Evaluation of mechanical and thermal nociception as objective tools to measure painful and nonpainful lameness phases in multiparous sows.  


The objective of this study was to quantify pain sensitivity differences using mechanical nociception threshold (MNT) and thermal nociception threshold (TNT) tests when sows were in painful and nonpainful transient lameness phases. A total of 24 mixed parity crossbred sows (220.15 ± 21.23 kg) were utilized for the MNT test, and a total of 12 sows (211.41 ± 20.21 kg) were utilized for the TNT test. On induction day (D0), all sows were anesthetized and injected with Amphotericin B (10mg/mL) in the distal interphalangeal joint space in both claws of one randomly selected hind limb to induce transient lameness. Three days were compared: (1) D-1 (sound phase, defined as 1 d before induction), (2) D+1 (most lame phase, defined as 1 d after induction), and (3) D+6 (resolution phase, defined as 6 d after induction). After completion of the first round, sows were given a 7-d rest period and then the procedures were repeated with lameness induced in the contralateral hind limb. During the MNT test, pressure was applied perpendicularly to 3 landmarks in a randomized sequence for each sow: 1) middle of cannon on the hind limb (cannon), 2) 1 cm above the coronary band on the medial hind claw (medial claw), and 3) 1 cm above the coronary band on the lateral hind claw (lateral claw). During the TNT test, a radiant heat stimulus was directed 1 cm above the coronary band. The data were analyzed using the MIXED procedure in SAS with sow as the experimental unit. Differences were analyzed between sound and lame limbs on each day. For the MNT test, pressure tolerated by the lame limb decreased for every landmark (P < 0.05) when comparing D-1 and D+1. The sound limb tolerated more pressure on D+1 and D+6 than on baseline D-1 (P < 0.05). Thermal stimulation tolerated by the sound limb did not change over the 3 d (P > 0.05). However, the sows tolerated less heat stimulation on their lame limb on D+1 compared to D-1 levels (P < 0.05). Both MNT and TNT tests indicated greater pain sensitivity thresholds when sows were acutely lame. PMID:24778335

Mohling, C M; Johnson, A K; Coetzee, J F; Karriker, L A; Stalder, K J; Abell, C E; Tyler, H D; Millman, S T



Experimental Pain and Opioid Analgesia in Volunteers at High Risk for Obstructive Sleep Apnea  

PubMed Central

Background Obstructive sleep apnea (OSA) is characterized by recurrent nocturnal hypoxia and sleep disruption. Sleep fragmentation caused hyperalgesia in volunteers, while nocturnal hypoxemia enhanced morphine analgesic potency in children with OSA. This evidence directly relates to surgical OSA patients who are at risk for airway compromise due to postoperative use of opioids. Using accepted experimental pain models, we characterized pain processing and opioid analgesia in male volunteers recruited based on their risk for OSA. Methods After approval from the Intitutional Review Board and informed consent, we assessed heat and cold pain thresholds and tolerances in volunteers after overnight polysomnography (PSG). Three pro-inflammatory and 3 hypoxia markers were determined in the serum. Pain tests were performed at baseline, placebo, and two effect site concentrations of remifentanil (1 and 2 µg/ml), an ?-opioid agonist. Linear mixed effects regression models were employed to evaluate the association of 3 PSG descriptors [wake after sleep onset, number of sleep stage shifts, and lowest oxyhemoglobin saturation (SaO2) during sleep] and all serum markers with pain thresholds and tolerances at baseline, as well as their changes under remifentanil. Results Forty-three volunteers (12 normal and 31 with a PSG-based diagnosis of OSA) were included in the analysis. The lower nadir SaO2 and higher insulin growth factor binding protein-1 (IGFBP-1) were associated with higher analgesic sensitivity to remifentanil (SaO2, P?=?0.0440; IGFBP-1, P?=?0.0013). Other pro-inflammatory mediators like interleukin-1? and tumor necrosis factor-? (TNF-?) were associated with an enhanced sensitivity to the opioid analgesic effect (IL-1?, P?=?0.0218; TNF-?, P?=?0.0276). Conclusions Nocturnal hypoxemia in subjects at high risk for OSA was associated with an increased potency of opioid analgesia. A serum hypoxia marker (IGFBP-1) was associated with hypoalgesia and increased potency to opioid analgesia; other pro-inflammatory mediators also predicted an enhanced opioid potency. Trial Registration: NCT00672737.

Doufas, Anthony G.; Tian, Lu; Padrez, Kevin A.; Suwanprathes, Puntarica; Cardell, James A.; Maecker, Holden T.; Panousis, Periklis



A 2Week, multicenter, randomized, double-blind, double-dummy, add-on study of the effects of titration on tolerability of tramadol\\/acetaminophen combination tablet in Korean adults with knee osteoarthritis pain  

Microsoft Academic Search

Background: Combined tramadol\\/acetaminophen is used to treat pain related to osteoarthritis. However, adverse events (AEs) leading to discontinuation can occur. Dose titration may decrease the risk for AEs.Objective: The aim of this study was to assess the effect of tramadol\\/acetaminophen titration on the development of AEs leading to treatment discontinuation in patients with knee osteoarthritis.Methods: This 2-week, multicenter, randomized, double-blind,

Chan-Bum Choi; Jung Soo Song; Young Mo Kang; Chang Hee Suh; Jisoo Lee; Jung-Yoon Choe; Choong Ki Lee; Seung Cheol Shim; Won Tae Chung; Gwan Gyu Song; Hyun Ah Kim; Jong Dae Ji; Eon Jeong Nam; Sung-Hoon Park; Young Hoon Hong; Dong Hyuk Sheen; Mi Kyoung Lim; Young II Seo; Yoon-Kyoung Sung; Tae-Hwan Kim; Jong-Tae Lee; Sang-Cheol Bae



Factor analysis of responses to thermal, electrical, and mechanical painful stimuli supports the importance of multi-modal pain assessment.  


During the last decade, a multi-modal approach has been established in human experimental pain research for assessing pain thresholds and responses to various experimental pain modalities. Studies have concluded that differences in responses to pain stimuli are mainly related to variation between individuals rather than variation in response to different stimulus modalities. In a factor analysis of 272 consecutive volunteers (137 men and 135 women) who underwent tests with different experimental pain modalities, it was determined whether responses to different pain modalities represent distinct individual uncorrelated dimensions of pain perception. Volunteers underwent single painful electrical stimulation, repeated painful electrical stimulation (temporal summation), test for reflex receptive field, pressure pain stimulation, heat pain stimulation, cold pain stimulation, and a cold pressor test (ice water test). Five distinct factors were found representing responses to 5 distinct experimental pain modalities: pressure, heat, cold, electrical stimulation, and reflex-receptive fields. Each of the factors explained approximately 8% to 35% of the observed variance, and the 5 factors cumulatively explained 94% of the variance. The correlation between the 5 factors was near null (median ?=0.00, range -0.03 to 0.05), with 95% confidence intervals for pairwise correlations between 2 factors excluding any relevant correlation. Results were almost similar for analyses stratified according to gender and age. Responses to different experimental pain modalities represent different specific dimensions and should be assessed in combination in future pharmacological and clinical studies to represent the complexity of nociception and pain experience. PMID:21396782

Neziri, Alban Y; Curatolo, Michele; Nüesch, Eveline; Scaramozzino, Pasquale; Andersen, Ole K; Arendt-Nielsen, Lars; Jüni, Peter



Pain Sensitivity and Observer Perception of Pain in Individuals with Autistic Spectrum Disorder  

PubMed Central

The peer-reviewed literature investigating the relationship between pain expression and perception of pain in individuals with ASD is sparse. The aim of the present systematic PRIMSA review was twofold: first, to see what evidence there is for the widely held belief that individuals with ASD are insensitive to pain or have a high pain threshold in the peer-reviewed literature and, second, to examine whether individuals with ASD react or express pain differently. Fifteen studies investigating pain in individuals with ASD were identified. The case studies all reported pain insensitivity in individuals with ASD. However, the majority of the ten experimental studies reviewed indicate that the idea that individuals with ASD are pain insensitive needs to be challenged. The findings also highlight the strong possibility that not all children with ASD express their physical discomfort in the same way as a neurotypical child would (i.e., cry, moan, seek comfort, etc.) which may lead caregivers and the medical profession to interpret this as pain insensitivity or incorrectly lead them to believe that the child is in no pain. These results have important implications for the assessment and management of pain in children with ASD.

Allely, C. S.



Capsaicin-based therapies for pain control.  


The TRPV1 receptor is known to play a role in nociceptive transmission in multiple organ systems, usually in response to the pain of inflammation. TRPV1 antagonism has so far shown limited benefit in antinociception. Capsaicin, a TRPV1 agonist, has been shown to induce a refractory period in the nerve terminal expressing TRPV1 and even, in sufficient dosing, to create long-term nerve terminal defunctionalization. This has led to research into topical capsaicin as a treatment for multiple painful conditions. The majority of work has focused on musculoskeletal pain and neuropathic pain and has revealed that although low-dose topical capsaicin has limited effectiveness as an analgesic, high-dose capsaicin, when tolerated, has the potential for long-term analgesia in certain types of neuropathic pain. PMID:24941667

Smith, Howard; Brooks, John R



Fault-tolerant almost exact state transmission  

PubMed Central

We show that a category of one-dimensional XY-type models may enable high-fidelity quantum state transmissions, regardless of details of coupling configurations. This observation leads to a fault-tolerant design of a state transmission setup. The setup is fault-tolerant, with specified thresholds, against engineering failures of coupling configurations, fabrication imperfections or defects, and even time-dependent noises. We propose an experimental implementation of the fault-tolerant scheme using hard-core bosons in one-dimensional optical lattices.

Wang, Zhao-Ming; Wu, Lian-Ao; Modugno, Michele; Yao, Wang; Shao, Bin



Perception of pain after resistance exercise  

PubMed Central

OBJECTIVES: The main objective was to assess the influence of resistance exercise on pain threshold and pain ratings. Secondary objectives included measuring state anxiety, body awareness, systolic blood pressure, diastolic blood pressure, and heart rate responses. METHODS: Pressure (3 kg force) was applied to the middle digit of the left hand for two minutes using a Forgione-Barber pain stimulator before and after (five minute and 15 minutes) resistance exercise and quiet rest. Resistance exercise consisted of 45 minutes of lifting three sets of 10 repetitions at 75% of an individual's one repetition maximum. Quiet rest consisted of sitting quietly in a room free from distractions. RESULTS: Data were analysed by repeated measures analysis of variance for multifactor experiments. Pain threshold was significantly higher (p<0.05) and pain ratings were significantly lower (p<0.05) five minutes after resistance exercise. Changes in pain perception were accompanied by changes in heart rate, systolic blood pressure, and body awareness after exercise. CONCLUSION: A single bout of resistance exercise is capable of modifying the sensation of experimentally induced pain. ?????

Koltyn, K. F.; Arbogast, R. W.



An increased response to experimental muscle pain is related to psychological status in women with chronic non-traumatic neck-shoulder pain  

PubMed Central

Background Neck-shoulder pain conditions, e.g., chronic trapezius myalgia, have been associated with sensory disturbances such as increased sensitivity to experimentally induced pain. This study investigated pain sensitivity in terms of bilateral pressure pain thresholds over the trapezius and tibialis anterior muscles and pain responses after a unilateral hypertonic saline infusion into the right legs tibialis anterior muscle and related those parameters to intensity and area size of the clinical pain and to psychological factors (sleeping problems, depression, anxiety, catastrophizing and fear-avoidance). Methods Nineteen women with chronic non-traumatic neck-shoulder pain but without simultaneous anatomically widespread clinical pain (NSP) and 30 age-matched pain-free female control subjects (CON) participated in the study. Results NSP had lower pressure pain thresholds over the trapezius and over the tibialis anterior muscles and experienced hypertonic saline-evoked pain in the tibialis anterior muscle to be significantly more intense and locally more widespread than CON. More intense symptoms of anxiety and depression together with a higher disability level were associated with increased pain responses to experimental pain induction and a larger area size of the clinical neck-shoulder pain at its worst. Conclusion These results indicate that central mechanisms e.g., central sensitization and altered descending control, are involved in chronic neck-shoulder pain since sensory hypersensitivity was found in areas distant to the site of clinical pain. Psychological status was found to interact with the perception, intensity, duration and distribution of induced pain (hypertonic saline) together with the spreading of clinical pain. The duration and intensity of pain correlated negatively with pressure pain thresholds.



Pregabalin in post traumatic neuropathic pain: Case studies  

PubMed Central

Pregabalin is effective in the treatment of peripheral and central neuropathic pain. This study evaluated the effectiveness of pregablin in management of post traumatic peripheral nerve injury facial pain not responding to other medication like analgesics. Pregabalin was well tolerated. The most common adverse effects were dizziness and tiredness.

Singh, Rakesh Kumar; Sinha, Vijay Prakash; Pal, U. S.; Yadav, Sharad C.; Singh, Maneesh K.



Prolonged Treatment with Transdermal Fentanyl in Neuropathic Pain  

Microsoft Academic Search

Forty-eight patients with noncancer neuropathic pain who had participated in a randomized controlled trial with intravenous fentanyl (FENiv) infusions received prolonged transdermal fentanyl (FENtd) in an open prospective study. Pain relief, side effects, tolerance, psychological dependence, mood changes, and quality of life were evaluated. The value of clinical baseline characteristics and the response to FENiv also was evaluated in terms

Paul L. I. Dellemijn; Hans van Duijn; Jan A. L. Vanneste



Chronic Pain Following Treatment for Cancer: The Role of Opioids  

Microsoft Academic Search

Opioids are the most effective analgesics for severe pain and the mainstay of acute and terminal cancer pain treatments. In those settings, opioids are used over a lim- ited time period so that opioid tolerance, if it develops, is relatively easy to overcome, and other problems of opioid use, including substance abuse, are unlikely to be prob- lematic. As cancer



Skeletal muscle contractility, self-reported pain and tissue sensitivity in females with neck/shoulder pain and upper Trapezius myofascial trigger points- a randomized intervention study  

PubMed Central

Background In relation to Myofascial Triggerpoints (MFTrPs) of the upper Trapezius, this study explored muscle contractility characteristics, the occurrence of post-intervention muscle soreness and the effect of dry needling on muscle contractile characteristics and clinical outcomes. Methods Seventy-seven female office workers (25-46yrs) with and without neck/shoulder pain were observed with respect to self-reported pain (NRS-101), pressure-pain threshold (PPT), maximum voluntary contraction (Fmax) and rate of force development (RFD) at baseline (pre-intervention), immediately post-intervention and 48 hours post-intervention. Symptomatic and asymptomatic participant groups were each randomized into two treatment sub-groups (superficial (SDN) and deep dry needling (DDN)) after baseline testing. At 48 hours post-intervention participants were asked whether delayed onset muscle soreness (DOMS) and/or post-needling soreness had developed. Results Muscle contractile characteristics did not differ between groups at baseline. Forty-six individuals developed muscle soreness (39 from mechanical testing and seven from needling). No inter-group differences were observed post-intervention for Fmax or RFD for the four sub-groups. Over the observation period, symptomatic participants reported less pain from both SDN (p= 0.003) and DDN (p=0.011). However, PPT levels were reduced for all participants (p=0.029). Those reporting DOMS experienced significant decreases in PPT, irrespective of symptom state or intervention (p=0.001). Conclusions In selected female neck/shoulder pain sufferers, maximum voluntary contraction and rapid force generation of the upper Trapezius was not influenced by clinically relevant self-reported pain or the presence of diagnostically relevant MFTrPs. Dry needling, deep or superficial, did not affect measured functional outcomes over the 48-hour observation period. DOMS affected participants uniformly irrespective of pain, MFTrP status or intervention type and therefore is like to act as a modifier. Trial registration Clinical NCT01710735 Significance and Innovations The present investigation is one of the first to examine the hypothesis of gross muscle contractile inhibition due to the presence of diagnostically relevant MFTrPs. Individuals suffering from clinically relevant levels of self-reported pain are able to tolerate maximum voluntary contraction testing, but delayed onset muscle soreness (DOMS) is a likely side-effect irrespective of symptom status. As a consequence, its confounding effect during subsequent testing must be taken into account.



Estradiol benzoate potentiates neuroactive steroids' effects on pain sensitivity  

Microsoft Academic Search

Progesterone (P), its metabolites, and other neuroactive steroids alter pain thresholds consistent with their efficacies at modulating ?-aminobutyric acid (GABAA) receptor complexes. We investigated whether estradiol benzoate (EB) potentiates low dosages of neuroactive steroids' effects on pain. Subcutaneous EB (10 ?g) or sesame oil vehicle was administered to ovariectomized Long-Evans rats (n = 40) 48 h before intracerebroventricular (ICV) infusion

Cheryl A. Frye; Jennifer E. Duncan



75 FR 60321 - Spinosad; Pesticide Tolerances  

Federal Register 2010, 2011, 2012, 2013 for infants and children in the case of for infants and children. This additional of infants and children would be adequately protected...immunotoxicity. In the chronic study with dogs, areteritis...Beagle dogs (``Beagle Pain Syndrome''),...



Neurobiology of Pain in Children: An Overview  

PubMed Central

The evaluation of pain in the newborn and the infant is difficult because pain is mainly a subjective phenomenon. Until a few years ago, several myths persisted. First, the myth that children, especially infants, do not feel pain the way adults do, therefore there is no untoward consequences for them. Second, lack of assessment and reassessment for the presence of pain. Third, misunderstanding of how to conceptualise and quantify a subjective experience. Fourth, lack of knowledge of pain treatment. Fifth, the notion that addressing pain in children takes too much time and effort, in ultimate analysis resulting in wasting time. Sixth, fears of hidden -and not easy to diagnose or prevent- adverse effects of analgesic medications, including respiratory depression and addiction. Finally, from a conceptual point of view, high thresholds of pain in neonates and infants were considered to be present by natural character, and useful in protecting infant from pain during birth and transit through the narrow vaginal channel. The present review is focused on the description of different theories on the pain pathogenesis in children.

Loizzo, Alberto; Loizzo, Stefano; Capasso, Anna



Fentanyl nasal spray (Lazanda) for pain.  


The FDA has approved a nasal spray formulation of fentanyl (Lazanda-Archimedes) for management of breakthrough pain in adult cancer patients who are already receiving and are tolerant to opioid therapy. Fentanyl is already available in the US for intravenous, intrathecal, epidural, transdermal and oral transmucosal use. PMID:22173454



Interaction of Tonic and Phasic Pain in Rabbit Ontogenesis  

Microsoft Academic Search

In the experiments on the 20–25-day-old and adult rabbits, effects of tonic pain focus (a subcutaneous injection of formalin into leg dorsal surface) on behavioral and electrophysiological characteristics of acute pain were studied. The effect of the 40–60-min-long tonic pain was seen as a decrease of defensive reaction threshold and an increase of inhibitory effect of brain “rewarding zones” on

I. P. Butkevich; V. A. Mikhailenko



Tinnitus, Diminished Sound-Level Tolerance, and Elevated Auditory Activity in Humans With Clinically Normal Hearing Sensitivity  

PubMed Central

Phantom sensations and sensory hypersensitivity are disordered perceptions that characterize a variety of intractable conditions involving the somatosensory, visual, and auditory modalities. We report physiological correlates of two perceptual abnormalities in the auditory domain: tinnitus, the phantom perception of sound, and hyperacusis, a decreased tolerance of sound based on loudness. Here, subjects with and without tinnitus, all with clinically normal hearing thresholds, underwent 1) behavioral testing to assess sound-level tolerance and 2) functional MRI to measure sound-evoked activation of central auditory centers. Despite receiving identical sound stimulation levels, subjects with diminished sound-level tolerance (i.e., hyperacusis) showed elevated activation in the auditory midbrain, thalamus, and primary auditory cortex compared with subjects with normal tolerance. Primary auditory cortex, but not subcortical centers, showed elevated activation specifically related to tinnitus. The results directly link hyperacusis and tinnitus to hyperactivity within the central auditory system. We hypothesize that the tinnitus-related elevations in cortical activation may reflect undue attention drawn to the auditory domain, an interpretation consistent with the lack of tinnitus-related effects subcortically where activation is less potently modulated by attentional state. The data strengthen, at a mechanistic level, analogies drawn previously between tinnitus/hyperacusis and other, nonauditory disordered perceptions thought to arise from neural hyperactivity such as chronic neuropathic pain and photophobia.

Halpin, Christopher F.; Nam, Eui-Cheol; Levine, Robert A.; Melcher, Jennifer R.



Spinal cord stimulation normalizes abnormal cortical pain processing in patients with cardiac syndrome X.  


Cardiac syndrome X (CSX) is characterized by effort angina, ST-segment depression during stress tests and normal coronary arteries. Abnormal nociception was suggested in these patients by studies showing a reduced cardiac pain threshold; furthermore, we recently found a lack of habituation to pain stimuli using recording of laser evoked potentials (LEPs). In CSX patients with severe angina, spinal cord stimulation (SCS) was shown to improve symptoms. In this study we investigated whether, in these patients, SCS has any effects on the excitability of the nociceptive system, assessed by LEPs recording. We studied 16 CSX patients (61.6+/-7 years; 4 men) who underwent SCS for refractory angina. Cortical LEPs were recorded during stimulation of the chest and right-hand during active SCS (SCS-ON) and in the absence of SCS (SCS-OFF), using a randomized cross-over design. Three sequences of painful stimuli were applied at each site during each test. During the first sequence of chest stimuli, the N2/P2 LEP amplitude was higher during the SCS-ON, compared to the SCS-OFF phase (18.2+/-7.8 vs. 11.5+/-4.4 microV, P=0.006). The N2/P2 amplitude did not change significantly across the three stimulation sequences during the SCS-OFF phase (P=0.22), whereas it decreased progressively during the second and third sequence (to 87.1+/-29.5% and 76.4+/-24.1%, respectively) compared with the first sequence, during the SCS-ON phase (P=0.014). Similar results were observed during right-hand stimulation. Our study shows that in CSX patients SCS is able to restore habituation to peripheral pain stimuli. This effect might contribute to restore the ability of CSX patients to better tolerate cardiac pain. PMID:18440702

Sestito, Alfonso; Lanza, Gaetano Antonio; Le Pera, Domenica; De Armas, Liala; Sgueglia, Gregory Angelo; Infusino, Fabio; Miliucci, Roberto; Tonali, Pietro Attilio; Crea, Filippo; Valeriani, Massimiliano



Tolerance to the mydriatic effect of buprenorphine, butorphanol, nalbuphine, and cyclorphan, and cross-tolerance to morphine in mice  

Microsoft Academic Search

An increase in the use of opioid derivatives in the treatment of pain syndrome in clinical practice, and especially in the\\u000a treatment of cancer, has added impetus to the search for an agent which does not induce tolerance and cross-tolerance to other\\u000a opiodis. The mydriatic effect of opioids in mice, the correlation between analgesia and mydriasis, and tolerance to the

Mohammed Kaadan; Anatoli Stav; Ruth Rabinowitz; Sara Shavit; Amos D. Korczyn



Detection Threshold Modelling Explained.  

National Technical Information Service (NTIS)

This document presents expressions for modeling the detection threshold for narrowband and broadband passive sonars using either power or amplitude detection, cross correlation sonars, CW and FM active sonars with or without replica correlation, as well a...

R. L. Dawe



Paining Out: An Integrative Pain Therapy Model  

Microsoft Academic Search

This article describes and evaluates an integrative pain therapy model as a beneficial form of pain-management for chronic\\u000a pain. The author based his model on cognitive-behavioral modalities, progressive relaxation combined with art therapy, sensory\\u000a awareness combined with indirect clinical hypnosis, formal clinical hypnosis and self-hypnosis. Those techniques were applied\\u000a in small group settings to systematically alter pain perception, pain interpretations

Mirko Pavlek



Urologic myofascial pain syndromes  

Microsoft Academic Search

Treatment of pain of urogenital origin, chronic pelvic pain syndrome, can be frustrating for patients and physicians. The\\u000a usual approaches do not always produce the desired results. Visceral pain from pelvic organs and myofascial pain from muscle\\u000a trigger points share common characteristics. Referred pain from myofascial trigger points can mimic visceral pain syndromes\\u000a and visceral pain syndromes can induce trigger

Ragi Doggweiler-Wiygul



Painful hypoadrenalism  

PubMed Central

A 61-year-old man presented with diffuse myalgia and arthralgia. The physical examination showed diffuse musculoskeletal tenderness and joint stiffness without the presence of synovitis or arthritis. Nerve conduction study showed combined mild axonal degenerative and demyelinating change. Muscle biopsy analysis showed unspecific mild muscle atrophy with myopathic changes found on electromyography. A diagnosis of isolated adrenocorticotropic hormone deficiency was made on the basis of endocrinological evaluation. The widespread musculoskeletal pain resolved as a result of administration of physiological dose of hydrocortisone replacement. In a patient with unexplained rheumatic symptoms, adrenocortical insufficiency should be considered in the possible aetiology.

Hoshino, Chisho; Satoh, Noriyuki; Narita, Masashi; Kikuchi, Akio; Inoue, Minoru



Acceptance- versus Change-Based Pain Management: The Role of Psychological Acceptance  

ERIC Educational Resources Information Center

This study compared two theoretically opposed strategies for acute pain management: an acceptance-based and a change-based approach. These two strategies were compared in a within-subjects design using the cold pressor test as an acute pain induction method. Participants completed a baseline pain tolerance assessment followed by one of the two…

Blacker, Kara J.; Herbert, James D.; Forman, Evan M.; Kounios, John



Risk Factor Assessment for Problematic Use of Opioids for Chronic Pain  

Microsoft Academic Search

Opioid analgesics provide effective treatment for noncancer pain, but many health providers have concerns about cognitive effects, tolerance, dependence, and addiction. Misuse of opioids is prominent in patients with chronic pain and early recognition of misuse risk could help providers offer adequate patient care while implementing appropriate levels of monitoring to reduce aberrant drug-related behaviors. Many persons with chronic pain

Robert N. Jamison; Robert R. Edwards



Pain in People with Learning Disabilities in Residential Settings--The Need for Change  

ERIC Educational Resources Information Center

This audit investigated residential staff beliefs around pain thresholds and strategies they adopt to recognise and manage pain in people with learning disabilities across Surrey. A structured interview was constructed to elicit information. Results demonstrated that pain is not being effectively recognised or managed by residential staff in…

Beacroft, Monica; Dodd, Karen



Barriers to pain management : focus on opioid therapy.  


Despite the availability of effective pain treatments, there are numerous barriers to effective management resulting in a large proportion of patients not achieving optimal pain control. Chronic pain is inadequately treated because of a combination of cultural, societal, educational, political and religious constraints. The consequences of inadequately treated pain are physiological and psychological effects on the patient, as well as socioeconomic implications. Unreasonable failure to treat pain is viewed as unethical and an infringement of basic human rights. The numerous barriers to the clinical management of pain vary depending on whether they are viewed from the standpoint of the patient, the physician, or the institution. Identification and acknowledgement of the barriers involved are the first steps to overcoming them. Successful initiatives to overcome patient, physician and institutional barriers need to be multifaceted in their approach. Multidisciplinary initiatives to improve pain management include dissemination of community-based information, education and awareness programmes to attempt to change attitudes towards pain treatment. A better awareness and insight into the problems caused by unrelieved pain and greater knowledge about the efficacy and tolerability of available pain management options should enable physicians to seek out and adhere to treatment guidelines, and participate in interventional and educational programmes designed to improve pain management, and for institutions to implement the initiatives required. Although much work is underway to identify and resolve the issues in pain management, many patients still receive inadequate treatment. Continued effort is required to overcome the known barriers to effective pain management. PMID:23389872

Zuccaro, Stefano Maria; Vellucci, Renato; Sarzi-Puttini, Piercarlo; Cherubino, Paolo; Labianca, Roberto; Fornasari, Diego



Gabapentin in Pain Management  

Microsoft Academic Search

role of gabapentin in pain treatment will be discussed with an attempt to identify pain symptoms that are likely to be responsive to gabapentin; 2) animal stud- ies of gabapentin on neuropathic pain and other pain behaviors will be evaluated; and 3) possible mecha- nisms of gabapentin actions will be considered in re- lation to mechanisms of neuropathic pain in

Jianren Mao; Lucy L. Chen



Medications for back pain  


... help with your back pain. Over-the-counter pain relievers Over-the-counter pain relievers can help with your back pain. Over-the- ... your health care provider. If you are taking pain relievers for more than a week, tell your doctor. ...


When Sex Is Painful  


How common is painful sex? Pain during intercourse is very common—nearly 3 out of 4 women have pain during intercourse at some time during ... a long-term problem. What causes pain during sex? Pain during sex may be a sign of ...


Neuropathic cranial pain  

Microsoft Academic Search

Neuropathic cranial pain, i.e. pain due to central or peripheral nervous system damage localized in cranial area, is a clinical challenge for the neurologist. Despite major advances in knowledge of physiology and biochemistry of pain, relief for many patients suffering from neuropathic pain remains incomplete. Adjuvant analgesics play a key role in the management of neuropathic pain. The introduction in

B. Colombo; P. O. L. Annovazzi; G. Comi



Dry needling for management of pain in the upper quarter and craniofacial region.  


Dry needling is a therapeutic intervention that has been growing in popularity. It is primarily used with patients that have pain of myofascial origin. This review provides background about dry needling, myofascial pain, and craniofacial pain. We summarize the evidence regarding the effectiveness of dry needling. For patients with upper quarter myofascial pain, a 2013 systematic review and meta-analysis of 12 randomized controlled studies reported that dry needling is effective in reducing pain (especially immediately after treatment) in patients with upper quarter pain. There have been fewer studies of patients with craniofacial pain and myofascial pain in other regions, but most of these studies report findings to suggest the dry needling may be helpful in reducing pain and improving other pain related variables such as the pain pressure threshold. More rigorous randomized controlled trials are clearly needed to more fully elucidate the effectiveness of dry needling. PMID:24912453

Kietrys, David M; Palombaro, Kerstin M; Mannheimer, Jeffrey S



Mitochondrial threshold effects.  

PubMed Central

The study of mitochondrial diseases has revealed dramatic variability in the phenotypic presentation of mitochondrial genetic defects. To attempt to understand this variability, different authors have studied energy metabolism in transmitochondrial cell lines carrying different proportions of various pathogenic mutations in their mitochondrial DNA. The same kinds of experiments have been performed on isolated mitochondria and on tissue biopsies taken from patients with mitochondrial diseases. The results have shown that, in most cases, phenotypic manifestation of the genetic defect occurs only when a threshold level is exceeded, and this phenomenon has been named the 'phenotypic threshold effect'. Subsequently, several authors showed that it was possible to inhibit considerably the activity of a respiratory chain complex, up to a critical value, without affecting the rate of mitochondrial respiration or ATP synthesis. This phenomenon was called the 'biochemical threshold effect'. More recently, quantitative analysis of the effects of various mutations in mitochondrial DNA on the rate of mitochondrial protein synthesis has revealed the existence of a 'translational threshold effect'. In this review these different mitochondrial threshold effects are discussed, along with their molecular bases and the roles that they play in the presentation of mitochondrial diseases.

Rossignol, Rodrigue; Faustin, Benjamin; Rocher, Christophe; Malgat, Monique; Mazat, Jean-Pierre; Letellier, Thierry



Prediction of post-operative pain following arthroscopic subacromial decompression surgery: an observational study  

PubMed Central

Background: Arthroscopic shoulder surgery is increasingly performed as a day case procedure. Optimal post-operative pain relief remains a challenge due to considerable variations in the level of pain experienced between individuals. Our aim was to examine whether the preoperative electrical pain threshold was a strong predictor of elevated postoperative pain levels following arthroscopic subacromial decompression (ASD) surgery. Methods: Forty consenting patients with American Society of Anesthesiologists (ASA) grade 1-2 presenting for elective ASD surgery were recruited. Patients’ electrical pain thresholds were measured preoperatively using a PainMatcher® (Cefar Medical AB, Lund, Sweden) device. Following surgery under general anaesthesia, the maximum pain experienced at rest and movement was recorded using a visual analogue scale until the end of postoperative day four. Results: In univariate analyses (t-test), the postoperative pain experienced (Area Under Curve) was significantly greater in patients with a low pain threshold as compared with a high pain threshold at both rest (mean 12.5, S.E. 1.7 v mean 6.5, S.E.1.2. P=0.008) and on movement (mean 18.7, S.E. 1.5 v mean 14.1, S.E.1.4. P=0.031). In multivariate analyses, adjusting for additional extra analgesia, the pain experienced postoperatively was significantly greater in the low pain threshold group both at rest (mean difference 4.9, 95% CI 1.5 to 8.4, P=0.007) and on movement (mean difference 4.1, 95%CI 0.03 to 8.2, P=0.049). Conclusions: Preoperative pain threshold can predict postoperative pain level following ASD of the shoulder. Trial registration: identifier: NCT01351363 Level of Evidence: II

Davis, Anthony



Prediction of post-operative pain following arthroscopic subacromial decompression surgery: an observational study.  


Background: Arthroscopic shoulder surgery is increasingly performed as a day case procedure. Optimal post-operative pain relief remains a challenge due to considerable variations in the level of pain experienced between individuals. Our aim was to examine whether the preoperative electrical pain threshold was a strong predictor of elevated postoperative pain levels following arthroscopic subacromial decompression (ASD) surgery. Methods: Forty consenting patients with American Society of Anesthesiologists (ASA) grade 1-2 presenting for elective ASD surgery were recruited. Patients' electrical pain thresholds were measured preoperatively using a PainMatcher® (Cefar Medical AB, Lund, Sweden) device. Following surgery under general anaesthesia, the maximum pain experienced at rest and movement was recorded using a visual analogue scale until the end of postoperative day four. Results: In univariate analyses (t-test), the postoperative pain experienced (Area Under Curve) was significantly greater in patients with a low pain threshold as compared with a high pain threshold at both rest (mean 12.5, S.E. 1.7 v mean 6.5, S.E.1.2. P=0.008) and on movement (mean 18.7, S.E. 1.5 v mean 14.1, S.E.1.4. P=0.031). In multivariate analyses, adjusting for additional extra analgesia, the pain experienced postoperatively was significantly greater in the low pain threshold group both at rest (mean difference 4.9, 95% CI 1.5 to 8.4, P=0.007) and on movement (mean difference 4.1, 95%CI 0.03 to 8.2, P=0.049). Conclusions: Preoperative pain threshold can predict postoperative pain level following ASD of the shoulder. Trial registration: identifier: NCT01351363 Level of Evidence: II. PMID:24358863

Davis, Anthony; Chinn, David J; Sharma, Sunil



Mechanical Data for Use in Damage Tolerance Analyses  

NASA Technical Reports Server (NTRS)

This report describes the results of a research program to determine the damage tolerance properties of metallic propeller materials. Three alloys were selected for investigation: 2025-T6 Aluminum, D6AC Steel and 4340 Steel. Mechanical response, fatigue (S-N) and fatigue crack growth rate data are presented for all of the alloys. The main conclusions that can be drawn from this study are as follows. The damage tolerant design of a propeller system will require a complete understanding of the fatigue crack growth threshold. There exists no experimental procedure to reliably develop the fatigue crack growth threshold data that is needed for damage tolerant design methods. Significant research will be required to fully understand the fatigue crack growth threshold. The development of alternative precracking methods, evaluating the effect of specimen configuration and attempting to identify micromechanical issues are simply the first steps to understanding the mechanics of the threshold.

Forth, Scott C.; James, Mark A.; Newman, John A.; Everett, Richard A., Jr.; Johnston, William M., Jr.



Spinal Microglial and Perivascular Cell Cannabinoid Receptor Type 2 Activation Reduces Behavioral Hypersensitivity without Tolerance after Peripheral Nerve Injury  

PubMed Central

Background Cannabinoids induce analgesia by acting on cannabinoid receptor (CBR) types 1 and/or 2. However, central nervous system side effects and antinociceptive tolerance from CBR1 limit their clinical use. CBR2 exist on spinal glia and perivascular cells, suggesting an immunoregulatory role of these receptors in the central nervous system. Previously, the authors showed that spinal CBR2 activation reduces paw incision hypersensitivity and glial activation. This study tested whether CBR2 are expressed in glia and whether their activation would induce antinociception, glial inhibition, central side effects, and antinociceptive tolerance in a neuropathic rodent pain model. Methods Rats underwent L5 spinal nerve transection or sham surgery, and CBR2 expression and cell localization were assessed by immunohistochemistry. Animals received intrathecal injections of CBR agonists and antagonists, and mechanical withdrawal thresholds and behavioral side effects were assessed. Results Peripheral nerve transection induced hypersensitivity, increased expression of CR3/CD11b and CBR2, and reduced ED2/CD163 expression in the spinal cord. The CBR2 were localized to microglia and perivascular cells. Intrathecal JWH015 reduced peripheral nerve injury hypersensitivity and CR3/CD11b expression and increased ED2/CD163 expression in a dose-dependent fashion. These effects were prevented by intrathecal administration of the CBR2 antagonist (AM630) but not the CBR1 antagonist (AM281). JWH015 did not cause behavioral side effects. Chronic intrathecal JWH015 treatment did not induce antinociceptive tolerance. Conclusions These data indicate that intrathecal CBR2 agonists may provide analgesia by modulating the spinal immune response and microglial function in chronic pain conditions without inducing tolerance and neurologic side effects.

Romero-Sandoval, Alfonso; Nutile-McMenemy, Nancy; DeLeo, Joyce A.



Pain drawings in somatoform-functional pain  

PubMed Central

Background Pain drawings are a diagnostic adjunct to history taking, clinical examinations, and biomedical tests in evaluating pain. We hypothesized that somatoform-functional pain, is mirrored in distinctive graphic patterns of pain drawings. Our aim was to identify the most sensitive and specific graphic criteria as a tool to help identifying somatoform-functional pain. Methods We compared 62 patients with somatoform-functional pain with a control group of 49 patients with somatic-nociceptive pain type. All patients were asked to mark their pain on a pre-printed body diagram. An investigator, blinded with regard to the patients’ diagnoses, analyzed the drawings according to a set of numeric or binary criteria. Results We identified 13 drawing criteria pointing with significance to a somatoform-functional pain disorder (all p-values???0.001). The most specific and most sensitive criteria combination for detecting somatoform-functional pain included the total number of marks, the length of the longest mark, and the presence of symmetric patterns. The area under the ROC-curve was 96.3% for this criteria combination. Conclusion Pain drawings are an easy-to-administer supplementary technique which helps to identify somatoform-functional pain in comparison to somatic-nociceptive pain.



Periaqueductal gray stimulation suppresses spontaneous pain behavior in rats.  


Methods for evaluating analgesic effect for spontaneous pain are increasingly important because it is reported by most patients with neuropathic pain. The present study assessed the analgesic effects of periaqueductal gray (PAG) stimulation in the spared nerve injury (SNI) model of neuropathic pain of the rat. Spontaneous rapid paw withdrawal movements were used as the index of spontaneous pain. Deep-brain stimulation in the PAG was performed in rats 3 weeks after SNI. Significant analgesic effects on spontaneous pain behavior were observed at the same stimulation parameter that reversed the reduced mechanical threshold of the von Frey test. Both analgesic effects lasted 30-40min beyond the 3min stimulation period. In summary, PAG stimulation was effective in alleviating spontaneous pain and mechanical allodynia in the SNI rat. The frequency of spontaneous paw lifting, a behavioral index of spontaneous pain used in this study, will be useful for future testing of therapeutic methods. PMID:22390899

Lee, Kuo-Sheng; Huang, Yu-Hsin; Yen, Chen-Tung



Taking Sides with Pain - Lateralization aspects Related to Cerebral Processing of Dental Pain  

PubMed Central

The current fMRI study investigated cortical processing of electrically induced painful tooth stimulation of both maxillary canines and central incisors in 21 healthy, right-handed volunteers. A constant current, 150% above tooth specific pain perception thresholds was applied and corresponding online ratings of perceived pain intensity were recorded with a computerized visual analog scale during fMRI measurements. Lateralization of cortical activations was investigated by a region of interest analysis. A wide cortical network distributed over several areas, typically described as the pain or nociceptive matrix, was activated on a conservative significance level. Distinct lateralization patterns of analyzed structures allow functional classification of the dental pain processing system. Namely, certain parts are activated independent of the stimulation site, and hence are interpreted to reflect cognitive emotional aspects. Other parts represent somatotopic processing and therefore reflect discriminative perceptive analysis. Of particular interest is the observed amygdala activity depending on the stimulated tooth that might indicate a role in somatotopic encoding.

Brugger, Mike; Ettlin, Dominik A.; Meier, Michael; Keller, Thierry; Luechinger, Roger; Barlow, Ashley; Palla, Sandro; Jancke, Lutz; Lutz, Kai



American Chronic Pain Association  


... to Chronic Pain Medications & Treatments The Art of Pain Management What We Have Learned Going to the ER Communication Tools Pain Management Programs Videos Resources Glossary FAQs Surveys September is ...


What Is Chronic Pain?  

MedlinePLUS Videos and Cool Tools

... Chronic Pain Medications & Treatments The Art of Pain Management What We Have Learned Going to the ER Communication Tools Pain Management Programs Videos Resources Glossary FAQs Surveys September is ...


Overview of Neck Pain  


... and Back) > Overview of Neck Pain Overview of Neck Pain Page Content Developing a Program That's Right for ... or activity? What Kinds of Problems Might Cause Neck Pain? Treatment for any neck condition is recommended as ...


Runner's Knee (Patellofemoral Pain)  


... and soccer players put heavy stress on their knees. Runner's knee is a term used to refer to a ... that cause pain around the front of the knee (patellofemoral pain). These conditions include anterior knee pain ...


Central Pain Syndrome  


... Mingled with the burning may be sensations of "pins and needles;" pressing, lacerating, or aching pain; and brief, intolerable bursts of sharp pain similar to the pain caused by a dental probe on an exposed nerve. Individuals may have ...


Pain Management: Post-Amputation Pain  


Pain Management Post-Amputation Pain Volume 8 · Issue 2 · March/April 1998 Text size Larger text Smaller text Java ... of the most frequently asked questions. Ideas about management are one of the frequent topics of conversation ...


What a Pain! Kids and Growing Pains  


... Games Kids' Medical Dictionary En Español What Other Kids Are Reading Swimming Going Away to Camp Swimmer's ... Page The Pink Locker Society What a Pain! Kids and Growing Pains KidsHealth > Kids > Illnesses & Injuries > Aches, ...


A direct comparison of affective pain processing underlying two traditional pain modalities in rodents.  


In the preclinical study of pain, two commonly used pain models are the L5 spinal nerve ligation (SNL) and the injection of carrageenan. Using a modified place escape/avoidance paradigm (mPEAP), a novel behavioral test that quantifies aversive behavior evoked by painful stimuli, we directly compared the affective component of the SNL and inflammation models. Fifty three Sprague-Dawley rats underwent baseline mechanical paw withdrawal threshold (MPWT) and mPEAP testing followed by an L5 SNL or sham surgery for the left paw and then a carrageenan or saline injection for the right paw. After recovering, animals underwent post-manipulation MPWT and mPEAP tests. Both pain conditions produced mechanical hypersensitivity, and animals with a single-paw condition demonstrated escape/avoidance behavior in response to stimulation of the affected paw. Animals with the bilateral pain condition did not show a preference for stimulation of one paw versus the other paw, and the avoidance behavior was not significantly different from the sham/saline control. The results indicate that the pain models are associated with significant avoidance behavior and that they produce comparable degrees of pain affect. These findings advance the preclinical study of pain by validating the simultaneous utilization of the SNL and inflammation models and will allow future studies that combine pain conditions to more closely resemble clinical conditions. PMID:22172927

McNabb, C T; Uhelski, M L; Fuchs, P N



Sensory characteristics of chronic non-specific low back pain: A subgroup investigation.  


It has been proposed that patients with chronic non-specific low back pain (CNSLBP) can be broadly classified based on clinical features that represent either predominantly a mechanical pain (MP) or non-mechanical pain (NMP) profile. The aim of this study was to establish if patients with CNSLBP who report features of NMP demonstrate differences in pain thresholds compared to those who report MP characteristics and pain-free controls. This study was a cross-sectional design investigating whether pressure pain threshold (PPT) and/or cold pain threshold (CPT) at three anatomical locations differed between patients with mechanical CNSLBP (n = 17) versus non-mechanical CNSLBP (n = 19 and healthy controls (n = 19) whilst controlling for confounders. The results of this study provide evidence of increased CPT at the wrist in the NMP profile group compared to both the MP profile and control subjects, when controlling for gender, sleep and depression (NMP versus MP group Odds Ratio (OR): 18.4, 95% confidence interval (CI): 2.5-133.1, p = 0.004). There was no evidence of lowered PPT at any site after adjustment for confounding factors. Those with an MP profile had similar pain thresholds to pain-free controls, whereas the NMP profile group demonstrated elevated CPT's consistent with central amplification of pain. These findings may represent different pain mechanisms associated with these patient profiles and may have implications for targeted management. PMID:24731602

O'Sullivan, Peter; Waller, Robert; Wright, Anthony; Gardner, Joseph; Johnston, Richard; Payne, Carly; Shannon, Aedin; Ware, Brendan; Smith, Anne



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


Some chronic painful conditions including e.g. fibromyalgia, whiplash associated disorders, endometriosis, and irritable bowel syndrome are associated with generalized musculoskeletal hyperalgesia. The aim of the present study was to determine whether generalized deep-tissue hyperalgesia could be demonstrated in a group of patients with chronic low-back pain with intervertebral disc herniation. Twelve patients with MRI confirmed lumbar intervertebral disc herniation and 12 age and sex matched controls were included. Subjects were exposed to quantitative nociceptive stimuli to the infraspinatus and anterior tibialis muscles. Mechanical pressure (thresholds and supra-threshold) and injection of hypertonic saline (pain intensity, duration, distribution) were used. Pain intensity to experimental stimuli was assessed on a visual analogue scale (VAS). Patients demonstrated significantly higher pain intensity (VAS), duration, and larger areas of pain referral following saline injection in both infraspinatus and tibialis anterior. The patients rated significantly higher pain intensity to supra-threshold mechanical pressure stimulation in both muscles. In patients, the pressure pain-threshold was lower in the anterior tibialis muscle compared to controls. In conclusion, generalized deep-tissue hyperalgesia was demonstrated in chronic low-back pain patients with radiating pain and MRI confirmed intervertebral disc herniation, suggesting that this central sensitization should also be addressed in the pain management regimes. PMID:16815054

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



Managing surgical pain in long-term opioid patients.  


The number of patients taking long-term opioid therapy for pain is increasing, with opioid use no longer being confined to advanced cancer patients. Challenges to peri- and postoperative pain management in chronic pain patients include complex existing drug regimens and problems arising from tolerance to opioid analgesia. Postoperatively, individualized, multimodal pain therapy involving a round-the-clock regimen of nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) inhibitors, paracetamol, and regional blocks should be used. Other considerations may include patients receiving opioids by intrathecal drug delivery systems, spinal cord stimulator (SCS), and potential substance abusers. PMID:23688513

Brill, Silviu



Threshold Group Testing  

Microsoft Academic Search

We introduce a natural generalization of the well-studied group testing prob- lem: A test gives a positive (negative) answer if the pool contains at least u (at most l) positive elements, and an arbitrary answer if the number of positive elements is between these fixed thresholds l and u. We show that the p posi- tive elements can be determined

Peter Damaschke



Peripheral Pain Mechanisms in Chronic Widespread Pain  

PubMed Central

Clinical symptoms of chronic widespread pain (CWP) conditions including fibromyalgia (FM), include pain, stiffness, subjective weakness, and muscle fatigue. Muscle pain in CWP is usually described as fluctuating and often associated with local or generalized tenderness (hyperalgesia and/or allodynia). This tenderness related to muscle pain depends on increased peripheral and/or central nervous system responsiveness to peripheral stimuli which can be either noxious (hyperalgesia) or non-noxious (allodynia). For example, patients with muscle hyperalgesia will rate painful muscle stimuli higher than normal controls, whereas patients with allodynia may perceive light touch as painful, something that a “normal” individual will never describe as painful. The pathogenesis of such peripheral and/or central nervous system changes in CWP is unclear, but peripheral soft tissue changes have been implicated. Indirect evidence from interventions that attenuate tonic peripheral nociceptive impulses in patients with CWP syndromes like FM suggest that overall FM pain is dependent on peripheral input. More importantly, allodynia and hyperalgesia can be improved or abolished by removal of peripheral impulse input. Another potential mechanism for CWP pain is central disinhibition. However, this pain mechanism also depends on tonic impulse input, even if only inadequately inhibited. Thus a promising approach to understanding CWP is to determine whether abnormal activity of receptors in deep tissues is fundamental to the development and maintenance of this chronic pain disorder. Conclusions Most CWP patients present with focal tissue abnormalities including myofascial trigger points, ligamentous trigger points, or osteoarthritis of the joints and spine. While not predictive for the development of CWP these changes nevertheless represent important pain generators that may initiate or perpetuate chronic pain. Local chemical mediators, including lactic acid, ATP, and cytokines seem to play an important role in sensitizing deep tissue nociceptors of CWP patients. Thus the combination of peripheral impulse input and increased central pain sensitivity may be responsible for wide-spread chronic pain disorders including FM.

Staud, Roland



Imipramine decreases oesophageal pain perception in human male volunteers  

PubMed Central

Background—Visceral hyperalgesia is a hallmark of functional gastrointestinal disorders. Antidepressants improve symptoms in these patients, although their mode of action is unclear. Antidepressant, anticholinergic, and analgesic mechanisms have been proposed. ?Aims—To investigate whether imipramine, which has a visceral analgesic effect, increases pain thresholds to experimental visceral pain. ?Methods—Visceral perception for first sensation and pain was measured with intraoesophageal balloon distension in 15 male volunteers. The effect of imipramine was studied in a double blind, placebo controlled, crossover study. Imipramine was given in ascending doses for 12 days (25 mg days 1-3, 50 mg days 4-6, 75 mg days 7-12), with oesophageal perception studied on day 13. ?Results—Inflation volumes and intraballoon pressures at first sensation were not different between placebo and imipramine. Balloon inflation volume at pain threshold was higher on imipramine (p=0.015). Median intraballoon pressures were not different at pain threshold for placebo and imipramine. Oesophageal wall compliance was not affected by imipramine. ?Conclusion—Increased pain thresholds on imipramine in this group of normal male volunteers in the absence of changes in oesophageal tone imply the presence of a visceral analgesic effect. ?? Keywords: antidepressants; imipramine; visceral hyperalgesia; oesophageal balloon; distension; functional bowel syndromes

Peghini, P; Katz, P; Castell, D



Cerebrospinal fluid levels of opioid peptides in fibromyalgia and chronic low back pain  

PubMed Central

Background The mechanism(s) of nociceptive dysfunction and potential roles of opioid neurotransmitters are unresolved in the chronic pain syndromes of fibromyalgia and chronic low back pain. Methods History and physical examinations, tender point examinations, and questionnaires were used to identify 14 fibromyalgia, 10 chronic low back pain and 6 normal control subjects. Lumbar punctures were performed. Met-enkephalin-Arg6-Phe7 (MEAP) and nociceptin immunoreactive materials were measured in the cerebrospinal fluid by radioimmunoassays. Results Fibromyalgia (117.6 pg/ml; 85.9 to 149.4; mean, 95% C.I.; p = 0.009) and low back pain (92.3 pg/ml; 56.9 to 127.7; p = 0.049) groups had significantly higher MEAP than the normal control group (35.7 pg/ml; 15.0 to 56.5). MEAP was inversely correlated to systemic pain thresholds. Nociceptin was not different between groups. Systemic Complaints questionnaire responses were significantly ranked as fibromyalgia > back pain > normal. SF-36 domains demonstrated severe disability for the low back pain group, intermediate results in fibromyalgia, and high function in the normal group. Conclusions Fibromyalgia was distinguished by higher cerebrospinal fluid MEAP, systemic complaints, and manual tender points; intermediate SF-36 scores; and lower pain thresholds compared to the low back pain and normal groups. MEAP and systemic pain thresholds were inversely correlated in low back pain subjects. Central nervous system opioid dysfunction may contribute to pain in fibromyalgia.

Baraniuk, James N; Whalen, Gail; Cunningham, Jill; Clauw, Daniel J



Effect of ibuprofen on isometric contractions and associated pain of the human masseter muscle.  


A randomized, single-blind crossover trial tested the effect of 1,000 mg of ibuprofen on jaw muscle pain induced by maximum voluntary teeth clenching (MVC). Subjects exercised MVC until there was onset of pain in the masseter muscles (pain latency in seconds), and until pain and exhaustion of the masseter and anterior temporalis muscles could no longer be endured (pain tolerance in seconds). Pain intensity was quantified by visual analogue scores, and pain sensitivity by the pain sensitivity range and the pain sensitivity ratio. During MVC the mean voltage of the left masseter muscle was recorded by cumulative surface electromyography. Ibuprofen had no significant effect on the pain latency and the pain tolerance. Neither did ibuprofen significantly decrease the pain intensity nor significantly affect the pain sensitivity range and the pain sensitivity ratio. After intake of ibuprofen, the number of electromyograms with a decrease in mean voltage was significantly increased--credibly, an expression of increased central fatigue with voluntary decruitment of motor units, and possibly the result of increased contraction times because of an undisclosed effect of ibuprofen. There was no circumstantial evidence of impaired motor activity that could be attributed to biosynthesis of prostaglandins. PMID:3475969

Christensen, L V



Understanding Cancer Pain.  

National Technical Information Service (NTIS)

This booklet is designed to give you important information about pain related to cancer. It will help you understand why patients have pain, the different ways pain can be treated, and what you need to do when you have pain. Your doctor, nurse, or social ...



Mechanisms of neuropathic pain  

Microsoft Academic Search

Neuropathic pain is defined as 'pain initiated or caused by a primary lesion or dysfunction in the nervous system'.94 The spectrum of neuropathic pain covers a variety of disease states (Table 1) and presents in the clinic with a variety of symptoms.145 Neuropathic pain is often reported as having a lancinating or continuous burning character and is often associated with

D. Bridges; S. W. N. Thompson; A. S. C. Rice



Pathobiology of neuropathic pain  

Microsoft Academic Search

This review deals with physiological and biological mechanisms of neuropathic pain, that is, pain induced by injury or disease of the nervous system. Animal models of neuropathic pain mostly use injury to a peripheral nerve, therefore, our focus is on results from nerve injury models. To make sure that the nerve injury models are related to pain, the behavior was

Manfred Zimmermann



Facial expression accompanying pain  

Microsoft Academic Search

The study of facial expression accompanying pain is of both practical and theoretical importance. It has been suggested that nonverbal behavior may provide accurate information on pain states to supplement self-report and that perhaps facial expressions could even serve as accurate measures of pain in the absence of verbal report. Recent studies of specific facial expressions accompanying pain have benefited

Linda LeResche; Samuel F. Dworkin



Intensity Thresholds for Aerobic Exercise-Induced Hypoalgesia  

PubMed Central

Despite many studies investigating exercise-induced hypoalgesia, there is limited understanding of the optimal intensity of aerobic exercise in producing hypoalgesic effects across different types of pain stimuli. Given that not all individuals are willing or capable of engaging in high intensity aerobic exercise, whether moderate intensity aerobic exercise is associated with a hypoalgesic response and whether this response generalizes to multiple pain induction techniques needs to be substantiated. Purpose This study’s purpose is to test for differences in the magnitude of pressure and heat pain modulation induced by moderate (MAE) and vigorous (VAE) intensity aerobic exercise. Methods Twelve healthy young males and 15 females completed one training session and three testing sessions consisting of 25 minutes of either 1) stationary cycling at 70% heart rate reserve (HRR), 2) stationary cycling at 50% HRR, or 3) quiet rest (control). Pain testing was conducted on both forearms prior to and immediately following each condition and included the following tests: pressure pain thresholds (PPT), suprathreshold pressure pain test, static continuous heat test, and repetitive pulse heat pain test. Repeated measures ANOVAs were conducted on each pain measure. Results VAE and MAE reduced pain ratings during static continuous heat stimuli and repetitive heat pulse stimuli, with VAE producing larger effects. VAE also increased PPTs, while neither exercise influenced suprathreshold pressure pain ratings. Conclusion These results suggest that MAE is capable of producing a hypoalgesic effect using continuous and repetitive pulse heat stimuli. However, a dose-response effect was evident as VAE produced larger effects than MAE.

Naugle, Kelly M.; Naugle, Keith E.; Fillingim, Roger B.; Samuels, Brian; Riley, Joseph L.



Threshold properties of a microcavity laser with submicroampere threshold current  

SciTech Connect

We report the threshold characteristics of small oxide-confined vertical-cavity surface emitting lasers. Abrupt threshold transitions 105 times the spontaneous emission background are obtained at injection currents as low as 470 nanoampere.

Choquette, K.D.; Hou, H.Q.; Lear, K.L.; Chow, W.W.; Mar, A.; Geib, K.M.; Hammons, B.E.



Transport near stochastic threshold  

SciTech Connect

Transport in a magnetic field configuration near stochastic threshold is investigated. The waiting time distribution near magnetic islands, and the size distribution of these islands are identified as the two fundamental functions which determine both the short time subdiffusive behavior, and the regular diffusive regime. These time and length distributions are studied, the mean square displacement is expressed in terms of these functions, and the result is compared to direct numerical simulation.

White, R.B.; Rax, J.M.; Wu, Y.



Breakthrough cancer pain.  


Breakthrough pain is a distinct pain state that is common in patients with cancer pain and which is associated with significant morbidity in this group of patients. The aim of this article is to highlight important journal articles relating to breakthrough pain that have been published within the last year, including a systematic review of the epidemiology of breakthrough pain, the largest-ever study of the clinical features of breakthrough pain, and a network meta-analysis of the treatment of breakthrough pain. PMID:24760489

Davies, Andrew N



Growing pains in children  

PubMed Central

We review the clinical manifestations of "growing pains", the most common form of episodic childhood musculoskeletal pain. Physicians should be careful to adhere to clear clinical criteria as described in this review before diagnosing a child with growing pain. We expand on current theories on possible causes of growing pains and describe the management of these pains and the generally good outcome in nearly all children.

Uziel, Yosef; Hashkes, Philip J



Pathophysiology of Neuropathic Pain  

Microsoft Academic Search

Cerebral responses to pain are complex and dynamic in nature and in the case of chronic pain, especially neuropathic pain,\\u000a changes involved are more profound and they are characterized by the involvement of entire pain-related peripheral and central\\u000a nervous system. Functional magnetic resonance imaging studies identified a number of cerebral, cortical, and subcortical structures\\u000a that are activated during pain stimuli.

Misha-Miroslav Backonja


Threshold Concepts in Research Education and Evidence of Threshold Crossing  

ERIC Educational Resources Information Center

Most work on threshold concepts has hitherto related to discipline-specific undergraduate education, however, the idea of generic doctoral-level threshold concepts appeared to us to provide a strong and useful framework to support research learning and teaching at the graduate level. The early work regarding research-level threshold concepts is…

Kiley, Margaret; Wisker, Gina



Functional MRI demonstrates pain perception in hand osteoarthritis has features of central pain processing  

PubMed Central

Background Hand osteoarthritis (HOA) is typified by pain and reduced function. We hypothesised that people with HOA have enhanced sensitivity and activation of peripheral nociceptors in the hand, thereby potentiating chronic pain. In our study we aimed to assess if central sensitisation mediates pain perception in osteoarthritis of the hand. Methods Participants with proximal and distal interphalangeal joint (PIP/DIP) HOA and non-OA controls were recruited. Clinical pain scores using the visual analogue scale (VAS) were recorded before and after performing a painful hand task. Central pain processing was evaluated with functional brain neuroimaging (fMRI) using a finger flexion-extension (FFE) task performed over 3 minutes. Data was analysed with FMRIB software ( Group mean activation of functional MRI signal between hand osteoarthritis and control non-arthritic participants was compared. Results Our group of hand OA participants reported high pain levels compared with non-arthritic controls as demonstrated by the mean VAS in hand OA participants of 59.31± 8.19 mm compared to 4.00 ± 1.89 mm in controls (p < 0.0001), despite all participants reporting analgesic use. Functional MRI analysis showed increased activation in the thalamus, cingulate, frontal and somatosensory cortex in the hand OA group but not in controls (thresholded at p < 0.05). Regions of activation were mapped to Brodmann areas 3, 4, 6, 9, 13, 22, 24 and 44. Activated regions found in our study are recognised higher brain pain processing centres implicated in central sensitisation. Conclusions People with hand osteoarthritis demonstrated features of central sensitisation that was evident after a finger flexion-extension task using functional MRI. Functional MRI is a useful biomarker in detecting pain in hand osteoarthritis and could be used in future hand osteoarthritis pain studies to evaluate pain modulation strategies.

Sofat, Nidhi; Smee, Cori; Hermansson, Monika; Howard, Matthew; Baker, Emma H; Howe, Franklyn A; Barrick, Thomas R



Ionic mechanisms in peripheral pain.  


Chronic pain constitutes an important and growing problem in society with large unmet needs with respect to treatment and clear implications for quality of life. Computational modeling is used to complement experimental studies to elucidate mechanisms involved in pain states. Models representing the peripheral nerve ending often address questions related to sensitization or reduction in pain detection threshold. In models of the axon or the cell body of the unmyelinated C-fiber, a large body of work concerns the role of particular sodium channels and mutations of these. Furthermore, in central structures: spinal cord or higher structures, sensitization often refers not only to enhanced synaptic efficacy but also to elevated intrinsic neuronal excitability. One of the recent developments in computational neuroscience is the emergence of computational neuropharmacology. In this area, computational modeling is used to study mechanisms of pathology with the objective of finding the means of restoring healthy function. This research has received increased attention from the pharmaceutical industry as ion channels have gained increased interest as drug targets. Computational modeling has several advantages, notably the ability to provide mechanistic links between molecular and cellular levels on the one hand and functions at the systems level on the other hand. These characteristics make computational modeling an additional tool to be used in the process of selecting pharmaceutical targets. Furthermore, large-scale simulations can provide a framework to systematically study the effects of several interacting disease parameters or effects from combinations of drugs. PMID:24560139

Fransén, Erik



Evidence of Increased Non-Verbal Behavioral Signs of Pain in Adults with Neurodevelopmental Disorders and Chronic Self-Injury  

ERIC Educational Resources Information Center

The role of pain in relation to self-injurious behavior (SIB) among individuals with intellectual disabilities is not well understood. Some models of SIB are based on altered endogenous opioid system activity which could result in elevated pain thresholds. In this study, non-verbal behavioral signs indicative of pain as measured by the…

Symons, Frank J.; Harper, Vicki N.; McGrath, Patrick J.; Breau, Lynn M.; Bodfish, James W.



Psychological aspects of pain.  


Introduction. Pain is defined "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage". Pain is a sensation of the body, and is always an unpleasant emotional experience. The role of psychology is auxiliary and supplemental to medicine. This is an aid addressed to the patient, physician and patient's caregivers: professional caregivers, family members and significant others. At each stage of the diagnostic and therapeutic process, psychology offers help, both from the cognitive and practical aspects. Objective. The objective of the article is to present important psychological aspects of studies concerning pain, and the psychological methods and techniques of pain treatment. State of knowledge. Pain is the leading reason for patients seeking medical care and is one of the most disabling, burdensome, and costly conditions. Pain accompanies many diseases, each one of which generates unique/separate diagnostic, therapeutic and research problems. Depression and related psychical disorders. There is a significant relationship between depression and pain symptoms, as well as between pain and suicidal thoughts. Patients with a long history of pain disorders also have increased depression and anxiety symptoms, as well as suicidal thoughts. Patients with more severe depression and anxiety symptoms also have an increase in pain problems. The intensity of pain correlates with the intensity of psychopathological symptoms - both with mood lowering and with anxiety symptoms and worry. Active pain coping strategies strive to function in spite of pain, or to distract oneself from pain, are associated with adaptive functioning. Passive strategies involve withdrawal or relinquishing control to an external force or agent and are related to greater pain and depression. Pain catastrophizing is a negatively distorted perception of pain as awful, horrible and unbearable. Catastrophizing is strongly associated with depression and pain. Studies in which functional magnetic resonance imaging (fMRI) was used showed that pain catastrophizing, independent of the influence of depression, was significantly associated with increased activity in brain areas related to anticipation of pain, attention to pain, emotional aspects of pain and motor control. Pain behaviour is a conditioned pain. Care and concern on the part of others, secondarily enhance a patient's pain behaviours, which lead to an increase in the intensity of the pain experienced. A history of early life adversity (ELA) - rejection, neglect, physical or sexual abuse is related to the development of irritable bowel syndrome (IBS) in adulthood. Ovarian hormones have been shown to modulate pain sensitivity. Imaging of the human brain in chronic pain. Acute pain and chronic pain are encoded in different regions of the brain. Chronic pain can be considered a driving force that carves cortical anatomy and physiology, creating the chronic pain brain/ mind state. Cognitive-behavioural methods of pain treatment in domains of pain experience, cognitive coping and appraisal (positive coping measures), and reduced pain experience are effective in reducing pain in patients. PMID:25000837

Gorczyca, Rafa?; Filip, Rafa?; Walczak, Ewa



Pain and Associated Substance Use among Opioid Dependent Individuals Seeking Office-Based Treatment with Buprenorphine-Naloxone: A Needs Assessment Study  

PubMed Central

Background and Objectives A paucity of studies has examined the pain experiences of opioid dependent individuals seeking office-based buprenorphine-naloxone treatment (BNT). We set out to examine, among those seeking BNT: (a) the prevalence of pain types (i.e., recent pain, chronic pain), (b) the characteristics of pain (intensity, frequency, duration, interference, location, and genesis), and (c) substance use to alleviate pain. Methods We surveyed 244 consecutive individuals seeking office-based buprenorphine-naloxone treatment (BNT) for opioid dependence about physical pain and associated substance use. Results Thirty-six percent of respondents reported chronic pain (CP) (i.e., pain lasting at least 3 months) and 36% reported “some pain” (SP) (i.e., past week pain not meeting the threshold for CP). In comparison to SP respondents, those with CP were, on average, older; reported greater current pain intensity, pain frequency, typical pain duration, typical pain intensity, and typical pain interference; were more likely to report shoulder or pelvis and less likely to report stomach or arms as their most bothersome pain location; and were more likely to report accident or nerve damage and less likely to report opioid withdrawal as the genesis of their pain. Both pain subgroups reported similarly high rates of past-week substance use to alleviate pain. Conclusions and Scientific Significance The high rates of pain and self-reported substance use to manage pain suggest the importance of assessing and addressing pain in BNT patients.

Barry, Declan T.; Savant, Jonathan D.; Beitel, Mark; Cutter, Christopher J.; Moore, Brent A.; Schottenfeld, Richard S.; Fiellin, David A.



Grossman's Missing Health Threshold?  

PubMed Central

We present a generalized solution to Grossman's model of health capital (1972), relaxing the widely used assumption that individuals can adjust their health stock instantaneously to an “optimal” level without adjustment costs. The Grossman model then predicts the existence of a health threshold above which individuals do not demand medical care. Our generalized solution addresses a significant criticism: the model's prediction that health and medical care are positively related is consistently rejected by the data. We suggest structural- and reduced-form equations to test our generalized solution and contrast the predictions of the model with the empirical literature.

Galama, Titus; Kapteyn, Arie



Mast cell stabilization promotes antinociceptive effects in a mouse model of postoperative pain  

PubMed Central

Background Nerve injury and consequent inflammatory responses produced by surgical incision result in a complicated pain status which still affects half of all surgical patients. Therefore, it is essential for anesthesiologists to identify the mechanisms of postoperative pain. Mast cells are resident cells of connective tissue and the mucosa that participate in the immune response. Degranulation of mast cells is involved in the development of postoperative pain and can be induced by surgical incision. The aim of this study was to investigate whether stabilization of mast cells causes an antinociceptive effect in a mouse model of postoperative pain. Methods Postoperative pain was induced by making an incision in the hind paw of BALB/c mice. The mast cell membrane stabilizer cromoglycate (200 ?g/20 ?L) was injected before incision of the paw, and postoperative pain responses were measured by assessing guarding behavior, withdrawal threshold to mechanical stimuli, and latency of heat pain behavior 1, 2, and 7 days after the incision. Results The incision produced guarding pain, mechanical allodynia, and heat hypersensitivity. Cromoglycate decreased the guarding pain score (day 1) and the withdrawal threshold to mechanical stimuli (days 1, 2, and 7). However, the withdrawal latency to heat was not affected by cromoglycate treatment. Conclusion Cromoglycate significantly attenuated the pain response expressed as guarding pain and mechanical allodynia in a mouse model of postoperative pain. Thus, mast cell activation is likely a mechanism of postoperative pain and is an interesting target for the development of new therapies.

Yasuda, Makoto; Kido, Kanta; Ohtani, Norimasa; Masaki, Eiji



Psychological factors associated with perception of experimental pain in vulvar vestibulitis syndrome.  


This study assessed the association between pain perception and psychological variables in women with vulvar vestibulitis syndrome (VVS) by comparing 28 VVS women with 50 healthy women. We assessed non genital systemic pain perception with quantitative sensory testing by administering experimental pain stimuli to the forearm. The VVS women demonstrated a lower pain threshold and a higher magnitude estimation of pain, combined with a higher trait anxiety, increased somatization, and a lower body image. Among the VVS women, nonvaginal pain catastrophizing was significantly related to reported pain during coitus. A cluster analysis revealed four subtypes of VVS women, as characterized by levels of pain and personality variables. I suggest implications for the assessment and treatment of women suffering from painful coitus. PMID:16020147

Granot, Michal; Lavee, Yoav



Lower-Order Pain-Related Constructs are More Predictive of Cold Pressor Pain Ratings than Higher-Order Personality Traits  

PubMed Central

Pain is a debilitating condition affecting millions each year, yet what predisposes certain individuals to be more sensitive to pain remains relatively unknown. Several psychological factors have been associated with pain perception, but the structural relations between multiple higher- and lower-order constructs and pain are not well understood. Thus, we aimed to examine the associations between pain perception using the cold pressor task (CPT), higher-order personality traits (neuroticism, negative affectivity, trait anxiety, extraversion, positive affectivity, psychoticism), and lower-order pain-related psychological constructs (pain catastrophizing [pre- and post], fear of pain, anxiety sensitivity, somatosensory amplification, hypochondriasis) in 66 pain-free adults. Factor analysis revealed three latent psychological variables: pain- or body-sensitivity, negative affect/neuroticism, and positive affect/extraversion. Similarly, pain responses factored into three domains: intensity, quality, and tolerance. Regression and correlation analyses demonstrated 1) all the lower-order pain constructs (fear, catastrophizing, and hypochondriasis) are related through a single underlying latent factor, that is partially related to the higher-order negative-valence personality traits; 2) pain- or body-sensitivity was more strongly predictive of pain quality than higher-order traits; and 3) the form of pain assessment is important – only qualitative pain ratings were significantly predicted by the psychological factors. Perspective: Consistent with the biopsychosocial model, these results suggest multiple pain-related psychological measures likely assess a common underlying factor, which is more predictive of qualitative than intensity pain ratings. This information may be useful for the development and advancement of pain assessments and treatments while considering the multidimensional nature of pain.

Lee, Jennifer E; Watson, David; Frey Law, Laura A



[Botulinum toxins for pain].  


We review the evidence of botulinum toxins in the treatment of pain. Main indications of botulinum toxin treatment, dystonia and spasticity, involve pain. Increasing evidence suggests direct analgesic effects of botulinum. Botulinum inhibits release of pain mediators (substance P, CGRP, excitatory amino acids, ATP, noradrenaline). Clinical trials have consistently shown analgesic effect of botulinum toxin in post-stroke shoulder pain, bladder dysfunction, chronic migraine, neuropathic pain, bruxism and lateral epicondylitis. Other pain conditions have been studied with yet uncertain results. It seems that the number of patients who would benefit from botulinum toxin treatment will increase considerably in the future. PMID:22238920

Soinila, Seppo; Haanpää, Maija



Coloring geographical threshold graphs  

SciTech Connect

We propose a coloring algorithm for sparse random graphs generated by the geographical threshold graph (GTG) model, a generalization of random geometric graphs (RGG). In a GTG, nodes are distributed in a Euclidean space, and edges are assigned according to a threshold function involving the distance between nodes as well as randomly chosen node weights. The motivation for analyzing this model is that many real networks (e.g., wireless networks, the Internet, etc.) need to be studied by using a 'richer' stochastic model (which in this case includes both a distance between nodes and weights on the nodes). Here, we analyze the GTG coloring algorithm together with the graph's clique number, showing formally that in spite of the differences in structure between GTG and RGG, the asymptotic behavior of the chromatic number is identical: {chi}1n 1n n / 1n n (1 + {omicron}(1)). Finally, we consider the leading corrections to this expression, again using the coloring algorithm and clique number to provide bounds on the chromatic number. We show that the gap between the lower and upper bound is within C 1n n / (1n 1n n){sup 2}, and specify the constant C.

Bradonjic, Milan [Los Alamos National Laboratory; Percus, Allon [Los Alamos National Laboratory; Muller, Tobias [EINDHOVEN UNIV. OF TECH



Quantitative sensory testing in children with migraine: preliminary evidence for enhanced sensitivity to painful stimuli especially in girls.  


Recent studies showed an enhanced general sensitivity to painful stimuli in adult migraineurs during as well as between attacks. Yet, the influence of a prolonged pain history and potential sex differences has not been studied. We used quantitative sensory testing to examine 25 children with migraine between attacks and 28 controls (age 9-15). The assessment included the measurement of heat and mechanical pain thresholds as well as measures of perceptual sensitization in response to repetitive (mechanical) or tonic (thermal) noxious stimulation at both trigeminal and thenar sites. In addition, the mother was either present or absent during the measurements. Heat pain thresholds were not significantly different between the two groups. However, the child migraineurs showed significantly lower mechanical pain thresholds. Children and especially girls with migraine displayed significantly more sensitization to a tonic heat stimulus at the trigeminal site when the mother was present. The migraineurs also showed a trend towards higher sensitization ratings for mechanical stimuli. Overall, heat pain thresholds were significantly higher in the presence of the mother. In the migraine group only, mechanical pain thresholds were significantly higher when the mother was present. To summarize, an enhanced sensitivity to painful stimuli can already be observed in children suffering from migraine for an average duration of 4.4 years. This may be the result of sensitization in nociceptive pain pathways caused by frequent pain experiences. Girls with migraine were more prone to such sensitization, which may increase their risk for continuing to suffer from migraine throughout adulthood. PMID:16495010

Zohsel, Katrin; Hohmeister, Johanna; Oelkers-Ax, Rieke; Flor, Herta; Hermann, Christiane



Noise thresholds for optical cluster-state quantum computation  

SciTech Connect

In this paper we do a detailed numerical investigation of the fault-tolerant threshold for optical cluster-state quantum computation. Our noise model allows both photon loss and depolarizing noise, as a general proxy for all types of local noise other than photon loss noise. We obtain a threshold region of allowed pairs of values for the two types of noise. Roughly speaking, our results show that scalable optical quantum computing is possible in the combined presence of both noise types, provided that the loss probability is less than 3x10{sup -3} and the depolarization probability is less than 10{sup -4}. Our fault-tolerant protocol involves a number of innovations, including a method for syndrome extraction known as telecorrection, whereby repeated syndrome measurements are guaranteed to agree. This paper is an extended version of Dawson et al. [Phys. Rev. Lett. 96, 020501 (2006)].

Dawson, Christopher M.; Nielsen, Michael A. [School of Physical Sciences, University of Queensland, Queensland 4072 (Australia); Haselgrove, Henry L. [School of Physical Sciences, University of Queensland, Queensland 4072 (Australia); Information Sciences Laboratory, Defence Science and Technology Organisation, Edinburgh 5111 (Australia)



Diabetic neuropathic pain: a role for testosterone metabolites.  


Diabetic neuropathy is associated with neuropathic pain in about 50% of diabetic subjects. Clinical management of neuropathic pain is complex and so far unsatisfactory. In this study, we analyzed the effects of the testosterone metabolites, dihydrotestosterone (DHT), and 3?-diol, on nociceptive and allodynia thresholds and on molecular and functional parameters related to pain modulation in the dorsal horns of the spinal cord and in the dorsal root ganglia of rats rendered diabetic by streptozotocin injection. Furthermore, the levels of DHT and 3?-diol were analyzed in the spinal cord. Diabetes resulted in a significant decrease in DHT levels in the spinal cord that was reverted by DHT or 3?-diol treatments. In addition, 3?-diol treatment resulted in a significant increase in 3?-diol in the spinal cord compared with control values. Both steroids showed analgesic properties on diabetic neuropathic pain, affecting different pain parameters and possibly by different mechanisms of action. Indeed, DHT counteracted the effect of diabetes on the mechanical nociceptive threshold, pre- and post-synaptic components, glutamate release, astrocyte immunoreactivity, and expression of interleukin-1? (IL1?), while 3?-diol was effective on tactile allodynia threshold, glutamate release, astrocyte immunoreactivity and the expression of substance P, toll-like receptor 4, tumor necrosis factor-?, transforming growth factor ?-1, IL1?, and translocator protein. These results indicate that testosterone metabolites are potential agents for the treatment of diabetic neuropathic pain. PMID:24424289

Calabrese, Donato; Giatti, Silvia; Romano, Simone; Porretta-Serapiglia, Carla; Bianchi, Roberto; Milanese, Marco; Bonanno, Giambattista; Caruso, Donatella; Viviani, Barbara; Gardoni, Fabrizio; Garcia-Segura, Luis Miguel; Melcangi, Roberto Cosimo



Geometric Tolerance Assessment.  

National Technical Information Service (NTIS)

The tolerance assessment problem is vital to effective quality improvement and it is important that all issues, from functional requirement, tolerance specification, measurement strategy to assessment algorithms are thought through and analyzed at the des...

A. B. Forbes



Lactose tolerance tests  


Hydrogen breath test for lactose tolerance ... Two common methods include: Lactose tolerance blood test Hydrogen breath test The hydrogen breath test is the preferred method. It measures the amount of hydrogen in the air you breathe out. ...


Associations between serotonin transporter gene polymorphisms and heat pain perception in adults with chronic pain  

PubMed Central

Background The triallelic serotonin transporter gene linked polymorphic region (5-HTTLPR) has been associated with alterations in thermal pain perception. The primary aim of this study was to investigate the associations between heat pain (HP) perception and the triallelic 5-HTTLPR in a large cohort of adults with chronic pain. Methods The cohort included 277 adults with chronic pain who met inclusion criteria, and were consecutively admitted to an outpatient pain rehabilitation program from March 2009 through March 2010. Individuals were genotyped for the triallelic 5-HTTLPR (including rs25531) and categorized as high, intermediate, or low expressors of the serotonin transporter. Standardized measures of HP perception were obtained using a validated quantitative sensory test method of levels. Results The distribution of the high, intermediate, and low expressing genotypes was 61 (22%), 149 (54%) and 67 (24%), respectively. The Hardy-Weinberg P-value was 0.204 which indicated no departure from equilibrium. A significant effect of genotype was observed for values of HP threshold (P?=?0.029). Individual group comparisons showed that values of HP threshold were significantly greater in the intermediate compared to the high expressing group (P?=?0.009) but not the low expressing group (P?>?0.1). In a multiple variable linear regression model, the intermediate group (P?=?0.034) and male sex (P?=?0.021) were associated with significantly greater values of HP 0.5, but no significant genotype-by-sex interaction effect was observed. Conclusions In this study that involved adults with chronic pain, the intermediate triallelic 5-HTTLPR expressing group, but not the low expressing group, was associated with greater HP thresholds compared to the high expressing group.



Sickle Cell Pain  


... manage pain. Distraction – engaging activities (such as hobbies, video games and movies) that change the patient's focus can help relieve stress and pain. Psychotherapy – speaking with a mental health professional about the stress and frustration of sickle ...


Chest Pain, Chronic  


... Yes Your pain may be caused by POSTHERPETIC NEURALGIA, a condition that can remain after the shingles infection. See your doctor. In many cases, postherpetic neuralgia can be treated with over-the-counter pain ...


Abdominal Pain Syndrome  


... of the structures within the abdomen or the abdominal wall. In addition, pain messages originating in the chest, ... lungs) Pulmonary embolism (blood clots to the lungs) Abdominal or chest wall pain: Shingles (herpes zoster infection) Costochondritis (inflammation of ...


Animals, pain and morality.  


While it is widely agreed that the infliction upon innocents of needless pain is immoral, many have argued that, even though nonhuman animals act as if they feel pain, there is no reason to think that they actually suffer painful experiences. And if our actions only appear to cause nonhuman animals pain, then such actions are not immoral. On the basis of the claim that certain behavioural responses to organismic harm are maladaptive, whereas the ability to feel pain is itself adaptive, this article argues that the experience of pain should be viewed as the proximate cause of such occasionally maladaptive behaviour. But as nonhuman animals also display such maladaptive traits, we have reason to conclude that they feel pain. Hence, we have reason to hold that it is indeed possible to inflict needless pain on nonhuman animals, which would be immoral. PMID:15948329

Carter, Alan



Adolescent Anterior Knee Pain  


... pain in the front and center of the knee (anterior knee pain) is common among active, healthy young people, ... not caused by any particular abnormality in the knee and does not mean that the knee will ...


Diclofenac Topical (osteoarthritis pain)  


... gel (Voltaren) is used to relieve pain from osteoarthritis (arthritis caused by a breakdown of the lining ... Diclofenac topical liquid (Pennsaid) is used to relieve osteoarthritis pain in the knees. Diclofenac is in a ...


What Is Back Pain?  


... any treatment, but you may want to take acetaminophen, aspirin, or ibuprofen to help ease the pain. ... medications are over-the-counter drugs such as acetaminophen and aspirin or prescription pain medications. Topical analgesics ...


Reduction of human experimental muscle pain by alfentanil and morphine.  


Musculoskeletal pain is a major clinical problem. By using various experimental models in humans, the understanding of the basic mechanisms behind muscle pain can increase, thereby giving hope for new and optimized treatment. Opioids are increasingly often used to treat muscle pain. There are, however, a limited number of previous studies on opioids and muscle pain, most of them using a relative low, single dose. Therefore, we wanted to further study the effect of two rather high doses of alfentanil (25 and 75ng/ml) and morphine (0.14 and 0.28mg/kg) in human volunteers. The study consisted of two parallel studies with morphine and alfentanil, respectively, and was conducted as randomized, double-blinded, placebo-controlled, 3-way cross-over. We used intramuscular infusion of hypertonic saline and intramuscular electrical stimulation to induce experimental pain. Visual analog scale (VAS)-score, intramuscular electrical pain thresholds and pain area (local and referred) were measured. Both alfentanil and morphine at their highest doses induced a 6 to 7-fold increase in pain thresholds to single and repetitive (5 stimulations, 2Hz) electrical stimulation. Alfentanil and morphine also reduced VAS score about 4 to 5-fold during suprathreshold electric stimulation and during infusion of hypertonic saline. None of the drugs decreased referred pain. There were no apparent differences between the drugs, in terms of effect or adverse reactions. In conclusion, this is the first study to compare two high doses of alfentanil and morphine on experimental muscle pain in humans. Both alfentanil and morphine reduced experimental muscle pain. There were no indications of any true pharmacodynamic differences between the two drugs. PMID:16414295

Schulte, Helène; Segerdahl, Märta; Graven-Nielsen, Thomas; Grass, Stefan



Posttonsillectomy pain in children.  


Tonsillectomy, used to treat a variety of pediatric disorders, including obstructive sleep apnea, peritonsillar cellulitis or abscesses, and very frequent throat infection, is known to produce nausea, vomiting, and prolonged, moderate-to-severe pain. The authors review the causes of posttonsillectomy pain, current findings on the efficacy of various pharmacologic and nonpharmacologic interventions in pain management, recommendations for patient and family teaching regarding pain management, and best practices for improving medication adherence. PMID:24445532

Sutters, Kimberly A; Isaacson, Glenn



Cancer pain and anxiety  

Microsoft Academic Search

Anxiety and pain can be understood with a multidimensional framework that accounts for somatic, emotional, cognitive, and\\u000a behavioral aspects of these conditions. Patients who have cancer or treatment-related pain are more likely to be anxious than\\u000a cancer patients without pain. Patients with cancer pain and anxiety cause difficult diagnostic dilemmas because some degree\\u000a of anxiety is a normal response to

Paul D. Thielking



Plant salt tolerance  

Microsoft Academic Search

Soil salinity adversely affects crop productivity and quality. The success of breeding programs aimed at salinity tolerant crop varieties is limited by the lack of a clear understanding of the molecular basis of salt tolerance. Recent advances in genetic analysis of Arabidopsis mutants defective in salt tolerance, and molecular cloning of these loci, have showed some insight into salt stress

Viswanathan Chinnusamy; Jian-Kang Zhu



Microsoft Academic Search

Neuromodulation and Chronic Pain Theodosiadis P, Samoladas E, Grosomanidis V, Karakoulas K, Vasilakos D Chronic pain causes extreme suffering for millions of people worldwide. It is the leading cause for lost workdays and patients often undergo expensive courses of treatment. Because chronic pain is often difficult to relieve for sustained periods of time, it can have a significant impact on

Theodosiadis Panagiotis; Samoladas Efthimios; Grosomanidis Vasilis; Elliot S. Krames



Pediatric Procedural Pain  

ERIC Educational Resources Information Center

This article reviews the various settings in which infants, children, and adolescents experience pain during acute medical procedures and issues related to referral of children to pain management teams. In addition, self-report, reports by others, physiological monitoring, and direct observation methods of assessment of pain and related constructs…

Blount, Ronald L.; Piira, Tiina; Cohen, Lindsey L.; Cheng, Patricia S.



Functional Abdominal Pain Syndrome  

Microsoft Academic Search

Functional abdominal pain syndrome (FAPS) differs from the other functional bowel disorders; it is less common, symptoms largely are unrelated to food intake and defecation, and it has higher comorbidity with psy- chiatric disorders. The etiology and pathophysiology are incompletely understood. Because FAPS likely repre- sents a heterogenous group of disorders, peripheral neu- ropathic pain mechanisms, alterations in endogenous pain




Treating myofascial pain  

Microsoft Academic Search

SummaryNeuropathic pain invariably affects the musculoskeletal system, causing muscle contracture and shortening: “Myofascial Pain”. Spondylosis, the universal outcome of age, wear and tear, is probably the most common cause of neuropathic pain. By irritating nerve roots, spondylosis can lead to peripheral neuropathy and muscle shortening. Many myofascial syndromes (from Achilles Tendonitis to Tennis Elbow) caused by muscle shortening of spondylotic

C Chan Gunn



Paine Appointed Administrator  

NASA Technical Reports Server (NTRS)

President Richard M. Nixon announcing the appointment of Dr. Thomas O. Paine as Administrator for the National Aeronautics and Space Administration. The ceremony was held at the White House. Paine had been serving as acting administrator. From left to right: President Richard M. Nixon NASA Administrator Dr. Thomas O. Paine Vice President Spiro T. Agnew



Definitions and Types of Pain  


... Types of Pain Defining Pain Pain is a perception that signals the individual that tissue damage has ... in the body that are involved in the perception of pain are called "nociception." Basic and clinical ...


Music can effectively reduce pain perception in women rather than men.  


Objective: Nowadays music is used to decrease pain and increase relaxation in clinical settings. It is hypothesized that music can affect women more easily than men. We assessed the effect of two types of music (Iranian folkloric and preferred music) on pain tolerance and pain rating in cold pressor test. Methodology: A consecutive sample of 50 healthy Iranian medical students was enrolled. They reported pain tolerance and pain rating in cold pressor test in three different musical conditions served as the outcome measures. The results were analyzed with repeated measurement analysis of variance. Result: Mean tolerance time was significantly higher in preferred music compared to Iranian folkloric music (F (1,48) =25.44, p=0.0001) and no music (F(1,48)=3.51, p=0.0001) conditions. There was a significant interaction when tolerance time in no music condition was compared to preferred music condition, regarding sex; Tolerance time increased more in females (F(1,48)=5.53, p=0.023). The results also indicated that pain ratings, regardless of sex, were different in three musical conditions (F(1.7,81.34)=15.37, p=0.0001). Conclusion: Music distracted attention from pain and Women can be impressed and distracted more easily by music. PMID:24353523

Ghaffaripour, Sina; Mahmoudi, Hilda; Sahmeddini, Mohammad Ali; Alipour, Abbas; Chohedri, Abdolhamid



Ethnic differences in pain and pain management  

PubMed Central

SUMMARY Considerable evidence demonstrates substantial ethnic disparities in the prevalence, treatment, progression and outcomes of pain-related conditions. Elucidating the mechanisms underlying these group differences is of crucial importance in reducing and eliminating disparities in the pain experience. Over recent years, accumulating evidence has identified a variety of processes, from neurophysiological factors to structural elements of the healthcare system, that may contribute to shaping individual differences in pain. For example, the experience of pain differentially activates stress-related physiological responses across various ethnic groups, members of different ethnic groups appear to use differing coping strategies in managing pain complaints, providers’ treatment decisions vary as a function of patient ethnicity and pharmacies in predominantly minority neighborhoods are far less likely to stock potent analgesics. These diverse factors, and others may all play a role in facilitating elevated levels of pain-related suffering among individuals from ethnic minority backgrounds. Here, we present a brief, nonexhaustive review of the recent literature and potential physiological and sociocultural mechanisms underlying these ethnic group disparities in pain outcomes.

Campbell, Claudia M; Edwards, Robert R



Persistent Peripheral Inflammation Attenuates Morphine-induced Periaqueductal Gray Glial Cell Activation and Analgesic Tolerance in the Male Rat  

PubMed Central

Morphine is among the most prevalent analgesics prescribed for chronic pain. However, prolonged morphine treatment results in the development of analgesic tolerance. An abundance of evidence has accumulated indicating that CNS glial cell activity facilitates pain transmission and opposes morphine analgesia. While the midbrain ventrolateral periaqueductal gray (vlPAG) is an important neural substrate mediating pain modulation and the development of morphine tolerance, no studies have directly assessed the role of PAG-glia. Here we test the hypothesis that morphine-induced increases in vlPAG glial cell activity contribute to the development of morphine tolerance. As morphine is primarily consumed for the alleviation of severe pain, the influence of persistent inflammatory pain was also assessed. Administration of morphine, in the absence of persistent inflammatory pain, resulted in the rapid development of morphine tolerance and was accompanied by a significant increase in vlPAG glial activation. In contrast, persistent inflammatory hyperalgesia, induced by intraplantar administration of Complete Freund’s Adjuvant (CFA), significantly attenuated the development of morphine tolerance. No significant differences were noted in vlPAG glial cell activation for CFA-treated animals versus controls. These results indicate that vlPAG glia are modulated by a persistent pain state, and implicate vlPAG glial cells as possible regulators of morphine tolerance. Perspective The development of morphine tolerance represents a significant impediment to its use in the management of chronic pain. We report that morphine tolerance is accompanied by increased glial cell activation within the vlPAG, and that the presence of a persistent pain state prevented vlPAG glial activation and attenuated morphine tolerance.

Eidson, Lori N.; Murphy, Anne Z.



Phenotyping chronic pelvic pain based on latent class modeling of physical examination.  


Introduction. Defining clinical phenotypes based on physical examination is required for clarifying heterogeneous disorders such as chronic pelvic pain (CPP). The objective of this study was to determine the number of classes within 4 examinable regions and then establish threshold and optimal exam criteria for the classes discovered. Methods. A total of 476 patients meeting the criteria for CPP were examined using pain pressure threshold (PPT) algometry and standardized numeric scale (NRS) pain ratings at 30 distinct sites over 4 pelvic regions. Exploratory factor analysis, latent profile analysis, and ROC curves were then used to identify classes, optimal examination points, and threshold scores. Results. Latent profile analysis produced two classes for each region: high and low pain groups. The optimal examination sites (and high pain minimum thresholds) were for the abdominal wall region: the pair at the midabdomen (PPT threshold depression of > 2); vulvar vestibule region: 10:00 position (NRS > 2); pelvic floor region: puborectalis (combined NRS > 6); vaginal apex region: uterosacral ligaments (combined NRS > 8). Conclusion. Physical examination scores of patients with CPP are best categorized into two classes: high pain and low pain. Standardization of the physical examination in CPP provides both researchers and general gynecologists with a validated technique. PMID:24455240

Fenton, B W; Grey, S F; Reichenbach, M; McCarroll, M; Von Gruenigen, V



Musculoskeletal chest wall pain  

PubMed Central

The musculoskeletal structures of the thoracic wall and the neck are a relatively common source of chest pain. Pain arising from these structures is often mistaken for angina pectoris, pleurisy or other serious disorders. In this article the clinical features, pathogenesis and management of the various musculoskeletal chest wall disorders are discussed. The more common causes are costochondritis, traumatic muscle pain, trauma to the chest wall, “fibrositis” syndrome, referred pain, psychogenic regional pain syndrome, and arthritis involving articulations of the sternum, ribs and thoracic spine. Careful analysis of the history, physical findings and results of investigation is essential for precise diagnosis and effective treatment. ImagesFig. 3Fig. 4Fig. 5

Fam, Adel G.; Smythe, Hugh A.



Greater trochanteric hip pain.  


In the patient with lateral hip pain, there is a broad differential diagnosis, making appropriate evaluation and management challenging. Greater trochanteric pain syndrome is a term used to denote chronic lateral hip pain and encompasses several painful soft tissue diagnoses including coxa saltans, trochanteric bursitis, and gluteus minimus and medius tendon tears. An overview of these common causes is presented through a series of cases that encompass the anatomic associations, classic presentations, diagnostic tests, and management strategies unique to each disorder. By reviewing this information, we hope to provide clinicians with the tools to evaluate greater trochanteric pain syndrome efficiently and effectively. PMID:24651142

Kimpel, Diane M; Garner, Chadwick C; Magone, Kevin M; May, Jedediah H; Lawless, Matthew W



Posterior knee pain  

PubMed Central

Posterior knee pain is a common patient complaint. There are broad differential diagnoses of posterior knee pain ranging from common causes such as injury to the musculotendinous structures to less common causes such as osteochondroma. A precise understanding of knee anatomy, the physical examination, and of the differential diagnosis is needed to accurately evaluate and treat posterior knee pain. This article provides a review of the anatomy and important aspects of the history and physical examination when evaluating posterior knee pain. It concludes by discussing the causes and management of posterior knee pain.

Perret, D.



Fatigue Crack Growth Threshold Testing of Metallic Rotorcraft Materials  

NASA Technical Reports Server (NTRS)

Results are presented for a program to determine the near-threshold fatigue crack growth behavior appropriate for metallic rotorcraft alloys. Four alloys, all commonly used in the manufacture of rotorcraft, were selected for study: Aluminum alloy 7050, 4340 steel, AZ91E Magnesium, and Titanium alloy Ti-6Al-4V (beta-STOA). The Federal Aviation Administration (FAA) sponsored this research to advance efforts to incorporate damage tolerance design and analysis as requirements for rotorcraft certification. Rotorcraft components are subjected to high cycle fatigue and are typically subjected to higher stresses and more stress cycles per flight hour than fixed-wing aircraft components. Fatigue lives of rotorcraft components are generally spent initiating small fatigue cracks that propagate slowly under near-threshold cracktip loading conditions. For these components, the fatigue life is very sensitive to the near-threshold characteristics of the material.

Newman, John A.; James, Mark A.; Johnson, William M.; Le, Dy D.



Immune Tolerance and Transplantation  

PubMed Central

Successful allogeneic hematopoietic stem cell transplantation (HSCT) and solid organ transplantation require development of a degree of immune tolerance against allogeneic antigens. T lymphocytes play a critical role in allograft rejection, graft failure, and graft versus host disease (GVHD). T cell tolerance occurs by two different mechanisms; i) depletion of self-reactive T cells during their maturation in the thymus (central tolerance) ii) suppression/elimination of self-reactive mature T cells in the periphery (peripheral tolerance). Induction of transplant tolerance improves transplantation outcomes. Adoptive immunotherapy with immune suppressor cells including regulatory T cells, NK-T cells, veto cells and facilitating cells are promising therapies for modulation of immune tolerance. Achieving mixed chimerism with the combination of thymic irradiation and T cell depleting antibodies, costimulatory molecule blockade with/without inhibitory signal activation and elimination of alloreactive T cells with varying methods including pre or post-transplant cyclophosphamide administration appear to be effective methods to induce transplant tolerance.

Alpdogan, Onder; van den Brink, Marcel RM



Learning foraging thresholds for lizards  

SciTech Connect

This work gives a proof of convergence for a randomized learning algorithm that describes how anoles (lizards found in the Carribean) learn a foraging threshold distance. This model assumes that an anole will pursue a prey if and only if it is within this threshold of the anole`s perch. This learning algorithm was proposed by the biologist Roughgarden and his colleagues. They experimentally confirmed that this algorithm quickly converges to the foraging threshold that is predicted by optimal foraging theory our analysis provides an analytic confirmation that the learning algorithm converses to this optimal foraging threshold with high probability.

Goldberg, L.A. [Univ. of Warwick, Coventry (United Kingdom). Dept. of Computer Science; Hart, W.E. [Sandia National Labs., Albuquerque, NM (United States); Wilson, D.B. [Massachusetts Inst. of Tech., Cambridge, MA (United States)



Clinical relevance of cannabis tolerance and dependence.  


Psychoactive drugs are often widely used before tolerance and dependence is fully appreciated. Tolerance to cannabis-induced cardiovascular and autonomic changes, decreased intraocular pressure, sleep and sleep EEG, mood and behavioral changes is acquired and, to a great degree, lost rapidly with optimal conditions. Mechanisms appear more functional than metabolic. Acquisition rate depends on dose and dose schedule. Dependence, manifested by withdrawal symptoms after as little as 7 days of THC administration, is characterized by irritability, restlessness, insomnia, anorexia, nausea, sweating, salivation, increased body temperature, altered sleep and waking EEG, tremor, and weight loss. Mild and transient in the 120 subjects studied, the syndrome was similar to sedative drug withdrawal. Tolerance to drug side effects can be useful. Tolerance to therapeutic effects or target symptoms poses problems. Clinical significance of dependence is difficult to assess since drug-seeking behavior has many determinants. Cannabis-induced super sensitivity should be considered wherever chronic drug administration is anticipated in conditions like epilepsy, glaucoma or chronic pain. Cannabis pharmacology suggests ways of minimizing tolerance and dependence problems. PMID:6271820

Jones, R T; Benowitz, N L; Herning, R I



Citalopram Treatment of Pediatric Recurrent Abdominal Pain and Comorbid Internalizing Disorders: An Exploratory Study  

ERIC Educational Resources Information Center

Objective: To assess the potential efficacy, tolerability, and safety of citalopram in the treatment of functional pediatric recurrent abdominal pain and comorbid internalizing disorders. Method: Twenty-five clinically referred children and adolescents with recurrent abdominal pain aged 7 to 18 years, inclusive, participated in a 12-week,…

Campo, John V.; Perel, James; Lucas, Amanda; Bridge, Jeff; Ehmann, Mary; Kalas, Catherine; Monk, Kelly; Axelson, David; Birmaher, Boris; Ryan, Neal; Di Lorenzo, Carlo; Brent, David A.



Avicenna's concept of pain  

PubMed Central

Ibn Sina (Latin name – Avicenna, 980–1037) is a famous Muslim physician who wrote The Canon of Medicine. Pain-related writings within The Canon were identified and analysed and compared to Galen and Modern Pain Theory. We found evidence in The Canon that Avicenna challenged Galen's concept of pain. Galen insisted that injuries (breach of continuity) were the only cause of pain. In contrast, Avicenna suggested that the true cause of pain was a change of the physical condition (temperament change) of the organ whether there was an injury present or not. Avicenna extended Galen's descriptions of 4 to 15 types of pain and used a terminology that is remarkably similar to that used in the McGill Pain Questionnaire.

Tashani, Osama A.; Johnson, Mark I.



Effects of Transcutaneous Electrical Nerve Stimulation on Pain, Pain Sensitivity, and Function in People With Knee Osteoarthritis: A Randomized Controlled Trial  

PubMed Central

Background Transcutaneous electrical nerve stimulation (TENS) is commonly used for the management of pain; however, its effects on several pain and function measures are unclear. Objective The purpose of this study was to determine the effects of high-frequency TENS (HF-TENS) and low-frequency TENS (LF-TENS) on several outcome measures (pain at rest, movement-evoked pain, and pain sensitivity) in people with knee osteoarthritis. Design The study was a double-blind, randomized clinical trial. Setting The setting was a tertiary care center. Participants Seventy-five participants with knee osteoarthritis (29 men and 46 women; 31–94 years of age) were assessed. Intervention Participants were randomly assigned to receive HF-TENS (100 Hz) (n=25), LF-TENS (4 Hz) (n=25), or placebo TENS (n=25) (pulse duration=100 microseconds; intensity=10% below motor threshold). Measurements The following measures were assessed before and after a single TENS treatment: cutaneous mechanical pain threshold, pressure pain threshold (PPT), heat pain threshold, heat temporal summation, Timed “Up & Go” Test (TUG), and pain intensity at rest and during the TUG. A linear mixed-model analysis of variance was used to compare differences before and after TENS and among groups (HF-TENS, LF-TENS, and placebo TENS). Results Compared with placebo TENS, HF-TENS and LF-TENS increased PPT at the knee; HF-TENS also increased PPT over the tibialis anterior muscle. There was no effect on the cutaneous mechanical pain threshold, heat pain threshold, or heat temporal summation. Pain at rest and during the TUG was significantly reduced by HF-TENS, LF-TENS, and placebo TENS. Limitations This study tested only a single TENS treatment. Conclusions Both HF-TENS and LF-TENS increased PPT in people with knee osteoarthritis; placebo TENS had no significant effect on PPT. Cutaneous pain measures were unaffected by TENS. Subjective pain ratings at rest and during movement were similarly reduced by active TENS and placebo TENS, suggesting a strong placebo component of the effect of TENS.

Vance, Carol Grace T.; Rakel, Barbara A.; Blodgett, Nicole P.; DeSantana, Josimari Melo; Amendola, Annunziato; Zimmerman, Miriam Bridget; Walsh, Deirdre M.



The ?2 adrenergic receptor regulates morphine tolerance and physical dependence  

Microsoft Academic Search

Adaptations to the chronic administration of opioids reduce the utility of these drugs in treating pain and support addiction. Recent genetics-based approaches have implicated the ?2 adrenergic receptor (?2-AR) in controlling some of these responses. We do not know, however, whether this receptor can modulate tolerance, dependence or changes in gene expression caused by chronic opioid administration. For our studies

De-Yong Liang; Xiaoyou Shi; Xiangqi Li; Jun Li; J. David Clark



[Neuropathic pain enhances expression of HCN2 channel in rat cerebrospinal fluid-contacting nucleus].  


The purpose of this research is to explore the distribution and expression of hyperpolarization-activated cyclic nucleotide-gated channels subtype 2 (HCN2) in cerebrospinal fluid (CSF)-contacting nucleus in neuropathic pain, and provide experimental evidence to reveal the biological function and regulation mechanisms of CSF-contacting nucleus in neuropathic pain. Neuropathic pain model was produced by chronic constriction injury (CCI) in Sprague-Dawley (SD) rats. Intracerebroventricular injection of cholera toxin subunit B (CTb) labeled with horseradish peroxidase (CB-HRP) was used to specifically mark distal CSF-contacting nucleus. The thermal withdrawal latency and mechanical withdrawal threshold of rats were recorded to detect the change of pain threshold. The expressions HCN2 channel and c-Fos proteins in CSF-contacting nucleus were detected by immunofluorescence and Western blot. The results showed that, compared with the control group, CTb-treated rats did not show any differences in the expressions of HCN2 channel and c-Fos proteins in CSF-contacting nucleus, as well as pain threshold. At 7, 14 d after CCI operation, the model rats showed not only significantly increased expressions of HCN2 channel and c-Fos in CSF-contacting nucleus, but also decreased pain threshold. ZD7288, a HCN2 channel blocker, could reverse the above changes in neuropathic pain model rats. These results suggest that the CSF-contacting nucleus may be involved in the process of neuropathic pain via the HCN2 channel. PMID:24964850

Wu, Tong; Cao, Jing; Zhang, Li-Cai



Social tolerance allows cooperation to prevail in an adaptive environment  

NASA Astrophysics Data System (ADS)

In real situations, individuals often have moderate tolerance toward ambient cooperative environment in which they tend to avoid unfavorable interactions and search for favorable ones. How such social tolerance affects the evolution of cooperation and the resulting cooperative networks remains to be answered. To address this issue, here we present an effective model of co-evolutionary prisoner’s dilemma by introducing cooperative environment and social tolerance for networked players. An individual’s level of cooperative environment characterizes the cooperativity and sustainability of its interaction environment centered on itself. In our model, for paired individuals we assume that the one in better cooperative environment has a certain tolerance threshold to the opponent. If the opponent’s cooperative environment level is beyond the tolerance threshold, the one in better cooperative environment cuts unilaterally the link, and rewires to others. Otherwise, the link is not severed, and meanwhile an inhomogeneous strategy imitation process between them is considered. Moreover, a player’s cooperative environment is adjusted in response to the strategy choices in the neighborhood. Interestingly, we find that there exists a moderate tolerance threshold warranting the best promotion of cooperation. We explain the nontrivial results by investigating the time ratio of strategy (network) updating during the whole process and properties in emerging networks. Furthermore, we investigate the effect of memory-dependent discounting of individuals’ cooperative environment on the evolution of cooperation. We also demonstrate the robustness of our results by considering two other modified co-evolutionary rules. Our results highlight the importance of appropriate tolerance threshold for the evolution of cooperation during the entangled co-evolution of strategy and structure.

Chen, Xiaojie; Fu, Feng; Wang, Long



Probabilistic Threshold Criterion  

SciTech Connect

The Probabilistic Shock Threshold Criterion (PSTC) Project at LLNL develops phenomenological criteria for estimating safety or performance margin on high explosive (HE) initiation in the shock initiation regime, creating tools for safety assessment and design of initiation systems and HE trains in general. Until recently, there has been little foundation for probabilistic assessment of HE initiation scenarios. This work attempts to use probabilistic information that is available from both historic and ongoing tests to develop a basis for such assessment. Current PSTC approaches start with the functional form of the James Initiation Criterion as a backbone, and generalize to include varying areas of initiation and provide a probabilistic response based on test data for 1.8 g/cc (Ultrafine) 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) and LX-17 (92.5% TATB, 7.5% Kel-F 800 binder). Application of the PSTC methodology is presented investigating the safety and performance of a flying plate detonator and the margin of an Ultrafine TATB booster initiating LX-17.

Gresshoff, M; Hrousis, C A



Targeting TRPV1 as an Alternative Approach to Narcotic Analgesics to Treat Chronic Pain Conditions  

Microsoft Academic Search

In spite of intense research efforts and after the dedicated Decade of Pain Control and Research, there are not many alternatives\\u000a to opioid-based narcotic analgesics in the therapeutic armamentarium to treat chronic pain conditions. Chronic opioid treatment\\u000a is associated with sedation, tolerance, dependence, hyperalgesia, respiratory depression, and constipation. Since the affective\\u000a component is an integral part of pain perception, perhaps

Louis S. Premkumar



Increased thermal and mechanical nociceptive thresholds in rats with depressive-like behaviors  

PubMed Central

Clinical observations suggest that depressed patients were less sensitive to experimental pain than healthy subjects. However, few animal studies are reported concerning the association of depression and pain. The purpose of this study was to investigate the effects of unpredictable chronic mild stress (UCMS) induced depression on the perceived intensity of painful stimulation in rats. We measured the thermal and mechanical paw withdrawal thresholds (PWT) of normal and spinal nerve ligated (SNL) rats using hot plate test and von Frey test, respectively. The results showed that rats exposed to UCMS exhibited significantly higher thermal and mechanical pain thresholds in comparison to the non-depressed controls. In particular, the PWT of the SNL group was restored to nearly normal level after three weeks of UCMS, and even comparable to that of the control group. These results strongly suggest that the depressed subjects have decreased sensitivity to externally applied noxious stimulation, which is consistent with our previous findings. Research Highlight ? Unpredictable chronic mild stress (UCMS) induces depressive behaviors in rats ? UCMS elevates contact heat paw withdrawal threshold in normal rats ? UCMS elevates mechanical paw withdrawal threshold in normal rats ? UCMS elevates mechanical paw withdrawal threshold in SNL rats

Shi, Miao; Qi, Wei-Jing; Gao, Ge; Wang, Jin-Yan; Luo, Fei



Peripartum pain management in opioid dependent women  

PubMed Central

Increased pain sensitivity and the development of opioid tolerance complicate the treatment of pain experienced by opioid maintained pregnant women during delivery and the perinatal period. The aim of the present study was to investigate differences in pain management of opioid maintained compared to non-dependent pregnant women during delivery and the postpartum period. 40 deliveries of 37 opioid dependent women enrolled in a double-blind, double-dummy randomized controlled trial (RCT) examining the safety and efficacy of methadone (mean dose at the time of delivery = 63.89 mg) and buprenorphine (mean dose at the time of delivery = 14.05 mg) during pregnancy were analyzed and participants were matched to a non-dependent comparison group of 80 pregnant women. Differences in pain management (opioid and non-opioid analgesic medication) during delivery and perinatal period were analyzed. Following cesarean delivery opioid maintained women received significantly less opioid analgesics (day of delivery p = 0.038; day 1: p = 0.02), NSAIDs were administered more frequently to opioid dependent patients than to the comparison group during cesarean section and on the third day postpartum. Significantly higher nicotine consumption in the group of opioid dependent women had a strong influence on the retrieved results, and might be considered as an independent factor of altered pain experience. Differences in pain treatment became evident when comparing opioid maintained women to healthy controls. These differences might be based on psychosocial consequences of opioid addiction along with the lack of an interdisciplinary consensus on pain treatment protocols for opioid dependent patients.

Hoflich, Anna S.; Langer, Martin; Jagsch, Reinhold; Bawert, Andjela; Winklbaur, Bernadette; Fischer, Gabriele; Unger, Annemarie



Prescription Pain Reliever Abuse and Dependence among Adolescents: A Nationally Representative Study  

ERIC Educational Resources Information Center

The study investigates the prevalence, patterns, and correlates of adolescents' abuse, sub-threshold dependence, and dependence on prescription pain relievers (PPRs) in a nationally representative sample. Results show dependence on PPRs can take place without abuse and that sub-threshold dependence could have implications for major diagnostic…

Wu, Li-Tzy; Ringwalt, Christopher L.; Mannelli, Paolo; Patkar, Ashwin A.



Hypothesizing that brain reward circuitry genes are genetic antecedents of pain sensitivity and critical diagnostic and pharmacogenomic treatment targets for chronic pain conditions  

PubMed Central

SUMMARY While it is well established that the principal ascending pathways for pain originate in the dorsal horn of the spinal cord and in the medulla, the control and sensitivity to pain may reside in additional neurological loci, especially in the mesolimbic system of the brain (i.e., a reward center), and a number of genes and associated polymorphisms may indeed impact pain tolerance and or sensitivity. It is hypothesized that these polymorphisms associate with a predisposition to intolerance or tolerance to pain. It is further hypothesized that identification of certain gene polymorphisms provides a unique therapeutic target to assist in the treatment of pain. It is hereby proposed that pharmacogenetic testing of certain candidate genes (i.e., mu receptors, PENK etc.) will result in pharmacogenomic solutions personalized to the individual patient, with potential improvement in clinical outcomes.

Chen, Amanda L.-C.; Chen, Thomas J.H.; Waite, Roger L.; Reinking, Jeffrey; Tung, Howard L.; Rhoades, Patrick; Downs, B. William; Braverman, Eric; Braverman, Dasha; Kerner, Mallory; Blum, Seth H.; DiNubile, Nicholas; Smith, David; Oscar-Berman, Marlene; Prihoda, Thomas J.; Floyd, John B.; O'Brien, David; Liu, H.H.; Blum, Kenneth



Threshold Concepts and Information Literacy  

ERIC Educational Resources Information Center

What do we teach when we teach information literacy in higher education? This paper describes a pedagogical approach to information literacy that helps instructors focus content around transformative learning thresholds. The threshold concept framework holds promise for librarians because it grounds the instructor in the big ideas and underlying…

Townsend, Lori; Brunetti, Korey; Hofer, Amy R.



On computational Gestalt detection thresholds  

Microsoft Academic Search

The aim of this paper is to show some recent developments of computational Gestalt theory, as pioneered by Desolneux, Moisan and Morel. The new results allow to predict much more accurately the detection thresholds. This step is unavoidable if one wants to analyze visual detection thresholds in the light of computational Gestalt theory. The paper first recalls the main elements

Rafael Grompone von Gioi; Jérémie Jakubowicz



Anomalous thresholds of reaction amplitudes  

Microsoft Academic Search

Summary  Anomalous thresholds of reaction amplitudes are studied without recourse to a partial wave expansion. Ft is shown that the\\u000a behavior of the amplitudes is quite similar to that of the partial wave projections even though the Legendre series does not\\u000a converge near the anomalous threshold.

P. G. O. Freund; R. Karplus



The Nature of Psychological Thresholds  

ERIC Educational Resources Information Center

Following G. T. Fechner (1966), thresholds have been conceptualized as the amount of intensity needed to transition between mental states, such as between a states of unconsciousness and consciousness. With the advent of the theory of signal detection, however, discrete-state theory and the corresponding notion of threshold have been discounted.…

Rouder, Jeffrey N.; Morey, Richard D.



GCH1-polymorphism and pain sensitivity among women with provoked vestibulodynia  

PubMed Central

Background Provoked vestibulodynia (PVD) is a pain disorder localized in the vestibular mucosa. It is the most common cause of dyspareunia among young women and it is associated with general pain hypersensitivity and other chronic pain conditions. Polymorphism in the guanosine triphosphate cyclohydrolase (GCH1) gene has been found to influence general pain sensitivity and the risk of developing a longstanding pain condition. The aim of this study was to investigate GCH1-polymorphism in women with PVD and healthy controls, in correlation to pain sensitivity. Results We found no correlation between the previously defined pain-protective GCH1-SNP combination and the diagnosis of PVD. Nor any correlation with pain sensitivity measured as pressure pain thresholds on the arm, leg and in the vestibule, coital pain scored on a visual analog scale and prevalence of other bodily pain conditions among women with PVD (n?=?98) and healthy controls (n?=?102). However, among patients with current treatment (n?=?36), there was a significant interaction effect of GCH1-gene polymorphism and hormonal contraceptive (HC) therapy on coital pain (p?=?0.04) as well as on pressure pain thresholds on the arm (p?=?0.04). PVD patients carrying the specified SNP combination and using HCs had higher pain sensitivity compared to non-carriers. In non-HC-users, carriers had lower pain sensitivity. Conclusions The results of this study gave no support to the hypothesis that polymorphism in the GCH1-gene contributes to the etiology of PVD. However, among patients currently receiving treatment an interaction effect of the defined SNP combination and use of hormonal contraceptives on pain sensitivity was found. This finding offers a possible explanation to the clinically known fact that some PVD patients improve after cessation of hormonal contraceptives, indicating that PVD patients carrying the defined SNP combination of GCH1 would benefit from this intervention.



Pain after earthquake  

PubMed Central

Introduction On 6 April 2009, at 03:32 local time, an Mw 6.3 earthquake hit the Abruzzi region of central Italy causing widespread damage in the City of L Aquila and its nearby villages. The earthquake caused 308 casualties and over 1,500 injuries, displaced more than 25,000 people and induced significant damage to more than 10,000 buildings in the L'Aquila region. Objectives This observational retrospective study evaluated the prevalence and drug treatment of pain in the five weeks following the L'Aquila earthquake (April 6, 2009). Methods 958 triage documents were analysed for patients pain severity, pain type, and treatment efficacy. Results A third of pain patients reported pain with a prevalence of 34.6%. More than half of pain patients reported severe pain (58.8%). Analgesic agents were limited to available drugs: anti-inflammatory agents, paracetamol, and weak opioids. Reduction in verbal numerical pain scores within the first 24 hours after treatment was achieved with the medications at hand. Pain prevalence and characterization exhibited a biphasic pattern with acute pain syndromes owing to trauma occurring in the first 15 days after the earthquake; traumatic pain then decreased and re-surged at around week five, owing to rebuilding efforts. In the second through fourth week, reports of pain occurred mainly owing to relapses of chronic conditions. Conclusions This study indicates that pain is prevalent during natural disasters, may exhibit a discernible pattern over the weeks following the event, and current drug treatments in this region may be adequate for emergency situations.



Neurological diseases and pain  

PubMed Central

Chronic pain is a frequent component of many neurological disorders, affecting 20–40% of patients for many primary neurological diseases. These diseases result from a wide range of pathophysiologies including traumatic injury to the central nervous system, neurodegeneration and neuroinflammation, and exploring the aetiology of pain in these disorders is an opportunity to achieve new insight into pain processing. Whether pain originates in the central or peripheral nervous system, it frequently becomes centralized through maladaptive responses within the central nervous system that can profoundly alter brain systems and thereby behaviour (e.g. depression). Chronic pain should thus be considered a brain disease in which alterations in neural networks affect multiple aspects of brain function, structure and chemistry. The study and treatment of this disease is greatly complicated by the lack of objective measures for either the symptoms or the underlying mechanisms of chronic pain. In pain associated with neurological disease, it is sometimes difficult to obtain even a subjective evaluation of pain, as is the case for patients in a vegetative state or end-stage Alzheimer's disease. It is critical that neurologists become more involved in chronic pain treatment and research (already significant in the fields of migraine and peripheral neuropathies). To achieve this goal, greater efforts are needed to enhance training for neurologists in pain treatment and promote greater interest in the field. This review describes examples of pain in different neurological diseases including primary neurological pain conditions, discusses the therapeutic potential of brain-targeted therapies and highlights the need for objective measures of pain.



Critical line in random-threshold networks with inhomogeneous thresholds.  


We calculate analytically the critical connectivity K_{c} of random-threshold networks (RTNs) for homogeneous and inhomogeneous thresholds, and confirm the results by numerical simulations. We find a superlinear increase of K_{c} with the (average) absolute threshold mid R:hmid R: , which approaches K_{c}(mid R:hmid R:) approximately h;{2}(2lnmid R:hmid R:) for large mid R:hmid R: , and show that this asymptotic scaling is universal for RTNs with Poissonian distributed connectivity and threshold distributions with a variance that grows slower than h;{2} . Interestingly, we find that inhomogeneous distribution of thresholds leads to increased propagation of perturbations for sparsely connected networks, while for densely connected networks damage is reduced; the crossover point yields a characteristic connectivity K_{d} , that has no counterpart in Boolean networks with transition functions not restricted to threshold-dependent switching. Last, local correlations between node thresholds and in-degree are introduced. Here, numerical simulations show that even weak (anti)correlations can lead to a transition from ordered to chaotic dynamics, and vice versa. PMID:19256916

Rohlf, Thimo



NSDL National Science Digital Library

While some groups only give lip service to spreading the good word about the importance of tolerance, the Southern Poverty Law Center has created this fine website to disseminate valuable materials for people interested in dismantling bigotry and creating communities that welcome and value diversity. The site has much to offer, including daily news updates about groups and individuals working for tolerance and fighting hate, guidebooks for adult and youth activists, and educational games for young children. The site is thematically divided into areas for teachers, teens, children, and parents. The parents section has some great resources, including a feature titled "10 Ways to Nurture Tolerance" and a list of helpful books on the theme of tolerance for parents that is quite handy. Educators will find the "Teaching Tolerance" area a welcome find, as it contains a number of classroom activities and the current edition (along with an archive) of their Teaching Tolerance magazine.


Occlusal Therapy in the Management of Chronic Orofacial Pain  

PubMed Central

Review of the literature indicates that most routine orofacial dysfunctions are characterized by deep pain. Various disorders of the masticatory systems, particularly musculoskeletal conditions, are thought to be triggered by occlusal disharmonies. The pain component develops following a pattern of bruxism, muscle hyperactivity, fatigue and spasm. Treatment for most disorders has been to modify the occlusion, although the rational for doing so appears questionable. Critical issues in the field of occlusion related to orofacial pain are reviewed: occlusal disharmonies, coincidence of retruded-intercuspal contact positions, non-working side interferences, maximum intercuspation of teeth, occlusal adjustment, and occlusal appliances. The studies reviewed fail to support the clinical objective of obtaining equal contact at retruded and intercuspal positions and that the lateral pterygoid muscles stabilize the temporomandibular joint. The relationship between non-working side interferences and pain dysfunction is also not readily supported by controlled studies. Occlusal adjustment appears to be unsatisfactory as a modality for management of pain: not all patients improved following treatment, some relapse occurs even with the most stable contacts, and other treatments such as intra-articular injections of corticosteroids reduced symptoms more readily. Occlusal splints seem to reduce most clinical signs and symptoms on both a short-term and long-term basis. Placement of mandibular orthopedic repositioning appliances results in reduction of pain in some patients, but usually this treatment is followed by extensive rehabilitation. Six major areas are suggested for clinical studies that attempt to relate occlusion to management of orofacial pain. These include: establishment of an ideal jaw position, sequencing of symptoms in the pain history, relationship of pain to other symptoms, development of physiological methods to assess how occlusal modification affects pain perception and pain tolerance, and determination of which treatment modalities produce the most effective relief of pain.

Bush, Francis M.



The neurologist facing pain in dementia.  


INTRODUCTION: Ageing, a common background in dementia, is usually associated with painful disorders. Nevertheless, the use of analgesics is limited due to poor communication. On the other hand, dementia lesions are placed in the nociceptive pathways. For this reason, the painful experience becomes different and distinctive for every lesional type. COURSE: The lateral nociceptive pathway (lateral thalamic nuclei and primary parietal cortex), which is in charge of the primary pain perception, is preserved in dementia. Thereafter, the shear painful perception, including pain intensity and threshold, remains unmodified. Distinctly, the medial pain pathways are affected by dementia lesions. In this pathway are included: the intralaminar thalamic nuclei, the pons (locus ceruleus:LC), the mesencephalon (periaacueductal grey substance: PGS), the hypothalamus (paraventricular nuclei, mamilary tuberculum) and different areas of the parietal (primary, secondary, operculum), temporal (amigdala, hypoccampus) and frontal (anterior cingular: ACC). As a consequence, the features of pain executed by these areas will be compromised: the cognitive assessment, the mood and emotion inherent to pain, the pain memory or the autonomic responses are modified in dementia. Specifically, in Alzheimer's disease (AD) there is a reduction in the anticipatory and avoidance responses and also a flattening of the autonomic responses. These are essentially secondary to the degenerative changes in the medial temporal (pain memory) and ACC (cognitive and mood aspects) areas. In vascular dementias, there is a cortico-subcortical deafferentation secondary to the white matter lesions. The consequence is the presence of hyperpathy and hyperalgesia. In the frontotemporal dementias, there is a reduction in pain expressivity. It is linked to the lesions in the orbitofrontal and anterior temporal areas, which are responsible of the emotional aspects of pain. In Parkinson's disease, painful conditions are a common characteristic. They are attributed to an early lesion in the LC, which reduces its prominent antinociceptive activity. Finally, in the demented patients there is a lack of expectations to analgesic treatments. This means an absence of the placebo effect, which is, alongside the pharmacokinetic action, an inherent part of the analgesic response. The placebo response is related to activity in the ACC and PGS. Giving its lack, higher doses of analgesics are necessary in dementias. CONCLUSIONS: The assessment of pain in dementia is rather complex, which is the main reason for the scarcity of the analgesic treatment in dementias. It must be specific and systematic. For this purpose, the pain scales are a useful tool. For communicative patients, simple visual scales are helpful, meanwhile in the non-communicative patients the multidimensional scales are the most suitable. By this means, the expressive, motor, emotional, functional and social interactions are evaluated. Pain may be responsible of progression and cognitive deterioration in dementia. This evolution could be reversible, and consequently it has to be foreseen in order to implement analgesic treatment. Trying to minimize adverse events, it has to be potent but closely monitored. PMID:22436370

Alvaro González, Luis Carlos



Sleep Disorders and their Association with Laboratory Pain Sensitivity in Temporomandibular Joint Disorder  

PubMed Central

Study Objectives: We characterized sleep disorder rates in temporomandibular joint disorder (TMD) and evaluated possible associations between sleep disorders and laboratory measures of pain sensitivity. Design: Research diagnostic examinations were conducted, followed by two consecutive overnight polysomnographic studies with morning and evening assessments of pain threshold. Setting: Orofacial pain clinic and inpatient sleep research facility Participants: Fifty-three patients meeting research diagnostic criteria for myofascial TMD. Interventions: N/A Measurements and Results: We determined sleep disorder diagnostic rates and conducted algometric measures of pressure pain threshold on the masseter and forearm. Heat pain threshold was measured on the forearm; 75% met self-report criteria for sleep bruxism, but only 17% met PSG criteria for active sleep bruxism. Two or more sleep disorders were diagnosed in 43% of patients. Insomnia disorder (36%) and sleep apnea (28.4%) demonstrated the highest frequencies. Primary insomnia (PI) (26%) comprised the largest subcategory of insomnia. Even after controlling for multiple potential confounds, PI was associated with reduced mechanical and thermal pain thresholds at all sites (P < 0.05). Conversely, the respiratory disturbance index was associated with increased mechanical pain thresholds on the forearm (P < 0.05). Conclusions: High rates of PI and sleep apnea highlight the need to refer TMD patients complaining of sleep disturbance for polysomnographic evaluation. The association of PI and hyperalgesia at a non-orofacial site suggests that PI may be linked with central sensitivity and could play an etiologic role in idiopathic pain disorders. The association between sleep disordered breathing and hypoalgesia requires further study and may provide novel insight into the complex interactions between sleep and pain-regulatory processes. Citation: Smith MT; Wickwire EM; Grace EG; Edwards RR; Buenaver LF; Peterson S; Klick B; Haythornthwaite JA. Sleep disorders and their association with laboratory pain sensitivity in temporomandibular joint disorder. SLEEP 2009;32(6):779–790.

Smith, Michael T.; Wickwire, Emerson M.; Grace, Edward G.; Edwards, Robert R.; Buenaver, Luis F.; Peterson, Stephen; Klick, Brendan; Haythornthwaite, Jennifer A.



Acid tolerance in amphibians  

SciTech Connect

Studies of amphibian acid tolerance provide information about the potential effects of acid deposition on amphibian communities. Amphibians as a group appear to be relatively acid tolerant, with many species suffering increased mortality only below pH 4. However, amphibians exhibit much intraspecific variation in acid tolerance, and some species are sensitive to even low levels of acidity. Furthermore, nonlethal effects, including depression of growth rates and increases in developmental abnormalities, can occur at higher pH.

Pierce, B.A.



Micro-cantilever shocking-acceleration switches with threshold adjusting and 'on'-state latching functions  

Microsoft Academic Search

A micromechanical shocking-acceleration switch is developed. By using electrostatic force combined with the dynamic shocking force, the switch features a threshold adjustable capability. Besides, an electrostatic pull-in phenomenon is used to enable the switch an 'on'-state latching ability. The former facilitates individual applications and can compensate for the threshold inaccuracy from fabrication tolerance. The latter can keep the switch at

Mengjun Jia; Xinxin Li; Zhaohui Song; Minhang Bao; Yuelin Wang; Heng Yang



Painful hip arthroplasty: definition  

PubMed Central

Summary Total hip arthroplasty (THA) has been indicated as the surgical intervention with greatest improvement in pain and physical function. However some patients continue to experience hip pain after elective surgery. We investigate prognostic factors that negatively affect treatment effectiveness and the patient outcome. The “hip region” constitutes the groin, buttock, upper lateral thigh, greater trochanteric area, and the iliac crest. Pain originating from various sources and not directly linked to prosthesis may be perceived here and includes the lumbosacral spine, referred pain from abdominal organs and soft tissue sources such as trochanteric bursitis, tendinitis, hip abductor dysfunction, and inguinal hernia. An accurate assessment of the pain cause is extremely difficult to construct and a complete differential diagnosis is fundamental. We assess all the possible causes of hip pain after THA and we divide them depending on the presence or absence of radiographic signs.

Ferrata, Paolo; Carta, Serafino; Fortina, Mattia; Scipio, Daniele; Riva, Alberto; Di Giacinto, Salvatore



Pain and functional imaging.  

PubMed Central

Functional neuroimaging has fundamentally changed our knowledge about the cerebral representation of pain. For the first time it has been possible to delineate the functional anatomy of different aspects of pain in the medial and lateral pain systems in the brain. The rapid developments in imaging methods over the past years have led to a consensus in the description of the central pain responses between different studies and also to a definition of a central pain matrix with specialized subfunctions in man. In the near future we will see studies where a systems perspective allows for a better understanding of the regulatory mechanisms in the higher-order frontal and parietal cortices. Also, pending the development of experimental paradigms, the functional anatomy of the emotional aspects of pain will become better known.

Ingvar, M



[Neuromusculoskeletal chest pain].  


To determine frequency of neuromusculoskeletal etiology of chest pain is performed. By means of a retrospective analysis and on the basis of the history of the patients' disease, data were collected after chest pain had been medically worked out. The causes to chest pain were in 82% of cardial etiology, in 9% of neuromusculoskeletal etiology, in 6% of gastrointestinal etiology and 3% others. All the patients suffering from neuromusculoskeletal causes to chest pain were, besides anti-rheumatic therapy, also treated by certain form of cardiac therapy. The task of a doctor is to accurately recognize serious disorders as possible causes to chest pain. However, the doctor must not make wrong diagnosis of potentially dangerous conditions thus causing unwanted psychological and economical consequences. In order to realize this, adequate diagnostic possibilities are necessary besides the knowledge about all possible causes to chest pain. PMID:15067819

Horvat, Davor



[Buttocks sciatic pain].  


Confusion between radicular and nerve trunk syndrome is not rare. With sciatic pain, any nerve trunk pain or an atypical nerve course should suggest nerve trunk pain of the sciatic nerve in the buttocks. The usual reflex with sciatic pain is vertebral-radicular conflict. The absence of spinal symptoms and the beginning of pain in the buttocks and not in the lumbar region should reorient the etiologic search. Once a tumor of the nerve trunk has been ruled out (rarely responsible for pain other than that caused by tumor pressure), a myofascial syndrome should be explored searching for clinical, electrophysiological, and radiological evidence of compression of the sciatic trunk by the piriform muscle but also the obturator internus muscle. Hamstring syndrome may be confused with this syndrome. Treatment is first and foremost physical therapy. Failures can be treated with classical CT-guided infiltrations with botulinum toxin. Surgery should only be entertained when all these solutions have failed. PMID:19744678

Labat, J-J; Robert, R; Riant, T; Louppe, J-M; Lucas, O; Hamel, O



Increased colonic pain sensitivity in irritable bowel syndrome is the result of an increased tendency to report pain rather than increased neurosensory sensitivity  

PubMed Central

Objective The aim was to determine whether lower visceral pain thresholds in irritable bowel syndrome (IBS) primarily reflect physiological or psychological factors. Methods Firstly, 121 IBS patients and 28 controls underwent balloon distensions in the descending colon using the ascending methods of limits (AML) to assess pain and urge thresholds. Secondly, sensory decision theory analysis was used to separate physiological from psychological components of perception: neurosensory sensitivity (p(A)) was measured by the ability to discriminate between 30?mm?Hg vs 34?mm?Hg distensions; psychological influences were measured by the report criterion—that is, the overall tendency to report pain, indexed by the median intensity rating for all distensions, independent of intensity. Psychological symptoms were assessed using the Brief Symptom Inventory (BSI). Results IBS patients had lower AML pain thresholds (median: 28?mm?Hg vs 40?mm Hg; p<0.001), but similar neurosensory sensitivity (median p(A): 0.5 vs 0.5; p?=?0.69; 42.6% vs 42.9% were able to discriminate between the stimuli better than chance) and a greater tendency to report pain (median report criterion: 4.0 (“mild” pain) vs 5.2 (“weak” pain); p?=?0.003). AML pain thresholds were not correlated with neurosensory sensitivity (r?=??0.13; p?=?0.14), but were strongly correlated with report criterion (r?=?0.67; p<0.0001). Report criterion was inversely correlated with BSI somatisation (r?=??0.26; p?=?0.001) and BSI global score (r?=??0.18; p?=?0.035). Similar results were seen for the non?painful sensation of urgency. Conclusion Increased colonic sensitivity in IBS is strongly influenced by a psychological tendency to report pain and urge rather than increased neurosensory sensitivity.

Dorn, Spencer D; Palsson, Olafur S; Thiwan, Syed I M; Kanazawa, Motoyori; Clark, W Crawford; van Tilburg, Miranda A L; Drossman, Douglas A; Scarlett, Yolanda; Levy, Rona L; Ringel, Yehuda; Crowell, Michael D; Olden, Kevin W; Whitehead, William E



Sulfur tolerant anode materials  

SciTech Connect

The goal of this program is the development of a molten carbonate fuel cell (MCFC) anode which is more tolerant of sulfur contaminants in the fuel than the current state-of-the-art nickel-based anode structures. This program addresses two different but related aspects of the sulfur contamination problem. The primary aspect is concerned with the development of a sulfur tolerant electrocatalyst for the fuel oxidation reaction. A secondary issue is the development of a sulfur tolerant water-gas-shift reaction catalyst and an investigation of potential steam reforming catalysts which also have some sulfur tolerant capabilities. These two aspects are being addressed as two separate tasks.

Not Available



Sulfur tolerant anode materials  

SciTech Connect

The goal of this program is the development of a molten carbonate fuel cell (MCFC) anode which is more tolerant of sulfur contaminants in the fuel than the current state-of-the-art nickel-based anode structures. This program addresses two different but related aspects of the sulfur contamination problem. The primary aspect is concerned with the development of a sulfur tolerant electrocatalyst for the fuel oxidation reaction. A secondary issue is the development of a sulfur tolerant water-gas-shift reaction catalyst and an investigation of potential steam reforming catalysts which also have some sulfur tolerant capabilities. These two aspects are being addressed as two separate tasks.

Not Available



Pain management: pharmacological approaches  

Microsoft Academic Search

\\u000a More than three quarters of patients with advanced cancer experience chronic pain that is severe enough to warrant therapy\\u000a with opioid drugs [1,2]. The most prevalent pain syndromes are disease related in adults and treatment related in children\\u000a [3,4]. In adults with metastatic solid tumors, disease-related pains are usually persistent and often progressive, a pattern\\u000a that reflects the limited availability

Russell K. Portenoy; Gerri Frager


Managing Breakthrough Pain  

Microsoft Academic Search

Breakthrough cancer pain (BTcP) has been defined as a transitory increase in pain intensity on a baseline pain of moderate\\u000a intensity in patients on regularly administered analgesic treatment. This review provides updated information about the classification,\\u000a assessment, and treatment of BTcP, with special emphasis on the use of opioids. Due to its slow onset to effect, oral opioids\\u000a cannot be

Sebastiano Mercadante


Administration of four different doses of gabapentin reduces awakening from breakthrough pain and adverse effects in outpatients with neuropathic pain during the initial titration  

PubMed Central

Background Gabapentin is a safe and well-tolerated anticonvulsant with a wide therapeutic index, and it is used for neuropathic pain. The aim of this study was to compare previous dosing methods with the administration of four different doses of gabapentin while maintaining the same maximum daily dose for the safe administration of high doses of the medication. Methods The subjects were outpatients with various neuropathic pain syndromes, with at least two of the following symptoms: allodynia, burning pain, shooting pain, or hyperalgesia. The TID group received equal doses of gabapentin 3 times per day, while the QID group received 4 different doses of gabapentin per day. The pain score, frequency of breakthrough pain (BTP), severity and the duration of pain, sleep disturbance due to nocturnal pain, and adverse effects were recorded each day. Results The average daily pain score and sleep disturbance were significantly reduced in the QID group between days 3 and 10 of the experiment. The adverse effects of the medication were also reduced in the QID group. However, the frequency of BTP and severity and duration of pain were not significantly different between two groups. Conclusions Administration of 4 different doses of gabapentin during the initial titration in outpatients with neuropathic pain resulted in a significant reduction in awakening from breakthrough pain and a reduction in the adverse effects of the medication.

Yang, Jong-Yeun; Lee, Won Il; Shin, Woo-Kyung; Kim, Cheul Hong; Baik, Seong-Wan



Management of Pain in the Cancer Patient.  

National Technical Information Service (NTIS)

Contents: Cancer pain management--diagnosis and evaluation; Cancer pain management--multidisciplinary pain clinics; Cancer pain management--psychologic technics; Cancer pain management--pharmacologic technics; Cancer pain management--neurosurgical technic...




PubMed Central

Neck and shoulder pains are presenting or incidental symptoms in a large variety of conditions. There may be similarities in the anatomicophysiological mechanism of pain production and in the clinical picture in many of these conditions. Many of the vague and refractory cases of neck and shoulder pain and of migraine may be due to cervical disc disease. Scalenus anticus syndrome and cardiac disease can be diagnosed or differentiated from cervical disc syndrome only by thorough investigation. Proper treatment of neck and shoulder pain is dependent upon correct diagnosis through complete history, physical examination and laboratory tests, as described in this presentation.

Fields, Albert; Hoesley, John



Painful Boney Metastases  

PubMed Central

Boney metastasis may lead to terrible suffering from debilitating pain. The most likely malignancies that spread to bone are prostate, breast, and lung. Painful osseous metastases are typically associated with multiple episodes of breakthrough pain which may occur with activities of daily living, weight bearing, lifting, coughing, and sneezing. Almost half of these breakthrough pain episodes are rapid in onset and short in duration and 44% of episodes are unpredictable. Treatment strategies include: analgesic approaches with "triple opioid therapy", bisphosphonates, chemotherapeutic agents, hormonal therapy, interventional and surgical approaches, steroids, radiation (external beam radiation, radiopharmaceuticals), ablative techniques (radiofrequency ablation, cryoablation), and intrathecal analgesics.

Smith, Howard S.



Painful boney metastases.  


Boney metastasis may lead to terrible suffering from debilitating pain. The most likely malignancies that spread to bone are prostate, breast, and lung. Painful osseous metastases are typically associated with multiple episodes of breakthrough pain which may occur with activities of daily living, weight bearing, lifting, coughing, and sneezing. Almost half of these breakthrough pain episodes are rapid in onset and short in duration and 44% of episodes are unpredictable. Treatment strategies include: analgesic approaches with "triple opioid therapy", bisphosphonates, chemotherapeutic agents, hormonal therapy, interventional and surgical approaches, steroids, radiation (external beam radiation, radiopharmaceuticals), ablative techniques (radiofrequency ablation, cryoablation), and intrathecal analgesics. PMID:23861996

Smith, Howard S; Mohsin, Intikhab



[Enduring pain II. Treatment].  


Pain disorders present highly challenging therapeutic problems, owing in part to complex co-morbidities associated with pain disorders, notably including psychiatric disorders characterized by depressed mood or anxiety. Many treatments are employed to treat pain-disorder patients, and most are unsatisfactory. Virtually all analgesic medicines in long-term use provide only partial efficacy and present substantial risks of adverse effects, loss of benefit over time, or dependency and risk of abuse. Commonly employed drugs with analgesic properties include non-opioids (mainly nonsteroidal anti-inflammatory agents [NSAIDs] or acetaminophen), many natural or synthetic opioids (including opiates and phenylpiperidines), some antidepressants (especially those with noradrenergic activity), a few anticonvulsants, skeletal muscle relaxants or topical remedies, and a growing variety of experimental treatments. The major overlap between pain and psychiatric disorders, as well as the currently unsatisfactory state of treatments available for chronic pain syndromes, encourage a comprehensive approach to assessment and clinical management of patients with chronic pain. Many current treatment programs for pain disorder patients offer narrowly specialized and incomplete treatment options. Ideally however, such care should be provided by multi-disciplinary teams with expertise in neurology, general medicine, pain management, physical medicine and rehabilitation, as well as psychiatry. Psychiatrists as well as pain specialists can serve an essential role in leading comprehensive assessment and general management of such complex and challenging patients who are typically only partially responsive to available treatments. PMID:24312919

Baldessarini, Ross; Selle, Valerio; Vigo, Daniel V



Pain in Sjögren's syndrome.  


Sjögren's syndrome (SjS) is an autoimmune disease that affects the salivary and lacrimal glands, but it can also have extra-glandular manifestations. Although pain has not yet been fully studied and characterized, it is a symptom that can be often found in patients with SjS, who mainly complain of neuropathic pain, followed by nociceptive pain. The latter when combined with widespread dysfunctional symptoms is defined fibromyalgia. The aim of this work is to analyze the scientific literature on the presence of pain in patients with primary Sjögren's syndrome. PMID:24938195

Giacomelli, C; Talarico, R; Baldini, C; Bazzichi, L



Bayesian estimation of dose thresholds  

NASA Technical Reports Server (NTRS)

An example is described of Bayesian estimation of radiation absorbed dose thresholds (subsequently simply referred to as dose thresholds) using a specific parametric model applied to a data set on mice exposed to 60Co gamma rays and fission neutrons. A Weibull based relative risk model with a dose threshold parameter was used to analyse, as an example, lung cancer mortality and determine the posterior density for the threshold dose after single exposures to 60Co gamma rays or fission neutrons from the JANUS reactor at Argonne National Laboratory. The data consisted of survival, censoring times and cause of death information for male B6CF1 unexposed and exposed mice. The 60Co gamma whole-body doses for the two exposed groups were 0.86 and 1.37 Gy. The neutron whole-body doses were 0.19 and 0.38 Gy. Marginal posterior densities for the dose thresholds for neutron and gamma radiation were calculated with numerical integration and found to have quite different shapes. The density of the threshold for 60Co is unimodal with a mode at about 0.50 Gy. The threshold density for fission neutrons declines monotonically from a maximum value at zero with increasing doses. The posterior densities for all other parameters were similar for the two radiation types.

Groer, P. G.; Carnes, B. A.



Supra-threshold scaling, temporal summation, and after-sensation: relationships to each other and anxiety/fear  

PubMed Central

This study investigated the relationship of thermal pain testing from three types of quantitative sensory testing (ie, supra-threshold stimulus response scaling, temporal summation, and after-sensation) at three anatomical sites (ie, upper extremity, lower extremity, and trunk). Pain ratings from these procedures were also compared with common psychological measures previously shown to be related to experimental pain responses and consistent with fear-avoidance models of pain. Results indicated that supra-threshold stimulus response scaling, temporal summation, and after-sensation, were significantly related to each other. The site of stimulation was also an important factor, with the trunk site showing the highest sensitivity in all three quantitative sensory testing procedures. Supra-threshold response measures were highly related to measures of fear of pain and anxiety sensitivity for all stimulation sites. For temporal summation and after-sensation, only the trunk site was significantly related to anxiety sensitivity, and fear of pain, respectively. Results suggest the importance of considering site of stimulation when designing and comparing studies. Furthermore, psychological influence on quantitative sensory testing is also of importance when designing and comparing studies. Although there was some variation by site of stimulation, fear of pain and anxiety sensitivity had consistent influences on pain ratings.

Robinson, Michael E; Bialosky, Joel E; Bishop, Mark D; Price, Donald D; George, Steven Z



Chronic spinal infusion of loperamide alleviates postsurgical pain in rats.  


Plantar incision in rat generates spontaneous pain behaviour. The opioid drug, morphine used to treat postsurgical pain produces tolerance after long-term administration. Loperamide, a potent mu-opioid agonist, has documented analgesic action in various pain conditions. However, loperamide analgesia and associated tolerance following continuous spinal administration in postsurgical pain has not been reported. Chronic spinal infusion of drugs was achieved using intrathecal catheters connected to osmotic minipump. Coinciding with the onset of spinal infusion of loperamide or morphine, rats were subjected to plantar incision. Pain-related behaviour was assessed by Hargreaves apparatus (thermal hyperalgesia) and von Frey filaments (mechanical allodynia). Morphine and loperamide (0.5, 1 and 2 microL/h) induced analgesia was observed until 7th day post-plantar incision in Sprague-Dawley rats. Morphine and loperamide produced dose-dependent analgesia. Loperamide, in the highest dose, produced analgesia till 7th day. However, the highest dose of morphine produced inhibition of thermal hyperalgesia till 5th day and mechanical allodynia only till 3rd day post-plantar incision. Morphine and loperamide produced analgesia in postsurgical pain, which may be mediated through different mechanisms. Longer duration of analgesia with loperamide could probably be due sustained blockade of calcium channels. PMID:24772934

Kumar, Rakesh; Reeta, K H; Ray, Subrata Basu



Cannabinoids in the management of difficult to treat pain  

PubMed Central

This article reviews recent research on cannabinoid analgesia via the endocannabinoid system and non-receptor mechanisms, as well as randomized clinical trials employing cannabinoids in pain treatment. Tetrahydrocannabinol (THC, Marinol®) and nabilone (Cesamet®) are currently approved in the United States and other countries, but not for pain indications. Other synthetic cannabinoids, such as ajulemic acid, are in development. Crude herbal cannabis remains illegal in most jurisdictions but is also under investigation. Sativex®, a cannabis derived oromucosal spray containing equal proportions of THC (partial CB1 receptor agonist ) and cannabidiol (CBD, a non-euphoriant, anti-inflammatory analgesic with CB1 receptor antagonist and endocannabinoid modulating effects) was approved in Canada in 2005 for treatment of central neuropathic pain in multiple sclerosis, and in 2007 for intractable cancer pain. Numerous randomized clinical trials have demonstrated safety and efficacy for Sativex in central and peripheral neuropathic pain, rheumatoid arthritis and cancer pain. An Investigational New Drug application to conduct advanced clinical trials for cancer pain was approved by the US FDA in January 2006. Cannabinoid analgesics have generally been well tolerated in clinical trials with acceptable adverse event profiles. Their adjunctive addition to the pharmacological armamentarium for treatment of pain shows great promise.

Russo, Ethan B



Sex differences in brain response to anticipated and experienced visceral pain in healthy subjects  

PubMed Central

Women demonstrate higher pain sensitivity and prevalence of chronic visceral pain conditions such as functional gastrointestinal disorders than men. The role of sex differences in the brain processing of visceral pain is still unclear. In 16 male and 16 female healthy subjects we compared personality, anxiety levels, skin conductance response (SCR), and brain processing using functional MRI during anticipation and pain induced by esophageal distension at pain toleration level. There was no significant difference in personality scores, anxiety levels, SCR, and subjective ratings of pain between sexes. In group analysis, both men and women demonstrated a similar pattern of brain activation and deactivation during anticipation and pain consistent with previous reports. However, during anticipation women showed significantly greater activation in the cuneus, precuneus, and supplementary motor area (SMA) and stronger deactivation in the right amygdala and left parahippocampal gyrus, whereas men demonstrated greater activation in the cerebellum. During pain, women demonstrated greater activation in the midcingulate cortex, anterior insula, premotor cortex, and cerebellum and stronger deactivation in the caudate, whereas men showed increased activity in the SMA. The pattern of brain activity suggests that, during anticipation, women may demonstrate stronger limbic inhibition, which is considered to be a cognitive modulation strategy for impending painful stimulation. During pain, women significantly activate brain areas associated with the affective and motivation components of pain. These responses may underlie the sex differences that exist in pain conditions, whereby women may attribute more emotional importance to painful stimuli compared with men.

Kano, Michiko; Farmer, Adam D.; Aziz, Qasim; Giampietro, Vincent P.; Brammer, Michael J.; Williams, Steven C. R.; Fukudo, Shin



The effects of sex and gender role on responses to pressure pain  

PubMed Central

Background: Several studies on experimental mechanical pain suggested a strong influence of sex demonstrating females to be more sensitive. We examined the hypothesis that not only sex but also gender role affects pain responsiveness and looked for mediators of this effect. Method: As indicators of pain the threshold the intensity and the unpleasantness of pressure stimuli were measured, as well as sensory and affective quality of pain. The gender role of 74 students was assessed by the Bem Sex Role Inventory (BSRI). Furthermore several psychological variables assumed to be potential mediators (catastrophising, fear of pain, depressive symptoms, pain coping) were obtained. Results: ANOVA revealed significant main effects of sex in all pain variables except affective quality of pain. Contrary to our hypothesis gender role had no influence on pain responses, neither was there an interaction of sex and gender. Fear of pain just missed the significance level identifying it as mediator of the sex effect on affective pain. Conclusions: In summary, our study corroborated previous findings that women are more responsive to mechanical pain stimuli with effect sizes being medium to large, whereas gender role did not predict any of the assessed pain parameters. No convincing evidence was found that the influence of sex is predominantly mediated by psychological characteristics of the individual.

Kroner-Herwig, Birgit; Gassmann, Jennifer; Tromsdorf, Marie; Zahrend, Elfi



The effects of sex and gender role on responses to pressure pain.  


Background: Several studies on experimental mechanical pain suggested a strong influence of sex demonstrating females to be more sensitive. We examined the hypothesis that not only sex but also gender role affects pain responsiveness and looked for mediators of this effect. Method: As indicators of pain the threshold the intensity and the unpleasantness of pressure stimuli were measured, as well as sensory and affective quality of pain. The gender role of 74 students was assessed by the Bem Sex Role Inventory (BSRI). Furthermore several psychological variables assumed to be potential mediators (catastrophising, fear of pain, depressive symptoms, pain coping) were obtained. Results: ANOVA revealed significant main effects of sex in all pain variables except affective quality of pain. Contrary to our hypothesis gender role had no influence on pain responses, neither was there an interaction of sex and gender. Fear of pain just missed the significance level identifying it as mediator of the sex effect on affective pain. Conclusions: In summary, our study corroborated previous findings that women are more responsive to mechanical pain stimuli with effect sizes being medium to large, whereas gender role did not predict any of the assessed pain parameters. No convincing evidence was found that the influence of sex is predominantly mediated by psychological characteristics of the individual. PMID:22400065

Kröner-Herwig, Birgit; Gaßmann, Jennifer; Tromsdorf, Marie; Zahrend, Elfi



Vitamin D, Race, and Experimental Pain Sensitivity in Older Adults with Knee Osteoarthritis  

PubMed Central

Objective Low levels of serum circulating 25-hydroxyvitamin D have been correlated with many health conditions, including chronic pain. Recent clinical practice guidelines define vitamin D levels < 20 ng/mL as deficient and values of 21–29 ng/mL as insufficient. Vitamin D insufficiency, including the most severe levels of deficiency, is more prevalent in black Americans. Ethnic and race group differences have been reported in both clinical and experimental pain, with black Americans reporting increased pain. The purpose of this study was to examine whether variation in vitamin D levels contribute to race differences in knee osteoarthritic pain. Methods The sample consisted of 94 participants (75% female), including 45 blacks and 49 whites with symptomatic knee osteoarthritis. Average age was 55.8 years (range 45–71 years). Participants completed a questionnaire on knee osteoarthritic symptoms and underwent quantitative sensory testing, including measures of heat and mechanical pain sensitivity. Results Blacks had significantly lower levels of vitamin D compared to whites, demonstrated greater clinical pain, and showed greater sensitivity to mechanical and heat pain. Low levels of vitamin D predicted increased experimental pain sensitivity, but did not predict self-reported clinical