Prediction of postoperative pain: a systematic review of predictive experimental pain studies

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Werner, Mads Utke; Mjöbo, Helena N; Nielsen, Per R

2010-01-01

Quantitative testing of a patient's basal pain perception before surgery has the potential to be of clinical value if it can accurately predict the magnitude of pain and requirement of analgesics after surgery. This review includes 14 studies that have investigated the correlation between...... preoperative responses to experimental pain stimuli and clinical postoperative pain and demonstrates that the preoperative pain tests may predict 4-54% of the variance in postoperative pain experience depending on the stimulation methods and the test paradigm used. The predictive strength is much higher than...

The Effect of a Combination of Diclofenac and Methadone Applied as Gel in a Human Experimental Pain Model- A Randomized, Placebo-Controlled Trial

DEFF Research Database (Denmark)

Larsen, Isabelle M; Drewes, Asbjørn M; Olesen, Anne E

2018-01-01

should be low. We hypothesized that anti-allodynic and anti-hyperalgesic effects of Diclometh could be demonstrated in a human experimental pain model, and that Diclometh would be safe to administer. Thus, the aims were: 1) To compare two doses of Diclometh versus placebo; 2) To assess the safety profile...... of Diclometh. The study was a cross-over, randomized, double-blind, placebo-controlled comparison of two doses of Diclometh gel (0.1% and 0.2%) administered topically in healthy participants. Nerve growth factor (NGF) and capsaicin intradermal injections were used as human pain models. Pressure stimulation...... of anti-allodynic effect of Diclometh 0.2% was found. Additionally, it was demonstrated that Diclometh was safe to use. This article is protected by copyright. All rights reserved....

Psychophysics, flare, and neurosecretory function in human pain models: capsaicin versus electrically evoked pain.

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Geber, Christian; Fondel, Ricarda; Krämer, Heidrun H; Rolke, Roman; Treede, Rolfe-Detlef; Sommer, Claudia; Birklein, Frank

2007-06-01

Intradermal capsaicin injection (CAP) and electrical current stimulation (ES) are analyzed in respect to patterns and test-retest reliability of pain as well as sensory and neurosecretory changes. In 10 healthy subjects, 2x CAP (50 microg) and 2x ES (5 to 30 mA) were applied to the volar forearm. The time period between 2 identical stimulations was about 4 months. Pain ratings, areas of mechanical hyperalgesia, and allodynia were assessed. The intensity of sensory changes was quantified by using quantitative sensory testing. Neurogenic flare was assessed by using laser Doppler imaging. Calcitonin gene-related peptide (CGRP) release was quantified by dermal microdialysis in combination with an enzyme immunoassay. Time course and peak pain ratings were different between CAP and ES. Test-retest correlation was high (r > or = 0.73). Both models induced primary heat hyperalgesia and primary plus secondary pin-prick hyperalgesia. Allodynia occurred in about half of the subjects. Maximum flare sizes did not differ between CAP and ES, but flare intensities were higher for ES. Test-retest correlation was higher for flare sizes than for flare intensity. A significant CGRP release could only be measured after CAP. The different time courses of pain stimulation (CAP: rapidly decaying pain versus ES: pain plateau) led to different peripheral neurosecretory effects but induced similar central plasticity and hyperalgesia. The present study gives a detailed overview of psychophysical and neurosecretory characteristics induced by noxious stimulation with capsaicin and electrical current. We describe differences, similarities, and reproducibility of these human pain models. These data might help to interpret past and future results of human pain studies using experimental pain.

Dose-specific effects of transcutaneous electrical nerve stimulation (TENS) on experimental pain: a systematic review.

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Claydon, Leica S; Chesterton, Linda S; Barlas, Panos; Sim, Julius

2011-09-01

To determine the hypoalgesic effects of transcutaneous electrical nerve stimulation (TENS) parameter combinations on experimental models in healthy humans. Searches were performed using the electronic databases Ovid MEDLINE, CINAHL, AMED, and Web of Science (from inception to December 2009). Manual searches of journals and reference lists of retrieved trials were also performed. Randomized controlled trials (RCTs) were included in the review if they compared the hypoalgesic effect of TENS relative with placebo and control, using an experimental pain model in healthy human participants. Two reviewers independently selected the trials, assessed their methodologic quality and extracted data. Forty-three RCTs were eligible for inclusion. A best evidence synthesis revealed: Overall "conflicting" (inconsistent findings in multiple RCTs) evidence of TENS efficacy on experimental pain irrespective of TENS parameters used. Overall intense TENS has "moderate" evidence of efficacy (1 high-quality and 2 low-quality trials). Conventional TENS has overall conflicting evidence of efficacy, this is derived from "strong" evidence of efficacy (generally consistent findings in multiple high-quality RCTs) on pressure pain but strong evidence of inefficacy on other pain models. "Limited" evidence (positive findings from 1 RCT) of hypoalgesia exists for some novel parameters. Low-intensity, low-frequency, local TENS has strong evidence of inefficacy. Inappropriate TENS (using "barely perceptible" intensities) has moderate evidence of inefficacy. The level of hypoalgesic efficacy of TENS is clearly dependent on TENS parameter combination selection (defined in terms of intensity, frequency, and stimulation site) and experimental pain model. Future clinical RCTs may consider these TENS dose responses.

New perspectives in EEG/MEG brain mapping and PET/fMRI neuroimaging of human pain.

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Chen, A C

2001-10-01

With the maturation of EEG/MEG brain mapping and PET/fMRI neuroimaging in the 1990s, greater understanding of pain processing in the brain now elucidates and may even challenge the classical theory of pain mechanisms. This review scans across the cultural diversity of pain expression and modulation in man. It outlines the difficulties in defining and studying human pain. It then focuses on methods of studying the brain in experimental and clinical pain, the cohesive results of brain mapping and neuroimaging of noxious perception, the implication of pain research in understanding human consciousness and the relevance to clinical care as well as to the basic science of human psychophysiology. Non-invasive brain studies in man start to unveil the age-old puzzles of pain-illusion, hypnosis and placebo in pain modulation. The neurophysiological and neurohemodynamic brain measures of experimental pain can now largely satisfy the psychophysiologist's dream, unimaginable only a few years ago, of modelling the body-brain, brain-mind, mind-matter duality in an inter-linking 3-P triad: physics (stimulus energy); physiology (brain activities); and psyche (perception). For neuropsychophysiology greater challenges lie ahead: (a) how to integrate a cohesive theory of human pain in the brain; (b) what levels of analyses are necessary and sufficient; (c) what constitutes the structural organisation of the pain matrix; (d) what are the modes of processing among and across the sites of these structures; and (e) how can neural computation of these processes in the brain be carried out? We may envision that modular identification and delineation of the arousal-attention, emotion-motivation and perception-cognition neural networks of pain processing in the brain will also lead to deeper understanding of the human mind. Two foreseeable impacts on clinical sciences and basic theories from brain mapping/neuroimaging are the plausible central origin in persistent pain and integration of

Effects of ethnicity and gender role expectations of pain on experimental pain: a cross-cultural study.

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Alabas, O A; Tashani, O A; Johnson, M I

2013-05-01

Gender role expectations of pain (GREP) have been shown to mediate sex differences in experimental pain. Few studies have investigated the role of ethnicity in shaping GREP. The aim of this study was to examine interactions between ethnicity and GREP on experimentally induced pressure and ischaemic pain in Libyan and white British students in their respective countries. Libyan (n = 124) and white British (n = 51) students completed a GREP questionnaire and their response to experimental pain was measured. Blunt pressure pain threshold (PPT) was measured over the 1st interosseous muscle using algometry. Pain intensity and pain unpleasantness (100 mm visual analogue scale) were measured at 1-min intervals during a submaximal effort tourniquet test on the forearm. Multivariate analysis of variance detected significant effects for Sex and Ethnicity on pain measurements. Men had higher PPTs than women (p 0.05). Libyan participants had higher pain intensity (p < 0.01) and pain unpleasantness (p < 0.05) ratings compared with white British participants. There were effects for Sex and Ethnicity for all GREP dimensions. Libyan participants exhibited stronger stereotypical views in GREP than white British participants (p < 0.001). GREP was the mediator of sex but not ethnic differences in pain report, suggesting that gender stereotypical attitudes to pain account for differences in pain expression between men and women. © 2012 European Federation of International Association for the Study of Pain Chapters.

Pain management: a fundamental human right.

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Brennan, Frank; Carr, Daniel B; Cousins, Michael

2007-07-01

This article surveys worldwide medical, ethical, and legal trends and initiatives related to the concept of pain management as a human right. This concept recently gained momentum with the 2004 European Federation of International Association for the Study of Pain (IASP) Chapters-, International Association for the Study of Pain- and World Health Organization-sponsored "Global Day Against Pain," where it was adopted as a central theme. We survey the scope of the problem of unrelieved pain in three areas, acute pain, chronic noncancer pain, and cancer pain, and outline the adverse physical and psychological effects and social and economic costs of untreated pain. Reasons for deficiencies in pain management include cultural, societal, religious, and political attitudes, including acceptance of torture. The biomedical model of disease, focused on pathophysiology rather than quality of life, reinforces entrenched attitudes that marginalize pain management as a priority. Strategies currently applied for improvement include framing pain management as an ethical issue; promoting pain management as a legal right, providing constitutional guarantees and statutory regulations that span negligence law, criminal law, and elder abuse; defining pain management as a fundamental human right, categorizing failure to provide pain management as professional misconduct, and issuing guidelines and standards of practice by professional bodies. The role of the World Health Organization is discussed, particularly with respect to opioid availability for pain management. We conclude that, because pain management is the subject of many initiatives within the disciplines of medicine, ethics and law, we are at an "inflection point" in which unreasonable failure to treat pain is viewed worldwide as poor medicine, unethical practice, and an abrogation of a fundamental human right.

Striatal μ-opioid receptor availability predicts cold pressor pain threshold in healthy human subjects

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Hagelberg, Nora; Aalto, Sargo; Tuominen, Lauri

2012-01-01

the potential associations between μ-opioid receptor BP(ND) and psychophysical measures. The results show that striatal μ-opioid receptor BP(ND) predicts cold pressor pain threshold, but not cold pressor pain tolerance or tactile sensitivity. This finding suggests that striatal μ-opioid receptor density......Previous PET studies in healthy humans have shown that brain μ-opioid receptor activation during experimental pain is associated with reductions in the sensory and affective ratings of the individual pain experience. The aim of this study was to find out whether brain μ-opioid receptor binding...... at the resting state, in absence of painful stimulation, can be a long-term predictor of experimental pain sensitivity. We measured μ-opioid receptor binding potential (BP(ND)) with μ-opioid receptor selective radiotracer [(11)C]carfentanil and positron emission tomography (PET) in 12 healthy male subjects...

Patterns of experimentally induced pain in pericranial muscles

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Schmidt-Hansen, Peter Thede; Svensson, Peter; Jensen, Troels Staehelin

2006-01-01

into the masseter muscle (anova: P pain areas (anova: P cervically innervated muscles had significantly different patterns of spread and referral of pain according to trigeminally vs....... cervically innervated dermatomes (P pain patterns and pain sensitivity in different craniofacial muscles in healthy volunteers, which may be of importance for further research on different craniofacial pain conditions.......Nociceptive mechanisms in the craniofacial muscle tissue are poorly understood. The pain pattern in individual pericranial muscles has not been described before. Experimental muscle pain was induced by standardized infusions of 0.2 ml 1 m hypertonic saline into six craniofacial muscles (masseter...

Neurochemical dynamics of acute orofacial pain in the human trigeminal brainstem nuclear complex.

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de Matos, Nuno M P; Hock, Andreas; Wyss, Michael; Ettlin, Dominik A; Brügger, Mike

2017-11-15

The trigeminal brainstem sensory nuclear complex is the first central relay structure mediating orofacial somatosensory and nociceptive perception. Animal studies suggest a substantial involvement of neurochemical alterations at such basal CNS levels in acute and chronic pain processing. Translating this animal based knowledge to humans is challenging. Human related examining of brainstem functions are challenged by MR related peculiarities as well as applicability aspects of experimentally standardized paradigms. Based on our experience with an MR compatible human orofacial pain model, the aims of the present study were twofold: 1) from a technical perspective, the evaluation of proton magnetic resonance spectroscopy at 3 T regarding measurement accuracy of neurochemical profiles in this small brainstem nuclear complex and 2) the examination of possible neurochemical alterations induced by an experimental orofacial pain model. Data from 13 healthy volunteers aged 19-46 years were analyzed and revealed high quality spectra with significant reductions in total N-acetylaspartate (N-acetylaspartate + N-acetylaspartylglutamate) (-3.7%, p = 0.009) and GABA (-10.88%, p = 0.041) during the pain condition. These results might reflect contributions of N-acetylaspartate and N-acetylaspartylglutamate in neuronal activity-dependent physiologic processes and/or excitatory neurotransmission, whereas changes in GABA might indicate towards a reduction in tonic GABAergic functioning during nociceptive signaling. Summarized, the present study indicates the applicability of 1 H-MRS to obtain neurochemical dynamics within the human trigeminal brainstem sensory nuclear complex. Further developments are needed to pave the way towards bridging important animal based knowledge with human research to understand the neurochemistry of orofacial nociception and pain. Copyright © 2017 Elsevier Inc. All rights reserved.

The influence of experimentally induced pain on shoulder muscle activity

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Diederichsen, L.P.; Winther, A.; Dyhre-Poulsen, P.

2009-01-01

healthy men (range 22-27 years), with no history of shoulder or cervical problems, were included in the study. Pain was induced by 5% hypertonic saline injections into the supraspinatus muscle or subacromially. Seated in a shoulder machine, subjects performed standardized concentric abduction (0A degrees......Muscle function is altered in painful shoulder conditions. However, the influence of shoulder pain on muscle coordination of the shoulder has not been fully clarified. The aim of the present study was to examine the effect of experimentally induced shoulder pain on shoulder muscle function. Eleven...... muscles. EMG was recorded before pain, during pain and after pain had subsided and pain intensity was continuously scored on a visual analog scale (VAS). During abduction, experimentally induced pain in the supraspinatus muscle caused a significant decrease in activity of the anterior deltoid, upper...

Effect of experimental chewing on masticatory muscle pain onset

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Paulo César Rodrigues Conti

2011-02-01

Full Text Available OBJECTIVES: To evaluate the effect of a chewing exercise on pain intensity and pressure-pain threshold in patients with myofascial pain. METHODS: Twenty-nine consecutive women diagnosed with myofascial pain (MFP according to the Research Diagnostic Criteria comprised the experimental group and 15 healthy age-matched female were used as controls. Subjects were asked to chew a gum stick for 9 min and to stay at rest for another 9 min afterwards. Pain intensity was rated on a visual analog scale (VAS every 3 min. At 0, 9 and 18 min, the pressure-pain threshold (PPT was measured bilaterally on the masseter and the anterior, medium, and posterior temporalis muscles. RESULTS: Patients with myofascial pain reported increase (76% and no change (24% on the pain intensity measured with the VAS. A reduction of the PPT at all muscular sites after the exercise and a non-significant recovery after rest were also observed. CONCLUSION: The following conclusions can be drawn: 1. there are at least two subtypes of patients with myofascial pain that respond differently to experimental chewing; 2. the chewing protocol had an adequate discriminative ability in distinguishing patients with myofascial pain from healthy controls.

Manipulation of pain catastrophizing: An experimental study of healthy participants

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Joel E Bialosky

2008-11-01

Full Text Available Joel E Bialosky1*, Adam T Hirsh2,3, Michael E Robinson2,3, Steven Z George1,3*1Department of Physical Therapy; 2Department of Clinical and Health Psychology; 3Center for Pain Research and Behavioral Health, University of Florida, Gainesville, Florida, USAAbstract: Pain catastrophizing is associated with the pain experience; however, causation has not been established. Studies which specifically manipulate catastrophizing are necessary to establish causation. The present study enrolled 100 healthy individuals. Participants were randomly assigned to repeat a positive, neutral, or one of three catastrophizing statements during a cold pressor task (CPT. Outcome measures of pain tolerance and pain intensity were recorded. No change was noted in catastrophizing immediately following the CPT (F(1,84 = 0.10, p = 0.75, partial η2 < 0.01 independent of group assignment (F(4,84 = 0.78, p = 0.54, partial η2 = 0.04. Pain tolerance (F(4 = 0.67, p = 0.62, partial η2 = 0.03 and pain intensity (F(4 = 0.73, p = 0.58, partial η2 = 0.03 did not differ by group. This study suggests catastrophizing may be difficult to manipulate through experimental pain procedures and repetition of specific catastrophizing statements was not sufficient to change levels of catastrophizing. Additionally, pain tolerance and pain intensity did not differ by group assignment. This study has implications for future studies attempting to experimentally manipulate pain catastrophizing.Keywords: pain, catastrophizing, experimental, cold pressor task, pain catastrophizing scale

A human experimental model of episodic pain

DEFF Research Database (Denmark)

Petrini, Laura; Hennings, Kristian; Li, Xi

2014-01-01

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

Modelling concentration-analgesia relationships for morphine to evaluate experimental pain models

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Sverrisdóttir, Eva; Foster, David John Richard; Upton, Richard Neil

2015-01-01

The aim of this study was to develop population pharmacokinetic-pharmacodynamic models for morphine in experimental pain induced by skin heat and muscle pressure, and to evaluate the experimental pain models with regard to assessment of morphine pharmacodynamics. In a randomized, double......-blind, placebo-controlled, crossover study, 39 healthy volunteers received an oral dose of 30 mg morphine hydrochloride or placebo. Non-linear mixed effects modelling was used to describe the plasma concentrations of morphine and metabolites, and the analgesic effect of morphine on experimental pain in skin...... and muscle. Baseline pain metrics varied between individuals and occasions, and were described with interindividual and interoccasion variability. Placebo-response did not change with time. For both pain metrics, morphine effect was proportional to baseline pain and was described with a linear model...

The Modulation of Pain by Circadian and Sleep-Dependent Processes: A Review of the Experimental Evidence

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Hagenauer, Megan; Crodelle, Jennifer; Piltz, Sofia Helena

2017-01-01

conditions, pain sensitivity varies across the 24 h day, with highest sensitivity occurring during the evening in humans. Pain sensitivity is also modulated by sleep behavior, with pain sensitivity increasing in response to the build-up of homeostatic sleep pressure following sleep deprivation or sleep...... of physiologically meaningful stimulation levels. Following this normalization, we find that the estimated impact of the daily rhythm and of sleep deprivation on experimental pain measurements is surprisingly consistent across different pain modalities. We also review evidence documenting the impact of circadian...... rhythms and sleep deprivation on the neural circuitry in the spinal cord underlying pain sensation. The characterization of sleep-dependent and circadian influences on pain sensitivity in this review paper is used to develop and constrain the mathematical models introduced in the two companion articles....

Vicarious pain experiences while observing another in pain: an experimental approach

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Sophie eVandenbroucke

2013-06-01

Full Text Available Objective: This study aimed at developing an experimental paradigm to assess vicarious pain experiences. We further explored the putative moderating role of observer’s characteristics such as hypervigilance for pain and dispositional empathy. Methods: Two experiments are reported using a similar procedure. Undergraduate students were selected based upon whether they reported vicarious pain in daily life, and categorized into a pain responder group or a comparison group. Participants were presented a series of videos showing hands being pricked whilst receiving occasionally pricking (electrocutaneous stimuli themselves. In congruent trials, pricking and visual stimuli were applied to the same spatial location. In incongruent trials, pricking and visual stimuli were in the opposite spatial location. Participants were required to report on which location they felt a pricking sensation. Of primary interest was the effect of viewing another in pain upon vicarious pain errors, i.e., the number of trials in which an illusionary sensation was reported. Furthermore, we explored the effect of individual differences in hypervigilance to pain, dispositional empathy and the rubber hand illusion (RHI upon vicarious pain errors. Results: Results of both experiments indicated that the number of vicarious pain errors was overall low. In line with expectations, the number of vicarious pain errors was higher in the pain responder group than in the comparison group. Self-reported hypervigilance for pain lowered the probability of reporting vicarious pain errors in the pain responder group, but dispositional empathy and the RHI did not. Conclusion: Our paradigm allows measuring vicarious pain experiences in students. However, the prevalence of vicarious experiences of pain is low, and only a small percentage of participants display the phenomenon. It remains however unknown which variables affect its occurrence.

Effects of experimental muscle pain on muscle activity and co-ordination during static and dynamic motor function.

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Graven-Nielsen, T; Svensson, P; Arendt-Nielsen, L

1997-04-01

The relation between muscle pain, muscle activity, and muscle co-ordination is still controversial. The present human study investigates the influence of experimental muscle pain on resting, static, and dynamic muscle activity. In the resting and static experiments, the electromyography (EMG) activity and the contraction force of m. tibialis anterior were assessed before and after injection of 0.5 ml hypertonic saline (5%) into the same muscle. In the dynamic experiment, injections of 0.5 ml hypertonic saline (5%) were performed into either m. tibialis anterior (TA) or m. gastrocnemius (GA) and the muscle activity and co-ordination were investigated during gait on a treadmill by EMG recordings from m. TA and m. GA. At rest no evidence of EMG hyperactivity was found during muscle pain. The maximal voluntary contraction (MVC) during muscle pain was significantly lower than the control condition (P Fibromyalgia and Myofascial Pain. Elsevier, Amsterdam, 1993, pp. 311-327.) which predicts increased activity of antagonistic muscle and decreased activity of agonistic muscle during experimental and clinical muscle pain.

IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP.

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Stephen F Murphy

Full Text Available Chronic pelvic pain syndrome (CPPS is the most common form of prostatitis, accounting for 90-95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17's role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS.

IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP).

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Murphy, Stephen F; Schaeffer, Anthony J; Done, Joseph; Wong, Larry; Bell-Cohn, Ashlee; Roman, Kenny; Cashy, John; Ohlhausen, Michelle; Thumbikat, Praveen

2015-01-01

Chronic pelvic pain syndrome (CPPS) is the most common form of prostatitis, accounting for 90-95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP) in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17's role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS.

Periodontal CGRP contributes to orofacial pain following experimental tooth movement in rats.

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Long, Hu; Liao, Lina; Gao, Meiya; Ma, Wenqiang; Zhou, Yang; Jian, Fan; Wang, Yan; Lai, Wenli

2015-08-01

Calcitonin-related gene peptide (CGRP) plays an important role in orofacial inflammatory pain. The aim of this study was to determine whether periodontal CGRP contributes to orofacial pain induced by experimental tooth movement in rats. Male Sprague-Dawley rats were used in this study. Closed coil springs were used to deliver forces. Rats were euthanized on 0d, 1d, 3d, 5d, 7d, and 14d following experimental tooth movement. Then, alveolar bones were obtained for immunostaining of periodontal tissues against CGRP. Two hours prior to euthanasia on each day, orofacial pain levels were assessed through rat grimace scale. CGRP and olcegepant (CGRP receptor antagonist) were injected into periodontal tissues to verify the roles of periodontal CGRP in orofacial pain induced by experimental tooth movement. Periodontal CGRP expression levels and orofacial pain levels were elevated on 1d, 3d, 5d, and 7d following experimental tooth movement. The two indices were significantly correlated with each other and fitted into a dose-response model. Periodontal administration of CGRP could elevate periodontal CGRP expressions and exacerbate orofacial pain. Moreover, olcegepant administration could decrease periodontal CGRP expressions and alleviate orofacial pain. Therefore, periodontal CGRP plays an important role in pain transmission and modulation following experimental tooth movement. We suggest that it may participate in a positive feedback aiming to amplify orofacial pain signals. Copyright © 2015 Elsevier B.V. All rights reserved.

A dyadic analysis of siblings' relationship quality, behavioural responses, and pain experiences during experimental pain.

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Schinkel, Meghan G; Chambers, Christine T; Corkum, Penny; Jacques, Sophie

2018-04-16

Research on family factors in paediatric pain has primarily focused on parents; the role of siblings has been largely ignored. This study examined whether sibling relationship quality was related to siblings' behaviours during experimental pain, and whether the behaviours of an observing sibling were related to children's pain outcomes. Ninety-two sibling dyads between 8-12 years old completed both observational and questionnaire measures of sibling relationship quality. Children took turns completing the cold pressor task (CPT) in a counterbalanced order with their sibling present. Pain outcomes (intensity, fear, tolerance) were recorded for each sibling, and the behaviour of the observing and participating siblings during the CPT were coded as attending, non-attending, and coping/encouragement. Structural equation modelling, using the actor-partner interdependence model, was conducted to analyse the dyadic data. While participating in the CPT with their sibling present, greater levels of warmth and positivity in the sibling relationship were related to children engaging in more non-attending behaviours and less attending behaviours. Greater levels of attending behaviours by the observing child was related to the sibling having a lower pain tolerance, and greater levels of coping/encouragement behaviours by the observing child was related to the sibling reporting greater pain intensity and fear during the CPT. Children with warmer/positive sibling relationships were more likely to respond to acute pain by shifting the focus away from their pain experience (e.g., through distraction) when a sibling was present. Pain-focused behaviours by an observing sibling are related to greater child pain and fear during experimental pain.

Topical acetylsalicylic, salicylic acid and indomethacin suppress pain from experimental tissue acidosis in human skin.

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Steen, K H; Reeh, P W; Kreysel, H W

1995-09-01

Topically applied acetylsalicylic acid (ASA), salicylic acid (SA) and indomethacin were tested in an experimental pain model that provides direct nociceptor excitation through cutaneous tissue acidosis. In 30 volunteers, sustained burning pain was produced in the palmar forearm through a continuous intradermal pressure infusion of a phosphate-buffered isotonic solution (pH 5.2). In 5 different, double-blind, randomized cross-over studies with 6 volunteers each, the flow rate of the syringe pump was individually adjusted to result in constant pain ratings of around 20% (50% in study 4) on a visual analog scale (VAS). The painful skin area was then covered with either placebo or the drugs which had been dissolved in diethylether. In the first study on 6 volunteers, ASA (60 mg/ml) or lactose (placebo) in diethylether (10 ml) was applied, using both arms at 3-day intervals. Both treatments resulted in sudden and profound pain relief due to the cooling effect of the evaporating ether. With lactose, however, the mean pain rating was restored close to the baseline within 6-8 min while, with ASA, it remained significantly depressed for the rest of the observation period (another 20 min). This deep analgesia was not accompanied by a loss of tactile sensation. The further studies served to show that indomethacin (4.5 mg/ml) and SA (60 mg/ml) were equally effective as ASA (each 92-96% pain reduction) and that the antinociceptive effects were due to local but not systemic actions, since ASA and SA dis not reach measurable plasma levels up to 3 h after topical applications. With a higher flow rate of acid buffer producing more intense pain (VAS 50%). ASA and SA were still able to significantly reduce the ratings by 90% or 84%, respectively. On the other hand, by increasing the flow rate by a factor of 2 on average, during the period of fully developed drug effect it was possible to overcome the pain suppression, which suggests a competitive mechanism of (acetyl-) salicylic

Experimental quadriceps muscle pain impairs knee joint control during walking

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Henriksen, Marius; Alkjaer, Tine; Lund, Hans

2007-01-01

Pain is a cardinal symptom in musculoskeletal diseases involving the knee joint, and aberrant movement patterns and motor control strategies are often present in these patients. However, the underlying neuromuscular mechanisms linking pain to movement and motor control are unclear. To investigate...... the functional significance of muscle pain on knee joint control during walking, three-dimensional gait analyses were performed before, during, and after experimentally induced muscle pain by means of intramuscular injections of hypertonic saline (5.8%) into vastus medialis (VM) muscle of 20 healthy subjects....... Isotonic saline (0.9%) was used as control. Surface electromyography (EMG) recordings of VM, vastus lateralis (VL), biceps femoris, and semitendinosus muscles were synchronized with the gait analyses. During experimental muscle pain, the loading response phase peak knee extensor moments were attenuated...

Viewing pictures of a romantic partner reduces experimental pain: involvement of neural reward systems.

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Younger, Jarred; Aron, Arthur; Parke, Sara; Chatterjee, Neil; Mackey, Sean

2010-10-13

The early stages of a new romantic relationship are characterized by intense feelings of euphoria, well-being, and preoccupation with the romantic partner. Neuroimaging research has linked those feelings to activation of reward systems in the human brain. The results of those studies may be relevant to pain management in humans, as basic animal research has shown that pharmacologic activation of reward systems can substantially reduce pain. Indeed, viewing pictures of a romantic partner was recently demonstrated to reduce experimental thermal pain. We hypothesized that pain relief evoked by viewing pictures of a romantic partner would be associated with neural activations in reward-processing centers. In this functional magnetic resonance imaging (fMRI) study, we examined fifteen individuals in the first nine months of a new, romantic relationship. Participants completed three tasks under periods of moderate and high thermal pain: 1) viewing pictures of their romantic partner, 2) viewing pictures of an equally attractive and familiar acquaintance, and 3) a word-association distraction task previously demonstrated to reduce pain. The partner and distraction tasks both significantly reduced self-reported pain, although only the partner task was associated with activation of reward systems. Greater analgesia while viewing pictures of a romantic partner was associated with increased activity in several reward-processing regions, including the caudate head, nucleus accumbens, lateral orbitofrontal cortex, amygdala, and dorsolateral prefrontal cortex--regions not associated with distraction-induced analgesia. The results suggest that the activation of neural reward systems via non-pharmacologic means can reduce the experience of pain.

Motor responses to experimental Achilles tendon pain

DEFF Research Database (Denmark)

Henriksen, Marius; Aaboe, Jens; Graven-Nielsen, Thomas

2011-01-01

of the exercise are affected by Achilles tendon pain. Objective The authors aimed to determine the effects of experimental Achilles tendon pain on motor function during one-legged weight bearing ankle plantar and dorsal flexion exercises. Methods In a crossover study, with 16 healthy subjects tested on two......Background Achilles tendinopathies are characterised by pain and reduced function, and heavy-load exercises have been shown to be effective in the treatment of painful chronic Achilles tendinopathies. However, basic information is needed on how the biomechanics and neuromuscular control...... different days separated by 1 week, three-dimensional ground reaction forces, ankle joint kinematics and surface electromyography (EMG) of the lower leg muscles were recorded during one-legged full weight-bearing ankle plantar (concentric) and dorsal (eccentric) flexion exercises. Measurements were done...

A comparative behavioural study of mechanical hypersensitivity in 2 pain models in rats and humans.

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Reitz, Marie-Céline; Hrncic, Dragan; Treede, Rolf-Detlef; Caspani, Ombretta

2016-06-01

The assessment of pain sensitivity in humans has been standardized using quantitative sensory testing, whereas in animals mostly paw withdrawal thresholds to diverse stimuli are measured. This study directly compares tests used in quantitative sensory testing (pinpricks, pressure algometer) with tests used in animal studies (electronic von Frey test: evF), which we applied to the dorsal hind limbs of humans after high frequency stimulation and rats after tibial nerve transection. Both experimental models induce profound mechanical hypersensitivity. At baseline, humans and rats showed a similar sensitivity to evF with 0.2 mm diameter tips, but significant differences for other test stimuli (all P pain models (P pain sensitivity, but probe size and shape should be standardized. Hypersensitivity to blunt pressure-the leading positive sensory sign after peripheral nerve injury in humans-is a novel finding in the tibial nerve transection model. By testing outside the primary zone of nerve damage (rat) or activation (humans), our methods likely involve effects of central sensitization in both species.

Masseter motor unit recruitment is altered in experimental jaw muscle pain

NARCIS (Netherlands)

Minami, I.; Akhter, R.; Albersen, I.; Burger, C.; Whittle, T.; Lobbezoo, F.; Peck, C.C.; Murray, G.M.

2013-01-01

Some management strategies for chronic orofacial pain are influenced by models (e.g., Vicious Cycle Theory, Pain Adaptation Model) proposing either excitation or inhibition within a painful muscle. The aim of this study was to determine if experimental painful stimulation of the masseter muscle

Measuring empathy for human and robot hand pain using electroencephalography.

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Suzuki, Yutaka; Galli, Lisa; Ikeda, Ayaka; Itakura, Shoji; Kitazaki, Michiteru

2015-11-03

This study provides the first physiological evidence of humans' ability to empathize with robot pain and highlights the difference in empathy for humans and robots. We performed electroencephalography in 15 healthy adults who observed either human- or robot-hand pictures in painful or non-painful situations such as a finger cut by a knife. We found that the descending phase of the P3 component was larger for the painful stimuli than the non-painful stimuli, regardless of whether the hand belonged to a human or robot. In contrast, the ascending phase of the P3 component at the frontal-central electrodes was increased by painful human stimuli but not painful robot stimuli, though the interaction of ANOVA was not significant, but marginal. These results suggest that we empathize with humanoid robots in late top-down processing similarly to human others. However, the beginning of the top-down process of empathy is weaker for robots than for humans.

Functional resonance magnetic imaging (fMRI) in adolescents with idiopathic musculoskeletal pain: a paradigm of experimental pain

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Molina, Juliana; Amaro, Edson; da Rocha, Liana Guerra Sanches; Jorge, Liliana; Santos, Flavia Heloisa; Len, Claudio A.

2017-01-01

Background Studies on functional magnetic resonance imaging (fMRI) have shown that adults with musculoskeletal pain syndromes tolerate smaller amount of pressure (pain) as well as differences in brain activation patterns in areas related to pain.The objective of this study was to evaluate, through fMRI, the brain activation in adolescents with idiopathic musculoskeletal pain (IMP) while performing an experimental paradigm of pain. Methods The study included 10 consecutive adolescents with idi...

Historical development of epistemology and the study of pain: Place of neuromodulation of electroacupuncture in the experimental pain research

Directory of Open Access Journals (Sweden)

Bárbara B. Garrido-Suárez

2013-10-01

Full Text Available Despite the diffusion of acupuncture and its related techniques in Cuba and the World, its mechanism of action is still controversial, being considered by the most sceptics as placebo or some kind oriental myth, and it only should by related to this subjects as a matter of cultural-historical elements and not to science. The purpose of this revision is to characterize the pain sensation, after a critical analysis of the different philosophical streams related to the human knowledge and its expression in the historical evolution of the algology. On the other hand, to emphasize the importance of electroacupuncture-induced neuro-modulation in the field of experimental pain researches. In this content will be analyzed the concept of Khun paradigm and his ideas about the structure of scientific revolution in the theory of gates control and the explosion of pain researches in the last decades. It will related the introduction to acupuncture and its techniques in pain clinics, with scientific context of the historical moment. In addition, a space will be dedicated to the topic of complementary and alternative medicine on the century of evidence based medicine, given its scientific needs of validation in ours times.

Pain and executive functions: A unique relationship between Stroop task and experimentally induced pain

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Bjekic, J.; Zivanovic, M.; Puric, D.; Oosterman, J.M.; Filipovic, S.R.

2018-01-01

There is a growing body of evidence that a higher level of cognitive inhibition is associated with lower experimental pain sensitivity. However, a systematic examination of the association between executive functions, which include not only inhibition but also updating and shifting, and experimental

Identifying experimental methods to determine the effect of pain on attention: a review of pain, caffeine, alcohol and nicotine studies.

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Moore, David J; Keogh, Edmund; Eccleston, Christopher

2009-12-01

To review published studies of the effects that pain and common psychopharmacological substances have on the attentional performance of healthy adults. To identify which attentional tasks have the greatest potential to investigate the effect of pain on attention and provide recommendations for future research. A search was conducted for reports of experimental studies of attention in the context of pain. This was supplemented with studies on attention and caffeine, nicotine and alcohol. Studies were included if they used a healthy adult sample, used experimental or quasi-experimental methods, were relevant to the study of attention or interruption of pain and/or examined the acute effects of a substance on attention. Thirty-two papers, with 49 different experimental studies were identified (12 pain, 21 nicotine, 7 caffeine, 9 alcohol). Fourteen different tasks were reviewed across six domains of attention. The most promising measures of attention were the continuous performance task, flanker task, endogenous pre-cuing task, n-back task, inhibition task and dual task. There are reliable tasks that could be used to determine the effects of pain on attention. Future research is required that develops the utility of these tasks to improve our understanding of the effects pain and analgesia have on attentional performance. Copyright (c) 2009 John Wiley & Sons, Ltd.

Nonpainful wide-area compression inhibits experimental pain.

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Honigman, Liat; Bar-Bachar, Ofrit; Yarnitsky, David; Sprecher, Elliot; Granovsky, Yelena

2016-09-01

Compression therapy, a well-recognized treatment for lymphoedema and venous disorders, pressurizes limbs and generates massive non-noxious afferent sensory barrages. The aim of this study was to study whether such afferent activity has an analgesic effect when applied on the lower limbs, hypothesizing that larger compression areas will induce stronger analgesic effects, and whether this effect correlates with conditioned pain modulation (CPM). Thirty young healthy subjects received painful heat and pressure stimuli (47°C for 30 seconds, forearm; 300 kPa for 15 seconds, wrist) before and during 3 compression protocols of either SMALL (up to ankles), MEDIUM (up to knees), or LARGE (up to hips) compression areas. Conditioned pain modulation (heat pain conditioned by noxious cold water) was tested before and after each compression protocol. The LARGE protocol induced more analgesia for heat than the SMALL protocol (P < 0.001). The analgesic effect interacted with gender (P = 0.015). The LARGE protocol was more efficient for females, whereas the MEDIUM protocol was more efficient for males. Pressure pain was reduced by all protocols (P < 0.001) with no differences between protocols and no gender effect. Conditioned pain modulation was more efficient than the compression-induced analgesia. For the LARGE protocol, precompression CPM efficiency positively correlated with compression-induced analgesia. Large body area compression exerts an area-dependent analgesic effect on experimental pain stimuli. The observed correlation with pain inhibition in response to robust non-noxious sensory stimulation may suggest that compression therapy shares similar mechanisms with inhibitory pain modulation assessed through CPM.

Effects of gabapentin on experimental somatic pain and temporal summation

DEFF Research Database (Denmark)

Arendt-Nielsen, Lars; Frøkjaer, Jens Brøndum; Staahl, Camilla

2007-01-01

at 2 Hz); (2) stimulus-response function relating pain intensity scores (visual analog scale, VAS) to increasing current intensities for electrical skin and muscle stimuli (single and repeated, determined at baseline); and (3) the pain intensity (VAS) and pain areas after intramuscular injection......, was to examine the effect of a single dose of 1200 mg gabapentin on multi-modal experimental cutaneous and muscle pain models. METHODS: The following pain models were applied: (1) pain thresholds to single and repeated cutaneous and intramuscular electrical stimulation (temporal summation to 5 stimuli delivered...... reduced the area under the pain intensity curve to hypertonic saline injections in the muscle (P = .02); and (3) significantly reduced the area of pain evoked by hypertonic saline (P = .03). CONCLUSIONS: Gabapentin reduces temporal summation of skin stimuli at pain threshold intensities; this may have...

Experimental headache in humans

DEFF Research Database (Denmark)

Iversen, Helle Klingenberg

1995-01-01

The need for valid human experimental models of headache is obvious. Several compounds have been proposed as headache-inducing agents, but only the nitroglycerin (NTG) model has been validated. In healthy subjects, intravenous infusions of the nitric oxide (NO) donor NTG induce a dose......-dependent headache and dilatation of the temporal, radial and middle cerebral artery. NTG-induced headache, although less intense, resembles migraine in pain characteristics, but the accompanying symptoms are rarely present. Cephalic large arteries are dilated during migraine headache as well as during NTG headache....... N-acetylcysteine enhances the formation of NO and potentiates NTG-induced headache, whereas mepyramine, a H1-antagonist capable of blocking histamine-induced headache, has no effect. Thus, the headache is dependent on NO or other steps in the NO cascade. The model is useful for pharmacological...

Transcutaneous electrical nerve stimulation: nonparallel antinociceptive effects on chronic clinical pain and acute experimental pain.

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Cheing, G L; Hui-Chan, C W

1999-03-01

To investigate to what extent a single 60-minute session of transcutaneous electrical nerve stimulation (TENS) would modify chronic clinical pain, acute experimental pain, and the flexion reflex evoked in chronic low back pain patients. Thirty young subjects with chronic low back pain were randomly allocated to two groups, receiving either TENS or placebo stimulation to the lumbosacral region for 60 minutes. The flexion reflex was elicited by an electrical stimulation applied to the subject's right sole and recorded electromyographically from the biceps femoris and the tibialis anterior muscles. Subjective sensation of low back pain and the electrically induced pain were measured by two separate visual analog scales, termed VAS(LBP) and VAS(FR), respectively. Data obtained before, during, and 60 minutes after TENS and placebo stimulations were analyzed using repeated measures ANOVA. The VAS(LBP) score was significantly reduced to 63.1% of the prestimulation value after TENS (pTENS protocol had different degrees of antinociceptive influence on chronic and acute pain in chronic low back pain patients.

Infusion pressure and pain during microneedle injection into skin of human subjects

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Gupta, Jyoti; Park, Sohyun; Bondy, Brian; Felner, Eric I.; Prausnitz, Mark R.

2011-01-01

Infusion into skin using hollow microneedles offers an attractive alternative to hypodermic needle injections. However, the fluid mechanics and pain associated with injection into skin using a microneedle have not been studied in detail before. Here, we report on the effect of microneedle insertion depth into skin, partial needle retraction, fluid infusion flow rate and the co-administration of hyaluronidase on infusion pressure during microneedle-based saline infusion, as well as on associated pain in human subjects. Infusion of up to a few hundred microliters of fluid required pressures of a few hundred mmHg, caused little to no pain, and showed weak dependence on infusion parameters. Infusion of larger volumes up to 1 mL required pressures up to a few thousand mmHg, but still usually caused little pain. In general, injection of larger volumes of fluid required larger pressures and application of larger pressures cause more pain, although other experimental parameters also played a significant role. Among the intradermal microneedle groups, microneedle length had little effect; microneedle retraction lowered infusion pressure but increased pain; lower flow rate reduced infusion pressure and kept pain low; and use of hyaluronidase also lowered infusion pressure and kept pain low. We conclude that microneedles offer a simple method to infuse fluid into the skin that can be carried out with little to no pain. PMID:21684001

Placebo effect of an inert gel on experimentally induced leg muscle pain

Directory of Open Access Journals (Sweden)

James G Hopker

2010-11-01

Full Text Available James G Hopker1, Abigail J Foad2, Christopher J Beedie2, Damian A Coleman2, Geoffrey Leach11Centre for Sports Studies, University of Kent, Chatham, Kent, UK; 2Department of Sports Science, Tourism and Leisure, Canterbury Christ Church University, Canterbury, Kent, UKPurpose: This study examined the therapeutic effects of an inert placebo gel on experimentally induced muscle pain in a sports therapy setting. It aimed to investigate the degree to which conditioned analgesia, coupled with an expectation of intervention, was a factor in subsequent analgesia.Methods: Participants were sixteen male and eight female sports therapy students at a UK University. With institutional ethics board approval and following informed consent procedures, each was exposed to pain stimulus in the lower leg in five conditions, ie, conditioning, prebaseline, experimental (two placebo gel applications, and postbaseline. In conditioning trials, participants identified a level of pain stimulus equivalent to a perceived pain rating of 6/10. An inert placebo gel was then applied to the site with the explicit instruction that it was an analgesic. Participants were re-exposed to the pain stimulus, the level of which, without their knowledge, had been decreased, creating the impression of an analgesic effect resulting from the gel. In experimental conditions, the placebo gel was applied and the level of pain stimulus required to elicit a pain rating of 6/10 recorded.Results: Following application of the placebo gel, the level of pain stimulus required to elicit a pain rating of 6/10 increased by 8.2%. Application of the placebo gel significantly decreased participant’s perceptions of muscle pain (P = 0.001.Conclusion: Subjects’ experience and expectation of pain reduction may be major factors in the therapeutic process. These factors should be considered in the sports therapeutic environment.Keywords: conditioning, expectation, perception, positive belief, sports therapy

Higher cortical modulation of pain perception in the human brain: Psychological determinant.

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Chen, Andrew Cn

2009-10-01

Pain perception and its genesis in the human brain have been reviewed recently. In the current article, the reports on pain modulation in the human brain were reviewed from higher cortical regulation, i.e. top-down effect, particularly studied in psychological determinants. Pain modulation can be examined by gene therapy, physical modulation, pharmacological modulation, psychological modulation, and pathophysiological modulation. In psychological modulation, this article examined (a) willed determination, (b) distraction, (c) placebo, (d) hypnosis, (e) meditation, (f) qi-gong, (g) belief, and (h) emotions, respectively, in the brain function for pain modulation. In each, the operational definition, cortical processing, neuroimaging, and pain modulation were systematically deliberated. However, not all studies had featured the brain modulation processing but rather demonstrated potential effects on human pain. In our own studies on the emotional modulation on human pain, we observed that emotions could be induced from music melodies or pictures perception for reduction of tonic human pain, mainly in potentiation of the posterior alpha EEG fields, likely resulted from underneath activities of precuneous in regulation of consciousness, including pain perception. To sum, higher brain functions become the leading edge research in all sciences. How to solve the information bit of thinking and feeling in the brain can be the greatest challenge of human intelligence. Application of higher cortical modulation of human pain and suffering can lead to the progress of social humanity and civilization.

A practical guide and perspectives on the use of experimental pain modalities with children and adolescents

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Birnie, Kathryn A; Caes, Line; Wilson, Anna C; Williams, Sara E; Chambers, Christine T

2014-01-01

SUMMARY Use of experimental pain is vital for addressing research questions that would otherwise be impossible to examine in the real world. Experimental induction of pain in children is highly scrutinized given the potential for harm and lack of direct benefit to a vulnerable population. However, its use has critically advanced our understanding of the mechanisms, assessment and treatment of pain in both healthy and chronically ill children. This article introduces various experimental pain modalities, including the cold pressor task, the water load symptom provocation test, thermal pain, pressure pain and conditioned pain modulation, and discusses their application for use with children and adolescents. It addresses practical implementation and ethical issues, as well as the advantages and disadvantages offered by each task. The incredible potential for future research is discussed given the array of experimental pain modalities now available to pediatric researchers. PMID:24641434

Association between Gene Polymorphisms and Pain Sensitivity Assessed in a Multi-Modal Multi-Tissue Human Experimental Model - An Explorative Study

DEFF Research Database (Denmark)

Nielsen, Lecia Møller; Olesen, Anne Estrup; Sato, Hiroe

2016-01-01

The genetic influence on sensitivity to noxious stimuli (pain sensitivity) remains controversial and needs further investigation. In the present study, the possible influence of polymorphisms in three opioid receptor (OPRM, OPRD and OPRK) genes and the catechol-O-methyltransferase (COMT) gene...... on pain sensitivity in healthy participants was investigated. Catechol-O-methyltransferase has an indirect effect on the mu opioid receptor by changing its activity through an altered endogenous ligand effect. Blood samples for genetic analysis were withdrawn in a multi-modal and multi-tissue experimental......, electrical and thermal visceral stimulations. A cold pressor test was also conducted. DNA was available from 38 of 40 participants. Compared to non-carriers of the COMT rs4680A allele, carriers reported higher bone pressure pain tolerance threshold (i.e. less pain) by up to 23.8% (p

Movement does not promote recovery of motor output following acute experimental muscle pain

DEFF Research Database (Denmark)

Schabrun, Siobhan M.; Palsson, Thorvaldur Skuli; Thapa, Tribikram

2018-01-01

Objective.:  To examine the effect of motor activity on the magnitude and duration of altered corticomotor output following experimental muscle pain. Design. : Experimental, pre-post test. Setting. : University laboratory. Subjects. : Twenty healthy individuals. Methods.:  Participants were rando....... Understanding corticomotor depression in the postpain period and what factors promote recovery has relevance for clinical pain syndromes where ongoing motor dysfunction, in the absence of pain, may predispose to symptom persistence or recurrence....

Women with dysmenorrhoea are hypersensitive to experimentally induced forearm ischaemia during painful menstruation and during the pain-free follicular phase.

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Iacovides, S; Avidon, I; Baker, F C

2015-07-01

Monthly primary dysmenorrhoeic pain is associated with increased sensitivity to painful stimuli, particularly in deep tissue. We investigated whether women with dysmenorrhoea, compared with controls, have increased sensitivity to experimentally induced deep-tissue muscle ischaemia in a body area distant from that of referred menstrual pain. The sub-maximal effort tourniquet test was used to induce forearm ischaemia in 11 women with severe dysmenorrhoea and in nine control women both during menstruation and in the follicular phase of the menstrual cycle. Von Frey hair assessments confirmed the presence of experimental ischaemia. Women rated the intensity of menstrual and ischaemic pain on a 100-mm visual analogue scale. Women with dysmenorrhoea [mean (SD): 68 (20) mm] reported significantly greater menstrual pain compared with controls [mean (SD): 2 (6) mm; p = 0.0001] during the menstruation phase. They also rated their forearm ischaemic pain as significantly greater than the controls during the menstruation [dysmenorrhoeics vs. controls mean (SD): 58 (19) mm vs. 31 (21) mm, p menstruation phase and pain-free follicular phase. These findings suggest the presence of long-lasting changes in muscle pain sensitivity in women with dysmenorrhoea. Our findings that dysmenorrhoeic women are hyperalgesic to a clinically relevant, deep-muscle ischaemic pain in areas outside of referred menstrual pain confirm other studies showing long-lasting changes in pain sensitivity outside of the painful period during menstruation. © 2014 European Pain Federation - EFIC®

Influence of intramuscular granisetron on experimentally induced muscle pain by acidic saline.

Science.gov (United States)

Louca, S; Ernberg, M; Christidis, N

2013-06-01

The aim of this study was to investigate whether intramuscular administration of the 5-HT(3) receptor antagonist granisetron reduces experimental muscle pain induced by repeated intramuscular injections of acidic saline into the masseter muscles. Twenty-eight healthy and pain-free volunteers, fourteen women and fourteen men participated in this randomized, double-blind and placebo-controlled study. After a screening examination and registration of the baseline pressure-pain threshold (PPT), the first simultaneous bilateral injections of 0·5 mL acidic saline (9 mg mL(-1) , pH 3·3) into the masseter muscles were performed. Two days later, PPT and pain (VAS) were re-assessed. The masseter muscle was then pre-treated with 0·5 mL granisetron (Kytril(®) 1 mg mL(-1) pH 5·3) on one side and control substance (isotonic saline, 9 mg mL(-1) pH 6) on the contralateral side. Two minutes thereafter a bilateral simultaneous injection of 0·5 mL acidic saline followed. The evoked pain intensity, pain duration, pain area and PPT were assessed. The volunteers returned 1 week later to re-assess VAS and PPT. On the side pre-treated with granisetron, the induced pain had significantly lower intensity and shorter duration (P granisetron on pain duration was significant only in women (P granisetron has a pain-reducing effect on experimentally induced muscle pain by repeated acidic saline injection. © 2013 John Wiley & Sons Ltd.

The influence of experimentally induced pain on shoulder muscle activity

DEFF Research Database (Denmark)

Diederichsen, L.P.; Winther, A.; Dyhre-Poulsen, P.

2009-01-01

muscles. EMG was recorded before pain, during pain and after pain had subsided and pain intensity was continuously scored on a visual analog scale (VAS). During abduction, experimentally induced pain in the supraspinatus muscle caused a significant decrease in activity of the anterior deltoid, upper......-105A degrees) at a speed of approximately 120A degrees/s, controlled by a metronome. During abduction, electromyographic (EMG) activity was recorded by intramuscular wire electrodes inserted in two deeply located shoulder muscles and by surface-electrodes over six superficially located shoulder...... trapezius and the infraspinatus and an increase in activity of lower trapezius and latissimus dorsi muscles. Following subacromial injection a significantly increased muscle activity was seen in the lower trapezius, the serratus anterior and the latissimus dorsi muscles. In conclusion, this study shows...

Pain perception in people with Down syndrome: a synthesis of clinical and experimental research

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McGuire, Brian E.; Defrin, Ruth

2015-01-01

People with an intellectual disability experience both acute and chronic pain with at least the same frequency as the general population. However, considerably less is known about the pain perception of people with Down syndrome. In this review paper, we evaluated the available clinical and experimental evidence. Some experimental studies of acute pain have indicated that pain threshold was higher than normal but only when using a reaction time method to measure pain sensitivity. However, when reaction time is not part of the calculation of the pain threshold, pain sensitivity in people with Down syndrome is in fact lower than normal (more sensitive to pain). Clinical studies of chronic pain have shown that people with an intellectual disability experience chronic pain and within that population, people with Down syndrome also experience chronic pain, but the precise prevalence of chronic pain in Down syndrome has yet to be established. Taken together, the literature suggests that people with Down syndrome experience pain, both acute and chronic, with at least the same frequency as the rest of the population. Furthermore, the evidence suggests that although acute pain expression appears to be delayed, once pain is registered, there appears to be a magnified pain response. We conclude by proposing an agenda for future research in this area. PMID:26283936

Slow brushing reduces heat pain in humans.

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Liljencrantz, J; Strigo, I; Ellingsen, D M; Krämer, H H; Lundblad, L C; Nagi, S S; Leknes, S; Olausson, H

2017-08-01

C-tactile (CT) afferents are unmyelinated low-threshold mechanoreceptors optimized for signalling affective, gentle touch. In three separate psychophysical experiments, we examined the contribution of CT afferents to pain modulation. In total, 44 healthy volunteers experienced heat pain and CT optimal (slow brushing) and CT sub-optimal (fast brushing or vibration) stimuli. Three different experimental paradigms were used: Concurrent application of heat pain and tactile (slow brushing or vibration) stimulation; Slow brushing, applied for variable duration and intervals, preceding heat pain; Slow versus fast brushing preceding heat pain. Slow brushing was effective in reducing pain, whereas fast brushing or vibration was not. The reduction in pain was significant not only when the CT optimal touch was applied simultaneously with the painful stimulus but also when the two stimuli were separated in time. For subsequent stimulation, the pain reduction was more pronounced for a shorter time interval between brushing and pain. Likewise, the effect was more robust when pain was preceded by a longer duration of brush stimulation. Strong CT-related pain reduction was associated with low anxiety and high calmness scores obtained by a state anxiety questionnaire. Slow brushing - optimal for CT activation - is effective in reducing pain from cutaneous heating. The precise mechanisms for the pain relief are as yet unknown but possible mechanisms include inhibition of nociceptive projection neurons at the level of the dorsal horn as well as analgesia through cortical mechanisms. Slow brushing stimuli - optimal for activation of C-tactile fibres - can reduce pain from cutaneous heating. No such effect was seen with fast brushing or vibration. These observations indicate the role of C-tactile fibres in pain modulation. © 2017 European Pain Federation - EFIC®.

Reorganized trunk muscle activity during multidirectional floor perturbations after experimental low back pain

DEFF Research Database (Denmark)

Larsen, Lars Henrik; Hirata, Rogerio Pessoto; Graven-Nielsen, Thomas

2016-01-01

Low back pain changes the trunk muscle activity after external perturbations but the relationship between pain intensities and distributions and their effect on the trunk muscle activity remains unclear. The effects of unilateral and bilateral experimental low back pain on trunk muscle activity w...

5-HT modulation of pain perception in humans.

Science.gov (United States)

Martin, Sarah L; Power, Andrea; Boyle, Yvonne; Anderson, Ian M; Silverdale, Monty A; Jones, Anthony K P

2017-10-01

Although there is clear evidence for the serotonergic regulation of descending control of pain in animals, little direct evidence exists in humans. The majority of our knowledge comes from the use of serotonin (5-HT)-modulating antidepressants as analgesics in the clinical management of chronic pain. Here, we have used an acute tryptophan depletion (ATD) to manipulate 5-HT function and examine its effects of ATD on heat pain threshold and tolerance, attentional manipulation of nociceptive processing and mood in human volunteers. Fifteen healthy participants received both ATD and balanced amino acid (BAL) drinks on two separate sessions in a double-blind cross-over design. Pain threshold and tolerance were determined 4 h post-drink via a heat thermode. Additional attention, distraction and temperature discrimination paradigms were completed using a laser-induced heat pain stimulus. Mood was assessed prior and throughout each session. Our investigation reported that the ATD lowered plasma TRP levels by 65.05 ± 7.29% and significantly reduced pain threshold and tolerance in response to the heat thermode. There was a direct correlation between the reduction in total plasma TRP levels and reduction in thermode temperature. In contrast, ATD showed no effect on laser-induced pain nor significant impact of the distraction-induced analgesia on pain perception but did reduce performance of the painful temperature discrimination task. Importantly, all findings were independent of any effects of ATD on mood. As far as we are aware, it is the first demonstration of 5-HT effects on pain perception which are not confounded by mood changes.

The human pain genetics database: an interview with Luda Diatchenko.

Science.gov (United States)

Diatchenko, Luda

2018-06-05

Luda Diatchenko, MD, PhD is a Canada Excellence Research Chair in Human Pain Genetics, Professor, Faculty of Medicine, Department of Anesthesia and Faculty of Dentistry at McGill University, Alan Edwards Centre for Research on Pain. She earned her MD and PhD in the field of molecular biology from the Russian State Medical University. She started her career in industry, she was a Leader of the RNA Expression Group at Clontech, Inc., and subsequently, Director of Gene Discovery at Attagene, Inc. During this time, she was actively involved in the development of several widely used and widely cited molecular tools for the analysis of gene expression and regulation. Her academic career started at 2000 in the Center for Neurosensory Disorders at University of North Carolina. Her research since then is focused on determining the cellular and molecular biological mechanisms by which functional genetic variations impact human pain perception and risk of development of chronic pain conditions, enabling new approaches to identify new drug targets, treatment responses to analgesics and diagnostic. Multiple collaborative activities allow the Diatchenko group to take basic genetic findings all the way from human association studies, through molecular and cellular mechanisms to animal models and ultimately to human clinical trials. In total, she has authored or co-authored over 120 peer-reviewed research papers in journals, ten book chapters and edited a book in human pain genetics. She is a member and an active officer of several national and international scientific societies, including the International Association for the Study of Pain and the American Pain Society.

Objective Markers of the analgesic response to morphine in experimental pain research

DEFF Research Database (Denmark)

Brokjær, Anne; Olesen, Anne Estrup; Kreilgaard, Mads

2015-01-01

INTRODUCTION: In experimental pain research the effect of opioids is normally assessed by verbal subjective response to analgesia. However, as many confounders in pain assessment exist, objective bed-side assessment of the effect is highly warranted. Therefore, we aimed to assess the effect...

Masseter motor unit recruitment is altered in experimental jaw muscle pain.

Science.gov (United States)

Minami, I; Akhter, R; Albersen, I; Burger, C; Whittle, T; Lobbezoo, F; Peck, C C; Murray, G M

2013-02-01

Some management strategies for chronic orofacial pain are influenced by models (e.g., Vicious Cycle Theory, Pain Adaptation Model) proposing either excitation or inhibition within a painful muscle. The aim of this study was to determine if experimental painful stimulation of the masseter muscle resulted in only increases or only decreases in masseter activity. Recordings of single-motor-unit (SMU, basic functional unit of muscle) activity were made from the right masseters of 10 asymptomatic participants during biting trials at the same force level and direction under infusion into the masseter of isotonic saline (no-pain condition), and in another block of biting trials on the same day, with 5% hypertonic saline (pain condition). Of the 36 SMUs studied, 2 SMUs exhibited a significant (p units were present only during the no-pain block and 10 units during the pain block only. The findings suggest that, rather than only excitation or only inhibition within a painful muscle, a re-organization of activity occurs, with increases and decreases occurring within the painful muscle. This suggests the need to re-assess management strategies based on models that propose uniform effects of pain on motor activity.

Evolving robot empathy towards humans with motor disabilities through artificial pain generation

Directory of Open Access Journals (Sweden)

Muh Anshar

2018-01-01

Full Text Available In contact assistive robots, a prolonged physical engagement between robots and humans with motor disabilities due to shoulder injuries, for instance, may at times lead humans to experience pain. In this situation, robots will require sophisticated capabilities, such as the ability to recognize human pain in advance and generate counter-responses as follow up emphatic action. Hence, it is important for robots to acquire an appropriate pain concept that allows them to develop these capabilities. This paper conceptualizes empathy generation through the realization of synthetic pain classes integrated into a robot’s self-awareness framework, and the implementation of fault detection on the robot body serves as a primary source of pain activation. Projection of human shoulder motion into the robot arm motion acts as a fusion process, which is used as a medium to gather information for analyses then to generate corresponding synthetic pain and emphatic responses. An experiment is designed to mirror a human peer’s shoulder motion into an observer robot. The results demonstrate that the fusion takes place accurately whenever unified internal states are achieved, allowing accurate classification of synthetic pain categories and generation of empathy responses in a timely fashion. Future works will consider a pain activation mechanism development.

Experimental knee joint pain during strength training and muscle strength gain in healthy subjects

DEFF Research Database (Denmark)

Sørensen, T J; Langberg, Henning; Hodges, P W

2012-01-01

Knee joint pain and reduced quadriceps strength are cardinal symptoms in many knee pathologies. In people with painful knee pathologies, quadriceps exercise reduces pain, improves physical function, and increases muscle strength. A general assumption is that pain compromises muscle function...... and thus may prevent effective rehabilitation. This study evaluated the effects of experimental knee joint pain during quadriceps strength training on muscle strength gain in healthy individuals....

Inhibition of c-Kit signaling is associated with reduced heat and cold pain sensitivity in humans.

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Ceko, Marta; Milenkovic, Nevena; le Coutre, Philipp; Westermann, Jörg; Lewin, Gary R

2014-07-01

The tyrosine kinase receptor c-Kit is critically involved in the modulation of nociceptive sensitivity in mice. Ablation of the c-Kit gene results in hyposensitivity to thermal pain, whereas activation of c-Kit produces hypersensitivity to noxious heat, without altering sensitivity to innocuous mechanical stimuli. In this study, we investigated the role of c-Kit signaling in human pain perception. We hypothesized that subjects treated with Imatinib or Nilotinib, potent inhibitors of tyrosine kinases including c-Kit but also Abl1, PDFGFRα, and PDFGFRβ, that are used to treat chronic myeloid leukemia (CML), would experience changes in thermal pain sensitivity. We examined 31 asymptomatic CML patients (14 male and 17 female) receiving Imatinib/Nilotinib treatment and compared them to 39 age- and sex-matched healthy controls (12 male and 27 female). We used cutaneous heat and cold stimulation to test normal and noxious thermal sensitivity, and a grating orientation task to assess tactile acuity. Thermal pain thresholds were significantly increased in the Imatinib/Nilotinib-treated group, whereas innocuous thermal and tactile thresholds were unchanged compared to those in the control group. In conclusion, our findings suggest that the biological effects of c-Kit inhibition are comparable in mice and humans in that c-Kit activity is required to regulate thermal pain sensitivity but does not affect innocuous thermal and mechanical sensation. The effect on experimental heat pain observed in our study is comparable to those of several common analgesics; thus modulation of the c-Kit pathway can be used to specifically modulate noxious heat and cold sensitivity in humans. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Experimental knee pain impairs submaximal force steadiness in isometric, eccentric, and concentric muscle actions.

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Rice, David A; McNair, Peter J; Lewis, Gwyn N; Mannion, Jamie

2015-09-12

Populations with knee joint damage, including arthritis, have noted impairments in the regulation of submaximal muscle force. It is difficult to determine the exact cause of such impairments given the joint pathology and associated neuromuscular adaptations. Experimental pain models that have been used to isolate the effects of pain on muscle force regulation have shown impaired force steadiness during acute pain. However, few studies have examined force regulation during dynamic contractions, and these findings have been inconsistent. The goal of the current study was to examine the effect of experimental knee joint pain on submaximal quadriceps force regulation during isometric and dynamic contractions. The study involved fifteen healthy participants. Participants were seated in an isokinetic dynamometer. Knee extensor force matching tasks were completed in isometric, eccentric, and concentric muscle contraction conditions. The target force was set to 10 % of maximum for each contraction type. Hypertonic saline was then injected into the infrapatella fat pad to generate acute joint pain. The force matching tasks were repeated during pain and once more 5 min after pain had subsided. Hypertonic saline resulted in knee pain with an average peak pain rating of 5.5 ± 2.1 (0-10 scale) that lasted for 18 ± 4 mins. Force steadiness significantly reduced during pain across all three muscle contraction conditions. There was a trend to increased force matching error during pain but this was not significant. Experimental knee pain leads to impaired quadriceps force steadiness during isometric, eccentric, and concentric contractions, providing further evidence that joint pain directly affects motor performance. Given the established relationship between submaximal muscle force steadiness and function, such an effect may be detrimental to the performance of tasks in daily life. In order to restore motor performance in people with painful arthritic conditions of the

Experimental tooth clenching. A model for studying mechanisms of muscle pain.

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Dawson, Andreas

2013-01-01

The overall goal of this thesis was to broaden knowledge of pain mechanisms in myofascial temporomandibular disorders (M-TMD). The specific aims were to: Develop a quality assessment tool for experimental bruxism studies (study I). Investigate proprioceptive allodynia after experimental tooth clenching exercises (study II). Evaluate the release of serotonin (5-HT), glutamate, pyruvate, and lactate in healthy subjects (study III) and in patients with M-TMD (study IV), after experimental tooth clenching exercises. In (I), tool development comprised 5 steps: (i) preliminary decisions, (ii) item generation, (iii) face-validity assessment, (iv) reliability and discriminative validity testing, and (v) instrument refinement. After preliminary decisions and a literature review, a list of 52 items to be considered for inclusion in the tool was generated. Eleven experts were invited to participate on the Delphi panel, of which 10 agreed. After four Delphi rounds, 8 items remained and were included in the Quality Assessment Tool for Experimental Bruxism Studies (Qu-ATEBS). Inter-observer reliability was acceptable (k = 0.77), and discriminative validity high (phi coefficient 0.79; P < 0.01). During refinement, 1 item was removed; the final tool comprised 7 items. In (II), 16 healthy females participated in three 60-min sessions, each with 24- and 48-h follow-ups. Participants were randomly assigned to a repetitive experimental tooth clenching task with a clenching level of 10%, 20%, or 40% of maximal voluntary clenching force (MVCF). Pain intensity, fatigue, perceived intensity of vibration (PIV), perceived discomfort (PD), and pressure pain threshold (PPT) were measured throughout. A significant increase in pain intensity and fatigue but not in PD was observed over time. A significant increase in PIV was only observed at 40 min, and PPT decreased significantly over time at 50 and 60 min compared to baseline. In (III), 30 healthy subjects (16 females, and 14 males

Dissociable Learning Processes Underlie Human Pain Conditioning.

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Zhang, Suyi; Mano, Hiroaki; Ganesh, Gowrishankar; Robbins, Trevor; Seymour, Ben

2016-01-11

Pavlovian conditioning underlies many aspects of pain behavior, including fear and threat detection [1], escape and avoidance learning [2], and endogenous analgesia [3]. Although a central role for the amygdala is well established [4], both human and animal studies implicate other brain regions in learning, notably ventral striatum and cerebellum [5]. It remains unclear whether these regions make different contributions to a single aversive learning process or represent independent learning mechanisms that interact to generate the expression of pain-related behavior. We designed a human parallel aversive conditioning paradigm in which different Pavlovian visual cues probabilistically predicted thermal pain primarily to either the left or right arm and studied the acquisition of conditioned Pavlovian responses using combined physiological recordings and fMRI. Using computational modeling based on reinforcement learning theory, we found that conditioning involves two distinct types of learning process. First, a non-specific "preparatory" system learns aversive facial expressions and autonomic responses such as skin conductance. The associated learning signals-the learned associability and prediction error-were correlated with fMRI brain responses in amygdala-striatal regions, corresponding to the classic aversive (fear) learning circuit. Second, a specific lateralized system learns "consummatory" limb-withdrawal responses, detectable with electromyography of the arm to which pain is predicted. Its related learned associability was correlated with responses in ipsilateral cerebellar cortex, suggesting a novel computational role for the cerebellum in pain. In conclusion, our results show that the overall phenotype of conditioned pain behavior depends on two dissociable reinforcement learning circuits. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

A quantitative review of ethnic group differences in experimental pain response: do biology, psychology, and culture matter?

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Rahim-Williams, Bridgett; Riley, Joseph L; Williams, Ameenah K K; Fillingim, Roger B

2012-04-01

Pain is a subjectively complex and universal experience. We examine research investigating ethnic group differences in experimental pain response and factors contributing to group differences. We conducted a systematic literature review and analysis of studies using experimental pain stimuli to assess pain sensitivity across multiple ethnic groups. Our search covered the period from 1944 to 2011, and used the PubMed bibliographic database; a reference source containing over 17 million citations. We calculated effect sizes; identified ethnic/racial group categories, pain stimuli, and measures; and examined findings regarding biopsychosociocultural factors contributing to ethnic/racial group differences. We found 472 studies investigating ethnic group differences and pain. Twenty-six of these met our review inclusion criteria of investigating ethnic group differences in experimental pain. The majority of studies included comparisons between African Americans (AA) and non-Hispanic Whites (NHW). There were consistently moderate to large effect sizes for pain tolerance across multiple stimulus modalities; AA demonstrated lower pain tolerance. For pain threshold, findings were generally in the same direction, but effect sizes were small to moderate across ethnic groups. Limited data were available for suprathreshold pain ratings. A subset of studies comparing NHW and other ethnic groups showed a variable range of effect sizes for pain threshold and tolerance. There are potentially important ethnic/racial group differences in experimental pain perception. Elucidating ethnic group differences has translational merit for culturally competent clinical care and for addressing and reducing pain treatment disparities among ethnically/racially diverse groups. Wiley Periodicals, Inc.

The influence of working memory capacity on experimental heat pain.

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Nakae, Aya; Endo, Kaori; Adachi, Tomonori; Ikeda, Takashi; Hagihira, Satoshi; Mashimo, Takashi; Osaka, Mariko

2013-10-01

Pain processing and attention have a bidirectional interaction that depends upon one's relative ability to use limited-capacity resources. However, correlations between the size of limited-capacity resources and pain have not been evaluated. Working memory capacity, which is a cognitive resource, can be measured using the reading span task (RST). In this study, we hypothesized that an individual's potential working memory capacity and subjective pain intensity are related. To test this hypothesis, we evaluated 31 healthy participants' potential working memory capacity using the RST, and then applied continuous experimental heat stimulation using the listening span test (LST), which is a modified version of the RST. Subjective pain intensities were significantly lower during the challenging parts of the RST. The pain intensity under conditions where memorizing tasks were performed was compared with that under the control condition, and it showed a correlation with potential working memory capacity. These results indicate that working memory capacity reflects the ability to process information, including precise evaluations of changes in pain perception. In this work, we present data suggesting that changes in subjective pain intensity are related, depending upon individual potential working memory capacities. Individual working memory capacity may be a phenotype that reflects sensitivity to changes in pain perception. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

Pain and Consciousness in Humans. Or Why Pain Subserves the Identity and Self-representation

Directory of Open Access Journals (Sweden)

Irene Venturella

2016-08-01

Full Text Available Traditional definitions of pain assume that an individual learns about pain through verbal usages related to the experience of injury in early life. This emphasis on the verbal correlates of pain restricts our understanding of pain to the context of adult human consciousness. In this paper we instead support the idea that our understanding of pain originates in neonatal experience and is not merely a verbally determined phenomenon. We also challenge the definition of pain as a merely sensory message related to peripheral tissue trauma. We aim to move beyond this definition by considering the relationship between the centre (Central Nervous System and periphery, taking into account certain phenomena such as phantom limbs and interoception. We show that pain helps an individual to develop a sense of awareness of himself immersed in a social context, and is thus a complex and adaptive phenomenon, that supports bodily integrity and social behavior.

Analgesic effect of clobazam in chronic low-back pain but not in experimentally induced pain.

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Schliessbach, J; Vuilleumier, P H; Siegenthaler, A; Bütikofer, L; Limacher, A; Juni, P; Zeilhofer, H U; Arendt-Nielsen, L; Curatolo, M

2017-09-01

Chronic pain is frequently associated with hypersensitivity of the nervous system, and drugs that increase central inhibition are therefore a potentially effective treatment. Benzodiazepines are potent modulators of GABAergic neurotransmission and are known to exert antihyperalgesic effects in rodents, but translation into patients are lacking. This study investigates the effect of the benzodiazepine clobazam in chronic low-back pain in humans. The aim of this study is to explore the effect of GABA modulation on chronic low-back pain and on quantitative sensory tests. In this double-blind cross-over study, 49 patients with chronic low-back pain received a single oral dose of clobazam 20 mg or active placebo tolterodine 1 mg. Pain intensity on the 0-10 numeric rating scale and quantitative sensory tests were assessed during 2 h after drug intake. Pain intensity in the supine position was significantly reduced by clobazam compared to active placebo (60 min: 2.9 vs. 3.5, p = 0.008; 90 min: 2.7 vs. 3.3, p = 0.024; 120 min: 2.4 vs. 3.1, p = 0.005). Pain intensity in the sitting position was not significantly different between groups. No effects on quantitative sensory tests were observed. This study suggests that clobazam has an analgesic effect in patients with chronic low-back pain. Muscle relaxation or sedation may have contributed to the effect. Development of substances devoid of these side effects would offer the potential to further investigate the antihyperalgesic action of GABAergic compounds. Modulation of GABAergic pain-inhibitory pathways may be a potential future therapeutic target. © 2017 European Pain Federation - EFIC®.

Calcitonin gene-related peptide and pain

DEFF Research Database (Denmark)

Schou, Wendy Sophie; Ashina, Sait; Amin, Faisal Mohammad

2017-01-01

and cerebrospinal fluid in subjects with musculoskeletal pain. A randomized clinical trial on monoclonal antibody, which selectively binds to and inhibits the activity of CGRP (galcanezumab) in patients with osteoarthritis knee pain, failed to demonstrate improvement of pain compared with placebo. No studies......BACKGROUND: Calcitonin gene-related peptide (CGRP) is widely distributed in nociceptive pathways in human peripheral and central nervous system and its receptors are also expressed in pain pathways. CGRP is involved in migraine pathophysiology but its role in non-headache pain has not been...... clarified. METHODS: We performed a systematic literature search on PubMed, Embase and ClinicalTrials.gov for articles on CGRP and non-headache pain covering human studies including experimental studies and randomized clinical trials. RESULTS: The literature search identified 375 citations of which 50...

Numbness in clinical and experimental pain--a cross-sectional study exploring the mechanisms of reduced tactile function.

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Geber, Christian; Magerl, Walter; Fondel, Ricarda; Fechir, Marcel; Rolke, Roman; Vogt, Thomas; Treede, Rolf-Detlef; Birklein, Frank

2008-09-30

Pain patients often report distinct numbness of the painful skin although no structural peripheral or central nerve lesion is obvious. In this cross-sectional study we assessed the reduction of tactile function and studied underlying mechanisms in patients with chronic pain and in healthy participants exposed to phasic and tonic experimental nociceptive stimulation. Mechanical detection (MDT) and pain thresholds (MPT) were assessed in the painful area and the non-painful contralateral side in 10 patients with unilateral musculoskeletal pain. Additionally, 10 healthy participants were exposed to nociceptive stimulation applied to the volar forearms (capsaicin; electrical stimulation, twice each). Areas of tactile hypaesthesia and mechanical hyperalgesia were assessed. MDT and MPT were quantified adjacent to the stimulation site. Tactile hypaesthesia in pain patients and in experimental pain (MDT-z-scores: -0.66+/-0.30 and -0.42+/-0.15, respectively, both p<0.01) was paralleled by mechanical hyperalgesia (MPT-z-scores: +0.51+/-0.27, p<0.05; and +0.48+/-0.10, p<0.001). However, hypaesthesia and hyperalgesia were not correlated. Although 9 patients reported numbness, only 3 of them were able to delineate circumscript areas of tactile hypaesthesia. In experimental pain, the area of tactile hypaesthesia could be mapped in 31/40 experiments (78%). Irrespective of the mode of nociceptive stimulation (phasic vs. tonic) tactile hypaesthesia and hyperalgesia developed with a similar time course and disappeared within approximately 1 day. Hypaesthesia (numbness) often encountered in clinical pain can be reproduced by experimental nociceptive stimulation. The time course of effects suggests a mechanism involving central plasticity.

The role of periodontal ASIC3 in orofacial pain induced by experimental tooth movement in rats.

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Gao, Meiya; Long, Hu; Ma, Wenqiang; Liao, Lina; Yang, Xin; Zhou, Yang; Shan, Di; Huang, Renhuan; Jian, Fan; Wang, Yan; Lai, Wenli

2016-12-01

This study aimed to clarify the roles of Acid-sensing ion channel 3 (ASIC3) in orofacial pain following experimental tooth movement. Sixty male Sprague-Dawley rats were divided into the experimental group (40g, n = 30) and the sham group (0g, n = 30). Closed coil springs were ligated between maxillary incisor and molars to achieve experimental tooth movement. Rat grimace scale (RGS) scores were assessed at 0, 1, 3, 5, 7, and 14 days after the placement of the springs. ASIC3 immunostaining was performed and the expression levels of ASIC3 were measured through integrated optical density/area in Image-Pro Plus 6.0. Moreover, 18 rats were divided into APETx2 group (n = 6), amiloride group (n = 6), and vehicle group (n = 6), and RGS scores were obtained compared among them to verify the roles of ASIC3 in orofacial pain following tooth movement. ASIC3 expression levels became significantly higher in the experimental group than in sham group on 1, 3, and 5 days and became similar on 7 and 14 days. Pain levels (RGS scores) increased in both groups and were significantly higher in the experimental group on 1, 3, 5, and 7 days and were similar on 14 days. Periodontal ASIC3 expression levels were correlated with orofacial pain levels following experimental tooth movement. Periodontal administrations of ASIC3 antagonists (APETx2 and amiloride) could alleviate pain. This study needs to be better evidenced by RNA interference of ASIC3 in periodontal tissues in rats following experimental tooth movement. Moreover, we hope further studies would concentrate on the pain perception of ASIC3 knockout (ASIC3 -/- ) mice. Our results suggest that periodontal ASIC3 plays an important role in orofacial pain induced by experimental tooth movement. © The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The dynamics of the pain system is intact in patients with knee osteoarthritis: An exploratory experimental study.

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Jørgensen, Tanja Schjødt; Henriksen, Marius; Rosager, Sara; Klokker, Louise; Ellegaard, Karen; Danneskiold-Samsøe, Bente; Bliddal, Henning; Graven-Nielsen, Thomas

2017-12-29

Background and aims Despite the high prevalence of knee osteoarthritis (OA) it remains one of the most frequent knee disorders without a cure. Pain and disability are prominent clinical features of knee OA. Knee OA pain is typically localized but can also be referred to the thigh or lower leg. Widespread hyperalgesia has been found in knee OA patients. In addition, patients with hyperalgesia in the OA knee joint show increased pain summation scores upon repetitive stimulation of the OA knee suggesting the involvement of facilitated central mechanisms in knee OA. The dynamics of the pain system (i.e., the adaptive responses to pain) has been widely studied, but mainly from experiments on healthy subjects, whereas less is known about the dynamics of the pain system in chronic pain patients, where the pain system has been activated for a long time. The aim of this study was to assess the dynamics of the nociceptive system quantitatively in knee osteoarthritis (OA) patients before and after induction of experimental knee pain. Methods Ten knee osteoarthritis (OA) patients participated in this randomized crossover trial. Each subject was tested on two days separated by 1 week. The most affected knee was exposed to experimental pain or control, in a randomized sequence, by injection of hypertonic saline into the infrapatellar fat pad and a control injection of isotonic saline. Pain areas were assessed by drawings on anatomical maps. Pressure pain thresholds (PPT) at the knee, thigh, lower leg, and arm were assessed before, during, and after the experimental pain and control conditions. Likewise, temporal summation of pressure pain on the knee, thigh and lower leg muscles was assessed. Results Experimental knee pain decreased the PPTs at the knee (P system in individuals with knee OA can be affected even after many years of nociceptive input. This study indicates that the adaptability in the pain system is intact in patients with knee OA, which opens for opportunities to

Experimental pain in human temporal muscle induced by hypertonic saline, potassium and acidity

DEFF Research Database (Denmark)

Jensen, K; Norup, M

1992-01-01

chloride (n = 12) induced significantly more pain than isotonic saline (ANOVA, p less than 0.0001). Compared to control injections, hypertonic saline and potassium chloride induced a significant reduction in pressure-pain threshold (ANOVA, p less than 0.0001 and p less than 0.05). Forty-eight percent...

Humans, but not animals, perceive the thermal grill illusion as painful.

Science.gov (United States)

Boettger, Michael K; Ditze, Günter; Bär, Karl-Juergen; Krüdewagen, Eva Maria; Schaible, Hans-Georg

2016-10-15

Simultaneous presentation of alternating innocuous warm and cold stimuli induces in most humans a painful sensation called thermal grill illusion (TGI). Here, pain is elicited although nociceptors are not activated. Upon back-translation of behavioural correlates from humans to animals, we found that neither cats nor rodents show adverse reactions when exposed to TGI stimulation. These results question that a TGI observed as a pain-related change in behaviour can be elicited in animals. While distinct neuronal patterns as previously reported may be measurable in animals upon TGI stimulation, their translational meaning towards the sensation elicited in humans is unclear. Copyright © 2016 Elsevier B.V. All rights reserved.

The Effect of Experimental Parkinson on Formalin-Induced Pain in Rat

Directory of Open Access Journals (Sweden)

Mohammad Sofiabadi

2014-04-01

Full Text Available Background & Objectives : Pain is one of the preceding claims of Parkinson's disease (PD, that its mechanisms have not been fully identified. The purpose of this study was to investigate the chemical pain responses induced by subcutaneous injection of formalin in male parkinsonized rats.   Method : In this experimental study, 40 Wistar male rats were used and PD was established by stereotaxic injection of 6-OHDA toxin into the striatum. Parkinson's disease severity determined by apomorphine-induced rotation test and then the pain response of 4 groups, the control, sham and 2 weak or full Parkinson groups, were evaluated using formalin test. Data were analyzed using ANOVA and Tukey test.   Results : In both acute and chronic phases of the formalin test, the symptoms of pain in different groups were same, but at the interphase stage, pain intensity increased more in Parkinson 's rats, especially in full PD group compared to control (p<0.01.   Conclusion: These results suggest that the nigrostriatal dopaminergic pathway have important modulating role on chronic pain.

Gait changes in patients with knee osteoarthritis are replicated by experimental knee pain

DEFF Research Database (Denmark)

Henriksen, Marius; Nielsen, Thomas Graven; Aaboe, Jens

2010-01-01

Medial knee osteoarthritis (OA) is characterized by pain and associated with abnormal knee moments during walking. The relationship between knee OA pain and gait changes remains to be clarified, and a better understanding of this link could advance the treatment and prevention of disease...... progression. This study investigated changes in knee moments during walking following experimental knee pain in healthy volunteers, and whether these changes replicated the joint moments observed in medial knee OA patients....

Inhibition of TRPM8 channels reduces pain in the cold pressor test in humans.

Science.gov (United States)

Winchester, Wendy J; Gore, Katrina; Glatt, Sophie; Petit, Wendy; Gardiner, Jennifer C; Conlon, Kelly; Postlethwaite, Michael; Saintot, Pierre-Philippe; Roberts, Sonia; Gosset, James R; Matsuura, Tomomi; Andrews, Mark D; Glossop, Paul A; Palmer, Michael J; Clear, Nicola; Collins, Susie; Beaumont, Kevin; Reynolds, David S

2014-11-01

The transient receptor potential (subfamily M, member 8; TRPM8) is a nonselective cation channel localized in primary sensory neurons, and is a candidate for cold thermosensing, mediation of cold pain, and bladder overactivity. Studies with TRPM8 knockout mice and selective TRPM8 channel blockers demonstrate a lack of cold sensitivity and reduced cold pain in various rodent models. Furthermore, TRPM8 blockers significantly lower body temperature. We have identified a moderately potent (IC50 = 103 nM), selective TRPM8 antagonist, PF-05105679 [(R)-3-[(1-(4-fluorophenyl)ethyl)(quinolin-3-ylcarbonyl)amino]methylbenzoic acid]. It demonstrated activity in vivo in the guinea pig bladder ice water and menthol challenge tests with an IC50 of 200 nM and reduced core body temperature in the rat (at concentrations >1219 nM). PF-05105679 was suitable for acute administration to humans and was evaluated for effects on core body temperature and experimentally induced cold pain, using the cold pressor test. Unbound plasma concentrations greater than the IC50 were achieved with 600- and 900-mg doses. The compound displayed a significant inhibition of pain in the cold pressor test, with efficacy equivalent to oxycodone (20 mg) at 1.5 hours postdose. No effect on core body temperature was observed. An unexpected adverse event (hot feeling) was reported, predominantly periorally, in 23 and 36% of volunteers (600- and 900-mg dose, respectively), which in two volunteers was nontolerable. In conclusion, this study supports a role for TRPM8 in acute cold pain signaling at doses that do not cause hypothermia. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Complex regional pain syndrome (CRPS) or continuous unilateral distal experimental pain stimulation in healthy subjects does not bias visual attention towards one hemifield.

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Filippopulos, Filipp M; Grafenstein, Jessica; Straube, Andreas; Eggert, Thomas

2015-11-01

In natural life pain automatically draws attention towards the painful body part suggesting that it interacts with different attentional mechanisms such as visual attention. Complex regional pain syndrome (CRPS) patients who typically report on chronic distally located pain of one extremity may suffer from so-called neglect-like symptoms, which have also been linked to attentional mechanisms. The purpose of the study was to further evaluate how continuous pain conditions influence visual attention. Saccade latencies were recorded in two experiments using a common visual attention paradigm whereby orientating saccades to cued or uncued lateral visual targets had to be performed. In the first experiment saccade latencies of healthy subjects were measured under two conditions: one in which continuous experimental pain stimulation was applied to the index finger to imitate a continuous pain situation, and one without pain stimulation. In the second experiment saccade latencies of patients suffering from CRPS were compared to controls. The results showed that neither the continuous experimental pain stimulation during the experiment nor the chronic pain in CRPS led to an unilateral increase of saccade latencies or to a unilateral increase of the cue effect on latency. The results show that unilateral, continuously applied pain stimuli or chronic pain have no or only very limited influence on visual attention. Differently from patients with visual neglect, patients with CRPS did not show strong side asymmetries of saccade latencies or of cue effects on saccade latencies. Thus, neglect-like clinical symptoms of CRPS patients do not involve the allocation of visual attention.

Higher cortical modulation of pain perception in the human brain: Psychological determinant

OpenAIRE

Chen, Andrew Cn

2009-01-01

Pain perception and its genesis in the human brain have been reviewed recently. In the current article, the reports on pain modulation in the human brain were reviewed from higher cortical regulation, i.e. top-down effect, particularly studied in psychological determinants. Pain modulation can be examined by gene therapy, physical modulation, pharmacological modulation, psychological modulation, and pathophysiological modulation. In psychological modulation, this article examined (a) willed d...

Sex differences in pain: a brief review of clinical and experimental findings.

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Bartley, E J; Fillingim, R B

2013-07-01

Recent years have witnessed substantially increased research regarding sex differences in pain. The expansive body of literature in this area clearly suggests that men and women differ in their responses to pain, with increased pain sensitivity and risk for clinical pain commonly being observed among women. Also, differences in responsivity to pharmacological and non-pharmacological pain interventions have been observed; however, these effects are not always consistent and appear dependent on treatment type and characteristics of both the pain and the provider. Although the specific aetiological basis underlying these sex differences is unknown, it seems inevitable that multiple biological and psychosocial processes are contributing factors. For instance, emerging evidence suggests that genotype and endogenous opioid functioning play a causal role in these disparities, and considerable literature implicates sex hormones as factors influencing pain sensitivity. However, the specific modulatory effect of sex hormones on pain among men and women requires further exploration. Psychosocial processes such as pain coping and early-life exposure to stress may also explain sex differences in pain, in addition to stereotypical gender roles that may contribute to differences in pain expression. Therefore, this review will provide a brief overview of the extant literature examining sex-related differences in clinical and experimental pain, and highlights several biopsychosocial mechanisms implicated in these male-female differences. The future directions of this field of research are discussed with an emphasis aimed towards further elucidation of mechanisms which may inform future efforts to develop sex-specific treatments.

Effects of unilateral and bilateral experimental low-back pain on trunk muscle activity during stair walking in healthy and recurrent low-back pain patients

DEFF Research Database (Denmark)

Larsen, Lars Henrik; Hirata, Rogerio Pessoto; Graven-Nielsen, Thomas

Aim To explore the trunk muscle activity in healthy and recurrent low back pain (R-LBP) patients with no present pain during stair ascent and descent before and after unilateral and bilateral experimental low back pain (LBP). Methods Twenty-five healthy controls and 25 pain-free R-LBP patients wi...... in the physical examination, but it remains unknown if the observed changes are appropriate strategies in relation to the pain condition. Acknowledgement The study was supported by CNAP, Aalborg University and UCN Department of physiotherapy, Denmark....

Pharmacodynamic Modelling of Placebo and Buprenorphine Effects on Event-Related Potentials in Experimental Pain

DEFF Research Database (Denmark)

Juul, Rasmus V; Foster, David J R; Upton, Richard N

2014-01-01

The purpose of the study was to investigate placebo and buprenorphine effects on event-related potentials (ERPs) in experimental pain and the potential benefit of population pharmacodynamic modelling in data analysis. Nineteen healthy volunteers received transdermal placebo and buprenorphine...... in a cross-over study. Drug plasma concentrations and ERPs after electrical stimulation at the median nerve with intensity adjusted to pain detection threshold were recorded until 144 hrs after administration. Placebo and concentration-effect models were fitted to data using non-linear mixed......, pharmacodynamic modelling was successfully implemented to allow for placebo and variability correction in ERP of experimental pain. Improved outcome of ERP studies can be expected if variation between subjects and study occasions can be identified and described....

The effect of electroacupuncture and tramadol on experimental tourniquet pain.

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Musial, Frauke; Choi, Kyung-Eun; Gabriel, Tim; Lüdtke, Rainer; Rampp, Thomas; Michalsen, Andreas; Dobos, Gustav

2012-03-01

The hypoalgesic effect of electroacupuncture (EA) was directly compared with the analgesic effect of pharmacological interventions using the submaximum effort tourniquet technique (SETT). 125 healthy subjects (mean age 24.44±4.46 years; 62.4% female, 37.6% male) performed SETT at baseline and under one of five experimental conditions (n=25 per group): EA (2 Hz with burst pulses in alternating one-phase-square wave pulses; burst length 180 μs, burst frequency 80 Hz, stimulation time/pulse width 3 s), tramadol (50 mg), ibuprofen (400 mg), placebo pill or non-treatment control. EA was performed at LI4 and LI10 contralaterally with stimulation beginning 20 min before SETT and lasting throughout SETT. The pharmacological interventions were given in a double-blind design 1 h before the SETT assessment. Subjects showed a hypoalgesic effect of the opiate and of the EA for subjective pain rating (EA p=0.0051; tramadol p=0.0299), and pain tolerance index (time/rating) (EA p=0.043; tramadol p=0.047) analysed using analysis of covariance. More subjects reached the strict time limit of 30 min (analysed by logistic regression and adjusted OR as a post-hoc analysis) under EA compared with most other experimental conditions. Only EA and tramadol were not significantly different (95% Wald confidence limits: non-treatment control vs EA 0.011 to 0.542; placebo pill vs EA 0.009 to 0.438; ibuprofen vs EA 0.021 to 0.766; tramadol vs EA 0.065 to 1.436). In a laboratory setting, an EA procedure was as effective as a single dose of an orally administered opiate in reducing experimentally induced ischaemic pain.

The effects of experimental pain and induced optimism on working memory task performance.

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Boselie, Jantine J L M; Vancleef, Linda M G; Peters, Madelon L

2016-07-01

Pain can interrupt and deteriorate executive task performance. We have previously shown that experimentally induced optimism can diminish the deteriorating effect of cold pressor pain on a subsequent working memory task (i.e., operation span task). In two successive experiments we sought further evidence for the protective role of optimism on pain-induced working memory impairments. We used another working memory task (i.e., 2-back task) that was performed either after or during pain induction. Study 1 employed a 2 (optimism vs. no-optimism)×2 (pain vs. no-pain)×2 (pre-score vs. post-score) mixed factorial design. In half of the participants optimism was induced by the Best Possible Self (BPS) manipulation, which required them to write and visualize about a life in the future where everything turned out for the best. In the control condition, participants wrote and visualized a typical day in their life (TD). Next, participants completed either the cold pressor task (CPT) or a warm water control task (WWCT). Before (baseline) and after the CPT or WWCT participants working memory performance was measured with the 2-back task. The 2-back task measures the ability to monitor and update working memory representation by asking participants to indicate whether the current stimulus corresponds to the stimulus that was presented 2 stimuli ago. Study 2 had a 2 (optimism vs. no-optimism)×2 (pain vs. no-pain) mixed factorial design. After receiving the BPS or control manipulation, participants completed the 2-back task twice: once with painful heat stimulation, and once without any stimulation (counter-balanced order). Continuous heat stimulation was used with temperatures oscillating around 1°C above and 1°C below the individual pain threshold. In study 1, the results did not show an effect of cold pressor pain on subsequent 2-back task performance. Results of study 2 indicated that heat pain impaired concurrent 2-back task performance. However, no evidence was found

Nav1.7 expression is increased in painful human dental pulp

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Levinson S Rock

2008-04-01

Full Text Available Abstract Background Animal studies and a few human studies have shown a change in sodium channel (NaCh expression after inflammatory lesions, and this change is implicated in the generation of pain states. We are using the extracted human tooth as a model system to study peripheral pain mechanisms and here examine the expression of the Nav1.7 NaCh isoform in normal and painful samples. Pulpal sections were labeled with antibodies against: 1 Nav1.7, N52 and PGP9.5, and 2 Nav1.7, caspr (a paranodal protein used to identify nodes of Ranvier, and myelin basic protein (MBP, and a z-series of optically-sectioned images were obtained with the confocal microscope. Nav1.7-immunofluorescence was quantified in N52/PGP9.5-identified nerve fibers with NIH ImageJ software, while Nav1.7 expression in myelinated fibers at caspr-identified nodal sites was evaluated and further characterized as either typical or atypical as based on caspr-relationships. Results Results show a significant increase in nerve area with Nav1.7 expression within coronal and radicular fiber bundles and increased expression at typical and atypical caspr-identified nodal sites in painful samples. Painful samples also showed an augmentation of Nav1.7 within localized areas that lacked MBP, including those associated with atypical caspr-identified sites, thus identifying NaCh remodeling within demyelinating axons as the basis for a possible pulpal pain mechanism. Conclusion This study identifies the increased axonal expression and augmentation of Nav1.7 at intact and remodeling/demyelinating nodes within the painful human dental pulp where these changes may contribute to constant, increased evoked and spontaneous pain responses that characterize the pain associated with toothache.

Healthy volunteers can be phenotyped using cutaneous sensitization pain models

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Werner, Mads U; Petersen, Karin; Rowbotham, Michael C

2013-01-01

Human experimental pain models leading to development of secondary hyperalgesia are used to estimate efficacy of analgesics and antihyperalgesics. The ability to develop an area of secondary hyperalgesia varies substantially between subjects, but little is known about the agreement following repe...... repeated measurements. The aim of this study was to determine if the areas of secondary hyperalgesia were consistently robust to be useful for phenotyping subjects, based on their pattern of sensitization by the heat pain models.......Human experimental pain models leading to development of secondary hyperalgesia are used to estimate efficacy of analgesics and antihyperalgesics. The ability to develop an area of secondary hyperalgesia varies substantially between subjects, but little is known about the agreement following...

Functional resonance magnetic imaging (fMRI) in adolescents with idiopathic musculoskeletal pain: a paradigm of experimental pain.

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Molina, Juliana; Amaro, Edson; da Rocha, Liana Guerra Sanches; Jorge, Liliana; Santos, Flavia Heloisa; Len, Claudio A

2017-11-14

Studies on functional magnetic resonance imaging (fMRI) have shown that adults with musculoskeletal pain syndromes tolerate smaller amount of pressure (pain) as well as differences in brain activation patterns in areas related to pain.The objective of this study was to evaluate, through fMRI, the brain activation in adolescents with idiopathic musculoskeletal pain (IMP) while performing an experimental paradigm of pain. The study included 10 consecutive adolescents with idiopathic musculoskeletal pain (average age 16.3±1.0) and 10 healthy adolescents age-matched. fMRI exams were performed in a 3 T scanner (Magnetom Trio, Siemens) using an event-related design paradigm. Pressure stimuli were performed in the nondominant hand thumb, divided into two stages, fixed pain and variable pain. The two local Research Ethics Committees (Ethics Committee from Universidade Federal de São Paulo- Brazil, process number 0688/11, on July 1st, 2011 and Ethics Committee from Hospital Israelita Albert Einsten - Brazil, process number 1673, on October 19th, 2011) approved the study. The idiopathic musculoskeletal pain (IMP) group showed a reduced threshold for pain (3.7 kg/cm 2 versus 4.45 kg/cm 2 , p = 0.005). Control group presented increased bain activation when compared to IMP group in the following areas: thalamus (p = 0.00001), precentral gyrus (p = 0.0004) and middle frontal gyrus (p = 0.03). In intragroup analysis, IMP group showed greater brain activation during the unpredictable stimuli of the variable pain stage, especially in the lingual gyrus (p = 0.0001), frontal lobe (p = 0.0001), temporal gyrus (p = 0.0001) and precentral gyrus (p = 0.03), when compared to predictable stimulus of fixed pain. The same intragroup analysis with the control group showed greater activation during the unpredictable stimuli in regions of the precentral gyrus (p = 0.0001), subcallosal area (p = 0.0001), right and left occipital fusiform gyrus (p�

Administrative Aspects of Human Experimentation.

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Irvine, George W.

1992-01-01

The following administrative aspects of scientific experimentation with human subjects are discussed: the definition of human experimentation; the distinction between experimentation and treatment; investigator responsibility; documentation; the elements and principles of informed consent; and the administrator's role in establishing and…

Induction and modulation of referred muscle pain in humans

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Laursen, René Johannes

correlated to pain intensity, and LP and RP thresholds were reproducible within and between sessions. Experimentally (electrical stimulation and infusion of hypertonic saline) induced muscle pain seems to be mediated by myelinated and unmyelinated afferents and the peripheral component of RP by myelinated...... afferents. Furthermore, cutaneous anesthesia of the RP area resulted in a reduction of RP intensity of 22%, while a complete nerve block of afferents from the RP area resulted in a 40% reduction. In summary, observations from the presented experiments suggest that elicitation of referred muscle pain...... is depending on and correlated to local muscle pain. Peripheral input from the RP area is involved, but is not a necessary condition for RP to appear. The present studies as well as others suggest that central hyperexcitability is involved in the generation of RP, but further investigations on mechanisms of RP...

The Effects of Sleep Deprivation on Pain

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Kundermann, Bernd; Krieg, Jürgen-Christian; Schreiber, Wolfgang; Lautenbacher, Stefan

2004-01-01

Chronic pain syndromes are associated with alterations in sleep continuity and sleep architecture. One perspective of this relationship, which has not received much attention to date, is that disturbances of sleep affect pain. To fathom this direction of cause, experimental human and animal studies on the effects of sleep deprivation on pain processing were reviewed. According to the majority of the studies, sleep deprivation produces hyperalgesic changes. Furthermore, sleep deprivation can c...

Pain modulatory phenotypes differentiate subgroups with different clinical and experimental pain sensitivity

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Vaegter, Henrik B.; Graven-Nielsen, Thomas

2016-01-01

between subgroups. Cuff algometry was performed on lower legs in 400 chronic pain patients to assess pressure pain threshold (cPPT), pressure pain tolerance (cPTT), temporal summation of pain (TSP: increase in pain scores to ten repeated stimulations), and conditioned pain modulation (CPM: increase in c......PPT during cuff pain conditioning on the contralateral leg). Heat detection (HDT) and heat pain thresholds (HPT) at clinical painful and non-painful body areas were assessed. Based on TSP and CPM four distinct groups were formed: Group 1 (n=85) had impaired CPM and facilitated TSP. Group 2 (n=148) had...... impaired CPM and normal TSP. Group 3 (n=45) had normal CPM and facilitated TSP. Group 4 (n=122) had normal CPM and normal TSP. Group 1 showed more pain regions compared with the other three groups (PCPM and facilitated TSP plays an important role in widespread pain. Group 1...

Role of synchronized oscillatory brain activity for human pain perception.

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Hauck, Michael; Lorenz, Jürgen; Engel, Andreas K

2008-01-01

The understanding of cortical pain processing in humans has significantly improved since the development of modern neuroimaging techniques. Non-invasive electrophysiological approaches such as electro- and magnetoencephalography have proven to be helpful tools for the real-time investigation of neuronal signals and synchronous communication between cortical areas. In particular, time-frequency decomposition of signals recorded with these techniques seems to be a promising approach because different pain-related oscillatory changes can be observed within different frequency bands, which are likely to be linked to specific sensory and motor functions. In this review we discuss the latest evidence on pain-induced time-frequency signals and propose that changes in oscillatory activity reflect an essential communication mechanism in the brain that is modulated during pain processing. The importance of synchronization processes for normal and pathological pain processing, such as chronic pain states, is discussed.

Kinesthetic illusions attenuate experimental muscle pain, as do muscle and cutaneous stimulation.

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Gay, André; Aimonetti, Jean-Marc; Roll, Jean-Pierre; Ribot-Ciscar, Edith

2015-07-30

In the present study, muscle pain was induced experimentally in healthy subjects by administrating hypertonic saline injections into the tibialis anterior (TA) muscle. We first aimed at comparing the analgesic effects of mechanical vibration applied to either cutaneous or muscle receptors of the TA or to both types simultaneously. Secondly, pain alleviation was compared in subjects in whom muscle tendon vibration evoked kinesthetic illusions of the ankle joint. Muscle tendon vibration, which primarily activated muscle receptors, reduced pain intensity by 30% (p<0.01). In addition, tangential skin vibration reduced pain intensity by 33% (p<0.01), primarily by activating cutaneous receptors. Concurrently stimulating both sensory channels induced stronger analgesic effects (-51%, p<0.01), as shown by the lower levels of electrodermal activity. The strongest analgesic effects of the vibration-induced muscle inputs occurred when illusory movements were perceived (-38%, p=0.01). The results suggest that both cutaneous and muscle sensory feedback reduce muscle pain, most likely via segmental and supraspinal processes. Further clinical trials are needed to investigate these new methods of muscle pain relief. Copyright © 2015 Elsevier B.V. All rights reserved.

Genetic Contributions to Clinical Pain and Analgesia: Avoiding Pitfalls in Genetic Research

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Kim, Hyungsuk; Clark, David; Dionne, Raymond A.

2010-01-01

Understanding the genetic basis of human variations in pain is critical to elucidating the molecular basis of pain sensitivity, variable responses to analgesic drugs, and, ultimately, to individualized treatment of pain and improved public health. With the help of recently accumulated knowledge and advanced technologies, pain researchers hope to gain insight into genetic mechanisms of pain and eventually apply this knowledge to pain treatment. Perspective We critically reviewed the published literature to examine the strength of evidence supporting genetic influences on clinical and human experimental pain. Based on this evidence and the experience of false associations that have occurred in other related disciplines, we provide recommendations for avoiding pitfalls in pain genetic research. PMID:19559388

Pain in adolescent girls receiving human papillomavirus vaccine with concomitantly administered vaccines.

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Walter, Emmanuel B; Kemper, Alex R; Dolor, Rowena J; Dunne, Eileen F

2015-02-01

Using the Faces Pain Scale - Revised, we assessed injection site pain 10 minutes after vaccination in young females randomized to receive either quadrivalent human papillomavirus vaccine (HPV4) before or after concomitantly administered vaccines. Although pain was modestly more after HPV4 injection than after other vaccines, the pain intensity after HPV4 injection was significantly less in those who received HPV4 before receiving other concomitant vaccines.

Sex differences in experimental measures of pain sensitivity and endogenous pain inhibition

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Bulls HW

2015-06-01

Full Text Available Hailey W Bulls,1 Emily L Freeman,1 Austen JB Anderson,2 Meredith T Robbins,3 Timothy J Ness,3 Burel R Goodin1,3 1Department of Psychology, University of Alabama at Birmingham, Birmingham, AL, USA; 2Department of Biology, Samford University, Birmingham, AL, USA; 3Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL, USA Abstract: It has been suggested that increased pain sensitivity and disruption of endogenous pain inhibitory processes may account, at least in part, for the greater prevalence and severity of chronic pain in women compared to men. However, previous studies addressing this topic have produced mixed findings. This study examined sex differences in pain sensitivity and inhibition using quantitative sensory testing (QST, while also considering the influence of other important factors such as depressive symptoms and sleep quality. Healthy men (n=24 and women (n=24 each completed a QST battery. This battery included an ischemic pain task (IPT that used a submaximal effort tourniquet procedure as well as a conditioned pain modulation (CPM procedure for the assessment of endogenous pain inhibition. Prior to QST, participants completed the Center for Epidemiologic Studies Depression Scale and the Pittsburgh Sleep Quality Index. Analyses revealed significant sex differences for the ischemic pain task and the conditioned pain modulation procedure, such that women tolerated the ischemic pain for a shorter amount of time and demonstrated less pain inhibition compared with men. This remained true even when accounting for sex differences in depressive symptoms and sleep quality. The results of this study suggest that women may be more pain sensitive and possess less-efficient endogenous pain inhibitory capacity compared with men. Whether interventions that decrease pain sensitivity and enhance pain inhibition in women ultimately improve their clinical pain outcomes is an area of research that deserves additional

Venlafaxine and Oxycodone Effects on Human Spinal and Supraspinal Pain Processing

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Lelic, D; Fischer, I W D; Olesen, Anne Estrup

2016-01-01

affect spinal and supraspinal pain processing. Twenty volunteers were included in this randomized cross-over study comparing 5-day treatment with venlafaxine, oxycodone and placebo. As a proxy of the spinal pain transmission, the nociceptive withdrawal reflex (NWR) to electrical stimulation on the sole......Severe pain is often treated with opioids. Antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) have also shown a pain relieving effect, but for both SNRI and opioids, the specific mode of action in humans remains vague. This study investigated how oxycodone and venlafaxine...

Prices need no preferences: social trends determine decisions in experimental markets for pain relief.

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Vlaev, Ivo; Seymour, Ben; Chater, Nick; Winston, Joel S; Yoshida, Wako; Wright, Nicholas; Symmonds, Mkael; Dolan, Ray

2014-01-01

A standard view in health economics is that, although there is no market that determines the "prices" for health states, people can nonetheless associate health states with monetary values (or other scales, such as quality adjusted life year [QALYs] and disability adjusted life year [DALYs]). Such valuations can be used to shape health policy, and a major research challenge is to elicit such values from people; creating experimental "markets" for health states is a theoretically attractive way to address this. We explore the possibility that this framework may be fundamentally flawed-because there may not be any stable values to be revealed. Instead, perhaps people construct ad hoc values, influenced by contextual factors, such as the observed decisions of others. The participants bid to buy relief from equally painful electrical shocks to the leg and arm in an experimental health market based on an interactive second-price auction. Thirty subjects were randomly assigned to two experimental conditions where the bids by "others" were manipulated to follow increasing or decreasing price trends for one, but not the other, pain. After the auction, a preference test asked the participants to choose which pain they prefer to experience for a longer duration. Players remained indifferent between the two pain-types throughout the auction. However, their bids were differentially attracted toward what others bid for each pain, with overbidding during decreasing prices and underbidding during increasing prices. Health preferences are dissociated from market prices, which are strongly referenced to others' choices. This suggests that the price of health care in a free-market has the capacity to become critically detached from people's underlying preferences. 2014 APA, all rights reserved

Time discounting and pain anticipation. Experimental evidence

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Brañas Garza, Pablo

2012-03-01

Full Text Available This paper deals with pain anticipation experienced before medical procedures. our experimental results show that individuals with lower time discount factors are more prone to suffer pain in advance. We provide a framework to rationalize the connection between pain anticipation and impatience. in this set up, more impatient subjects, who only value very near events, mainly take into account the present negative effects of medical procedures (the costs, whereas more patient individuals have a net positive valuation of medical events, given that they are able to value both the cost incurred now and all the benefits to be accrued in the future.

Este artículo trata de la anticipación del dolor experimentada antes de los procedimientos médicos. nuestros resultados experimentales muestran que los individuos con factor de descuento temporal más bajo son más proclives a sufrir dolor por adelantado. el artículo proporciona un marco en el que racionalizar la relación existente entre impaciencia y anticipación del dolor. en este marco, los sujetos más impacientes, que evalúan sólo los eventos muy próximos en el tiempo, focalizan su atención principalmente en los efectos negativos de los procedimientos médicos (sólo los costes, mientras que los individuos más pacientes tienen una valoración neta positiva de los actos médicos puesto que valoran tanto el coste en el que se incurre en el presente como los beneficios que se obtendrán en el futuro.

Human Mendelian pain disorders: a key to discovery and validation of novel analgesics.

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Goldberg, Y P; Pimstone, S N; Namdari, R; Price, N; Cohen, C; Sherrington, R P; Hayden, M R

2012-10-01

We have utilized a novel application of human genetics, illuminating the important role that rare genetic disorders can play in the development of novel drugs that may be of relevance for the treatment of both rare and common diseases. By studying a very rare Mendelian disorder of absent pain perception, congenital indifference to pain, we have defined Nav1.7 (endocded by SCN9A) as a critical and novel target for analgesic development. Strong human validation has emerged with SCN9A gain-of-function mutations causing inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder, both Mendelian disorder of spontaneous or easily evoked pain. Furthermore, variations in the Nav1.7 channel also modulate pain perception in healthy subjects as well as in painful conditions such as osteoarthritis and Parkinson disease. On the basis of this, we have developed a novel compound (XEN402) that exhibits potent, voltage-dependent block of Nav1.7. In a small pilot study, we showed that XEN402 blocks Nav1.7 mediated pain associated with IEM thereby demonstrating the use of rare genetic disorders with mutant target channels as a novel approach to rapid proof-of-concept. Our approach underscores the critical role that human genetics can play by illuminating novel and critical pathways pertinent for drug discovery. © 2012 John Wiley & Sons A/S.

The effects of blocking N/OFQ receptors on orofacial pain following experimental tooth movement in rats.

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Shan, Di; He, Yuwei; Long, Hu; Zhou, Yang; Liu, He; Xu, Rui; Huang, Renhuan; Lai, Wenli

2016-11-01

The aim of this study was to determine the effects of nociceptin/orphanin FQ peptide receptor (N/OFQ receptor) antagonist on orofacial pain induced by experimental tooth movement in rats. A total of 36 male Sprague-Dawley rats weighing 200-300 g were divided into six groups: a control group, force group, force+saline intraperitoneal group, force+saline periodontal group, force+UFP-101 ([Nphe¹,Arg¹⁴,Lys¹⁵]N/OFQ-NH ₂ antagonist for N/OFQ receptor) intraperitoneal group, and force+UFP-1 01 periodontal group. Closed coil springs were ligated between the upper incisors and first molar to exert an orthodontic force (40 g) between the teeth. Injectable administration dosages were 30 μl saline or 30 μl saline containing 0.03 mg/kg UFP-1 01. Following the injections, orofacial pain levels were assessed through directed face grooming (mouth wiping). Statistical analyses were performed in SPSS 17.0 (Statistical Package for the Social Sciences) and p values less than 0.05 were considered as statistically significant. Orofacial pain levels were significantly higher in the force group than in the control group. Orofacial pain levels differed significantly between the force)group, force+saline periodontal group and force+UFP-101 periodontal group, but were similar between the control group, force+UFP-101 intraperitoneal group and force+saline intraperitoneal group. Moreover, orofacial pain levels did not differ between the force group, force+saline intraperitoneal group and force+UFP-1 01 intraperitoneal group. Periodontal, but not intraperitoneal, administration of UFP-101 could alleviate orofacial pain induced by experimental tooth movement in rats, suggesting that periodontal N/OFQ receptors participate in orofacial pain induced by experimental tooth movement.

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

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

2017-12-01

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

Pain Adaptability in Individuals With Chronic Musculoskeletal Pain Is Not Associated With Conditioned Pain Modulation.

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Wan, Dawn Wong Lit; Arendt-Nielsen, Lars; Wang, Kelun; Xue, Charlie Changli; Wang, Yanyi; Zheng, Zhen

2018-03-27

Healthy humans can be divided into the pain adaptive (PA) and the pain nonadaptive (PNA) groups; PA showed a greater decrease in pain rating to a cold pressor test (CPT) than PNA. This study examined if the dichotomy of pain adaptability existed in individuals with chronic musculoskeletal pain. CPTs at 2°C and 7°C were used to assess the status of pain adaptability in participants with either chronic nonspecific low back pain or knee osteoarthritis. The participants' potency of conditioned pain modulation (CPM) and local inhibition were measured. The strengths of pain adaptability at both CPTs were highly correlated. PA and PNA did not differ in their demographic characteristics, pain thresholds from thermal and pressure stimuli, or potency of local inhibition or CPM. PA reached their maximum pain faster than PNA (t 41 = -2.76, P adaptability exists in musculoskeletal pain patients. Consistent with the healthy human study, the strength of pain adaptability and potency of CPM are not related. Pain adaptability could be another form of endogenous pain inhibition of which clinical implication is yet to be understood. The dichotomy of pain adaptability was identified in healthy humans. The current study confirms that this dichotomy also exists in individuals with chronic musculoskeletal pain, and could be reliably assessed with CPTs at 2°C and 7°C. Similar to the healthy human study, pain adaptability is not associated with CPM, and may reflect the temporal aspect of pain inhibition. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

Effect of ambient temperature on human pain and temperature perception.

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Strigo, I A; Carli, F; Bushnell, M C

2000-03-01

Animal studies show reduced nociceptive responses to noxious heat stimuli and increases in endogenous beta-endorphin levels in cold environments, suggesting that human pain perception may be dependent on ambient temperature. However, studies of changes in local skin temperature on human pain perception have yielded variable results. This study examines the effect of both warm and cool ambient temperature on the perception of noxious and innocuous mechanical and thermal stimuli. Ten subjects (7 men and 3 women, aged 20-23 yr) used visual analog scales to rate the stimulus intensity, pain intensity, and unpleasantness of thermal (0-50 degrees C) and mechanical (1.2-28.9 g) stimuli applied on the volar forearm with a 1-cm2 contact thermode and von Frey filaments, respectively. Mean skin temperatures were measured throughout the experiment by infrared pyrometer. Each subject was tested in ambient temperatures of 15 degrees C (cool), 25 degrees C (neutral), and 35 degrees C (warm) on separate days, after a 30-min acclimation to the environment. Studies began in the morning after an 8-h fast. Mean skin temperature was altered by ambient temperature (cool room: 30.1 degrees C; neutral room: 33.4 degrees C; warm room: 34.5 degrees C; P cool than in the neutral environment (P cool room and that noxious heat stimuli were more unpleasant in a warm environment. Environmental temperature did not alter ratings of warm (37 and 40 degrees C) or mechanical stimuli. These results indicate that, in humans, a decrease in skin temperature following exposure to cool environments reduces thermal pain. Suppression of Adelta primary afferent cold fiber activity has been shown to increase cold pain produced by skin cooling. Our current findings may represent the reverse phenomenon, i.e., a reduction in thermal nociceptive transmission by the activation of Adelta cutaneous cold fibers.

The effect of transcranial direct current stimulation on experimentally induced heat pain.

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Aslaksen, Per M; Vasylenko, Olena; Fagerlund, Asbjørn J

2014-06-01

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulatory technique that can affect human pain perception. Placebo effects are present in most treatments and could therefore also interact with treatment effects in tDCS. The present study investigated whether short-term tDCS reduced heat pain intensity, stress, blood pressure and increased heat pain thresholds in healthy volunteers when controlling for placebo effects. Seventy-five (37 females) participants were randomized into three groups: (1) active tDCS group receiving anodal tDCS (2 mA) for 7 min to the primary motor cortex (M1), (2) placebo group receiving the tDCS electrode montage but only active tDCS stimulation for 30 s and (3) natural history group that got no tDCS montage but the same pain stimulation as the active tDCS and the placebo group. Heat pain was induced by a PC-controlled thermode attached to the left forearm. Pain intensity was significantly lower in the active tDCS group when examining change scores (pretest-posttest) for the 47 °C condition. The placebo group displayed lower pain compared with the natural history group, displaying a significant placebo effect. In the 43 and 45 °C conditions, the effect of tDCS could not be separated from placebo effects. The results revealed no effects on pain thresholds. There was a tendency that active tDCS reduced stress and systolic blood pressure, however, not significant. In sum, tDCS had an analgesic effect on high-intensity pain, but the effect of tDCS could not be separated from placebo effects for medium and low pain.

Comparison of acceptance and distraction strategies in coping with experimentally induced pain

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Moore H

2015-03-01

Full Text Available Hazel Moore,1 Ian Stewart,1 Dermot Barnes-Holmes,2 Yvonne Barnes-Holmes,2 Brian E McGuire1,31School of Psychology, National University of Ireland, Galway, 2Department of Psychology, National University of Ireland, Maynooth, 3Centre for Pain Research, National University of Ireland, Galway, IrelandBackground: This study compared an acceptance-based strategy with a control-based strategy (distraction in terms of the ability of participants to tolerate a painful stimulus, across two experiments. In addition, participants were either actively encouraged, or not, to link pain tolerance with pursuit of valued goals to examine the impact of pursuing a personally meaningful goal or value on the extent to which pain will be tolerated.Methods: Participants in experiment 1 (n=41 and experiment 2 (n=52 were equally assigned to acceptance or distraction protocols. Further, half the participants in each group generated examples from their own lives in which they had pursued a valued objective, while the other half did not. In experiment 2, the values focus was enhanced to examine the impact on pain tolerance.Results: There were no significant differences overall between the acceptance and distraction groups on pain tolerance in either experiment. However, in experiment 2, individuals classified as accepting in terms of general coping style and who were assigned to the acceptance strategy showed significantly better pain tolerance than accepting individuals who were in the distraction condition. Across both experiments, those with strong goal-driven values in both protocols were more tolerant of pain. Participants appeared to have more difficulty adhering to acceptance than to distraction as a strategy.Conclusion: Acceptance may be associated with better tolerance of pain, but may also be more difficult to operationalize than distraction in experimental studies. Matching coping style and coping strategy may be most effective, and enhancement of goal

Are preoperative experimental pain assessments correlated with clinical pain outcomes after surgery?

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Sangesland, Anders; Støren, Carl; Vaegter, Henrik B.

2017-01-01

of surgery, QST variables, clinical pain outcome measure and main result. Results Most studies showed moderate to high risk of bias. Type of surgery investigated include 7 studies on total knee replacement, 5 studies on caesarean section, 4 studies on thoracic surgery, 2 studies on herniotomy, 2 studies......Background Pain after surgery is not uncommon with 30% of patients reporting moderate to severe postoperative pain. Early identification of patients prone to postoperative pain may be a step forward towards individualized pain medicine providing a basis for improved clinical management through......, and (3) the association between QST and pain after surgery was investigated. Forty-four unique studies were identified, with 30 studies on 2738 subjects meeting inclusion criteria. The methodological quality of the include studies was assessed and data extraction included study population, type...

Experimental knee joint pain during strength training and muscle strength gain in healthy subjects: a randomized controlled trial.

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Sørensen, T J; Langberg, H; Hodges, P W; Bliddal, H; Henriksen, M

2012-01-01

Knee joint pain and reduced quadriceps strength are cardinal symptoms in many knee pathologies. In people with painful knee pathologies, quadriceps exercise reduces pain, improves physical function, and increases muscle strength. A general assumption is that pain compromises muscle function and thus may prevent effective rehabilitation. This study evaluated the effects of experimental knee joint pain during quadriceps strength training on muscle strength gain in healthy individuals. Twenty-seven healthy untrained volunteers participated in a randomized controlled trial of quadriceps strengthening (3 times per week for 8 weeks). Participants were randomized to perform resistance training either during pain induced by injections of painful hypertonic saline (pain group, n = 13) or during a nonpainful control condition with injection of isotonic saline (control group, n = 14) into the infrapatellar fat pad. The primary outcome measure was change in maximal isokinetic muscle strength in knee extension/flexion (60, 120, and 180 degrees/second). The group who exercised with pain had a significantly larger improvement in isokinetic muscle strength at all angular velocities of knee extension compared to the control group. In knee flexion there were improvements in isokinetic muscle strength in both groups with no between-group differences. Experimental knee joint pain improved the training-induced gain in muscle strength following 8 weeks of quadriceps training. It remains to be studied whether knee joint pain has a positive effect on strength gain in patients with knee pathology. Copyright © 2012 by the American College of Rheumatology.

Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain.

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Bannister, Kirsty; Qu, Chaoling; Navratilova, Edita; Oyarzo, Janice; Xie, Jennifer Yanhua; King, Tamara; Dickenson, Anthony H; Porreca, Frank

2017-12-01

Gabapentin (GBP) is a first-line therapy for neuropathic pain, but its mechanisms and sites of action remain uncertain. We investigated GBP-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal GBP reversed evoked mechanical hypersensitivity and produced conditioned place preference (CPP) and dopamine (DA) release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal GBP also significantly inhibited dorsal horn wide-dynamic-range neuronal responses to a range of evoked stimuli in SNL rats. By contrast, GBP microinjected bilaterally into the rostral anterior cingulate cortex (rACC), produced CPP, and elicited NAc DA release selectively in SNL rats but did not reverse tactile allodynia and had marginal effects on wide-dynamic-range neuronal activity. Moreover, blockade of endogenous opioid signaling in the rACC prevented intravenous GBP-induced CPP and NAc DA release but failed to block its inhibition of tactile allodynia. Gabapentin, therefore, can potentially act to produce its pain relieving effects by (a) inhibition of injury-induced spinal neuronal excitability, evoked hypersensitivity, and ongoing pain and (b) selective supraspinal modulation of affective qualities of pain, without alteration of reflexive behaviors. Consistent with previous findings of pain relief from nonopioid analgesics, GBP requires engagement of rACC endogenous opioid circuits and downstream activation of mesolimbic reward circuits reflected in learned pain-motivated behaviors. These findings support the partial separation of sensory and affective dimensions of pain in this experimental model and suggest that modulation of affective-motivational qualities of pain may be the preferential mechanism of GBP's analgesic effects in patients.

Effects of target-controlled infusion of high-dose naloxone on pain and hyperalgesia in a human thermal injury model

DEFF Research Database (Denmark)

Springborg, Anders D; Jensen, Elisabeth K; Taylor, Bradley K

2016-01-01

/kg, 4 mg/mL) or placebo (normal saline) intravenous. The primary outcome was SHA assessed by weighted-pin instrument (128 mN) 0, 1, 2, and 165 to 169 hours after the thermal injury (day 1-4). The secondary outcomes were pin-prick pain thresholds assessed by weighted-pin instrument (8-512 mN) at primary......Mu-opioid-receptor antagonists have been extensively studied in experimental research as pharmacological tools uncovering mechanisms of pain modulation by the endogenous opioid system. In rodents, administration of high doses of mu-opioid-receptor antagonists after the resolution of an inflammatory...... injury has demonstrated reinstatement of nociceptive hypersensitivity indicating unmasking of latent sensitization. In a recent human study, pain hypersensitivity assessed as secondary hyperalgesia area (SHA), was reinstated 7 days after a mild thermal injury, in 4 out of 12 subjects after a naloxone...

Social interaction and pain: An arctic expedition.

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Block, Per; Heathcote, Lauren C; Burnett Heyes, Stephanie

2018-01-01

Complex human behaviour can only be understood within its social environment. However, disentangling the causal links between individual outcomes and social network position is empirically challenging. We present a research design in a closed real-world setting with high-resolution temporal data to understand this interplay within a fundamental human experience - physical pain. Study participants completed an isolated 3-week hiking expedition in the Arctic Circle during which they were subject to the same variation in environmental conditions and only interacted amongst themselves. Adolescents provided daily ratings of pain and social interaction partners. Using longitudinal network models, we analyze the interplay between social network position and the experience of pain. Specifically, we test whether experiencing pain is linked to decreasing popularity (increasing isolation), whether adolescents prefer to interact with others experiencing similar pain (homophily), and whether participants are increasingly likely to report similar pain as their interaction partners (contagion). We find that reporting pain is associated with decreasing popularity - interestingly, this effect holds for males only. Further exploratory analyses suggest this is at least partly driven by males withdrawing from contact with females when in pain, enhancing our understanding of pain and masculinity. Contrary to recent experimental and clinical studies, we found no evidence of pain homophily or contagion in the expedition group. Copyright © 2018 Elsevier Ltd. All rights reserved.

Psychological Factors Predict Local and Referred Experimental Muscle Pain: A Cluster Analysis in Healthy Adults

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

2012-01-01

Background Recent studies suggest an underlying three- or four-factor structure explains the conceptual overlap and distinctiveness of several negative emotionality and pain-related constructs. However, the validity of these latent factors for predicting pain has not been examined. Methods A cohort of 189 (99F; 90M) healthy volunteers completed eight self-report negative emotionality and pain-related measures (Eysenck Personality Questionnaire-Revised; Positive and Negative Affect Schedule; State-Trait Anxiety Inventory; Pain Catastrophizing Scale; Fear of Pain Questionnaire; Somatosensory Amplification Scale; Anxiety Sensitivity Index; Whiteley Index). Using principal axis factoring, three primary latent factors were extracted: General Distress; Catastrophic Thinking; and Pain-Related Fear. Using these factors, individuals clustered into three subgroups of high, moderate, and low negative emotionality responses. Experimental pain was induced via intramuscular acidic infusion into the anterior tibialis muscle, producing local (infusion site) and/or referred (anterior ankle) pain and hyperalgesia. Results Pain outcomes differed between clusters (multivariate analysis of variance and multinomial regression), with individuals in the highest negative emotionality cluster reporting the greatest local pain (p = 0.05), mechanical hyperalgesia (pressure pain thresholds; p = 0.009) and greater odds (2.21 OR) of experiencing referred pain compared to the lowest negative emotionality cluster. Conclusion Our results provide support for three latent psychological factors explaining the majority of the variance between several pain-related psychological measures, and that individuals in the high negative emotionality subgroup are at increased risk for (1) acute local muscle pain; (2) local hyperalgesia; and (3) referred pain using a standardized nociceptive input. PMID:23165778

Mechanisms of Stress-Induced Visceral Pain: Implications in Irritable Bowel Syndrome.

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Greenwood-Van Meerveld, B; Moloney, R D; Johnson, A C; Vicario, M

2016-08-01

Visceral pain is a term describing pain originating from the internal organs of the body and is a common feature of many disorders, including irritable bowel syndrome (IBS). Stress is implicated in the development and exacerbation of many visceral pain disorders. Recent evidence suggests that stress and the gut microbiota can interact through complementary or opposing factors to influence visceral nociceptive behaviours. The Young Investigator Forum at the International Society of Psychoneuroendocrinology (ISPNE) annual meeting reported experimental evidence suggesting the gut microbiota can affect the stress response to affect visceral pain. Building upon human imaging data showing abnormalities in the central processing of visceral stimuli in patients with IBS and knowledge that the amygdala plays a pivotal role in facilitating the stress axis, the latest experimental evidence supporting amygdala-mediated mechanisms in stress-induced visceral pain was reviewed. The final part of the session at ISPNE reviewed experimental evidence suggesting that visceral pain in IBS may be a result, at least in part, of afferent nerve sensitisation following increases in epithelial permeability and mucosal immune activation. © 2016 British Society for Neuroendocrinology.

Preliminary findings of cerebral responses on transcutaneous vagal nerve stimulation on experimental heat pain.

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Usichenko, Taras; Laqua, René; Leutzow, Bianca; Lotze, Martin

2017-02-01

Transcutaneous vagal nerve stimulation (TVNS) is a promising complementary method of pain relief. However, the neural networks associated with its analgesic effects are still to be elucidated. Therefore, we conducted two functional magnetic resonance imaging (fMRI) sessions, in a randomized order, with twenty healthy subjects who were exposed to experimental heat pain stimulation applied to the right forearm using a Contact Heat-Evoked Potential Stimulator. While in one session TVNS was administered bilaterally to the concha auriculae with maximal, non-painful intensity, the stimulation device was switched off in the other session (placebo condition). Pain thresholds were measured before and after each session. Heat stimulation elicited fMRI activation in cerebral pain processing regions. Activation magnitude in the secondary somatosensory cortex, posterior insula, anterior cingulate and caudate nucleus was associated with heat stimulation without TVNS. During TVNS, this association was only seen for the right anterior insula. TVNS decreased fMRI signals in the anterior cingulate cortex in comparison with the placebo condition; however, there was no relevant pain reducing effect over the group as a whole. In contrast, TVNS compared to the placebo condition showed an increased activation in the primary motor cortex, contralateral to the site of heat stimulation, and in the right amygdala. In conclusion, in the protocol used here, TVNS specifically modulated the cerebral response to heat pain, without having a direct effect on pain thresholds.

An investigation into the effects of frequency-modulated transcutaneous electrical nerve stimulation (TENS) on experimentally-induced pressure pain in healthy human participants.

Science.gov (United States)

Chen, Chih-Chung; Johnson, Mark I

2009-10-01

Frequency-modulated transcutaneous electrical nerve stimulation (TENS) delivers currents that fluctuate between preset boundaries over a fixed period of time. This study compared the effects of constant-frequency TENS and frequency-modulated TENS on blunt pressure pain in healthy human volunteers. Thirty-six participants received constant-frequency TENS (80 pps), frequency-modulated TENS (20 to 100 pps), and placebo (no current) TENS at a strong nonpainful intensity in a randomized cross-over manner. Pain threshold was taken from the forearm using pressure algometry. There were no statistical differences between constant-frequency TENS and frequency-modulated TENS after 20 minutes (OR = 1.54; CI, 0.29, 8.23, P = 1.0). Both constant-frequency TENS and frequency-modulated TENS were superior to placebo TENS (OR = 59.5, P TENS does not influence hypoalgesia to any greater extent than constant-frequency TENS when currents generate a strong nonpainful paraesthesia at the site of pain. The finding that frequency-modulated TENS and constant-frequency TENS were superior to placebo TENS provides further evidence that a strong yet nonpainful TENS intensity is a prerequisite for hypoalgesia. This study provides evidence that TENS, delivered at a strong nonpainful intensity, increases pain threshold to pressure algometry in healthy participants over and above that seen with placebo (no current) TENS. Frequency-modulated TENS does not increase hypoalgesia to any appreciable extent to that seen with constant-frequency TENS.

Does experimental low back pain change posteroanterior lumbar spinal stiffness and trunk muscle activity? A randomized crossover study.

Science.gov (United States)

Wong, Arnold Y L; Parent, Eric C; Prasad, Narasimha; Huang, Christopher; Chan, K Ming; Kawchuk, Gregory N

2016-05-01

While some patients with low back pain demonstrate increased spinal stiffness that decreases as pain subsides, this observation is inconsistent. Currently, the relation between spinal stiffness and low back pain remains unclear. This study aimed to investigate the effects of experimental low back pain on temporal changes in posteroanterior spinal stiffness and concurrent trunk muscle activity. In separate sessions five days apart, nine asymptomatic participants received equal volume injections of hypertonic or isotonic saline in random order into the L3-L5 interspinous ligaments. Pain intensity, spinal stiffness (global and terminal stiffness) at the L3 level, and the surface electromyographic activity of six trunk muscles were measured before, immediately after, and 25-minute after injections. These outcome measures under different saline conditions were compared by generalized estimating equations. Compared to isotonic saline injections, hypertonic saline injections evoked significantly higher pain intensity (mean difference: 5.7/10), higher global (mean difference: 0.73N/mm) and terminal stiffness (mean difference: 0.58N/mm), and increased activity of four trunk muscles during indentation (Ppain subsided. While previous clinical research reported inconsistent findings regarding the association between spinal stiffness and low back pain, our study revealed that experimental pain caused temporary increases in spinal stiffness and concurrent trunk muscle co-contraction during indentation, which helps explain the temporal relation between spinal stiffness and low back pain observed in some clinical studies. Our results substantiate the role of spinal stiffness assessments in monitoring back pain progression. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Animal Model of Spinal Cord Injury as an Experimental Pain Model

Directory of Open Access Journals (Sweden)

Aya Nakae

2011-01-01

Full Text Available Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results can be easily misunderstood and falsely interpreted. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models.

The Animal Model of Spinal Cord Injury as an Experimental Pain Model

Science.gov (United States)

Nakae, Aya; Nakai, Kunihiro; Yano, Kenji; Hosokawa, Ko; Shibata, Masahiko; Mashimo, Takashi

2011-01-01

Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results can be easily misunderstood and falsely interpreted. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models. PMID:21436995

Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain

DEFF Research Database (Denmark)

Hald, Andreas; Ding, Ming; Egerod, Kristoffer Lihme

2008-01-01

Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment with can......Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment...... with cannabinoid agonists. However, the use of cannabinoid agonists in humans may be hampered by CNS related side effects and development of tolerance. In the present study, we investigated the effect of repeated low dose administration of the synthetic cannabinoid agonist WIN 55,212-2 on bone cancer pain...... and neuropathic pain in mice. In addition, we investigated the development of CNS related side effects and tolerance. We found that 0.5 mg/kg/day for 18 days reduced pain related behavior and expression of spinal glial fibrillary acidic protein in the bone cancer pain model but not in the neuropathic pain model...

Experimental pain leads to reorganisation of trapezius electromyography during computer work with active and passive pauses

DEFF Research Database (Denmark)

Samani, Afshin; Holtermann, Andreas; Søgaard, Karen

2009-01-01

The aim of this laboratory study was to investigate acute effects of experimental muscle pain on spatial electromyographic (EMG) activity of the trapezius muscle during computer work with active and passive pauses. Twelve healthy male subjects performed four sessions of computer work for 2 min...... in one day, with passive (relax) and active (30% maximum voluntary contraction of shoulder elevation) pauses given every 40 s without and with presence of experimental pain. Surface EMG signals were recorded from four parts of the trapezius. The centroid of exposure variation analysis along the time axis...... was lower during computer work with active pauses when compared with passive one in all muscle parts (P

Unraveling dynamics of human physical activity patterns in chronic pain conditions

Science.gov (United States)

Paraschiv-Ionescu, Anisoara; Buchser, Eric; Aminian, Kamiar

2013-06-01

Chronic pain is a complex disabling experience that negatively affects the cognitive, affective and physical functions as well as behavior. Although the interaction between chronic pain and physical functioning is a well-accepted paradigm in clinical research, the understanding of how pain affects individuals' daily life behavior remains a challenging task. Here we develop a methodological framework allowing to objectively document disruptive pain related interferences on real-life physical activity. The results reveal that meaningful information is contained in the temporal dynamics of activity patterns and an analytical model based on the theory of bivariate point processes can be used to describe physical activity behavior. The model parameters capture the dynamic interdependence between periods and events and determine a `signature' of activity pattern. The study is likely to contribute to the clinical understanding of complex pain/disease-related behaviors and establish a unified mathematical framework to quantify the complex dynamics of various human activities.

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

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

2013-11-01

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

Comparative Analysis of Pain Behaviours in Humanized Mouse Models of Sickle Cell Anemia.

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Jianxun Lei

Full Text Available Pain is a hallmark feature of sickle cell anemia (SCA but management of chronic as well as acute pain remains a major challenge. Mouse models of SCA are essential to examine the mechanisms of pain and develop novel therapeutics. To facilitate this effort, we compared humanized homozygous BERK and Townes sickle mice for the effect of gender and age on pain behaviors. Similar to previously characterized BERK sickle mice, Townes sickle mice show more mechanical, thermal, and deep tissue hyperalgesia with increasing age. Female Townes sickle mice demonstrate more hyperalgesia compared to males similar to that reported for BERK mice and patients with SCA. Mechanical, thermal and deep tissue hyperalgesia increased further after hypoxia/reoxygenation (H/R treatment in Townes sickle mice. Together, these data show BERK sickle mice exhibit a significantly greater degree of hyperalgesia for all behavioral measures as compared to gender- and age-matched Townes sickle mice. However, the genetically distinct "knock-in" strategy of human α and β transgene insertion in Townes mice as compared to BERK mice, may provide relative advantage for further genetic manipulations to examine specific mechanisms of pain.

Hypnosis and Local Anesthesia for Dental Pain Relief-Alternative or Adjunct Therapy?-A Randomized, Clinical-Experimental Crossover Study.

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Wolf, Thomas Gerhard; Wolf, Dominik; Callaway, Angelika; Below, Dagna; d'Hoedt, Bernd; Willershausen, Brita; Daubländer, Monika

2016-01-01

This prospective randomized clinical crossover trial was designed to compare hypnosis and local anesthesia for experimental dental pain relief. Pain thresholds of the dental pulp were determined. A targeted standardized pain stimulus was applied and rated on the Visual Analogue Scale (0-10). The pain threshold was lower under hypnosis (58.3 ± 17.3, p local anesthesia. The pain stimulus was scored higher under hypnosis (3.9 ± 3.8) than with local anesthesia (0.0, p Local anesthesia was superior to hypnosis and is a safe and effective method for pain relief in dentistry. Hypnosis seems to produce similar effects observed under sedation. It can be used in addition to local anesthesia and in individual cases as an alternative for pain control in dentistry.

Effect of gender and hand laterality on pain processing in human neonates.

Science.gov (United States)

Ozawa, Mio; Kanda, Katsuya; Hirata, Michio; Kusakawa, Isao; Suzuki, Chieko

2011-01-01

Previous studies in adults have reported that handedness and gender can affect pain perception. However, it is currently unclear when these differences emerge in human development. Therefore, we examined prefrontal responses to pain stimulation among newborns during their first acute pain experience after birth. Forty newborns at 4-6 days postnatal age were observed during clinically required blood sampling while prefrontal activation was measured with near infrared spectroscopy. Blood sampling in this study was the first experience of a procedure involving skin breaking for these infants. We divided subjects into a right-hand stimulation group (n=21) and a left-hand stimulation group (n=19), depending on whether blood was sampled from the right or the left hand. A three-way analysis of variance (ANOVA) was conducted to examine the effects of several variables on the magnitude of the oxy-Hb value in response to pain stimulus, including stimulus side (right hand or left hand), gender (male or female), recording side (right prefrontal area or left prefrontal area) and interactions between these variables. The data revealed a significant effect of stimulus side (F (1, 72)=9.892, P=0.002), showing that the right-hand stimulation induced a greater prefrontal activation than the left-hand stimulation. No significant gender difference or interactions were found. Our findings suggest that hand laterality affects pain perception even in neonates. However, gender differences in pain perception did not appear to occur during the neonatal period. Further investigations using brain-imaging techniques are required to identify laterality- or gender-related differences in pain processing in humans. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Animal experimentation

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Laz, Alak; Cholakova, Tanya Stefanova; Vrablova, Sofia; Arshad, Naverawaheed

2016-01-01

Animal experimentation is a crucial part of medical science. One of the ways to define it is any scientific experiment conducted for research purposes that cause any kind of pain or suffering to animals. Over the years, the new discovered drugs or treatments are first applied on animals to test their positive outcomes to be later used by humans. There is a debate about violating ethical considerations by exploiting animals for human benefits. However, different ethical theories have been made...

Antinociceptive effect of intrathecal microencapsulated human pheochromocytoma cell in a rat model of bone cancer pain.

Science.gov (United States)

Li, Xiao; Li, Guoqi; Wu, Shaoling; Zhang, Baiyu; Wan, Qing; Yu, Ding; Zhou, Ruijun; Ma, Chao

2014-07-08

Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l) lysine-alginate (APA) microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat model of bone cancer pain, and this effect was blocked by opioid antagonist naloxone and alpha 2-adrenergic antagonist rauwolscine. Neurochemical changes of cerebrospinal fluid are in accordance with the analgesic responses. Taken together, these data support that human pheochromocytoma cell implant-induced antinociception was mediated by met-enkephalin and norepinephrine secreted from the cell implants and acting at spinal receptors. Spinal implantation of microencapsulated human pheochromocytoma cells may provide an alternative approach for the therapy of chronic intractable pain.

Effect of family presence on pain and anxiety during invasive nursing procedures in an emergency department: A randomized controlled experimental study.

Science.gov (United States)

İşlekdemir, Burcu; Kaya, Nurten

2016-01-01

Patients generally prefer to have their family present during medical or nursing interventions. Family presence is assumed to reduce anxiety, especially during painful interventions. This study employed a randomized controlled experimental design to determine the effects of family presence on pain and anxiety during invasive nursing procedures. The study population consisted of patients hospitalized in the observation unit of the internal medicine section in the emergency department of a university hospital. The sample comprised 138 patients assigned into the experimental and control groups by drawing lots. The invasive nursing procedure was carried out in the presence of family members, for members of the experimental group, and without family members, for members of the control group. Thus, the effects of family presence on pain and anxiety during the administration of an invasive nursing procedure to patients were analyzed. The results showed that members of the experimental and control groups did not differ with respect to the pain and state anxiety scores during the intervention. Family presence does not influence the participants' pain and anxiety during an invasive nursing procedure. Thus, the decision regarding family presence during such procedures should be based on patient preference. Copyright © 2015 Elsevier Ltd. All rights reserved.

The flaws and human harms of animal experimentation.

Science.gov (United States)

Akhtar, Aysha

2015-10-01

Nonhuman animal ("animal") experimentation is typically defended by arguments that it is reliable, that animals provide sufficiently good models of human biology and diseases to yield relevant information, and that, consequently, its use provides major human health benefits. I demonstrate that a growing body of scientific literature critically assessing the validity of animal experimentation generally (and animal modeling specifically) raises important concerns about its reliability and predictive value for human outcomes and for understanding human physiology. The unreliability of animal experimentation across a wide range of areas undermines scientific arguments in favor of the practice. Additionally, I show how animal experimentation often significantly harms humans through misleading safety studies, potential abandonment of effective therapeutics, and direction of resources away from more effective testing methods. The resulting evidence suggests that the collective harms and costs to humans from animal experimentation outweigh potential benefits and that resources would be better invested in developing human-based testing methods.

Effect of peripheral morphine in a human model of acute inflammatory pain

DEFF Research Database (Denmark)

Lillesø, J; Hammer, N A; Pedersen, J L

2000-01-01

Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo-controlled, th......Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo......-controlled, three-way crossover design in a human model of acute inflammatory pain (heat injury). We studied 18 healthy volunteers who each received morphine locally (2 mg), morphine systemically (2 mg), or placebo on three separate study days. The subjects received morphine infiltration subcutaneously (s.c.). 1 h......, but local morphine infiltration neither reduced pain during the burn, nor primary or secondary hyperalgesia to mechanical and heat stimuli after the burn. In conclusion, peripherally applied morphine had no acute antinociceptive effects in this human model of acute inflammatory pain....

Antinociceptive Effect of Intrathecal Microencapsulated Human Pheochromocytoma Cell in a Rat Model of Bone Cancer Pain

Directory of Open Access Journals (Sweden)

Xiao Li

2014-07-01

Full Text Available Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l lysine-alginate (APA microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat model of bone cancer pain, and this effect was blocked by opioid antagonist naloxone and alpha 2-adrenergic antagonist rauwolscine. Neurochemical changes of cerebrospinal fluid are in accordance with the analgesic responses. Taken together, these data support that human pheochromocytoma cell implant-induced antinociception was mediated by met-enkephalin and norepinephrine secreted from the cell implants and acting at spinal receptors. Spinal implantation of microencapsulated human pheochromocytoma cells may provide an alternative approach for the therapy of chronic intractable pain.

Do intensity ratings and skin conductance responses reliably discriminate between different stimulus intensities in experimentally induced pain?

Science.gov (United States)

Breimhorst, Markus; Sandrock, Stephan; Fechir, Marcel; Hausenblas, Nadine; Geber, Christian; Birklein, Frank

2011-01-01

The present study addresses the question whether pain-intensity ratings and skin conductance responses (SCRs) are able to detect different intensities of phasic painful stimuli and to determine the reliability of this discrimination. For this purpose, 42 healthy participants of both genders were assigned to either electrical, mechanical, or laser heat-pain stimulation (each n = 14). A whole range of single brief painful stimuli were delivered on the right volar forearm of the dominant hand in a randomized order. Pain-intensity ratings and SCRs were analyzed. Using generalizability theory, individual and gender differences were the main contributors to the variability of both intensity ratings and SCRs. Most importantly, we showed that pain-intensity ratings are a reliable measure for the discrimination of different pain stimulus intensities in the applied modalities. The reliability of SCR was adequate when mechanical and heat stimuli were tested but failed for the discrimination of electrical stimuli. Further studies are needed to reveal the reason for this lack of accuracy for SCRs when applying electrical pain stimuli. Our study could help researchers to better understand the relationship between pain and activation of the sympathetic nervous system. Pain researchers are furthermore encouraged to consider individual and gender differences when measuring pain intensity and the concomitant SCRs in experimental settings. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

Reliability of four experimental mechanical pain tests in children

DEFF Research Database (Denmark)

Søe, Ann-Britt Langager; Thomsen, Lise L; Tornoe, Birte

2013-01-01

In order to study pain in children, it is necessary to determine whether pain measurement tools used in adults are reliable measurements in children. The aim of this study was to explore the intrasession reliability of pressure pain thresholds (PPT) in healthy children. Furthermore, the aim was a...... was also to study the intersession reliability of the following four tests: (1) Total Tenderness Score; (2) PPT; (3) Visual Analog Scale score at suprapressure pain threshold; and (4) area under the curve (stimulus-response functions for pressure versus pain).......In order to study pain in children, it is necessary to determine whether pain measurement tools used in adults are reliable measurements in children. The aim of this study was to explore the intrasession reliability of pressure pain thresholds (PPT) in healthy children. Furthermore, the aim...

The Effects of Sleep Deprivation on Pain

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Bernd Kundermann

2004-01-01

Full Text Available Chronic pain syndromes are associated with alterations in sleep continuity and sleep architecture. One perspective of this relationship, which has not received much attention to date, is that disturbances of sleep affect pain. To fathom this direction of cause, experimental human and animal studies on the effects of sleep deprivation on pain processing were reviewed. According to the majority of the studies, sleep deprivation produces hyperalgesic changes. Furthermore, sleep deprivation can counteract analgesic effects of pharmacological treatments involving opioidergic and serotoninergic mechanisms of action. The heterogeneity of the human data and the exclusive interest in rapid eye movement sleep deprivation in animals so far do not allow us to draw firm conclusions as to whether the hyperalgesic effects are due to the deprivation of specific sleep stages or whether they result from a generalized disruption of sleep continuity. The significance of opioidergic and serotoninergic processes as mediating mechanisms of the hyperalgesic changes produced by sleep deprivation are discussed.

Social laughter is correlated with an elevated pain threshold.

Science.gov (United States)

Dunbar, R I M; Baron, Rebecca; Frangou, Anna; Pearce, Eiluned; van Leeuwen, Edwin J C; Stow, Julie; Partridge, Giselle; MacDonald, Ian; Barra, Vincent; van Vugt, Mark

2012-03-22

Although laughter forms an important part of human non-verbal communication, it has received rather less attention than it deserves in both the experimental and the observational literatures. Relaxed social (Duchenne) laughter is associated with feelings of wellbeing and heightened affect, a proximate explanation for which might be the release of endorphins. We tested this hypothesis in a series of six experimental studies in both the laboratory (watching videos) and naturalistic contexts (watching stage performances), using change in pain threshold as an assay for endorphin release. The results show that pain thresholds are significantly higher after laughter than in the control condition. This pain-tolerance effect is due to laughter itself and not simply due to a change in positive affect. We suggest that laughter, through an endorphin-mediated opiate effect, may play a crucial role in social bonding.

Multidimensional study of orofacial chronic neuropathic pain: An experimental study in rats.

Directory of Open Access Journals (Sweden)

Claudia Daniela Montes-Angeles

2017-10-01

Full Text Available Orofacial neuropathic chronic pain (NCP is frequently attributed to lesions caused by orofacial surgeries and dental treatments. There are many experimental models available to study orofacial NCP, however, many are extremely painful for the animal due to the amplitude of the innervated region. A previously proposed mental nerve constriction model, mNC, was used in this project. Forty Wistar rats were randomly divided into two groups: one group included rats with mNC (n=20, and another rats with sham lesions (n=20. Through the use of the fixed ratio program and the progressive program, a decrease of motivation for a sweet substance, caused by the lesion, was evaluated. The possibility of alterations in cognitive learning and adaptation abilities was also assessed using the go/no-go behavioral task. The mNC group showed low induced and spontaneously evoked pain responses, as well as a decrease in the motivation for sucrose, a sign of anhedonia. This decrease does not depend on taste processing. Finally, although no alterations in the learning-memory process were observed, the mNC group did show alterations when adapting to a new rule.

Quality Improvement Project to Improve Patient Satisfaction With Pain Management: Using Human-Centered Design.

Science.gov (United States)

Trail-Mahan, Tracy; Heisler, Scott; Katica, Mary

2016-01-01

In this quality improvement project, our health system developed a comprehensive, patient-centered approach to improving inpatient pain management and assessed its impact on patient satisfaction across 21 medical centers. Using human-centered design principles, a bundle of 6 individual and team nursing practices was developed. Patient satisfaction with pain management, as measured by the Hospital Consumer Assessment of Healthcare Providers and Systems pain composite score, increased from the 25th to just under the 75th national percentile.

Neural correlates of heat-evoked pain memory in humans.

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

2016-03-01

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

Effect of bidirectional rotation of an acupuncture needle at LI10 on acupuncture needle sensation and experimentally-induced contact heat pain in healthy human volunteers.

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Benham, Alex; Johnson, Mark I

2014-06-01

There is insufficient evidence of a relationship between acupuncture needle sensations (de qi) and hypoalgesia. The aim of this study was to investigate the effects of bidirectional needle rotation at LI10 on acupuncture needle sensations and heat pain thresholds. Twenty-two healthy participants received one acupuncture needle at LI10 with bidirectional rotation of the needle in one experimental session and one acupuncture needle at LI10 with mock rotation in a separate session, in a randomised order. Measurements of heat pain thresholds were taken before needle insertion, during needle retention and 15 min after needle removal. At each measurement time point, participants rated needle sensations using the Massachusetts Acupuncture Sensation Scale (MASS) and a visual analogue scale (VAS) of overall intensity of needle sensation. Bidirectional needle rotation produced significantly higher scores for VAS, MASStotal, MASSpain and MASSsensation compared with mock rotation (all psensation and change in pain threshold after needling was only found when data from mock and rotation interventions were combined. Needle rotation increases the magnitude of hypoalgesia. There is tentative evidence that needle sensation may be associated with the amount of change in pain threshold. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Human radiation experimentation: a health physics perspective

International Nuclear Information System (INIS)

Kathren, R.L.

1996-01-01

This paper observes ethical human experimentation can be considered in terms of two basic principles or tests: informed, willing and knowledgeable subjects; and expectation of benefits. A number of human experiments are evaluated in terms of these principles, including a sixteenth century toxicology experiment, the deliberate exposure by an x-ray pioneer, and the plutonium injection cases of the 1940's. The following rational ethic is proposed for the practice of health physics with respect to human radiation experimentation: At all levels, the health physicist has a professional as well as personal obligation to ensure that proper human requirements, including proper informed consent and willing subjects, arc carried out with respect to human radiation experimentation, and must be convinced that the real or potential benefits to be derived from the experiment clearly exceed the potential detriment and risk. (author)

Length of perineal pain relief after ice pack application: A quasi-experimental study.

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de Souza Bosco Paiva, Caroline; Junqueira Vasconcellos de Oliveira, Sonia Maria; Amorim Francisco, Adriana; da Silva, Renata Luana; de Paula Batista Mendes, Edilaine; Steen, Mary

2016-04-01

Ice pack is effective for alleviating postpartum perineal pain in primiparous women while multiparous women's levels of perineal pain appear to be poorly explored. Ice pack is a low-cost non-invasive localised treatment that can be used with no impact on breastfeeding. However, how long perineal analgesia persists after applying an ice pack is still unknown. To evaluate if perineal analgesia is maintained up to 2h after applying an ice pack to the perineum for 20min. A quasi-experimental study, using a pre and post-test design, was undertaken with a sample size of 50 multiparous women in Brazil. Data was collected by structured interview. The intervention involved a single application of an ice pack applied for 20min to the perineal area of women who reported perineal pain ≥3 by use of a numeric rating scale (0-10), with intact perineum, 1st or 2nd degree lacerations or episiotomy, between 6 and 24h after spontaneous vaginal birth. Perineal pain was evaluated at three points of time: before, immediately after and 2h after applying an ice pack. Immediately after applying an ice pack to the perineal area, there was a significant reduction in the severity of perineal pain reported (5.4 vs. 1.0, p<0.0005), which continued for 1h 35min up to 2h after the local application. Ice pack application for 20min is effective for alleviating postpartum perineal pain and continues to be effective between 1h 35min for up to 2h. Copyright © 2015 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Complex muscular adaptation to perturbations after induction of experimental low back pain in healthy participants

DEFF Research Database (Denmark)

Larsen, Lars Henrik; Hirata, Rogerio Pessoto; Graven-Nielsen, Thomas

2014-01-01

Background and aims Spine stability is affected in low back (LB) pain and potentially by muscle fatigue and soreness. This study assessed motor control responses to unexpected surface perturbations during stance during experimental LB muscle pain combined with fatigue and muscle soreness. Methods...... Nineteen healthy participants were examined day 1-3 before and after bilateral injections of hypertonic saline into m. longissimus. Pain intensity was scored on a visual analogue scale (VAS). Day 2 included injections during post-exercise LB muscle fatigue and day 3 during delayed onset back muscle...... soreness (DOMS). Twenty perturbations were conducted randomly with tilts in sagittal and frontal plane or displacements in the frontal plane. Bilateral electromyography (EMG) was recorded from 12 trunk muscles. The root-mean-square (RMS-EMG) was extracted. Changes (DeltaRMS) and absolute changes (Delta...

Explicit episodic memory for sensory-discriminative components of capsaicin-induced pain: immediate and delayed ratings.

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Jantsch, H H F; Gawlitza, M; Geber, C; Baumgärtner, U; Krämer, H H; Magerl, W; Treede, R D; Birklein, F

2009-05-01

Pain memory is thought to affect future pain sensitivity and thus contribute to clinical pain conditions. Systematic investigations of the human capacity to remember sensory features of experimental pain are sparse. In order to address long-term pain memory, nine healthy male volunteers received intradermal injections of three doses of capsaicin (0.05, 1 and 20 microg, separated by 15 min breaks), each given three times in a balanced design across three sessions at one week intervals. Pain rating was performed using a computerized visual analogue scale (0-100) digitized at 1/s, either immediately online or one hour or one day after injection. Subjects also recalled their pains one week later. Capsaicin injection reliably induced a dose-dependent flare (pmemory traces. These results indicate a reliable memory for magnitude and duration of experimentally induced pain. The data further suggest that the consolidation of this memory is an important interim stage, and may take up to one day.

Effects of a Pain Catastrophizing Induction on Sensory Testing in Women with Chronic Low Back Pain: A Pilot Study

OpenAIRE

Taub, Chloe J.; Sturgeon, John A.; Johnson, Kevin A.; Mackey, Sean C.; Darnall, Beth D.

2017-01-01

Pain catastrophizing, a pattern of negative cognitive-emotional responses to actual or anticipated pain, maintains chronic pain and undermines response to treatments. Currently, precisely how pain catastrophizing influences pain processing is not well understood. In experimental settings, pain catastrophizing has been associated with amplified pain processing. This study sought to clarify pain processing mechanisms via experimental induction of pain catastrophizing. Forty women with chronic l...

The impact of patients' gender, race, and age on health care professionals' pain management decisions: an online survey using virtual human technology.

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Wandner, Laura D; Heft, Marc W; Lok, Benjamin C; Hirsh, Adam T; George, Steven Z; Horgas, Anne L; Atchison, James W; Torres, Calia A; Robinson, Michael E

2014-05-01

Previous literature indicates that biases exist in pain ratings. Healthcare professionals have been found to use patient demographic cues such as sex, race, and age when making decisions about pain treatment. However, there has been little research comparing healthcare professionals' (i.e., physicians and nurses) pain decision policies based on patient demographic cues. The current study used virtual human technology to examine the impact of patients' sex, race, and age on healthcare professionals' pain ratings. One hundred and ninety-three healthcare professionals (nurses and physicians) participated in this online study. Healthcare professionals assessed virtual human patients who were male and African American to be experiencing greater pain intensity and were more willing to administer opioid analgesics to them than to their demographic counterparts. Similarly, nurses were more willing to administer opioids make treatment decisions than physicians. There was also a significant virtual human-sex by healthcare professional interaction for pain assessment and treatment decisions. The sex difference (male>female) was greater for nurses than physicians. Results replicated findings of previous studies using virtual human patients to assess the effect of sex, race, and age in pain decision-making. In addition, healthcare professionals' pain ratings differed depending on healthcare profession. Nurses were more likely to rate pain higher and be more willing to administer opioid analgesics than were physicians. Healthcare professionals rated male and African American virtual human patients as having higher pain in most pain assessment and treatment domains compared to their demographic counterparts. Similarly the virtual human-sex difference ratings were more pronounced for nurses than physicians. Given the large number of patients seen throughout the healthcare professionals' careers, these pain practice biases have important public health implications. This study

When pain meets … pain-related choice behavior and pain perception in different goal conflict situations.

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Schrooten, Martien G S; Wiech, Katja; Vlaeyen, Johan W S

2014-11-01

Individuals in pain often face the choice between avoiding pain and pursuing other equally valued goals. However, little is known about pain-related choice behavior and pain perception in goal conflict situations. Seventy-eight healthy volunteers performed a computerized task requiring repeated choices between incompatible options, differing in their effect on probability to receive painful stimulation and money. Depending on group assignment, participants chose between increased pain probability versus decreased money probability (avoidance-avoidance conflict situation); decreased pain probability versus increased money probability (approach-approach conflict situation); or decrease versus increase in both probabilities (double approach/avoidance conflict situation). During the choice task, participants rated painfulness, unpleasantness, threat, and fearfulness associated with the painful stimulation and how they felt. Longer choice latency and more choice switching were associated with higher retrospective ratings of conflict and of decision difficulty, and more equal importance placed on pain avoidance and earning money. Groups did not differ in choice behavior, pain stimulus ratings, or affect. Across groups, longer choice latencies were nonsignificantly associated with higher pain, unpleasantness, threat, and fearfulness. In the avoidance-avoidance group, more choice switching was associated with higher pain-related threat and fearfulness, and with more negative affect. These results of this study suggest that associations between choice behaviors, pain perception, and affect depend on conflict situation. We present a first experimental demonstration of the relationship between pain-related choice behaviors, pain, and affect in different goal conflict situations. This experimental approach allows us to examine these relationships in a controlled fashion. Better understanding of pain-related goal conflicts and their resolution may lead to more effective pain

Body awareness and responses to experimentally Induced pain

Directory of Open Access Journals (Sweden)

M. Minev

2017-09-01

Full Text Available PURPOSE. The aim of this study is to discuss personal and demographic factors that influence the relationship between physical activity and awareness of one's own body, as well as the pain response (threshold and tolerance of pain, situational anxiety and personality. In the study 38 healthy individual- volunteers, students in Trakia University - Stara Zagora were selected. All participants were divided into two groups: actively involved in individual or team sport (n = 19 and healthy normaly active subjects (non-athletes, n = 19. The age of the study participants ranged between 18 and 39 years, while the gender breakdown was as follows: men - 22 women – 16. Methods: Psychological Questionnaires: Body Awareness Questionnaire that asks subjects to rate, on a 4 point scale, the degree to which they were currently experiencing symptoms of sympathetic arousal, State Trait Anger Scale, and State Trait Anxiety Scale. Objective methods (cold pressure test are used only to determine the pain sensation and pain tolerance thresholds. The results of investigation support significant differences between athletes and non-athletes in pain thershold, body awareness and anxiety. The study conclusions discuss body awareness as an increasing factor for pain resistance in athletes and as an integral part of the learning process among them.

Altering gender role expectations: effects on pain tolerance, pain threshold, and pain ratings.

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Robinson, Michael E; Gagnon, Christine M; Riley, Joseph L; Price, Donald D

2003-06-01

The literature demonstrating sex differences in pain is sizable. Most explanations for these differences have focused on biologic mechanisms, and only a few studies have examined social learning. The purpose of this study was to examine the contribution of gender-role stereotypes to sex differences in pain. This study used experimental manipulation of gender-role expectations for men and women. One hundred twenty students participated in the cold pressor task. Before the pain task, participants were given 1 of 3 instructional sets: no expectation, 30-second performance expectation, or a 90-second performance expectation. Pain ratings, threshold, and tolerance were recorded. Significant sex differences in the "no expectation" condition for pain tolerance (t = 2.32, df = 38, P differ in their pain tolerance, pain threshold, or pain ratings. This is the first empirical study to show that manipulation of expectations alters sex differences in laboratory pain.

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

DEFF Research Database (Denmark)

Sonnesen, Liselotte; Svensson, Peter

2013-01-01

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

Effect of painful and non-painful sensorimotor manipulations on subjective body midline

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Jason eBouffard

2013-03-01

Full Text Available Patients with chronic pain often show disturbances in their body perception. Understanding the exact role played by pain is however complex, as confounding factors can contribute to the observed deficits in these clinical populations. To address this question, acute experimental pain was used to test the effect of lateralized pain on body perception in healthy subjects. Subjects were asked to indicate the position of their body midline (subjective body midline, SBM by stopping a moving luminescent dot projected on a screen placed in front of them, in a completely dark environment. The effect of other nonpainful sensorimotor manipulations was also tested to assess the potential unspecific attentional effects of stimulating one side of the body. SBM judgment was made in seventeen volunteers under control and three experimental conditions: 1 painful (heat stimulation; 2 nonpainful vibrotactile stimulation; and 3 muscle contraction. The effects of the stimulated side and the type of trial (control vs. experimental condition, were tested separately for each condition with a 2 x 2 repeated measures ANOVA. The analyses revealed a significant interaction in both pain (p = 0.05 and vibration conditions (p = 0.04. Post-hoc tests showed opposite effects of pain and vibration. Pain applied on the right arm deviated the SBM toward the right (stimulated side (p = 0.03 while vibration applied on the left arm deviated the SBM toward the right (not stimulated side (p = 0.01. These opposite patterns suggest that the shift in SBM is likely to be specifically linked to the stimulation modality. It is concluded that acute experimental pain can induce an SBM shift toward the stimulated side, which might be functionally beneficial to protect the painful area of the body. Interestingly, it appears to be easier to bias SBM toward the right side, regardless of the modality and of the stimulated side.

Chronic Pelvic Pain Development and Prostate Inflammation in Strains of Mice With Different Susceptibility to Experimental Autoimmune Prostatitis.

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Breser, Maria L; Motrich, Ruben D; Sanchez, Leonardo R; Rivero, Virginia E

2017-01-01

Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of the prostate characterized by peripheral prostate-specific autoimmune responses associated with prostate inflammation. EAP is induced in rodents upon immunization with prostate antigens (PAg) plus adjuvants and shares important clinical and immunological features with the human disease chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). EAP was induced in young NOD, C57BL/6, and BALB/c male mice by immunization with PAg plus complete Freund́s adjuvant. Tactile allodynia was assessed using Von Frey fibers as a measure of pelvic pain at baseline and at different time points after immunization. Using conventional histology, immunohistochemistry, FACS analysis, and protein arrays, an interstrain comparative study of prostate cell infiltration and inflammation was performed. Chronic pelvic pain development was similar between immunized NOD and C57BL/6 mice, although the severity of leukocyte infiltration was greater in the first case. Coversely, minimal prostate cell infiltration was observed in immunized BALB/c mice, who showed no pelvic pain development. Increased numbers of mast cells, mostly degranulated, were detected in prostate samples from NOD and C57BL/6 mice, while lower total counts and resting were observed in BALB/c mice. Prostate tissue from NOD mice revealed markedly increased expression levels of inflammatory cytokines, chemokines, adhesion molecules, vascular endothelial growth factor, and metalloproteinases. Similar results, but to a lesser extent, were observed when analyzing prostate tissue from C57BL/6 mice. On the contrary, the expression of the above mediators was very low in prostate tissue from immunized BALB/c mice, showing significantly slight increments only for CXCL1 and IL4. Our results provide new evidence indicating that NOD, C57BL/6, and BALB/c mice develop different degrees of chronic pelvic pain, type, and amount of prostate cell infiltration

Attenuation of Experimental Pain by Vibro-Tactile Stimulation in Patients with Chronic Local or Widespread Musculoskeletal Pain

OpenAIRE

Staud, Roland; Robinson, Michael E.; Goldman, Casey T.; Price, Donald D.

2011-01-01

Patients with chronic pain syndromes, like fibromyalgia (FM) complain of widespread pain and tenderness, as well as non-refreshing sleep, cognitive dysfunction, and negative mood. Several lines of evidence implicate abnormalities of central pain processing as contributors for chronic pain, including dysfunctional descending pain inhibition. One form of endogenous pain inhibition, diffuse noxious inhibitory controls (DNIC), has been found to be abnormal in some chronic pain patients and eviden...

Determining the Neural Substrate for Encoding a Memory of Human Pain and the Influence of Anxiety.

Science.gov (United States)

Tseng, Ming-Tsung; Kong, Yazhuo; Eippert, Falk; Tracey, Irene

2017-12-06

To convert a painful stimulus into a briefly maintainable construct when the painful stimulus is no longer accessible is essential to guide human behavior and avoid dangerous situations. Because of the aversive nature of pain, this encoding process might be influenced by emotional aspects and could thus vary across individuals, but we have yet to understand both the basic underlying neural mechanisms as well as potential interindividual differences. Using fMRI in combination with a delayed-discrimination task in healthy volunteers of both sexes, we discovered that brain regions involved in this working memory encoding process were dissociable according to whether the to-be-remembered stimulus was painful or not, with the medial thalamus and the rostral anterior cingulate cortex encoding painful and the primary somatosensory cortex encoding nonpainful stimuli. Encoding of painful stimuli furthermore significantly enhanced functional connectivity between the thalamus and medial prefrontal cortex (mPFC). With regards to emotional aspects influencing encoding processes, we observed that more anxious participants showed significant performance advantages when encoding painful stimuli. Importantly, only during the encoding of pain, the interindividual differences in anxiety were associated with the strength of coupling between medial thalamus and mPFC, which was furthermore related to activity in the amygdala. These results indicate not only that there is a distinct signature for the encoding of a painful experience in humans, but also that this encoding process involves a strong affective component. SIGNIFICANCE STATEMENT To convert the sensation of pain into a briefly maintainable construct is essential to guide human behavior and avoid dangerous situations. Although this working memory encoding process is implicitly contained in the majority of studies, the underlying neural mechanisms remain unclear. Using fMRI in a delayed-discrimination task, we found that the

Genome-wide analysis of pain-, nerve- and neurotrophin -related gene expression in the degenerating human annulus

Science.gov (United States)

2012-01-01

Background In spite of its high clinical relevance, the relationship between disc degeneration and low back pain is still not well understood. Recent studies have shown that genome-wide gene expression studies utilizing ontology searches provide an efficient and valuable methodology for identification of clinically relevant genes. Here we use this approach in analysis of pain-, nerve-, and neurotrophin-related gene expression patterns in specimens of human disc tissue. Control, non-herniated clinical, and herniated clinical specimens of human annulus tissue were studied following Institutional Review Board approval. Results Analyses were performed on more generated (Thompson grade IV and V) discs vs. less degenerated discs (grades I-III), on surgically operated discs vs. control discs, and on herniated vs. control discs. Analyses of more degenerated vs. less degenerated discs identified significant upregulation of well-recognized pain-related genes (bradykinin receptor B1, calcitonin gene-related peptide and catechol-0-methyltransferase). Nerve growth factor was significantly upregulated in surgical vs. control and in herniated vs. control discs. All three analyses also found significant changes in numerous proinflammatory cytokine- and chemokine-related genes. Nerve, neurotrophin and pain-ontology searches identified many matrix, signaling and functional genes which have known importance in the disc. Immunohistochemistry was utilized to confirm the presence of calcitonin gene-related peptide, catechol-0-methyltransferase and bradykinin receptor B1 at the protein level in the human annulus. Conclusions Findings point to the utility of microarray analyses in identification of pain-, neurotrophin and nerve-related genes in the disc, and point to the importance of future work exploring functional interactions between nerve and disc cells in vitro and in vivo. Nerve, pain and neurotrophin ontology searches identified numerous changes in proinflammatory cytokines and

A preliminary report on stem cell therapy for neuropathic pain in humans

Directory of Open Access Journals (Sweden)

Vickers ER

2014-05-01

Full Text Available E Russell Vickers,1 Elisabeth Karsten,2 John Flood,3 Richard Lilischkis21Sydney Oral and Maxillofacial Surgery, NSW, Australia; 2Regeneus Ltd, Gordon, NSW, Australia; 3St Vincents Hospital, Sydney, NSW, AustraliaObjective: Mesenchymal stem cells (MSCs have been shown in animal models to attenuate chronic neuropathic pain. This preliminary study investigated if: i injections of autologous MSCs can reduce human neuropathic pain and ii evaluate the safety of the procedure.Methods: Ten subjects with symptoms of neuropathic trigeminal pain underwent liposuction. The lipoaspirate was digested with collagenase and washed with saline three times. Following centrifugation, the stromal vascular fraction was resuspended in saline, and then transferred to syringes for local injections into the pain fields. Outcome measures at 6 months assessed reduction in: i pain intensity measured by standard numerical rating scale from 0–10 and ii daily dosage requirements of antineuropathic pain medication.Results: Subjects were all female (mean age 55.3 years ± standard deviation [SD] 14.67; range 27–80 years with pain symptoms lasting from 4 months to 6 years and 5 months. Lipoaspirate collection ranged from 102–214 g with total cell numbers injected from 33 million to 162 million cells. Cell viability was 62%–91%. There were no systemic or local tissue side effects from the stem cell therapy (n=41 oral and facial injection sites. Clinical pain outcomes showed that at 6 months, 5/9 subjects had reduced both pain intensity scores and use of antineuropathic medication. The mean pain score pre-treatment was 7.5 (SD 1.58 and at 6 months had decreased to 4.3 (SD 3.28, P=0.018, Wilcoxon signed-rank test. Antineuropathic pain medication use showed 5/9 subjects reduced their need for medication (gabapentin, P=0.053, Student's t-test.Conclusion: This preliminary open-labeled study showed autologous administration of stem cells for neuropathic trigeminal pain

Brain Network Response to Acupuncture Stimuli in Experimental Acute Low Back Pain: An fMRI Study

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Yu Shi

2015-01-01

Full Text Available Most neuroimaging studies have demonstrated that acupuncture can significantly modulate brain activation patterns in healthy subjects, while only a few studies have examined clinical pain. In the current study, we combined an experimental acute low back pain (ALBP model and functional magnetic resonance imaging (fMRI to explore the neural mechanisms of acupuncture analgesia. All ALBP subjects first underwent two resting state fMRI scans at baseline and during a painful episode and then underwent two additional fMRI scans, once during acupuncture stimulation (ACUP and once during tactile stimulation (SHAM pseudorandomly, at the BL40 acupoint. Our results showed that, compared with the baseline, the pain state had higher regional homogeneity (ReHo values in the pain matrix, limbic system, and default mode network (DMN and lower ReHo values in frontal gyrus and temporal gyrus; compared with the OFF status, ACUP yielded broad deactivation in subjects, including nearly all of the limbic system, pain status, and DMN, and also evoked numerous activations in the attentional and somatosensory systems; compared with SHAM, we found that ACUP induced more deactivations and fewer activations in the subjects. Multiple brain networks play crucial roles in acupuncture analgesia, suggesting that ACUP exceeds a somatosensory-guided mind-body therapy for ALBP.

Are Pain-Related Fears Mediators for Reducing Disability and Pain in Patients with Complex Regional Pain Syndrome Type 1? An Explorative Analysis on Pain Exposure Physical Therapy

Science.gov (United States)

Barnhoorn, Karlijn J.; Staal, J. Bart; van Dongen, Robert T. M.; Frölke, Jan Paul M.; Klomp, Frank P.; van de Meent, Henk; Samwel, Han; Nijhuis-van der Sanden, Maria W. G.

2015-01-01

Objective To investigate whether pain-related fears are mediators for reducing disability and pain in patients with Complex Regional Pain Syndrome type 1 when treating with Pain Exposure Physical Therapy. Design An explorative secondary analysis of a randomised controlled trial. Participants Fifty-six patients with Complex Regional Pain Syndrome type 1. Interventions The experimental group received Pain Exposure Physical Therapy in a maximum of five treatment sessions; the control group received conventional treatment following the Dutch multidisciplinary guideline. Outcome measures Levels of disability, pain, and pain-related fears (fear-avoidance beliefs, pain catastrophizing, and kinesiophobia) were measured at baseline and after 3, 6, and 9 months follow-up. Results The experimental group had a significantly larger decrease in disability of 7.77 points (95% CI 1.09 to 14.45) and in pain of 1.83 points (95% CI 0.44 to 3.23) over nine months than the control group. The potential mediators pain-related fears decreased significantly in both groups, but there were no significant differences between groups, which indicated that there was no mediation. Conclusion The reduction of pain-related fears was comparable in both groups. We found no indication that pain-related fears mediate the larger reduction of disability and pain in patients with Complex Regional Pain Syndrome type 1 treated with Pain Exposure Physical Therapy compared to conventional treatment. Trial registration International Clinical Trials Registry NCT00817128 PMID:25919011

Thermal and pressure pain sensitivity in patients with unilateral shoulder pain: comparison of involved and uninvolved sides.

Science.gov (United States)

Coronado, Rogelio A; Kindler, Lindsay L; Valencia, Carolina; George, Steven Z

2011-03-01

Cross-sectional. In the examination of patients with unilateral shoulder pain, pain provocation testing to compare the involved and uninvolved sides has been considered useful. However, side-to-side comparisons of experimental pain sensitivity in patients with unilateral shoulder pain are not widely reported in the literature. To compare experimental pain sensitivity between the involved and uninvolved sides in patients with unilateral shoulder pain. In consecutive patients seeking operative treatment for shoulder pain, sensitivity measures of bilateral pressure pain threshold at the shoulder and forearm, and thermal pain threshold, tolerance, and temporal summation at the forearm, were examined. Pressure sensitivity was tested with a Fischer pressure algometer, and thermal sensitivity with a computer-controlled Medoc neurosensory analyzer. The involved and uninvolved sides were compared with an analysis of variance. Influence of sex and location of testing were considered as covariates in the analysis. Fifty-nine consecutively recruited participants completed experimental pain sensitivity testing. Participants reported significantly lower pressure pain thresholds in the involved side compared to the uninvolved side (F1,56 = 4.96, P = .030). In addition, female compared to male participants demonstrated lower pressure pain thresholds in the bilateral shoulder regions (F1,56 = 10.84, P = .002). There was no difference in thermal pain sensitivity between sides. Average clinical pain intensity was negatively correlated with pressure pain threshold at the involved local site (r = -0.284, P = .029), indicating an influence of clinical pain intensity on local pressure pain. The results of this study provide evidence for higher experimental pressure pain sensitivity in the involved side of patients with unilateral shoulder pain and no difference between sides for thermal pain sensitivity. Females demonstrated higher pain sensitivity than males to pressure stimuli at the

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

DEFF Research Database (Denmark)

Pedersen, J L; Kehlet, H

1998-01-01

as significant for all variables with fewer than 12 subjects in a cross-over design (2alpha = 5% and power = 80%). Between-day comparisons demanded up to 25 subjects to detect changes of the same magnitude. The burns caused mild to moderate pain (VAS: mean 29, SD 14) and the subjects (all right-handed) were more......The aim of the study was to examine reproducibility of primary and secondary hyperalgesia in a psychophysical model of human inflammatory pain. Mild burns were produced on the crura of 12 volunteers with a 50 x 25 mm thermode (47 degrees C, 7 min). Assessments of (i) cold and warm detection...... thresholds, (ii) mechanical and heat pain thresholds, (iii) pain to heat (43 degrees C and 45 degrees C, 5 s), (iv) secondary hyperalgesia, and (v) skin erythema were made 1.75 and 0.5 h before, and 0, 1, 2, 4, and 6 h after a burn injury. Sensory thresholds and hyperalgesia to heat and mechanical stimuli...

Intradiscal application of a PCLA-PEG-PCLA hydrogel loaded with celecoxib for the treatment of back pain in canines: What's in it for humans?

Science.gov (United States)

Tellegen, Anna R; Willems, Nicole; Beukers, Martijn; Grinwis, Guy C M; Plomp, Saskia G M; Bos, Clemens; van Dijk, Maarten; de Leeuw, Mike; Creemers, Laura B; Tryfonidou, Marianna A; Meij, Björn P

2018-03-01

Chronic low back pain is a common clinical problem in both the human and canine population. Current pharmaceutical treatment often consists of oral anti-inflammatory drugs to alleviate pain. Novel treatments for degenerative disc disease focus on local application of sustained released drug formulations. The aim of this study was to determine safety and feasibility of intradiscal application of a poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-bpoly(ε-caprolactone-co-lactide) PCLA-PEG-PCLA hydrogel releasing celecoxib, a COX-2 inhibitor. Biocompatibility was evaluated after subcutaneous injection in mice, and safety of intradiscal injection of the hydrogel was evaluated in experimental dogs with early spontaneous intervertebral disc (IVD) degeneration. COX-2 expression was increased in IVD samples surgically obtained from canine patients, indicating a role of COX-2 in clinical IVD disease. Ten client-owned dogs with chronic low back pain related to IVD degeneration received an intradiscal injection with the celecoxib-loaded hydrogel. None of the dogs showed adverse reactions after intradiscal injection. The hydrogel did not influence magnetic resonance imaging signal at long-term follow-up. Clinical improvement was achieved by reduction of back pain in 9 of 10 dogs, as was shown by clinical examination and owner questionnaires. In 3 of 10 dogs, back pain recurred after 3 months. This study showed the safety and effectiveness of intradiscal injections in vivo with a thermoresponsive PCLA-PEG-PCLA hydrogel loaded with celecoxib. In this set-up, the dog can be used as a model for the development of novel treatment modalities in both canine and human patients with chronic low back pain. Copyright © 2017 John Wiley & Sons, Ltd.

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

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Selvaraj Deepitha

2010-03-01

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

Hemorrhoids: an experimental model in monkeys

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Plapler Hélio

2006-01-01

Full Text Available PURPOSE: Hemorrhoids are a matter of concern due to a painful outcome. We describe a simple, easy and reliable experimental model to produce hemorrhoids in monkeys. METHODS: 14 monkeys (Cebus apella were used. After general anesthesia, hemorrhoids were induced by ligation of the inferior hemorrhoidal vein, which is very alike to humans. The vein was located through a perianal incision, dissected and ligated with a 3-0 vicryl. The skin was sutured with a 4-0 catgut thread. Animals were kept in appropriate cages and evaluated daily. RESULTS: Nine days later there were hemorrhoidal piles in the anus in fifty percent (50% of the animals. Outcome was unremarkable. There was no bleeding and all animals showed no signs of pain or suffering. CONCLUSION: This is an affordable and reliable experimental model to induce hemorrhoids for experimental studies.

A word expressing affective pain activates the anterior cingulate cortex in the human brain: an fMRI study.

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Osaka, Naoyuki; Osaka, Mariko; Morishita, Masanao; Kondo, Hirohito; Fukuyama, Hidenao

2004-08-12

We present an fMRI study demonstrating that an onomatopoeia word highly suggestive of subjective pain, heard by the ear, significantly activates the anterior cingulate cortex (ACC) while hearing non-sense words that did not imply affective pain under the same task does not activate this area in humans. We concluded that the ACC would be a pivotal locus for perceiving affective pain evoked by an onomatopoeia word that implied affective pain closely associated with the unpleasantness of pain. We suggest that the pain affect sustained by pain unpleasantness may depend on ACC-prefrontal cortical interactions that modify cognitive evaluation of emotions associated with word-induced pain.

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

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

2014-05-01

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. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Lack of influence of GTP cyclohydrolase gene (GCH1 variations on pain sensitivity in humans

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Dionne Raymond A

2007-03-01

Full Text Available Abstract Objectives To assess the effect of variations in GTP cyclohydrolase gene (GCH1 on pain sensitivity in humans. Methods Thermal and cold pain sensitivity were evaluated in a cohort of 735 healthy volunteers. Among this cohort, the clinical pain responses of 221 subjects after the surgical removal of impacted third molars were evaluated. Genotyping was done for 38 single nucleotide polymorphisms (SNPs whose heterozygosity > 0.2 in GCH1. Influence of the genetic variations including SNPs and haplotypes on pain sensitivity were analyzed. Results Minor allele frequencies and linkage disequilibrium show significant differences in European Americans, African Americans, Hispanic Americans and Asian Americans. Association analyses in European Americans do not replicate the previously reported important influence of GCH1 variations on pain sensitivity. Conclusion Considering population stratification, previously reported associations between GCH1 genetic variations and pain sensitivity appear weak or negligible in this well characterized model of pain.

Prediction of postoperative pain by preoperative pain response to heat stimulation in total knee arthroplasty

DEFF Research Database (Denmark)

Lunn, Troels H; Gaarn-Larsen, Lissi; Kehlet, Henrik

2013-01-01

It has been estimated that up to 54% of the variance in postoperative pain experience may be predicted with preoperative pain responses to experimental stimuli, with suprathreshold heat pain as the most consistent test modality. We aimed to explore if 2 heat test paradigms could predict postopera......It has been estimated that up to 54% of the variance in postoperative pain experience may be predicted with preoperative pain responses to experimental stimuli, with suprathreshold heat pain as the most consistent test modality. We aimed to explore if 2 heat test paradigms could predict...... and logistic regressions analyses were carried out including 8 potential preoperative explanatory variables (among these anxiety, depression, preoperative pain and pain catastrophizing) to assess pain response to preoperative heat pain stimulation as independent predictor for postoperative pain. 100 patients...... by the linear and logistic regression analyses, where only anxiety, preoperative pain and pain catastrophizing were significant explanatory variables (but with low R-Squares;0.05-0.08). Pain responses to 2 types of preoperative heat stimuli were not independent clinical relevant predictors for postoperative...

Relationships between craniofacial pain and bruxism.

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Svensson, P; Jadidi, F; Arima, T; Baad-Hansen, L; Sessle, B J

2008-07-01

A still commonly held view in the literature and clinical practice is that bruxism causes pain because of overloading of the musculoskeletal tissue and craniofacial pain, on the other hand, triggers more bruxism. Furthermore, it is often believed that there is a dose-response gradient so that more bruxism (intensity, duration) leads to more overloading and pain. Provided the existence of efficient techniques to treat bruxism, it would be straightforward in such a simple system to target bruxism as the cause of pain and hence treat the pain. Of course, human biological systems are much more complex and therefore, it is no surprise that the relationship between bruxism and pain is far from being simple or even linear. Indeed, there are unexpected relationships, which complicate the establishment of adequate explanatory models. Part of the reason is the complexity of the bruxism in itself, which presents significant challenges related to operationalized criteria and diagnostic tools and underlying pathophysiology issues, which have been dealt with in other reviews in this issue. However, another important reason is the multifaceted nature of craniofacial pain. This review will address our current understanding of classification issues, epidemiology and neurobiological mechanisms of craniofacial pain. Experimental models of bruxism may help to further the understanding of the relationship between craniofacial pain and bruxism in addition to insights from intervention studies. The review will enable clinicians to understand the reasons why simple cause-effect relationships between bruxism and craniofacial pain are inadequate and the current implications for management of craniofacial pain.

Effects of Hemibridge with Ball and Balloon Exercise on Forced Expiratory Volume and Pain in Patients with Chronic Low Back Pain: An Experimental Study

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Jorida Fernandes

2017-08-01

Full Text Available Background and objectives: Suboptimal breathing patterns and impairments of posture and trunk stability are often associated with musculoskeletal complaints such as low back pain. Respiration is also affected by poor neuromuscular control of core muscles. Immediate effects of hemibridge with ball and balloon exercise has been studied on chronic pain in athlete population. Objective: To evaluate the effects of hemibridge with ball and balloon exercise on pain, forced expiratory volume and functional abilities in patients with chronic low back pain using Visual Analogue Scale (VAS, Forced Expiratory Volume (FEV and Modified Oswestry Disability Questionnaire (MODQ. Methods: The present experimental study was conducted among 30 participants between the age of 21 to 55 years with chronic non-specific LBP. The participants were given a hemibridge with ball and balloon exercise. Pre-interventional and 3rd day Post-interventional outcome measurements were taken using VAS, FEV1 and FEV6 and MODQ. Results: The difference between pre-and post of VAS was statistically highly significant (p=0.0001. The p value of FEV6 and MODQ by paired t test was statistically significant with p value of 0.02 and 0.0007 respectively. Conclusion: The study concludes that there is an immediate effect of hemibridge with ball and balloon exercise on pain, FEV6 and functional ability in patients with chronic LBP.

Neuropathic pain in experimental autoimmune neuritis is associated with altered electrophysiological properties of nociceptive DRG neurons.

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Taha, Omneya; Opitz, Thoralf; Mueller, Marcus; Pitsch, Julika; Becker, Albert; Evert, Bernd Oliver; Beck, Heinz; Jeub, Monika

2017-11-01

Guillain-Barré syndrome (GBS) is an acute, immune-mediated polyradiculoneuropathy characterized by rapidly progressive paresis and sensory disturbances. Moderate to severe and often intractable neuropathic pain is a common symptom of GBS, but its underlying mechanisms are unknown. Pathology of GBS is classically attributed to demyelination of large, myelinated peripheral fibers. However, there is increasing evidence that neuropathic pain in GBS is associated with impaired function of small, unmyelinated, nociceptive fibers. We therefore examined the functional properties of small DRG neurons, the somata of nociceptive fibers, in a rat model of GBS (experimental autoimmune neuritis=EAN). EAN rats developed behavioral signs of neuropathic pain. This was accompanied by a significant shortening of action potentials due to a more rapid repolarization and an increase in repetitive firing in a subgroup of capsaicin-responsive DRG neurons. Na + current measurements revealed a significant increase of the fast TTX-sensitive current and a reduction of the persistent TTX-sensitive current component. These changes of Na + currents may account for the significant decrease in AP duration leading to an overall increase in excitability and are therefore possibly directly linked to pathological pain behavior. Thus, like in other animal models of neuropathic and inflammatory pain, Na + channels seem to be crucially involved in the pathology of GBS and may constitute promising targets for pain modulating pharmaceuticals. Copyright © 2017 Elsevier Inc. All rights reserved.

Salmon and human thrombin differentially regulate radicular pain, glial-induced inflammation and spinal neuronal excitability through protease-activated receptor-1.

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Jenell R Smith

Full Text Available Chronic neck pain is a major problem with common causes including disc herniation and spondylosis that compress the spinal nerve roots. Cervical nerve root compression in the rat produces sustained behavioral hypersensitivity, due in part to the early upregulation of pro-inflammatory cytokines, the sustained hyperexcitability of neurons in the spinal cord and degeneration in the injured nerve root. Through its activation of the protease-activated receptor-1 (PAR1, mammalian thrombin can enhance pain and inflammation; yet at lower concentrations it is also capable of transiently attenuating pain which suggests that PAR1 activation rate may affect pain maintenance. Interestingly, salmon-derived fibrin, which contains salmon thrombin, attenuates nerve root-induced pain and inflammation, but the mechanisms of action leading to its analgesia are unknown. This study evaluates the effects of salmon thrombin on nerve root-mediated pain, axonal degeneration in the root, spinal neuronal hyperexcitability and inflammation compared to its human counterpart in the context of their enzymatic capabilities towards coagulation substrates and PAR1. Salmon thrombin significantly reduces behavioral sensitivity, preserves neuronal myelination, reduces macrophage infiltration in the injured nerve root and significantly decreases spinal neuronal hyperexcitability after painful root compression in the rat; whereas human thrombin has no effect. Unlike salmon thrombin, human thrombin upregulates the transcription of IL-1β and TNF-α and the secretion of IL-6 by cortical cultures. Salmon and human thrombins cleave human fibrinogen-derived peptides and form clots with fibrinogen with similar enzymatic activities, but salmon thrombin retains a higher enzymatic activity towards coagulation substrates in the presence of antithrombin III and hirudin compared to human thrombin. Conversely, salmon thrombin activates a PAR1-derived peptide more weakly than human thrombin. These

Effect of riluzole on acute pain and hyperalgesia in humans

DEFF Research Database (Denmark)

Hammer, N A; Lillesø, J; Pedersen, J L

1999-01-01

Riluzole modulates several transmitter systems which may be involved in nociception. Antinociceptive effects have been shown in animal studies, but there are no human data. Therefore, we have examined the acute analgesic effect of riluzole in a human model of inflammatory pain induced by a thermal...... injury on the distal leg (47 degrees C, 7 min, 12.5 cm2) in 20 healthy volunteers. Hyperalgesia to mechanical and heat stimuli were examined by von Frey hairs and thermodes. We used a randomized, double-blind, placebo-controlled design, and subjects received riluzole 100 mg or placebo for 2 days...

The development of human factors experimental evaluation techniques

Energy Technology Data Exchange (ETDEWEB)

Sim, Bong Shick; Oh, In Suk; Cha, Kyung Ho; Lee, Hyun Chul; Park, Geun Ok; Cheon, Se Woo; Suh, Sang Moon

1997-07-01

New human factors issues, such as evaluation of information navigation, the consideration of operator characteristics, and operator performance assessment, related to the HMI design based on VDUs are being risen. Thus, in order to solve these human factors issues, this project aims to establish the experimental technologies including the techniques for experimental design, experimental measurement, data collection and analysis, and to develop ITF (Integrated Test Facility) suitable for the experiment of HMI design evaluation. For the establish of the experimental data analysis and evaluation methodologies, we developed as the following: (1) a paradigm for human factors experimentation including experimental designs, procedures, and data analysis. (2) the methods for the assessment of operator`s mental workload (3) DAEXESS (data analysis and experiment evaluation supporting system). Also, we have established a experiment execution technologies through the preliminary experiments, such as the suitability evaluation of information display on a LSDP, the evaluation of information display on a LSDP, the evaluation of computerized operation procedure and an experiment of advanced alarm system (ADIOS). Finally, we developed the ITF including human machine simulator, telemetry system, an eye tracking system, an audio/video data measurement system, and three dimensional micro behaviour analysis system. (author). 81 refs., 68 tabs., 73 figs.

Effects of experimental muscle pain on shoulder-abduction force steadiness and muscle activity in healthy subjects

DEFF Research Database (Denmark)

Bandholm, Thomas Quaade; Rasmussen, Lars; Aagaard, Per

2007-01-01

We previously demonstrated that the steadiness of shoulder abduction is reduced in patients with subacromial impingement syndrome (SIS), which might be related to shoulder pain associated with the SIS. The aim of the present study was to examine the acute effects of experimental shoulder muscle p...

Internal and external factors affecting the development of neuropathic pain in rodents. Is it all about pain?

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Vissers, K; De Jongh, R; Hoffmann, V; Heylen, R; Crul, B; Meert, T

2003-12-01

It is important to know the factors that will influence animal models of neuropathic pain. A good reproducibility and predictability in different strains of animals for a given test increases the clinical relevance and possible targeting. An obligatory requirement for enabling comparisons of results of different origin is a meticulous definition of the specific sensitivities of a model for neuropathic pain and a description of the test conditions. Factors influencing neuropathic pain behavior can be subdivided in external and internal factors. The most important external factors are; timing of the measurement of pain after induction of neuropathy, circadian rhythms, seasonal influences, air humidity, influence of order of testing, diet, social variables, housing and manipulation, cage density, sexual activity, external stress factors, and influences of the experimenter. The internal factors are related to the type of animal, its genetic background, gender, age, and the presence of homeostatic adaptation mechanisms to specific situations or stress. In practice, the behavioral presentations to pain depend on the combination of genetic and environmental factors such as accepted social behavior. It also depends on the use of genetic manipulation of the animals such as in transgenic animals. These make the interpretation of data even more difficult. Differences of pain behavior between in- and outbred animals will be better understood by using modern analysis techniques. Substrains of animals with a high likelihood for developing neuropathic pain make the unraveling of specific pathophysiological mechanisms possible. Concerning the effect of stress on pain, it is important to differentiate between external and internal stress such as social coping behavior. The individual dealing with this stress is species sensitive, and depends on the genotype and the social learning. In the future, histo-immunological and genetic analysis will highlight similarities of the different

Remote Effects of Electromagnetic Millimeter Waves on Experimentally Induced Cold Pain: A Double-Blinded Crossover Investigation in Healthy Volunteers.

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Partyla, Tomasz; Hacker, Henriette; Edinger, Hardy; Leutzow, Bianca; Lange, Joern; Usichenko, Taras

2017-03-01

The hypoalgesic effect of electromagnetic millimeter waves (MW) is well studied in animal model; however, the results of human research are controversial. The aim of this study was to evaluate the effects of various frequency ranges of MW on hypoalgesia using the cold pressor test (CPT). Experimental pain was induced using standardized CPT protocols in 20 healthy male volunteers. The skin of the lower part of sternum was exposed to MW with a frequency of 42.25 GHz (active generator); MW within 50-75 GHz frequency range (noise generator); or an inactive MW device (placebo generator) in a random crossover double-blinded manner. Pain threshold, measured using the CPT, was the primary outcome. Other CPT parameters, heart rate, blood pressure, incidence of subjective sensations (paresthesia) during exposure, as well as quality of volunteers' blinding were also recorded. The end points of the condition with exposure to 42.25 GHz, were compared with baseline; exposure to noise 50-75 GHz; and placebo generators. Pain threshold increased during exposure to the 42.25 GHz generator when compared with baseline: median difference (MD), 1.97 seconds (95% confidence interval [CI], 0.35-3.73) and noise generator: MD, 1.27 seconds (95% CI, 0.05-2.33) but not compared with the placebo generator. Time to onset of cold and increasing pain sensations as well as diastolic blood pressure increased under the exposure to the 42.25 GHz generator when compared with baseline and noise generator. Other outcome measures were comparable among the study conditions. We were able to partially confirm the previously suggested hypoalgesic effects of low-intensity electromagnetic MW. However, the effect was indistinguishable from the placebo condition in our investigation.

Effects of a Pain Catastrophizing Induction on Sensory Testing in Women with Chronic Low Back Pain: A Pilot Study

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Chloe J. Taub

2017-01-01

Full Text Available Pain catastrophizing, a pattern of negative cognitive-emotional responses to actual or anticipated pain, maintains chronic pain and undermines response to treatments. Currently, precisely how pain catastrophizing influences pain processing is not well understood. In experimental settings, pain catastrophizing has been associated with amplified pain processing. This study sought to clarify pain processing mechanisms via experimental induction of pain catastrophizing. Forty women with chronic low back pain were assigned in blocks to an experimental condition, either a psychologist-led 10-minute pain catastrophizing induction or a control (10-minute rest period. All participants underwent a baseline round of several quantitative sensory testing (QST tasks, followed by the pain catastrophizing induction or the rest period, and then a second round of the same QST tasks. The catastrophizing induction appeared to increase state pain catastrophizing levels. Changes in QST pain were detected for two of the QST tasks administered, weighted pin pain and mechanical allodynia. Although there is a need to replicate our preliminary results with a larger sample, study findings suggest a potential relationship between induced pain catastrophizing and central sensitization of pain. Clarification of the mechanisms through which catastrophizing affects pain modulatory systems may yield useful clinical insights into the treatment of chronic pain.

Effects of a Pain Catastrophizing Induction on Sensory Testing in Women with Chronic Low Back Pain: A Pilot Study.

Science.gov (United States)

Taub, Chloe J; Sturgeon, John A; Johnson, Kevin A; Mackey, Sean C; Darnall, Beth D

2017-01-01

Pain catastrophizing, a pattern of negative cognitive-emotional responses to actual or anticipated pain, maintains chronic pain and undermines response to treatments. Currently, precisely how pain catastrophizing influences pain processing is not well understood. In experimental settings, pain catastrophizing has been associated with amplified pain processing. This study sought to clarify pain processing mechanisms via experimental induction of pain catastrophizing. Forty women with chronic low back pain were assigned in blocks to an experimental condition, either a psychologist-led 10-minute pain catastrophizing induction or a control (10-minute rest period). All participants underwent a baseline round of several quantitative sensory testing (QST) tasks, followed by the pain catastrophizing induction or the rest period, and then a second round of the same QST tasks. The catastrophizing induction appeared to increase state pain catastrophizing levels. Changes in QST pain were detected for two of the QST tasks administered, weighted pin pain and mechanical allodynia. Although there is a need to replicate our preliminary results with a larger sample, study findings suggest a potential relationship between induced pain catastrophizing and central sensitization of pain. Clarification of the mechanisms through which catastrophizing affects pain modulatory systems may yield useful clinical insights into the treatment of chronic pain.

Effects of a Pain Catastrophizing Induction on Sensory Testing in Women with Chronic Low Back Pain: A Pilot Study

Science.gov (United States)

Sturgeon, John A.; Johnson, Kevin A.

2017-01-01

Pain catastrophizing, a pattern of negative cognitive-emotional responses to actual or anticipated pain, maintains chronic pain and undermines response to treatments. Currently, precisely how pain catastrophizing influences pain processing is not well understood. In experimental settings, pain catastrophizing has been associated with amplified pain processing. This study sought to clarify pain processing mechanisms via experimental induction of pain catastrophizing. Forty women with chronic low back pain were assigned in blocks to an experimental condition, either a psychologist-led 10-minute pain catastrophizing induction or a control (10-minute rest period). All participants underwent a baseline round of several quantitative sensory testing (QST) tasks, followed by the pain catastrophizing induction or the rest period, and then a second round of the same QST tasks. The catastrophizing induction appeared to increase state pain catastrophizing levels. Changes in QST pain were detected for two of the QST tasks administered, weighted pin pain and mechanical allodynia. Although there is a need to replicate our preliminary results with a larger sample, study findings suggest a potential relationship between induced pain catastrophizing and central sensitization of pain. Clarification of the mechanisms through which catastrophizing affects pain modulatory systems may yield useful clinical insights into the treatment of chronic pain. PMID:28348505

Neonatal Pain in Very Preterm Infants: Long-Term Effects on Brain, Neurodevelopment and Pain Reactivity

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Ruth Eckstein Grunau

2013-10-01

Full Text Available Effects of early life psychosocial adversity have received a great deal of attention, such as maternal separation in experimental animal models and abuse/neglect in young humans. More recently, long-term effects of the physical stress of repetitive procedural pain have begun to be addressed in infants hospitalized in neonatal intensive care. Preterm infants are more sensitive to pain and stress, which cannot be distinguished in neonates. The focus of this review is clinical studies of long-term effects of repeated procedural pain-related stress in the neonatal intensive care unit (NICU in relation to brain development, neurodevelopment, programming of stress systems, and later pain sensitivity in infants born very preterm (24–32 weeks’ gestational age. Neonatal pain exposure has been quantified as the number of invasive and/or skin-breaking procedures during hospitalization in the NICU. Emerging studies provide convincing clinical evidence for an adverse impact of neonatal pain/stress in infants at a time of physiological immaturity, rapidly developing brain microstructure and networks, as well as programming of the hypothalamic-pituitary-adrenal axis. Currently it appears that early pain/stress may influence the developing brain and thereby neurodevelopment and stress-sensitive behaviors, particularly in the most immature neonates. However, there is no evidence for greater prevalence of pain syndromes compared to children and adults born healthy at full term. In addressing associations between pain/stress and outcomes, careful consideration of confounding clinical factors related to prematurity is essential. The need for pain management for humanitarian care is widely advocated. Non-pharmacological interventions to help parents reduce their infant’s stress may be brain-protective.

Operant conditioning of facial displays of pain.

Science.gov (United States)

Kunz, Miriam; Rainville, Pierre; Lautenbacher, Stefan

2011-06-01

The operant model of chronic pain posits that nonverbal pain behavior, such as facial expressions, is sensitive to reinforcement, but experimental evidence supporting this assumption is sparse. The aim of the present study was to investigate in a healthy population a) whether facial pain behavior can indeed be operantly conditioned using a discriminative reinforcement schedule to increase and decrease facial pain behavior and b) to what extent these changes affect pain experience indexed by self-ratings. In the experimental group (n = 29), the participants were reinforced every time that they showed pain-indicative facial behavior (up-conditioning) or a neutral expression (down-conditioning) in response to painful heat stimulation. Once facial pain behavior was successfully up- or down-conditioned, respectively (which occurred in 72% of participants), facial pain displays and self-report ratings were assessed. In addition, a control group (n = 11) was used that was yoked to the reinforcement plans of the experimental group. During the conditioning phases, reinforcement led to significant changes in facial pain behavior in the majority of the experimental group (p .136). Fine-grained analyses of facial muscle movements revealed a similar picture. Furthermore, the decline in facial pain displays (as observed during down-conditioning) strongly predicted changes in pain ratings (R(2) = 0.329). These results suggest that a) facial pain displays are sensitive to reinforcement and b) that changes in facial pain displays can affect self-report ratings.

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

DEFF Research Database (Denmark)

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

2000-01-01

-infusions interval of 3 min. Infusions of isotonic saline (NaCl, 0.9%) were given as control. Pain intensity was continuously scored on a visual analogue scale (VAS), and subjects drew the distribution of the pain areas on an anatomical map. Pressure pain thresholds (PPTs) were assessed with an electronic algometer....... In addition, PPTs were significantly decreased (Peffect of bradykinin in producing experimental muscle pain and muscle hyperalgesia to mechanical stimuli. The combination of serotonin and bradykinin can produce muscle...

Increased circulating rather than spinal cytokines accompany chronic pain behaviors in experimental bone cancer and arthritis

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Line Pourtau

2014-12-01

Full Text Available Aim: Peripheral cytokines contribute to arthritis and bone cancer pain through sensory nerve actions. However, increased spinal cytokine and glial filament expression, coined neuroinflammation, has also been proposed to play a part in chronic pain. Therefore, spinal cord, dorsal root ganglia and circulating cytokines were compared in murine arthritis and bone cancer models in relationship to behavioral signs of pain. Methods: Exploratory behaviors were studied after intra-articular complete Freund's adjuvant or bone intramedullary sarcoma cell injection. Nervous tissue and blood cytokine expression were determined by real-time polymerase chain reaction (PCR and multiplex immunoassays, respectively. Results: PCR analysis did not reveal any hallmark of spinal neuroinflammation in spontaneously-behaving mice with cartilage or bone lesions. However, imposed paw stimulation during joint inflammation increased spinal interleukin-1β (IL-1β expression. Spontaneous paw guarding during rearing was displayed by animals with joint inflammation and bone destruction and was accompanied by increased circulating IL-6 and monocyte chemoattractant protein-1, respectively. In addition, dorsal root ganglia were found to constitutively express receptors for this chemotactic cytokine. Conclusion: Our findings indicate that spinal neuroinflammation is not a necessary condition for chronic pain and suggest that circulating cytokine action in dorsal root ganglia may contribute to experimental joint inflammation and bone cancer pain.

Reduced thoracolumbar fascia shear strain in human chronic low back pain

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Konofagou Elisa E

2011-09-01

Full Text Available Abstract Background The role played by the thoracolumbar fascia in chronic low back pain (LBP is poorly understood. The thoracolumbar fascia is composed of dense connective tissue layers separated by layers of loose connective tissue that normally allow the dense layers to glide past one another during trunk motion. The goal of this study was to quantify shear plane motion within the thoracolumbar fascia using ultrasound elasticity imaging in human subjects with and without chronic low back pain (LBP. Methods We tested 121 human subjects, 50 without LBP and 71 with LBP of greater than 12 months duration. In each subject, an ultrasound cine-recording was acquired on the right and left sides of the back during passive trunk flexion using a motorized articulated table with the hinge point of the table at L4-5 and the ultrasound probe located longitudinally 2 cm lateral to the midline at the level of the L2-3 interspace. Tissue displacement within the thoracolumbar fascia was calculated using cross correlation techniques and shear strain was derived from this displacement data. Additional measures included standard range of motion and physical performance evaluations as well as ultrasound measurement of perimuscular connective tissue thickness and echogenicity. Results Thoracolumbar fascia shear strain was reduced in the LBP group compared with the No-LBP group (56.4% ± 3.1% vs. 70.2% ± 3.6% respectively, p Conclusion Thoracolumbar fascia shear strain was ~20% lower in human subjects with chronic low back pain. This reduction of shear plane motion may be due to abnormal trunk movement patterns and/or intrinsic connective tissue pathology. There appears to be some sex-related differences in thoracolumbar fascia shear strain that may also play a role in altered connective tissue function.

Preventing Chronic Pain: A Human Systems Approach-Results From a Massive Open Online Course.

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Fricton, James; Anderson, Kathleen; Clavel, Alfred; Fricton, Regina; Hathaway, Kate; Kang, Wenjun; Jaeger, Bernadette; Maixner, William; Pesut, Daniel; Russell, Jon; Weisberg, Mark B; Whitebird, Robin

2015-09-01

Chronic pain conditions are the top reason patients seek care, the most common reason for disability and addiction, and the biggest driver of healthcare costs; their treatment costs more than cancer, heart disease, dementia, and diabetes care. The personal impact in terms of suffering, disability, depression, suicide, and other problems is incalculable. There has been much effort to prevent many medical and dental conditions, but little effort has been directed toward preventing chronic pain. To address this deficit, a massive open online course (MOOC) was developed for students and healthcare professionals. "Preventing Chronic Pain: A Human Systems Approach" was offered by the University of Minnesota through the online platform Coursera. The first offering of this free open course was in the spring of 2014 and had 23 650 participants; 53% were patients or consumers interested in pain. This article describes the course concepts in preventing chronic pain, the analytic data from course participants, and postcourse evaluation forms.

Pain sensation and nociceptive reflex excitability in surgical patients and human volunteers

DEFF Research Database (Denmark)

Dahl, J B; Erichsen, C J; Fuglsang-Frederiksen, A

1992-01-01

Pain threshold, nociceptive flexion reflex (NFR) threshold and responses to suprathreshold stimulation were investigated in 15 female patients (mean age 32 yr (range 22-48 yr)) before and 68 (range 48-96) h after gynaecological laparotomy. Control measurements were performed in 17 healthy human v...

Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy

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Liu Xian-Guo

2011-03-01

Full Text Available Abstract Long-term potentiation (LTP in nociceptive spinal pathways shares several features with hyperalgesia and has been proposed to be a cellular mechanism of pain amplification in acute and chronic pain states. Spinal LTP is typically induced by noxious input and has therefore been hypothesized to contribute to acute postoperative pain and to forms of chronic pain that develop from an initial painful event, peripheral inflammation or neuropathy. Under this assumption, preventing LTP induction may help to prevent the development of exaggerated postoperative pain and reversing established LTP may help to treat patients who have an LTP component to their chronic pain. Spinal LTP is also induced by abrupt opioid withdrawal, making it a possible mechanism of some forms of opioid-induced hyperalgesia. Here, we give an overview of targets for preventing LTP induction and modifying established LTP as identified in animal studies. We discuss which of the various symptoms of human experimental and clinical pain may be manifestations of spinal LTP, review the pharmacology of these possible human LTP manifestations and compare it to the pharmacology of spinal LTP in rodents.

Concept priming and pain: an experimental approach to understanding gender roles in sex-related pain differences.

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Fowler, Stephanie L; Rasinski, Heather M; Geers, Andrew L; Helfer, Suzanne G; France, Christopher R

2011-04-01

Prior research has found that sex differences in pain are partially due to individual variations in gender roles. In a laboratory study, we tested the hypothesis that the presence of covert gender role cues can also moderate the extent to which women and men experience pain. Specifically, we varied gender role cues by asking male and female participants to write about instances in which they behaved in a stereotypically feminine, masculine, or neutral manner. Pain and cardiovascular reactivity to the cold pressor task were then assessed. Results revealed that, when primed with femininity, men reported less pain and anxiety from the cold pressor task than women. However, no differences existed between the sexes in the masculine or neutral prime conditions. The results indicate that covert gender cues can alter pain reports. Further, at least in some situations, feminine role cues may be more influential on pain reports than masculine role cues.

Pain adaptability in individuals with chronic musculoskeletal pain is not associated with conditioned pain modulation

DEFF Research Database (Denmark)

Wan, Dawn Wong Lit; Arendt-Nielsen, Lars; Wang, Kelun

2018-01-01

(MSK). CPTs at 2°C and 7°C were used to assess the status of pain adaptability in participants with either chronic non-specific low back pain or knee osteoarthritis. The participants' potency of conditioned pain modulation (CPM) and local inhibition were measured. The strengths of pain adaptability...... at both CPTs were highly correlated. PA and PNA did not differ in their demographics, pain thresholds from thermal and pressure stimuli, or potency of local inhibition or CPM. PA reached their maximum pain faster than PNA (t41=-2.76, p... days whereas PNA did not (F (6,246) = 3.01, p = 0.01). The dichotomy of pain adaptability exists in MSK patients. Consistent with the healthy human study, the strength of pain adaptability and potency of CPM are not related. Pain adaptability could be another form of endogenous pain inhibition which...

Temporal characteristics of cold pain perception.

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Frölich, Michael A; Bolding, Mark S; Cutter, Gary R; Ness, Timothy J; Zhang, Kui

2010-08-09

Adaptation to a sustained stimulus is an important phenomenon in psychophysical experiments. When studying the response to an experimental task, the investigator has to account for the change in perceived stimulus intensity with repeated stimulus application and, if the stimulus is sustained, for the change in intensity during the presentation. An example of a sustained stimulus is the cold pressor task (CPT). The task has been used both as an experimental pain task and to study cardiovascular physiology. In functional imaging research, the CPT has been used to evaluate cognitive processing of a noxious stimulus. Investigators typically model the stimulus in a block design as a categorical (on-off) stimulus and do not account for a temporal change in stimulus perception. If the perceived stimulus changes over time, the results may be misleading. Therefore, we characterized the time course of cold pain in human volunteers and developed a model of the temporal characteristics of perceived cold pain. Fifteen healthy participants underwent cold pain testing by immersing their right foot into a container filled with ice water (2 degrees C) for 30s alternating with a 30s immersion into a container filled with tepid water 32 degrees C (control). Participants rated the pain intensity using an electronic slide algometer. Using a mixed general linear model (effectively a polynomial regression model), we determined that pain ratings follow a crescendo-decrescendo pattern that can be described well using a quadratic model. We conclude that the time course of quantitative perception differs fundamentally from the time course of stimulus presentation. This may be important when looking for the physiological correlates of perception as opposed to the presence of a stimulus per se. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Relevance of physical fitness levels and exercise-related beliefs for self-reported and experimental pain in fibromyalgia: an explorative study.

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de Bruijn, Saskia T; van Wijck, Albert J M; Geenen, Rinie; Snijders, Tom J; van der Meulen, Wout J T M; Jacobs, Johannes W G; Veldhuijzen, Dieuwke Swaantje

2011-09-01

It has been suggested that low physical fitness is a contributor to pain in fibromyalgia and that exercise-related beliefs play a role in the persistence of this association. Yet the association between physical fitness and pain is hardly explored in detail. The aim of this exploratory study in patients with fibromyalgia was to investigate the association of physical fitness levels with self-reported and experimental pain as well as with pain catastrophizing and activity-avoidance beliefs. Physical fitness of 18 patients with fibromyalgia was examined using maximal ergocycling and the 6-minute walking test (6MWT). Pain intensity was assessed using self-report scales and quantitative sensory testing. A reduced walking distance on the 6MWT was correlated with more severe self-reported pain on the Fibromyalgia Impact Questionnaire (r = -0.52, P physically fit and experienced more severe pain. The results demonstrate some associations between physical fitness and pain in fibromyalgia and point to the importance of activity avoidance. Although the causal directionality of the associations needs substantiation in clinical research, the findings support the notion that low fitness and activity-avoidance beliefs should be targeted while treating pain in fibromyalgia.

Reliability of four experimental mechanical pain tests in children

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Soee AL

2013-02-01

Full Text Available Ann-Britt L Soee,1 Lise L Thomsen,2 Birte Tornoe,1,3 Liselotte Skov11Department of Pediatrics, Children’s Headache Clinic, Copenhagen University Hospital Herlev, Copenhagen, Denmark; 2Department of Neuropediatrics, Juliane Marie Centre, Copenhagen University Hospital Rigshospitalet, København Ø, Denmark; 3Department of Physiotherapy, Medical Department O, Copenhagen University Hospital Herlev, Herlev, DenmarkPurpose: In order to study pain in children, it is necessary to determine whether pain measurement tools used in adults are reliable measurements in children. The aim of this study was to explore the intrasession reliability of pressure pain thresholds (PPT in healthy children. Furthermore, the aim was also to study the intersession reliability of the following four tests: (1 Total Tenderness Score; (2 PPT; (3 Visual Analog Scale score at suprapressure pain threshold; and (4 area under the curve (stimulus–response functions for pressure versus pain.Participants and methods: Twenty-five healthy school children, 8–14 years of age, participated. Test 2, PPT, was repeated three times at 2 minute intervals on the same day to estimate PPT intrasession reliability using Cronbach’s alpha. Tests 1–4 were repeated after median 21 (interquartile range 10.5–22 days, and Pearson’s correlation coefficient was used to describe the intersession reliability.Results: The PPT test was precise and reliable (Cronbach’s alpha ≥ 0.92. All tests showed a good to excellent correlation between days (intersessions r = 0.66–0.81. There were no indications of significant systematic differences found in any of the four tests between days.Conclusion: All tests seemed to be reliable measurements in pain evaluation in healthy children aged 8–14 years. Given the small sample size, this conclusion needs to be confirmed in future studies.Keywords: repeatability, intraindividual reliability, pressure pain threshold, pain measurement, algometer

Tanezumab: a selective humanized mAb for chronic lower back pain

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Webb MP

2018-02-01

Full Text Available Michael P Webb,1 Erik M Helander,2 Bethany L Menard,2 Richard D Urman,3 Alan D Kaye2 1Department of Anesthesiology, North Shore Hospital, Auckland, New Zealand; 2Department of Anesthesiology, LSU School of Medicine, New Orleans, LA, USA; 3Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Abstract: Chronic lower back pain is a significant disease that affects nearly 20% of the worldwide population. Along with hindering patients’ quality of life, chronic lower back pain is considered to be the second most common cause of disability among Americans. Treating chronic lower back pain is often a challenge for providers, especially in light of our current opioid epidemic. With this epidemic and an increased aging population, there is an imminent need for development of new pharmacologic therapeutic options, which are not only effective but also pose minimal adverse effects to the patient. With these considerations, a novel therapeutic agent called tanezumab has been developed and studied. Tanezumab is a humanized monoclonal immunoglobulin G2 antibody that works by inhibiting the binding of NGF to its receptors. NGF is involved in the function of sensory neurons and fibers involved in nociceptive transduction. It is commonly seen in excess in inflammatory joint conditions and in chronic pain patients. Nociceptors are dependent on NGF for growth and ongoing function. The inhibition of NGF binding to its receptors is a mechanism by which pain pathways can be interrupted. In this article, a number of recent randomized controlled trials are examined relating to the efficacy and safety of tanezumab in the treatment of chronic lower back pain. Although tanezumab was shown to be an effective pain modulator in major trials, several adverse effects were seen among different doses of the medication, one of which led to a clinical hold placed by the US Food and Drug

Acute pain induces insulin resistance in humans

DEFF Research Database (Denmark)

Greisen, J.; Juhl, C.B.; Grøfte, Thorbjørn

2001-01-01

Background: Painful trauma results in a disturbed metabolic state with impaired insulin sensitivity, which is related to the magnitude of the trauma. The authors explored whether pain per se influences hepatic and extrahepatic actions of insulin. Methods: Ten healthy male volunteers underwent two...... randomly sequenced hyperinsulinemic–euglycemic (insulin infusion rate, 0.6 mU · kg-1 · min-1 for 180 min) clamp studies 4 weeks apart. Self-controlled painful electrical stimulation was applied to the abdominal skin for 30 min, to a pain intensity of 8 on a visual analog scale of 0–10, just before...... the clamp procedure (study P). In the other study, no pain was inflicted (study C). Results: Pain reduced whole-body insulin-stimulated glucose uptake from 6.37 ± 1.87 mg · kg-1 · min-1 (mean ± SD) in study C to 4.97 ± 1.38 mg · kg-1 · min-1 in study P (P

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

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

2014-06-01

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

Combined glutamate and glutamine levels in pain-processing brain regions are associated with individual pain sensitivity.

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Zunhammer, Matthias; Schweizer, Lauren M; Witte, Vanessa; Harris, Richard E; Bingel, Ulrike; Schmidt-Wilcke, Tobias

2016-10-01

The relationship between glutamate and γ-aminobutyric acid (GABA) levels in the living human brain and pain sensitivity is unknown. Combined glutamine/glutamate (Glx), as well as GABA levels can be measured in vivo with single-voxel proton magnetic resonance spectroscopy. In this cross-sectional study, we aimed at determining whether Glx and/or GABA levels in pain-related brain regions are associated with individual differences in pain sensitivity. Experimental heat, cold, and mechanical pain thresholds were obtained from 39 healthy, drug-free individuals (25 men) according to the quantitative sensory testing protocol and summarized into 1 composite measure of pain sensitivity. The Glx levels were measured using point-resolved spectroscopy at 3 T, within a network of pain-associated brain regions comprising the insula, the anterior cingulate cortex, the mid-cingulate cortex, the dorsolateral prefrontal cortex, and the thalamus. GABA levels were measured using GABA-edited spectroscopy (Mescher-Garwood point-resolved spectroscopy) within the insula, the anterior cingulate cortex, and the mid-cingulate cortex. Glx and/or GABA levels correlated positively across all brain regions. Gender, weekly alcohol consumption, and depressive symptoms were significantly associated with Glx and/or GABA levels. A linear regression analysis including all these factors indicated that Glx levels pooled across pain-related brain regions were positively associated with pain sensitivity, whereas no appreciable relationship with GABA was found. In sum, we show that the levels of the excitatory neurotransmitter glutamate and its precursor glutamine across pain-related brain regions are positively correlated with individual pain sensitivity. Future studies will have to determine whether our findings also apply to clinical populations.

Old and in pain: Enduring and situational effects of cultural aging stereotypes on older people's pain experiences.

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Bernardes, S F; Marques, S; Matos, M

2015-08-01

This study aimed to investigate the interplay between enduring and situational aging stereotype (AS) effects in older adults' self-reports of clinical and experimentally induced pain. We expected that, as compared with the situational activation of positive AS or a neutral condition, the activation of negative AS would lead to more severe self-reports of clinical pain (H1, hypothesis 1), higher cold pressor task (CPT) pain threshold (H2) and lower CPT pain tolerance (H3), especially among older adults who more strongly endorsed AS. This was a prospective study across two moments in time. At time 1 (T1), 52 older adults (Mage  = 74.7; 51.9% women) filled out measures of cultural AS endorsement, clinical pain severity and interference. Three months afterwards (T2), some of these participants collaborated in an experimental study on the effects of AS activation on reported clinical pain (n = 40) and experimentally induced (using CPT) pain threshold and tolerance (n = 35). Our results supported H2, i.e., as compared with the activation of positive AS or a neutral condition, when negative AS were activated older adults showed higher CPT pain thresholds, but this effect was more salient among those who more strongly endorsed AS at T1. This study stresses the influence of cultural AS in older adults' pain experiences showing that the situational activation of negative AS greatly increases experimentally induced pain thresholds of elders who more strongly endorse those stereotypes. It also highlights the relevance of interventions at the level of the physical and/or social environments surrounding elders in pain. © 2014 European Pain Federation - EFIC®

Extensibility and stiffness of the hamstrings in patients with nonspecific low back pain

NARCIS (Netherlands)

Halbertsma, JPK; Goeken, LNH; Hof, AL; Groothoff, JW; Eisma, WH; Göeken, L.N.H.

Objective: To investigate the extensibility and stiffness of the hamstrings in patients with nonspecific low back pain (LBP). Design: An experimental design. Setting: A university laboratory for human movement analysis in a department of rehabilitation medicine. Participants: Forty subjects, a

Tetrodotoxin (TTX as a Therapeutic Agent for Pain

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Cruz Miguel Cendán

2012-01-01

Full Text Available Tetrodotoxin (TTX is a potent neurotoxin that blocks voltage-gated sodium channels (VGSCs. VGSCs play a critical role in neuronal function under both physiological and pathological conditions. TTX has been extensively used to functionally characterize VGSCs, which can be classified as TTX-sensitive or TTX-resistant channels according to their sensitivity to this toxin. Alterations in the expression and/or function of some specific TTX-sensitive VGSCs have been implicated in a number of chronic pain conditions. The administration of TTX at doses below those that interfere with the generation and conduction of action potentials in normal (non-injured nerves has been used in humans and experimental animals under different pain conditions. These data indicate a role for TTX as a potential therapeutic agent for pain. This review focuses on the preclinical and clinical evidence supporting a potential analgesic role for TTX. In addition, the contribution of specific TTX-sensitive VGSCs to pain is reviewed.

Experimental orofacial pain and sensory deprivation lead to perceptual distortion of the face in healthy volunteers.

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Dagsdóttir, Lilja Kristín; Skyt, Ina; Vase, Lene; Baad-Hansen, Lene; Castrillon, Eduardo; Svensson, Peter

2015-09-01

Patients suffering from persistent orofacial pain may sporadically report that the painful area feels "swollen" or "differently," a phenomenon that may be conceptualized as a perceptual distortion because there are no clinical signs of swelling present. Our aim was to investigate whether standardized experimental pain and sensory deprivation of specific orofacial test sites would lead to changes in the size perception of these face areas. Twenty-four healthy participants received either 0.2 mL hypertonic saline (HS) or local anesthetics (LA) into six regions (buccal, mental, lingual, masseter muscle, infraorbital and auriculotemporal nerve regions). Participants estimated the perceived size changes in percentage (0 % = no change, -100 % = half the size or +100 % = double the size), and somatosensory function was checked with tactile stimuli. The pain intensity was rated on a 0-10 Verbal Numerical Rating Scale (VNRS), and sets of psychological questionnaires were completed. HS and LA were associated with significant self-reported perceptual distortions as indicated by consistent increases in perceived size of the adjacent face areas (P ≤ 0.050). Perceptual distortion was most pronounced in the buccal region, and the smallest increase was observed in the auriculotemporal region. HS was associated with moderate levels of pain VNRS = 7.3 ± 0.6. Weak correlations were found between HS-evoked perceptual distortion and level of dissociation in two regions (P pain and transient sensory deprivation evoked perceptual distortions in all face regions and overall demonstrated the importance of afferent inputs for the perception of the face. We propose that perceptual distortion may be an important phenomenon to consider in persistent orofacial pain conditions.

Ansiedade experimental humana Human experimental anxiety

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Frederico Guilherme Graeff

2007-01-01

Full Text Available CONTEXTO: A ansiedade experimental no ser humano constitui-se em ponte entre os modelos animais e os ensaios clínicos. OBJETIVO: Este artigo focaliza métodos químicos e psicológicos utilizados para provocar ansiedade experimental em seres humanos. MÉTODOS: Realizou-se revisão seletiva da literatura. RESULTADOS: Os desafios farmacológicos têm sido usados principalmente para induzir ataques de pânico em pacientes com transtorno de pânico, os quais são mais sensíveis a eles que indivíduos normais ou pacientes portadores de outros transtornos psiquiátricos. Uma das mais importantes contribuições deste método é a de ter mostrado que os agentes panicogênicos mais seletivos, como o lactato ou a inalação de CO2, não ativam o eixo hormonal do estresse. Entre os métodos psicológicos, destacam-se o condicionamento de respostas elétricas da condutância da pele, cujo perfil farmacológico se aproxima daquele do transtorno de ansiedade generalizada, e o teste da simulação do falar em público, cuja farmacologia é semelhante à do transtorno de pânico. CONCLUSÕES: Tais resultados salientam a diferença entre a neurobiologia da ansiedade e a do pânico.BACKGROUND: Human experimental anxiety methods bridge the gap between animal models and clinical assays. OBJECTIVE: This article is focused on chemical and psychological procedures used to generate experimental anxiety in human beings. METHODS: A selective review of the literature has been carried out. RESULTS: Pharmacological challenges have been mainly used to induce panic attacks in panic disorder patients, who are more susceptible than normal individuals or patients with other psychiatric disorders. One of the most important contributions of this method is to have shown that the most selective panicogenic agents, such as lactate or CO2 inhalation, do not activate the hormonal stress axis. Among the psychological methods stand the conditioning of the electrical skin conductance

Sacroiliac joint pain: Prospective, randomised, experimental and comparative study of thermal radiofrequency with sacroiliac joint block.

Science.gov (United States)

Cánovas Martínez, L; Orduña Valls, J; Paramés Mosquera, E; Lamelas Rodríguez, L; Rojas Gil, S; Domínguez García, M

2016-05-01

To compare the analgesic effects between the blockade and bipolar thermal radiofrequency in the treatment of sacroiliac joint pain. Prospective, randomised and experimental study conducted on 60 patients selected in the two hospitals over a period of nine months, who had intense sacroiliac joint pain (Visual Analogue Scale [VAS]>6) that lasted more than 3 months. Patients were randomised into three groups (n=20): Group A (two intra-articular sacroiliac injections of local anaesthetic/corticosteroid guided by ultrasound in 7 days). Group B: conventional bipolar radiofrequency "palisade". Target points were the lateral branch nerves of S1, S2, and S3, distance needles 1cm. Group C: modified bipolar radiofrequency "palisade" (needle distance >1cm). Patients were evaluated at one month, three months, and one year. Demographic data, VAS reduction, and side effects of the techniques were assessed. One month after the treatment, pain reduction was >50% in the three groups PDolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Sixty-eight years of experimental occlusal interference studies: what have we learned?

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Clark, G T; Tsukiyama, Y; Baba, K; Watanabe, T

1999-12-01

Understanding is needed regarding the effect that occlusal interferences have on the teeth, periodontium, and especially on jaw function. This article summarizes research in which experimental occlusal interferences have been placed on the teeth of animals and human volunteers. Data from 18 human and 10 animals studies were reviewed. Experimental occlusal interferences were grouped into those that alter intercuspal position and those contacting on lateral jaw movement only. The outcome of these interferences were analyzed according to their local pulpal-periodontal, jaw function, or bruxism effects. Experimental occlusal interferences in maximum intercuspation had a deleterious effect on periodontal and pulpal tissues of the affected tooth; sometimes this produces a disruption of smooth jaw function and occasionally jaw muscle pain and clicking. Experimental occlusal interferences that contact only in a lateral jaw movement are infrequently harmful to jaw function. Furthermore, no reliable evidence demonstrates that occlusal interferences can cause nocturnal bruxism, or stop it. Transient local tooth pain, loosening of the tooth, a slight change in postural muscle tension levels, chewing stroke patterns, and sometimes a clicking joint can be induced by an experimental occlusal interference. Because such findings are present in relatively asymptomatic patients, these data do not prove that occlusal interferences are causally related to a chronic jaw muscle pain or temporomandibular joint dysfunction problems.

VICTORIA Class Submarine Human-in-the-Loop Experimentation Plan

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2014-06-01

1472G. VICTORIA Class Submarine Human-in-the-Loop Experimentation Plan and Preliminary Results © Her Majesty the Queen in Right of...19 th International Command and Control Research and Technology Symposium Title: VICTORIA Class Submarine Human-in-the-Loop...TYPE 3. DATES COVERED 00-00-2014 to 00-00-2014 4. TITLE AND SUBTITLE VICTORIA Class Submarine Human-in-the-Loop Experimentation Plan 5a. CONTRACT

A theory-based educational intervention targeting nurses' attitudes and knowledge concerning cancer-related pain management: A study protocol of a quasi-experimental design

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Gustafsson Markus

2011-09-01

Full Text Available Abstract Background Pain is one of the most frequent problems among patients diagnosed with cancer. Despite the availability of effective pharmacological treatments, this group of patients often receives less than optimal treatment. Research into nurses' pain management highlights certain factors, such as lack of knowledge and attitudes and inadequate procedures for systematic pain assessment, as common barriers to effective pain management. However, educational interventions targeting nurses' pain management have shown promise. As cancer-related pain is also known to have a negative effect on vital aspects of the patient's life, as well as being commonly associated with problems such as sleep, fatigue, depression and anxiety, further development of knowledge within this area is warranted. Methods/design A quasi-experimental study design will be used to investigate whether the implementation of guidelines for systematic daily pain assessments following a theory-based educational intervention will result in an improvement in knowledge and attitude among nurses. A further aim is to investigate whether the intervention that targets nurses' behaviour will improve hospital patients' perception of pain. Data regarding nurses' knowledge and attitudes to pain (primary outcome, patient perception regarding pain (secondary outcome, together with socio-demographic variables, will be collected at baseline and at four weeks and 12 weeks following the intervention. Discussion Nursing care is nowadays acknowledged as an increasingly complicated activity and "nursing complexity is such that it can be seen as the quintessential complex intervention." To be able to change and improve clinical practice thus requires multiple points of attack appropriate to meet complex challenges. Consequently, we expect the theory-based intervention used in our quasi-experimental study to improve care as well as quality of life for this group of patients and we also envisage that

A theory-based educational intervention targeting nurses' attitudes and knowledge concerning cancer-related pain management: a study protocol of a quasi-experimental design.

Science.gov (United States)

Borglin, Gunilla; Gustafsson, Markus; Krona, Hans

2011-09-23

Pain is one of the most frequent problems among patients diagnosed with cancer. Despite the availability of effective pharmacological treatments, this group of patients often receives less than optimal treatment. Research into nurses' pain management highlights certain factors, such as lack of knowledge and attitudes and inadequate procedures for systematic pain assessment, as common barriers to effective pain management. However, educational interventions targeting nurses' pain management have shown promise. As cancer-related pain is also known to have a negative effect on vital aspects of the patient's life, as well as being commonly associated with problems such as sleep, fatigue, depression and anxiety, further development of knowledge within this area is warranted. A quasi-experimental study design will be used to investigate whether the implementation of guidelines for systematic daily pain assessments following a theory-based educational intervention will result in an improvement in knowledge and attitude among nurses. A further aim is to investigate whether the intervention that targets nurses' behaviour will improve hospital patients' perception of pain. Data regarding nurses' knowledge and attitudes to pain (primary outcome), patient perception regarding pain (secondary outcome), together with socio-demographic variables, will be collected at baseline and at four weeks and 12 weeks following the intervention. Nursing care is nowadays acknowledged as an increasingly complicated activity and "nursing complexity is such that it can be seen as the quintessential complex intervention." To be able to change and improve clinical practice thus requires multiple points of attack appropriate to meet complex challenges. Consequently, we expect the theory-based intervention used in our quasi-experimental study to improve care as well as quality of life for this group of patients and we also envisage that evidence-based guidelines targeting this patient group's pain

Masticatory sensory-motor changes after an experimental chewing test influenced by pain catastrophizing and neck-pain-related disability in patients with headache attributed to temporomandibular disorders.

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La Touche, Roy; Paris-Alemany, Alba; Gil-Martínez, Alfonso; Pardo-Montero, Joaquín; Angulo-Díaz-Parreño, Santiago; Fernández-Carnero, Josué

2015-03-05

Recent research has shown a relationship of craniomandibular disability with neck-pain-related disability has been shown. However, there is still insufficient information demonstrating the influence of neck pain and disability in the sensory-motor activity in patients with headache attributed to temporomandibular disorders (TMD). The purpose of this study was to investigate the influence of neck-pain-related disability on masticatory sensory-motor variables. An experimental case-control study investigated 83 patients with headache attributed to TMD and 39 healthy controls. Patients were grouped according to their scores on the neck disability index (NDI) (mild and moderate neck disability). Initial assessment included the pain catastrophizing scale and the Headache Impact Test-6. The protocol consisted of baseline measurements of pressure pain thresholds (PPT) and pain-free maximum mouth opening (MMO). Individuals were asked to perform the provocation chewing test, and measurements were taken immediately after and 24 hours later. During the test, patients were assessed for subjective feelings of fatigue (VAFS) and pain intensity. VAFS was higher at 6 minutes (mean 51.7; 95% CI: 50.15-53.26) and 24 hours after (21.08; 95% CI: 18.6-23.5) for the group showing moderate neck disability compared with the mild neck disability group (6 minutes, 44.16; 95% CI 42.65-45.67/ 24 hours after, 14.3; 95% CI: 11.9-16.7) and the control group. The analysis shows a decrease in the pain-free MMO only in the group of moderate disability 24 hours after the test. PPTs of the trigeminal region decreased immediately in all groups, whereas at 24 hours, a decrease was observed in only the groups of patients. PPTs of the cervical region decreased in only the group with moderate neck disability 24 hours after the test. The strongest negative correlation was found between pain-free MMO immediately after the test and NDI in both the mild (r = -0.49) and moderate (r = -0.54) neck disability

Effect of music therapy on pain behaviors in rats with bone cancer pain.

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Gao, Ji; Chen, Shaoqin; Lin, Suyong; Han, Hongjing

2016-01-01

To investigate the effects of music therapy on the pain behaviors and survival of rats with bone cancer pain and analyze the mediating mechanism of mitogen activated protein kinase (MAPK) signal transduction pathway. Male Wistar rats aged 5-8 weeks and weighing 160-200 g were collected. The rat models of colorectal cancer bone cancer pain was successfully established. Animals were divided into experimental and control group, each with 10 rats. The animals in the observation group were given Mozart K448 sonata, sound intensity of 60 db, played the sonata once every 1 hr in the daytime, stopped playing during the night, and this cycle was kept for 2 weeks. On the other hand, rats in the control group were kept under the same environment without music. Animals in the experimental group consumed more feed and gained significant weight in comparison to the control group. The tumor volume of the experimental group was significantly smaller than that of the control group (pMusic therapy may improve the pain behaviors in rats with bone cancer pain, which might be related with low expression of p38á and p38β in the MAPK signal transduction pathway.

Opponent appetitive-aversive neural processes underlie predictive learning of pain relief.

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Seymour, Ben; O'Doherty, John P; Koltzenburg, Martin; Wiech, Katja; Frackowiak, Richard; Friston, Karl; Dolan, Raymond

2005-09-01

Termination of a painful or unpleasant event can be rewarding. However, whether the brain treats relief in a similar way as it treats natural reward is unclear, and the neural processes that underlie its representation as a motivational goal remain poorly understood. We used fMRI (functional magnetic resonance imaging) to investigate how humans learn to generate expectations of pain relief. Using a pavlovian conditioning procedure, we show that subjects experiencing prolonged experimentally induced pain can be conditioned to predict pain relief. This proceeds in a manner consistent with contemporary reward-learning theory (average reward/loss reinforcement learning), reflected by neural activity in the amygdala and midbrain. Furthermore, these reward-like learning signals are mirrored by opposite aversion-like signals in lateral orbitofrontal cortex and anterior cingulate cortex. This dual coding has parallels to 'opponent process' theories in psychology and promotes a formal account of prediction and expectation during pain.

Electrical stimulation of the insular cortex as a novel target for the relief of refractory pain: An experimental approach in rodents.

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Dimov, Luiz Fabio; Toniolo, Elaine Flamia; Alonso-Matielo, Heloísa; de Andrade, Daniel Ciampi; Garcia-Larrea, Luis; Ballester, Gerson; Teixeira, Manoel Jacobsen; Dale, Camila Squarzoni

2018-07-02

Cortical electrical stimulation (CES) has shown to be an effective therapeutic alternative for neuropathic pain refractory to pharmacological treatment. The primary motor cortex(M1) was the main cortical target used in the vast majority of both invasive and non-invasive studies. Despite positive results M1-based approaches still fail to relieve pain in a significant proportion of individuals. It has been advocated that the direct stimulation of cortical areas directly implicated in the central integration of pain could increase the efficacy of analgesic brain stimulation. Here, we evaluated the behavioral effects of electrical stimulation of the insular cortex (ESI) on pain sensitivity in an experimental rat model of peripheral neuropathy, and have described the pathways involved. Animals underwent chronic constriction of the sciatic nerve in the right hind limb and had concentric electrodes implanted in the posterior dysranular insular cortex. Mechanical nociception responses were evaluated before and at the end of a 15-min session of ESI (60Hz, 210μs, 1V). ESI reversed mechanical hypersensitivity in the paw contralateral to the brain hemisphere stimulated, without inducing motor impairment in the open-field test. Pharmacological blockade of μ-opioid (MOR) or type 1-cannabinoid receptors (CB1R) abolished ESI-induced antinociceptive effects. Evaluation of CB1R and MOR spatial expression demonstrated differential modulation of CB1R and MOR in the periaqueductal gray matter (PAG) of ESI-treated rats in sub-areas involved in pain processing/modulation. These results indicate that ESI induces antinociception by functionally modulating opioid and cannabinoid systems in the PAG pain circuitry in rats with experimentally induced neuropathic pain. Copyright © 2017 Elsevier B.V. All rights reserved.

Use of localized human growth hormone and testosterone injections in addition to manual therapy and exercise for lower back pain: a case series with 12-month follow-up

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Dubick MN

2015-06-01

Full Text Available Marc N Dubick,1 Thomas H Ravin,2 Yvonne Michel,3 David C Morrisette4 1Interventional Pain Management, Division of Anesthesiology, Bon Secours St Francis Hospital, Charleston, SC, USA; 2Musculoskeletal Medicine, Val d'Isere Health Clinic, Denver, CO, USA; 3Statistical Consultant, Private Practice, Daniel Island, SC, USA; 4Division of Physical Therapy, Medical University of South Carolina, SC, USA Objective: The objective of this case series was to investigate the feasibility and safety of a novel method for the management of chronic lower back pain. Injections of recombinant human growth hormone and testosterone to the painful and dysfunctional areas in individuals with chronic lower back pain were used. In addition, the participants received manual therapies and exercise addressing physical impairments such as motor control, strength, endurance, pain, and loss of movement. Pain ratings and self-rated functional outcomes were assessed.Study design: This is a case series involving consecutive patients with chronic lower back pain who received the intervention of injections of recombinant human growth hormone and testosterone, and attended chiropractic and/or physical therapy. Outcomes were measured at 12 months from the time of injection.Setting: A community based hospital affiliated office, and a private practice block suite.Participants: A total of 60 consecutive patients attending a pain management practice for chronic lower back pain were recruited for the experimental treatment. Most participants were private pay.Interventions: Participants who provided informed consent and were determined not to have radicular pain received diagnostic blocks. Those who responded favorably to the diagnostic blocks received injections of recombinant human growth hormone and testosterone in the areas treated with the blocks. Participants also received manipulation- and impairment-based exercises.Outcome measures: Outcomes were assessed at 12 months through pain

Can a theory-based educational intervention change nurses' knowledge and attitudes concerning cancer pain management? A quasi-experimental design.

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Gustafsson, Markus; Borglin, Gunilla

2013-08-19

Registered Nurses (RNs) play an important role in caring for patients suffering from cancer pain. A lack of knowledge regarding pain management and the RNs' own perception of cancer pain could act as barriers to effective pain management. Educational interventions that target RNs' knowledge and attitudes have proved promising. However, an intervention consisting of evidence-based practice is a multifaceted process and demands behavioural and cognitive changes to sustain the effects of the intervention. Therefore, our study aimed to investigate if a theory-based educational intervention could change RNs' knowledge and attitudes to cancer pain and pain management, both four and 12 weeks after the start of the intervention. A quasi-experimental design with non-equivalent control groups was used. The primary outcome was measured using a modified version of the instrument Nurses' Knowledge and Attitudes Survey Regarding Pain (NKAS) at baseline, four weeks and 12 weeks after the start of the intervention to evaluate its persistence. The intervention's educational curriculum was based on the principles of Ajzen's Theory of Planned Behaviour and consisted of interactive learning activities conducted in workshops founded on evidence-based knowledge. The RN's own experiences from cancer pain management were used in the learning process. The theory-based educational intervention aimed at changing RNs knowledge and attitudes regarding cancer pain management measured by primary outcome NKAS resulted in a statistical significant (presearched and needs to be evaluated further in larger projects. Clinical Trials. Gov: NCT01313234.

Seeing and identifying with a virtual body decreases pain perception.

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Hänsel, Alexander; Lenggenhager, Bigna; von Känel, Roland; Curatolo, Michele; Blanke, Olaf

2011-09-01

Pain and the conscious mind (or the self) are experienced in our body. Both are intimately linked to the subjective quality of conscious experience. Here, we used virtual reality technology and visuo-tactile conflicts in healthy subjects to test whether experimentally induced changes of bodily self-consciousness (self-location; self-identification) lead to changes in pain perception. We found that visuo-tactile stroking of a virtual body but not of a control object led to increased pressure pain thresholds and self-location. This increase was not modulated by the synchrony of stroking as predicted based on earlier work. This differed for self-identification where we found as predicted that synchrony of stroking increased self-identification with the virtual body (but not a control object), and positively correlated with an increase in pain thresholds. We discuss the functional mechanisms of self-identification, self-location, and the visual perception of human bodies with respect to pain perception. Copyright © 2011 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

Mechano-sensitive nociceptors are required to detect heat pain thresholds and cowhage itch in human skin.

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Weinkauf, B; Dusch, M; van der Ham, J; Benrath, J; Ringkamp, M; Schmelz, M; Rukwied, R

2016-02-01

Mechano-sensitive and mechano-insensitive C-nociceptors in human skin differ in receptive field sizes and electrical excitation thresholds, but their distinct functional roles are yet unclear. After blocking the lateral femoral cutaneous nerve (NCFL) in eight healthy male subjects (3-mL Naropin(®) 1%), we mapped the skin innervation territory being anaesthetic to mechanical pin prick but sensitive to painful transcutaneous electrical stimuli. Such 'differentially anaesthetic zones' indicated that the functional innervation with mechano-sensitive nociceptors was absent but the innervation with mechano-insensitive nociceptors remained intact. In these areas, we explored heat pain thresholds, low pH-induced pain, cowhage- and histamine-induced itch, and axon reflex flare. In differentially anaesthetic skin, heat pain thresholds were above the cut-off of 50°C (non-anaesthetized skin 47 ± 0.4°C). Pain ratings to 30 μL pH 4 injections were reduced compared to non-anaesthetized skin (48 ± 9 vs. 79 ± 6 VAS; p pain. The mechano-sensitive nociceptors are crucial for cowhage-induced itch and for the assessment of heat pain thresholds. © 2015 European Pain Federation - EFIC®

Reward and motivation in pain and pain relief

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Navratilova, Edita; Porreca, Frank

2015-01-01

Pain is fundamentally unpleasant, a feature that protects the organism by promoting motivation and learning. Relief of aversive states, including pain, is rewarding. The aversiveness of pain, as well as the reward from relief of pain, is encoded by brain reward/motivational mesocorticolimbic circuitry. In this Review, we describe current knowledge of the impact of acute and chronic pain on reward/motivation circuits gained from preclinical models and from human neuroimaging. We highlight emerging clinical evidence suggesting that anatomical and functional changes in these circuits contribute to the transition from acute to chronic pain. We propose that assessing activity in these conserved circuits can offer new outcome measures for preclinical evaluation of analgesic efficacy to improve translation and speed drug discovery. We further suggest that targeting reward/motivation circuits may provide a path for normalizing the consequences of chronic pain to the brain, surpassing symptomatic management to promote recovery from chronic pain. PMID:25254980

Neuromuscular adaptations predict functional disability independently of clinical pain and psychological factors in patients with chronic non-specific low back pain.

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Dubois, Jean-Daniel; Abboud, Jacques; St-Pierre, Charles; Piché, Mathieu; Descarreaux, Martin

2014-08-01

Patients with chronic low back pain exhibit characteristics such as clinical pain, psychological symptoms and neuromuscular adaptations. The purpose of this study was to determine the independent contribution of clinical pain, psychological factors and neuromuscular adaptations to disability in patients with chronic low back pain. Clinical pain intensity, pain catastrophizing, fear-avoidance beliefs, anxiety, neuromuscular adaptations to chronic pain and neuromuscular responses to experimental pain were assessed in 52 patients with chronic low back pain. Lumbar muscle electromyographic activity was assessed during a flexion-extension task (flexion relaxation phenomenon) to assess both chronic neuromuscular adaptations and neuromuscular responses to experimental pain during the task. Multiple regressions showed that independent predictors of disability included neuromuscular adaptations to chronic pain (β=0.25, p=0.006, sr(2)=0.06), neuromuscular responses to experimental pain (β=-0.24, p=0.011, sr(2)=0.05), clinical pain intensity (β=0.28, p=0.002, sr(2)=0.08) and psychological factors (β=0.58, ppain intensity and psychological factors, and contribute to inter-individual differences in patients' disability. This suggests that disability, in chronic low back pain patients, is determined by a combination of factors, including clinical pain, psychological factors and neuromuscular adaptations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Towards Development of a Dermal Pain Model: In Vitro Activation of Rat and Human Transient Receptor Potential Ankyrin Repeat 1 and Safe Dermal Injection of o-Chlorobenzylidene Malononitrile to Rat.

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Annas, Anita; Berg, Anna-Lena; Nyman, Eva; Meijer, Thomas; Lundgren, Viveka; Franzén, Bo; Ståhle, Lars

2015-12-01

During clinical development of analgesics, it is important to have access to pharmacologically specific human pain models. o-Chlorobenzylidene malononitrile (CS) is a selective and potent agonist of the transient receptor potential ankyrin repeat 1 (TRPA1), which is a transducer molecule in nociceptors sensing reactive chemical species. While CS has been subject to extensive toxicological investigations in animals and human beings, its effects on intradermal or subcutaneous injection have not previously been reported. We have investigated the potential of CS to be used as an agonist on TRPA1 in human experimental pain studies. A calcium influx assay was used to confirm the capacity of CS to activate TRPA1 with >100,000 times the selectivity over the transient receptor potential vanilloid receptor 1. CS dose-dependently (EC50 0.9 μM) released calcitonin gene-related peptide in rat dorsal root ganglion cultures, supporting involvement in pain signalling. In a local tolerance study, injection of a single intradermal dose of 20 mM CS to rats resulted in superficial, circular crusts at the injection sites after approximately 4 days. The histopathology evaluation revealed a mild, acute inflammatory reaction in the epidermis and dermis at the intradermal CS injection site 1 day after administration. After 14 days, the epidermal epithelium was fully restored. The symptoms were not considered to be adverse, and it is suggested that doses up to 20 μL of 20 mM CS can be safely administered to human beings. In conclusion, our data support development of a CS human dermal pain model. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Cancer pain and current theory for pain control.

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Kahan, Brian

2014-05-01

This article discusses current trends in managing cancer pain, with specific regard to opioid transmission, descending pathway inhabitation, and ways to facilitate the endogenous antinociceptive chemicals in the human body. Various techniques for opioid and nonopioid control of potential pain situations of patients with cancer are discussed. The benefits of using pharmacogenetics to assess the appropriate medications are addressed. Finally, specific treatment of abdominal cancer pain using radiofrequency lesioning is discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

Pain emotion and homeostasis.

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Panerai, Alberto E

2011-05-01

Pain has always been considered as part of a defensive strategy, whose specific role is to signal an immediate, active danger. This definition partially fits acute pain, but certainly not chronic pain, that is maintained also in the absence of an active noxa or danger and that nowadays is considered a disease by itself. Moreover, acute pain is not only an automatic alerting system, but its severity and characteristics can change depending on the surrounding environment. The affective, emotional components of pain have been and are the object of extensive attention and research by psychologists, philosophers, physiologists and also pharmacologists. Pain itself can be considered to share the same genesis as emotions and as a specific emotion in contributing to the maintenance of the homeostasis of each unique subject. Interestingly, this role of pain reaches its maximal development in the human; some even argue that it is specific for the human primate.

Doubling Your Payoff: Winning Pain Relief Engages Endogenous Pain Inhibition

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Becker, Susanne; Gandhi, Wiebke; Kwan, Saskia; Ahmed, Alysha-Karima; Schweinhardt, Petra

2015-01-01

When in pain, pain relief is much sought after, particularly for individuals with chronic pain. In analogy to augmentation of the hedonic experience ("liking") of a reward by the motivation to obtain a reward ("wanting"), the seeking of pain relief in a motivated state might increase the experience of pain relief when obtained. We tested this hypothesis in a psychophysical experiment in healthy human subjects, by assessing potential pain-inhibitory effects of pain relief "won" in a wheel of fortune game compared with pain relief without winning, exploiting the fact that the mere chance of winning induces a motivated state. The results show pain-inhibitory effects of pain relief obtained by winning in behaviorally assessed pain perception and ratings of pain intensity. Further, the higher participants scored on the personality trait novelty seeking, the more pain inhibition was induced. These results provide evidence that pain relief, when obtained in a motivated state, engages endogenous pain-inhibitory systems beyond the pain reduction that underlies the relief in the first place. Consequently, such pain relief might be used to improve behavioral pain therapy, inducing a positive, perhaps self-amplifying feedback loop of reduced pain and improved functionality.

Painful dilemmas: the ethics of animal-based pain research

DEFF Research Database (Denmark)

Magalhães-Sant'Ana, M.; Sandøe, Peter; Olsson, I. A. S.

2009-01-01

While it has the potential to deliver important human benefits, animal-based pain research raises ethical questions, because it involves inducing pain in sentient beings. Ethical decision-making, connected with this variety of research, requires informed harm-benefit analysis, and the aim of this...

Local cooling does not prevent hyperalgesia following burn injury in humans

DEFF Research Database (Denmark)

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

2002-01-01

One of the oldest methods of pain relief following a burn injury is local application of ice or cold water. Experimental data indicate that cooling may also reduce the severity of tissue injury and promote wound healing, but there are no controlled studies in humans evaluating the anti-inflammato......One of the oldest methods of pain relief following a burn injury is local application of ice or cold water. Experimental data indicate that cooling may also reduce the severity of tissue injury and promote wound healing, but there are no controlled studies in humans evaluating the anti...

Personalized pain medicine: the clinical value of psychophysical assessment of pain modulation profile.

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Granovsky, Yelena; Yarnitsky, David

2013-01-01

Experimental pain stimuli can be used to simulate patients' pain experience. We review recent developments in psychophysical pain testing, focusing on the application of the dynamic tests-conditioned pain modulation (CPM) and temporal summation (TS). Typically, patients with clinical pain of various types express either less efficient CPM or enhanced TS, or both. These tests can be used in prediction of incidence of acquiring pain and of its intensity, as well as in assisting the correct choice of analgesic agents for individual patients. This can help to shorten the commonly occurring long and frustrating process of adjusting analgesic agents to the individual patients. We propose that evaluating pain modulation can serve as a step forward in individualizing pain medicine.

Testing the impact of a multimedia video CD of patient-controlled analgesia on pain knowledge and pain relief in patients receiving surgery.

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Chen, Hsing-Hsia; Yeh, Mei-Ling; Yang, Hui-Ju

2005-07-01

This study aimed to develop a multimedia video CD (VCD) of patient-controlled analgesia (PCA) and test its effects on pain knowledge and pain relief in patients receiving surgery. This multimedia VCD of PCA was created to convey fundamental knowledge to both patients and their family members and help patients properly utilize PCA devices to relieve pain and improve recovery. The content of multimedia VCD of PCA included pre-admission pain education, introduction of PCA, nursing care procedures, and questions and answers. This study used a quasi-experimental research design to test effects of the multimedia education program in the experimental group of 30 subjects compared to the control subjects of equal number (without the multimedia VCD of PCA). (1) The intervention of multimedia VCD of PCA resulted in a statistically significant difference in pain knowledge between the experimental and control groups. (2) Subjects in the experimental group obtained a better outcome of pain relief compared to control subjects. (3) Subjects in the experimental group indicated that the multimedia VCD of PCA indeed helped them effectively operate their PCA devices to relieve surgery pain. The clinical application of the multimedia VCD of PCA could help patients improve knowledge on pain, learn how to use PCA devices, achieve proper pain relief, and increase effectiveness of recovery activities.

Towards a physiology-based measure of pain: patterns of human brain activity distinguish painful from non-painful thermal stimulation.

Directory of Open Access Journals (Sweden)

Justin E Brown

Full Text Available Pain often exists in the absence of observable injury; therefore, the gold standard for pain assessment has long been self-report. Because the inability to verbally communicate can prevent effective pain management, research efforts have focused on the development of a tool that accurately assesses pain without depending on self-report. Those previous efforts have not proven successful at substituting self-report with a clinically valid, physiology-based measure of pain. Recent neuroimaging data suggest that functional magnetic resonance imaging (fMRI and support vector machine (SVM learning can be jointly used to accurately assess cognitive states. Therefore, we hypothesized that an SVM trained on fMRI data can assess pain in the absence of self-report. In fMRI experiments, 24 individuals were presented painful and nonpainful thermal stimuli. Using eight individuals, we trained a linear SVM to distinguish these stimuli using whole-brain patterns of activity. We assessed the performance of this trained SVM model by testing it on 16 individuals whose data were not used for training. The whole-brain SVM was 81% accurate at distinguishing painful from non-painful stimuli (p<0.0000001. Using distance from the SVM hyperplane as a confidence measure, accuracy was further increased to 84%, albeit at the expense of excluding 15% of the stimuli that were the most difficult to classify. Overall performance of the SVM was primarily affected by activity in pain-processing regions of the brain including the primary somatosensory cortex, secondary somatosensory cortex, insular cortex, primary motor cortex, and cingulate cortex. Region of interest (ROI analyses revealed that whole-brain patterns of activity led to more accurate classification than localized activity from individual brain regions. Our findings demonstrate that fMRI with SVM learning can assess pain without requiring any communication from the person being tested. We outline tasks that should be

Glia and pain: is chronic pain a gliopathy?

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Ji, Ru-Rong; Berta, Temugin; Nedergaard, Maiken

2013-12-01

Activation of glial cells and neuro-glial interactions are emerging as key mechanisms underlying chronic pain. Accumulating evidence has implicated 3 types of glial cells in the development and maintenance of chronic pain: microglia and astrocytes of the central nervous system (CNS), and satellite glial cells of the dorsal root and trigeminal ganglia. Painful syndromes are associated with different glial activation states: (1) glial reaction (ie, upregulation of glial markers such as IBA1 and glial fibrillary acidic protein (GFAP) and/or morphological changes, including hypertrophy, proliferation, and modifications of glial networks); (2) phosphorylation of mitogen-activated protein kinase signaling pathways; (3) upregulation of adenosine triphosphate and chemokine receptors and hemichannels and downregulation of glutamate transporters; and (4) synthesis and release of glial mediators (eg, cytokines, chemokines, growth factors, and proteases) to the extracellular space. Although widely detected in chronic pain resulting from nerve trauma, inflammation, cancer, and chemotherapy in rodents, and more recently, human immunodeficiency virus-associated neuropathy in human beings, glial reaction (activation state 1) is not thought to mediate pain sensitivity directly. Instead, activation states 2 to 4 have been demonstrated to enhance pain sensitivity via a number of synergistic neuro-glial interactions. Glial mediators have been shown to powerfully modulate excitatory and inhibitory synaptic transmission at presynaptic, postsynaptic, and extrasynaptic sites. Glial activation also occurs in acute pain conditions, and acute opioid treatment activates peripheral glia to mask opioid analgesia. Thus, chronic pain could be a result of "gliopathy," that is, dysregulation of glial functions in the central and peripheral nervous system. In this review, we provide an update on recent advances and discuss remaining questions. Copyright © 2013 International Association for the

Prediction of pain in orthodontic patients based on preoperative pain assessment

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Zheng, Baoyu; Ren, Manman; Lin, Feiou; Yao, Linjie

2016-01-01

Aim To investigate whether pretreatment assessment of experimental pain can predict the level of pain after archwire placement. Methods One hundred and twenty-one general university students seeking orthodontic treatment were enrolled in this study. A cold pressor test was performed to estimate the pain tolerance of subjects before treatment. Self-reported pain intensity was calculated using a 10 cm visual analog scale during the 7 days after treatment. The relationship between pain tolerance and orthodontic pain was analyzed using Spearman’s correlation analysis. Results The maximum mean level of pain intensity occurred at 24 hours after bonding (53.31±16.13) and fell to normal levels at day 7. Spearman’s correlation analysis found a moderate positive association between preoperative pain tolerance and self-reported pain after archwire placement (P0.05). Conclusion A simple and noninvasive preoperative sensory test (the cold pressor test) was useful in predicting the risk of developing unbearable pain in patients after archwire placement. Self-reported pain after archwire placement decreased as individual pain tolerance increased. PMID:27042019

Pain genes.

Directory of Open Access Journals (Sweden)

Tom Foulkes

2008-07-01

Full Text Available 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 pain pathways using model organisms have identified the molecular nature of the transducers, regulatory mechanisms involved in changing neuronal activity, as well as the critical role of immune system cells in driving pain pathways. In man, mapping of human pain mutants as well as twin studies and association studies of altered pain behaviour have identified important regulators of the pain system. In turn, new drug targets for chronic pain treatment have been validated in transgenic mouse studies. Thus, genetic studies of pain pathways have complemented the traditional neuroscience approaches of electrophysiology and pharmacology to give us fresh insights into the molecular basis of pain perception.

Investigation into the effects of using two or four acupuncture needles with bidirectional rotation on experimentally-induced contact heat pain in healthy subjects.

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Paley, Carole A; Johnson, Mark I

2015-02-01

There is growing evidence from experimental studies that the acupuncture dose or technique influences the speed of onset of hypoalgesia. The aim of this study was to investigate the effects of acupuncture using two or four needles on experimental contact thermal pain in healthy volunteers. Forty two participants were randomised into three groups: four-needle group (LI4, LI11, LI10, TE5), two-needle group (verum at LI4, LI11 and mock at LI10, TE5) and mock acupuncture group (LI4, LI11, LI10, TE5). Each participant rated pain intensity (visual analogue scale, VAS) to a series of noxious stimuli administered to the forearm 2°C above the heat pain threshold during needling and immediately after removal of the needles. Experimentally-induced heat pain intensity (VAS) during and after the intervention was lower than pre-intervention but there were no statistically significant differences in this change between groups. There were no statistically significant differences between groups in the time taken for pain intensity to decrease by 33% from pre-intervention. However, a 33% decrease in pain intensity within 3 min of needle insertion was observed for 13 participants (92.9%) in the four-needle group compared with 66.7% of participants in the two-needle group and 57.1% in the mock acupuncture group. There was less variance in VAS in the four-needle group, suggesting more consistency in hypoalgesic response when using more needles. There is tentative evidence that four needles may be superior to two needles in generating rapid onset hypoalgesia. The findings suggest that further investigation is warranted. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effects of intravenous propranolol on heat pain sensitivity in healthy men.

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Schweinhardt, P; Abulhasan, Y B; Koeva, V; Balderi, T; Kim, D J; Alhujairi, M; Carli, F

2013-05-01

Clinical studies have shown opioid-sparing effects of β-adrenergic antagonists perioperatively and β-blockers are being investigated for chronic musculoskeletal pain. However, the direct analgesic effects of β-blockers have rarely been examined in healthy humans. In a randomized, counter-balanced, double-blind, within-subject crossover design, we tested the effect of the lipophilic β-blocker propranolol (0.035 mg/kg body weight i.v.) on heat pain sensitivity in 39 healthy males, compared with placebo. To test for peripheral versus central effects, the peripherally acting β-blocker sotalol was also examined. Experimental stimuli were brief superficial noxious heat stimuli applied to the volar forearm. Non-painful cold stimuli were included to test for specificity. Sedation, mood and anxiety were assessed to investigate potential mechanisms underlying any analgesic effect. β-blocker effects on blood pressure were incorporated into the analysis because of a known inverse relationship between pain sensitivity and systolic blood pressure. Propranolol significantly decreased perceived intensity of heat pain stimuli but only in participants with small propranolol-induced blood pressure decreases. Even in this group, the effect was small (4%). Propranolol did not influence perceived intensity of non-noxious stimuli and had no effect on sedation, anxiety or mood. Sotalol did not influence heat pain sensitivity. Propranolol decreased pain sensitivity but its analgesic effects were small and counteracted by blood pressure decreases. The analgesic effects were not mediated by peripheral β-receptor blockade, sedation, mood or anxiety. The small effect indicates that the utility of β-blockers for clinical pain must be related to factors that do not play a significant role for experimental pain. © 2012 European Federation of International Association for the Study of Pain Chapters.

Short-Term Sensorimotor Effects of Experimental Occlusal Interferences on the Wake-Time Masseter Muscle Activity of Females with Masticatory Muscle Pain.

Science.gov (United States)

Cioffi, Iacopo; Farella, Mauro; Festa, Paola; Martina, Roberto; Palla, Sandro; Michelotti, Ambrosina

2015-01-01

To investigate the effects of the application of an acute alteration of the occlusion (ie, interference) on the habitual masseter electromyographic (EMG) activity of females with temporomandibular disorders (TMD)-related muscular pain during wakefulness. Seven female volunteers with masticatory myofascial pain participated in a crossover randomized clinical trial. Gold foils were glued on an occlusal contact area (active occlusal interference, AI) or on the vestibular surface of the same molar (dummy interference, DI) and left for 8 days. The masseter electromyogram was recorded during wakefulness in the natural environment by portable recorders under interference-free, dummy-interference, and active-interference conditions. The number, amplitude, and duration of EMG signal fractions with amplitudes above 10% of the maximum voluntary contraction (activity periods, APs) were computed in all experimental conditions. Muscle pain, headache, and perceived stress were each assessed with a visual analog scale (VAS), and an algometer was used to assess masseter and temporalis pressure pain thresholds. Data were analyzed by means of analysis of variance. The frequency and duration of the recorded APs did not differ significantly between the experimental conditions (P>.05), but a small and significant reduction of the EMG mean amplitude of the APs occurred with AI (P.05). An active occlusal interference in female volunteers with masticatory muscle pain had little influence on the masseter EMG activity pattern during wakefulness and did not affect the pressure tenderness of the masseter and temporalis.

Evaluation of hypnotherapy in pain management of cancer patients: A clinical trial from India

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Vikas Kumar Sharma

2017-01-01

Full Text Available Context: In the present era, cancer is one of the major growing diseases in human beings. People with cancer often experience a lot of problems ranging from psychological impairments to pain, fatigue, and sleep disorders. Pain is closely associated with all types of cancer. Cancer patients feel intense pain in the affected organ not only because of cancer but also because of the medical treatment procedure. Aim: The present study aimed at exploring the efficacy of hypnotherapy in mollifying the pain in persons with cancer. Settings and Design: This study was systematically planned through before and after control group design with matching; a quasi-experimental research design.Subjects and Methods: The present study was carried out by taking a total of 57 cancer patients as per inclusion/exclusion criteria from Jawaharlal Nehru Cancer Hospital and Research Center, Bhopal, Madhya Pradesh, through convenience sampling method. Out of these 57 participants, the experimental group consisted of thirty participants who were given intervention in the form of 15 sessions of hypnotherapy along with medical treatments. The control group consisted of another 27 participants who were administered medical treatments alone. Participants were given Numerical Rating Scale for a rating of pain in cancer patients. Statistical Analysis Used: Independent samples t-test and Eta-squared statistics were used to analyze the mean difference between experimental group and control group on pain and computing the magnitude of the effect of intervention, respectively. Results: The directional hypothesis was accepted P < 0.005 (one-tailed. Thus, mean score of pain (mean = 3.23, standard deviation [SD] = 1.36 for experimental group is statistically significant lower than posttest score (mean = 6.00, SD = 2.15 for control group. For power analysis, Cohen's d was estimated at 0.38 which indicates a large effect of the intervention on pain. Conclusions: The finding of the present

Pain in Times of Stress

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AHMAD, Asma Hayati; ZAKARIA, Rahimah

2015-01-01

Stress modulates pain perception, resulting in either stress-induced analgesia or stress-induced hyperalgesia, as reported in both animal and human studies. The responses to stress include neural, endocrine, and behavioural changes, and built-in coping strategies are in place to address stressors. Peculiar to humans are additional factors that modulate pain that are experienced in times of stress, notably psychological factors that potentially influence the directionality of pain perception.

Effects of perceived and exerted pain control on neural activity during pain relief in experimental heat hyperalgesia: a fMRI study.

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Mohr, C; Leyendecker, S; Petersen, D; Helmchen, C

2012-04-01

Perceived control over pain can attenuate pain perception by mechanisms of endogenous pain control and emotional reappraisal irrespective of whether this control is exerted or only perceived. Self-initiated termination of pain elicits different expectations of subsequent pain relief as compared to perceived pain control. It is unknown whether and how this perceived vs. exerted control on pain differs and affects subsequent pain relief. Using fMRI, we studied two factors of pain control on pain relief: the (i) sense of control (perceived control but no execution) and (ii) the execution of control (exerted control). To account for the impact of factual execution of pain control on pain relief we applied bearable short and hardly bearable long contact-heat stimuli which were applied either controllable or not. Using controllability as factor, there was dissociable neural activity during pain relief: following the perceived control condition neural activity was found in the orbitofrontal and mediofrontal cortex and, following the exerted control condition, in the anterolateral and dorsolateral prefrontal cortex and posterior parietal cortex. We conclude that (i) pain controllability has an impact on pain relief and (ii) the prefrontal cortex shows dissociable neural activity during pain relief following exerted vs. perceived pain control. This might reflect the higher grade of uncertainty during pain relief following perceived pain control mediated by the orbitofrontal and medial prefrontal cortex and processes of working memory and updating expectations during pain relief following exerted control mediated by the lateral prefrontal cortex. © 2011 European Federation of International Association for the Study of Pain Chapters.

Human psychophysics and rodent spinal neurones exhibit peripheral and central mechanisms of inflammatory pain in the UVB and UVB heat rekindling models.

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O'Neill, Jessica; Sikandar, Shafaq; McMahon, Stephen B; Dickenson, Anthony H

2015-09-01

Translational research is key to bridging the gaps between preclinical findings and the patients, and a translational model of inflammatory pain will ideally induce both peripheral and central sensitisation, more effectively mimicking clinical pathophysiology in some chronic inflammatory conditions. We conducted a parallel investigation of two models of inflammatory pain, using ultraviolet B (UVB) irradiation alone and UVB irradiation with heat rekindling. We used rodent electrophysiology and human quantitative sensory testing to characterise nociceptive processing in the peripheral and central nervous systems in both models. In both species, UVB irradiation produces peripheral sensitisation measured as augmented evoked activity of rat dorsal horn neurones and increased perceptual responses of human subjects to mechanical and thermal stimuli. In both species, UVB with heat rekindling produces central sensitisation. UVB irradiation alone and UVB with heat rekindling are translational models of inflammation that produce peripheral and central sensitisation, respectively. The predictive value of laboratory models for human pain processing is crucial for improving translational research. The discrepancy between peripheral and central mechanisms of pain is an important consideration for drug targets, and here we describe two models of inflammatory pain that involve ultraviolet B (UVB) irradiation, which can employ peripheral and central sensitisation to produce mechanical and thermal hyperalgesia in rats and humans. We use electrophysiology in rats to measure the mechanically- and thermally-evoked activity of rat spinal neurones and quantitative sensory testing to assess human psychophysical responses to mechanical and thermal stimulation in a model of UVB irradiation and in a model of UVB irradiation with heat rekindling. Our results demonstrate peripheral sensitisation in both species driven by UVB irradiation, with a clear mechanical and thermal hypersensitivity of

Effects of a Peer-Led Pain Management Program for Nursing Home Residents with Chronic Pain: A Pilot Study.

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Tse, Mimi Mun Yee; Yeung, Suey Shuk Yu; Lee, Paul Hong; Ng, Shamay Sheung Mei

2016-09-01

OBJECTIVES : To examine the feasibility of a peer-led pain management program among nursing home residents. DESIGN : A quasi-experimental design. SETTING : Two nursing homes. SUBJECTS : Fifty nursing home residents. METHODS : The experimental group (n = 32) was given a 12-week group-based peer-led pain management program. There were two 1-hour sessions per week. Education in pain and demonstrations of nonpharmacological pain management strategies were provided. The research team and 12 trained peers led the sessions. The control group (n = 18) received one 1-hour session of pain management program each week over 12 weeks from the research team only. Outcome measures for the participants were collected at baseline (P1) and at week 12 (P2). Data from peer volunteers were collected prior to training (V1) and at week 12 (V2). T-tests were used to compare the differences in outcome measures collected at two time points. RESULTS : There was a significant reduction in pain intensity from 5.8 ± 2.6 (P1) to 3.4 ± 2.5 (P2) for the experimental group (p = 0.003) and from 6.3 ± 3.0 (P1) to 3.1 ± 2.4 (P2) for the control group (p = 0.001). Activities of daily living significantly improved for both the experimental group (p = 0.008) and the control group (p = 0.014). There was an enhancement in happiness level for the experimental group (p pain management knowledge (2.9 ± 2.6 to 8.1 ± 1.2, p pain management program was feasible and has potential in relieving chronic pain and enhancing the physical and psychological health of nursing home residents. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Personalized Pain Medicine: The Clinical Value of Psychophysical Assessment of Pain Modulation Profile

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Yelena Granovsky

2013-10-01

Full Text Available Experimental pain stimuli can be used to simulate patients’ pain experience. We review recent developments in psychophysical pain testing, focusing on the application of the dynamic tests—conditioned pain modulation (CPM and temporal summation (TS. Typically, patients with clinical pain of various types express either less efficient CPM or enhanced TS, or both. These tests can be used in prediction of incidence of acquiring pain and of its intensity, as well as in assisting the correct choice of analgesic agents for individual patients. This can help to shorten the commonly occurring long and frustrating process of adjusting analgesic agents to the individual patients. We propose that evaluating pain modulation can serve as a step forward in individualizing pain medicine.

Pain physiology education improves health status and endogenous pain inhibition in fibromyalgia: a double-blind randomized controlled trial.

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Van Oosterwijck, Jessica; Meeus, Mira; Paul, Lorna; De Schryver, Mieke; Pascal, Aurelie; Lambrecht, Luc; Nijs, Jo

2013-10-01

There is evidence that education on pain physiology can have positive effects on pain, disability, and catastrophization in patients with chronic musculoskeletal pain disorders. A double-blind randomized controlled trial (RCT) was performed to examine whether intensive pain physiology education is also effective in fibromyalgia (FM) patients, and whether it is able to influence the impaired endogenous pain inhibition of these patients. Thirty FM patients were randomly allocated to either the experimental (receiving pain physiology education) or the control group (receiving pacing self-management education). The primary outcome was the efficacy of the pain inhibitory mechanisms, which was evaluated by spatially accumulating thermal nociceptive stimuli. Secondary outcome measures included pressure pain threshold measurements and questionnaires assessing pain cognitions, behavior, and health status. Assessments were performed at baseline, 2 weeks, and 3 months follow-up. Repeated measures ANOVAS were used to reveal possible therapy effects and effect sizes were calculated. After the intervention the experimental group had improved knowledge of pain neurophysiology (Pphysiology. Pain physiology education seems to be a useful component in the treatment of FM patients as it improves health status and endogenous pain inhibition in the long term.

Fear of pain potentiates nocebo hyperalgesia

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Aslaksen PM

2015-10-01

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

DRG Voltage-Gated Sodium Channel 1.7 Is Upregulated in Paclitaxel-Induced Neuropathy in Rats and in Humans with Neuropathic Pain.

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Li, Yan; North, Robert Y; Rhines, Laurence D; Tatsui, Claudio Esteves; Rao, Ganesh; Edwards, Denaya D; Cassidy, Ryan M; Harrison, Daniel S; Johansson, Caj A; Zhang, Hongmei; Dougherty, Patrick M

2018-01-31

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect experienced by cancer patients receiving treatment with paclitaxel. The voltage-gated sodium channel 1.7 (Na v 1.7) plays an important role in multiple preclinical models of neuropathic pain and in inherited human pain phenotypes, and its gene expression is increased in dorsal root ganglia (DRGs) of paclitaxel-treated rats. Hence, the potential of change in the expression and function of Na v 1.7 protein in DRGs from male rats with paclitaxel-related CIPN and from male and female humans with cancer-related neuropathic pain was tested here. Double immunofluorescence in CIPN rats showed that Na v 1.7 was upregulated in small DRG neuron somata, especially those also expressing calcitonin gene-related peptide (CGRP), and in central processes of these cells in the superficial spinal dorsal horn. Whole-cell patch-clamp recordings in rat DRG neurons revealed that paclitaxel induced an enhancement of ProTx II (a selective Na v 1.7 channel blocker)-sensitive sodium currents. Bath-applied ProTx II suppressed spontaneous action potentials in DRG neurons occurring in rats with CIPN, while intrathecal injection of ProTx II significantly attenuated behavioral signs of CIPN. Complementarily, DRG neurons isolated from segments where patients had a history of neuropathic pain also showed electrophysiological and immunofluorescence results indicating an increased expression of Na v 1.7 associated with spontaneous activity. Na v 1.7 was also colocalized in human cells expressing transient receptor potential vanilloid 1 and CGRP. Furthermore, ProTx II decreased firing frequency in human DRGs with spontaneous action potentials. This study suggests that Na v 1.7 may provide a potential new target for the treatment of neuropathic pain, including chemotherapy (paclitaxel)-induced neuropathic pain. SIGNIFICANCE STATEMENT This work demonstrates that the expression and function of the voltage-gated sodium channel Na

Evaluation of pain management interventions for neonatal circumcision pain.

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Joyce, B A; Keck, J F; Gerkensmeyer, J

2001-01-01

The purpose of the study was to determine the efficacy of music and eutectic mixture of local anesthetics (EMLA) on pain responses of neonates undergoing circumcision. A randomized, double-blind experimental design was used with 23 neonates. Pain response was measured using an observational pain intensity rating scale and the physiologic parameters of heart rate, respiratory rate, oxygen saturation levels, salivary cortisol levels, and length of cry. Each infant's state was examined for a potential contribution to the pain response. Infant state, salivary cortisol levels, and respiratory rates were not significant. Pain ratings had considerable variability for all treatment conditions, but both single treatment groups had less pain by the end of the procedure. The heart rate was significantly lower for the EMLA group and remained stable for the music group. Oxygen saturation differences were statistically significant for the music group (P =.02) and approached significance for the EMLA group. Preliminary support was provided for the efficacy of EMLA and music to contribute to the pain relief of neonates undergoing circumcision. Further study is warranted. Neonates deserve interventions that will provide them with a less painful start in life.

Association Between Human Pain-Related Genotypes and Variability in Opioid Analgesia

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Nielsen, Lecia M; Olesen, Anne E; Branford, Ruth

2015-01-01

On an individual level, there is a difference in the analgesic response to a given opioid. Various factors such as gender, age, and genetic variation can affect the analgesic response. The genetic variation can influence pharmacokinetics (eg drug transporters and drug-metabolizing enzymes) and...... as opioid consumption or changes in pain scores. Studies have shown promising results regarding pharmacogenetics as a diagnostic tool for predicting the individual response to a given opioid in the experimental settings; however, in the clinic, it is a more complicated task to accomplish....

Influence of Polymorphisms in the HTR3A and HTR3B Genes on Experimental Pain and the Effect of the 5-HT3 Antagonist Granisetron.

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Louca Jounger, Sofia; Christidis, Nikolaos; Hedenberg-Magnusson, Britt; List, Thomas; Svensson, Peter; Schalling, Martin; Ernberg, Malin

2016-01-01

The aim of this study was to investigate experimentally if 5-HT3 single nucleotide polymorphisms (SNP) contribute to pain perception and efficacy of the 5-HT3-antagonist granisetron and sex differences. Sixty healthy participants were genotyped regarding HTR3A (rs1062613) and HTR3B (rs1176744). First, pain was induced by bilateral hypertonic saline injections (HS, 5.5%, 0.2 mL) into the masseter muscles. Thirty min later the masseter muscle on one side was pretreated with 0.5 mL granisetron (1 mg/mL) and on the other side with 0.5 mL placebo (isotonic saline) followed by another HS injection (0.2 mL). Pain intensity, pain duration, pain area and pressure pain thresholds (PPTs) were assessed after each injection. HS evoked moderate pain, with higher intensity in the women (P = 0.023), but had no effect on PPTs. None of the SNPs influenced any pain variable in general, but compared to men, the pain area was larger in women carrying the C/C (HTR3A) (P = 0.015) and pain intensity higher in women with the A/C alleles (HTR3B) (P = 0.019). Pre-treatment with granisetron reduced pain intensity, duration and area to a lesser degree in women (P granisetron. Women carrying the C/T & T/T (HTR3A) genotype had less reduction of pain intensity (P = 0.041) and area (P = 0.005), and women with the C/C genotype (HTR3B) had less reduction of pain intensity (P = 0.030), duration (P = 0.030) and area compared to men (P = 0.017). In conclusion, SNPs did not influence experimental muscle pain or the effect of granisetron on pain variables in general, but there were some sex differences in pain variables that seem to be influenced by genotypes. However, due to the small sample size further research is needed before any firm conclusions can be drawn.

Influence of Polymorphisms in the HTR3A and HTR3B Genes on Experimental Pain and the Effect of the 5-HT3 Antagonist Granisetron.

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Sofia Louca Jounger

Full Text Available The aim of this study was to investigate experimentally if 5-HT3 single nucleotide polymorphisms (SNP contribute to pain perception and efficacy of the 5-HT3-antagonist granisetron and sex differences. Sixty healthy participants were genotyped regarding HTR3A (rs1062613 and HTR3B (rs1176744. First, pain was induced by bilateral hypertonic saline injections (HS, 5.5%, 0.2 mL into the masseter muscles. Thirty min later the masseter muscle on one side was pretreated with 0.5 mL granisetron (1 mg/mL and on the other side with 0.5 mL placebo (isotonic saline followed by another HS injection (0.2 mL. Pain intensity, pain duration, pain area and pressure pain thresholds (PPTs were assessed after each injection. HS evoked moderate pain, with higher intensity in the women (P = 0.023, but had no effect on PPTs. None of the SNPs influenced any pain variable in general, but compared to men, the pain area was larger in women carrying the C/C (HTR3A (P = 0.015 and pain intensity higher in women with the A/C alleles (HTR3B (P = 0.019. Pre-treatment with granisetron reduced pain intensity, duration and area to a lesser degree in women (P < 0.05, but the SNPs did not in general influence the efficacy of granisetron. Women carrying the C/T & T/T (HTR3A genotype had less reduction of pain intensity (P = 0.041 and area (P = 0.005, and women with the C/C genotype (HTR3B had less reduction of pain intensity (P = 0.030, duration (P = 0.030 and area compared to men (P = 0.017. In conclusion, SNPs did not influence experimental muscle pain or the effect of granisetron on pain variables in general, but there were some sex differences in pain variables that seem to be influenced by genotypes. However, due to the small sample size further research is needed before any firm conclusions can be drawn.

The role of state anxiety in children's memories for pain.

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Noel, Melanie; Chambers, Christine T; McGrath, Patrick J; Klein, Raymond M; Stewart, Sherry H

2012-06-01

To investigate the impact of experimentally manipulated state anxiety and the influence of anxiety-related variables on children's memories for pain. A total of 110 children (60 boys) between the ages of 8 and 12 years were randomly assigned to complete a state anxiety induction task or a control task. Following experimental manipulation, children completed a laboratory pain task, pain ratings, and questionnaire measures of anxiety-related variables. 2 weeks later, children provided pain ratings based on their memories of the pain task. The experimental manipulation effectively induced state anxiety; however, pain memories did not differ between groups. Irrespective of group assignment, children with higher state anxiety had more negative pain memories. State anxiety uniquely predicted children's pain memories over and above other well established factors. Anxiety sensitivity and trait anxiety were significant predictors of recalled pain-related fear. These data highlight the importance of anxiety in the development of children's memories for pain.

Central Pain Processing in Early-Stage Parkinson's Disease: A Laser Pain fMRI Study.

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Christine Petschow

Full Text Available Pain is a common non-motor symptom in Parkinson's disease. As dopaminergic dysfunction is suggested to affect intrinsic nociceptive processing, this study was designed to characterize laser-induced pain processing in early-stage Parkinson's disease patients in the dopaminergic OFF state, using a multimodal experimental approach at behavioral, autonomic, imaging levels.13 right-handed early-stage Parkinson's disease patients without cognitive or sensory impairment were investigated OFF medication, along with 13 age-matched healthy control subjects. Measurements included warmth perception thresholds, heat pain thresholds, and central pain processing with event-related functional magnetic resonance imaging (erfMRI during laser-induced pain stimulation at lower (E = 440 mJ and higher (E = 640 mJ target energies. Additionally, electrodermal activity was characterized during delivery of 60 randomized pain stimuli ranging from 440 mJ to 640 mJ, along with evaluation of subjective pain ratings on a visual analogue scale.No significant differences in warmth perception thresholds, heat pain thresholds, electrodermal activity and subjective pain ratings were found between Parkinson's disease patients and controls, and erfMRI revealed a generally comparable activation pattern induced by laser-pain stimuli in brain areas belonging to the central pain matrix. However, relatively reduced deactivation was found in Parkinson's disease patients in posterior regions of the default mode network, notably the precuneus and the posterior cingulate cortex.Our data during pain processing extend previous findings suggesting default mode network dysfunction in Parkinson's disease. On the other hand, they argue against a genuine pain-specific processing abnormality in early-stage Parkinson's disease. Future studies are now required using similar multimodal experimental designs to examine pain processing in more advanced stages of Parkinson's disease.

Voluntary wheel running delays disease onset and reduces pain hypersensitivity in early experimental autoimmune encephalomyelitis (EAE).

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Benson, Curtis; Paylor, John W; Tenorio, Gustavo; Winship, Ian; Baker, Glen; Kerr, Bradley J

2015-09-01

Multiple sclerosis (MS) is classically defined by motor deficits, but it is also associated with the secondary symptoms of pain, depression, and anxiety. Up to this point modifying these secondary symptoms has been difficult. There is evidence that both MS and the animal model experimental autoimmune encephalomyelitis (EAE), commonly used to study the pathophysiology of the disease, can be modulated by exercise. To examine whether limited voluntary wheel running could modulate EAE disease progression and the co-morbid symptoms of pain, mice with EAE were allowed access to running wheels for 1h every day. Allowing only 1h every day of voluntary running led to a significant delay in the onset of clinical signs of the disease. The development of mechanical allodynia was assessed using Von Frey hairs and indicated that wheel running had a modest positive effect on the pain hypersensitivity associated with EAE. These behavioral changes were associated with reduced numbers of cFOS and phosphorylated NR1 positive cells in the dorsal horn of the spinal cord compared to no-run EAE controls. In addition, within the dorsal horn, voluntary wheel running reduced the number of infiltrating CD3(+) T-cells and reduced the overall levels of Iba1 immunoreactivity. Using high performance liquid chromatography (HPLC), we observed that wheel-running lead to significant changes in the spinal cord levels of the antioxidant glutathione. Oxidative stress has separately been shown to contribute to EAE disease progression and neuropathic pain. Together these results indicate that in mice with EAE, voluntary motor activity can delay the onset of clinical signs and reduce pain symptoms associated with the disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Hormones in pain modulation and their clinical implications for pain control: a critical review.

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Chen, Xueyin; Zhang, Jinyuan; Wang, Xiangrui

2016-07-01

Recently, more and more studies have found that pain generation, transmission and modulation are under hormonal regulation. Indeed, hormonal dysregulation is a common component of chronic pain syndromes. Studies have attempted to determine whether the relationship between the pain and its perception and hormones is a causative relationship and how these processes interrelate. This review summarizes and analyzes the current experimental data and provides an overview of the studies addressing these questions. The relationship between pain perception and endocrine effects suggests that hormones can be used as important biomarkers of chronic pain syndromes and/or be developed into therapeutic agents in the fight against pain.

Simultaneous fMRI-PET of the opioidergic pain system in human brain

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Wey, Hsiao-Ying; Catana, Ciprian; Hooker, Jacob M

2014-01-01

distinct components of the blood oxygenation level dependent (BOLD) fMRI signal has not yet been shown. We obtained sixteen fMRI-PET data sets from eight healthy volunteers. Each subject participated in randomized order in a pain scan and a control (nonpainful pressure) scan on the same day. Dynamic PET......MRI and PET provide complementary information for studying brain function. While the potential use of simultaneous MRI/PET for clinical diagnostic and disease staging has been demonstrated recently; the biological relevance of concurrent functional MRI-PET brain imaging to dissect neurochemically...... data were acquired with an opioid radioligand, [(11)C]diprenorphine, to detect endogenous opioid releases in response to pain. BOLD fMRI data were collected at the same time to capture hemodynamic responses. In this simultaneous human fMRI-PET imaging study, we show co-localized responses in thalamus...

Reconsidering the International Association for the Study of Pain definition of pain.

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Cohen, Milton; Quintner, John; van Rysewyk, Simon

2018-03-01

The definition of pain promulgated by the International Association for the Study of Pain (IASP) is widely accepted as a pragmatic characterisation of that human experience. Although the Notes that accompany it characterise pain as "always subjective," the IASP definition itself fails to sufficiently integrate phenomenological aspects of pain. This essay reviews the historical development of the IASP definition, and the commentaries and suggested modifications to it over almost 40 years. Common factors of pain experience identified in phenomenological studies are described, together with theoretical insights from philosophy and biology. A fuller understanding of the pain experience and of the clinical care of those experiencing pain is achievable through greater attention to the phenomenology of pain, the social "intersubjective space" in which pain occurs, and the limitations of language. Based on these results, a revised definition of pain is offered: Pain is a mutually recognizable somatic experience that reflects a person's apprehension of threat to their bodily or existential integrity.

Cancer Pain Management Education Rectifies Patients' Misconceptions of Cancer Pain, Reduces Pain, and Improves Quality of Life.

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Koh, Su-Jin; Keam, Bhumsuk; Hyun, Min Kyung; Ju Seo, Jeong; Uk Park, Keon; Oh, Sung Yong; Ahn, Jinseok; Lee, Ja Youn; Kim, JinShil

2018-03-26

More than half of the patients have reported improper management of breakthrough cancer pain. Empirical evidence is lacking concerning the effectiveness of cancer pain education on breakthrough pain control. This study aimed to examine the effects of individual pain education on pain control, use of short-acting analgesics for breakthrough pain, quality of life outcomes, and rectification of patients' misconceptions regarding cancer pain. A quasi-experimental design was used. In total, 176 (102 inpatients and 74 outpatients) and 163 (93 inpatients and 70 outpatients) cancer patients completed questionnaires on pain intensity, quality of life, use of short-acting medication for breakthrough pain, and misconceptions about cancer pain and opioid use before and immediately and/or seven days after individual pain education. The mean age of the participants was 60.9 years (±11.2), and 56.3% were male. The most common cancers were lung cancer (17.0%), colon cancer (15.9%), and breast cancer (12.5%). The subjects' reasons for attrition were conditional deterioration, death, or voluntary withdrawal (N = 13, 7.4%). Following the education, there was a significant reduction in overall pain intensity over 24 hours (P < 0.001). The outpatients showed more use of short-acting analgesics for breakthrough pain. Sleep quality change was most significantly associated with intervention; other quality of life aspects (e.g., general feelings and life enjoyment) also improved. Pain education also significantly reduced misconceptions regarding cancer pain management. The present educational intervention was effective in encouraging short-acting analgesic use for breakthrough pain, improving quality of life outcomes, and rectifying patients' misconceptions about analgesic use.

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

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

2017-09-01

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

Effect of static magnetic field on pain level and expression of P2X3 receptors in the trigeminal ganglion in mice following experimental tooth movement.

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Zhu, Yafen; Wang, Shengguo; Long, Hu; Zhu, Jingyi; Jian, Fan; Ye, Niansong; Lai, Wenli

2017-01-01

Recent research has demonstrated that static magnetic fields (SMF) can generate an analgesic effect in different conditions. The present study explored effects of SMF on pain levels and expressions of P2X3 receptors in trigeminal ganglion (TG) in mice after experimental tooth movement (tooth movement induced by springs between teeth). Experiments were performed in male mice (body mass: 25-30 g) and divided into SMF + force group, force group, and no force group. Exposure time was over 22 h per day. Mouse Grimace Scale was used for evaluating orofacial pain levels during experimental tooth movement at 4 h and 1, 3, 7, and 14 days. Meanwhile, expression levels of P2X3 receptors in the TG were evaluated by immunohistochemistry and western blotting at same time points. We finally found that during experimental tooth movement, pain levels of mice peaked at 3 days, and then decreased. While pain levels of mice were reduced in the SMF environment at 4 h, 1 and 3 days, there was a significant difference at 1 and 3 days. Meanwhile, under the action of SMF, expression levels of P2X3 receptors in TG were significantly lower at 4 h, 3 and 7 days. These results suggest that SMF can reduce pain levels in mice, and down-regulate P2X3 receptors in TG. Bioelectromagnetics. 38:22-30, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Different pain responses to chronic and acute pain in various ethnic/racial groups.

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Rahavard, Behnoosh B; Candido, Kenneth D; Knezevic, Nebojsa Nick

2017-09-01

Our goal in this study was to review the similarities and differences among ethnic groups and their respective responses to acute and chronic clinically related and experimentally induced pain. In this review, the PUBMED and Google-Scholar databases were searched to analyze articles that have assessed the variations in both acute and chronic pain responses among different ethnic/racial groups. According to the results from 42 reviewed articles, significant differences exist among ethnic-racial groups for pain prevalence as well as responses to acute and chronic pain. Compared with Caucasians, other ethnic groups are more susceptible to acute pain responses to nociceptive stimulation and to the development of long-term chronic pain. These differences need to be addressed and assessed more extensively in the future in order to minimize the pain management disparities among various ethnic-racial groups and also to improve the relationship between pain management providers and their patients.

Pain without nociceptors?

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Minett, Michael S; Falk, Sarah; Santana-Varela, Sonia

2014-01-01

Nav1.7, a peripheral neuron voltage-gated sodium channel, is essential for pain and olfaction in mice and humans. We examined the role of Nav1.7 as well as Nav1.3, Nav1.8, and Nav1.9 in different mouse models of chronic pain. Constriction-injury-dependent neuropathic pain is abolished when Nav1.......7 is deleted in sensory neurons, unlike nerve-transection-related pain, which requires the deletion of Nav1.7 in sensory and sympathetic neurons for pain relief. Sympathetic sprouting that develops in parallel with nerve-transection pain depends on the presence of Nav1.7 in sympathetic neurons. Mechanical...... and cold allodynia required distinct sets of neurons and different repertoires of sodium channels depending on the nerve injury model. Surprisingly, pain induced by the chemotherapeutic agent oxaliplatin and cancer-induced bone pain do not require the presence of Nav1.7 sodium channels or Nav1.8-positive...

An Exploratory Human Laboratory Experiment Evaluating Vaporized Cannabis in the Treatment of Neuropathic Pain From Spinal Cord Injury and Disease.

Science.gov (United States)

Wilsey, Barth; Marcotte, Thomas D; Deutsch, Reena; Zhao, Holly; Prasad, Hannah; Phan, Amy

2016-09-01

Using 8-hour human laboratory experiments, we evaluated the analgesic efficacy of vaporized cannabis in patients with neuropathic pain related to injury or disease of the spinal cord, most of whom were experiencing pain despite traditional treatment. After obtaining baseline data, 42 participants underwent a standardized procedure for inhaling 4 puffs of vaporized cannabis containing either placebo, 2.9%, or 6.7% delta 9-THC on 3 separate occasions. A second dosing occurred 3 hours later; participants chose to inhale 4 to 8 puffs. This flexible dosing was used to attempt to reduce the placebo effect. Using an 11-point numerical pain intensity rating scale as the primary outcome, a mixed effects linear regression model showed a significant analgesic response for vaporized cannabis. When subjective and psychoactive side effects (eg, good drug effect, feeling high, etc) were added as covariates to the model, the reduction in pain intensity remained significant above and beyond any effect of these measures (all P analgesic potency, the lower dose appears to offer the best risk-benefit ratio in patients with neuropathic pain associated with injury or disease of the spinal cord. A crossover, randomized, placebo-controlled human laboratory experiment involving administration of vaporized cannabis was performed in patients with neuropathic pain related to spinal cord injury and disease. This study supports consideration of future research that would include longer duration studies over weeks to months to evaluate the efficacy of medicinal cannabis in patients with central neuropathic pain. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Kinin B1 receptors contributes to acute pain following minor surgery in humans

Directory of Open Access Journals (Sweden)

Brahim Jaime S

2010-02-01

Full Text Available Abstract Background Kinins play an important role in regulation of pain and hyperalgesia after tissue injury and inflammation by activating two types of G-protein-coupled receptors, the kinin B1 and B2 receptors. It is generally accepted that the B2 receptor is constitutively expressed, whereas the B1 receptor is induced in response to inflammation. However, little is known about the regulatory effects of kinin receptors on the onset of acute inflammation and inflammatory pain in humans. The present study investigated the changes in gene expression of kinin receptors and the levels of their endogenous ligands at an early time point following tissue injury and their relation to clinical pain, as well as the effect of COX-inhibition on their expression levels. Results Tissue injury resulted in a significant up-regulation in the gene expression of B1 and B2 receptors at 3 hours post-surgery, the onset of acute inflammatory pain. Interestingly, the up-regulation in the gene expression of B1 and B2 receptors was positively correlated to pain intensity only after ketorolac treatment, signifying an interaction between prostaglandins and kinins in the inflammatory pain process. Further, the gene expression of both B1 and B2 receptors were correlated. Following tissue injury, B1 ligands des-Arg9-BK and des-Arg10-KD were significantly lower at the third hour compared to the first 2 hours in both the placebo and the ketorolac treatment groups but did not differ significantly between groups. Tissue injury also resulted in the down-regulation of TRPV1 gene expression at 3 hours post-surgery with no significant effect by ketorolac treatment. Interestingly, the change in gene expression of TRPV1 was correlated to the change in gene expression of B1 receptor but not B2 receptor. Conclusions These results provide evidence at the transcriptional level in a clinical model of tissue injury that up-regulation of kinin receptors are involved in the development of the

The Effectiveness of Cognitive-Behavioral Therapy on Alexithymia and Pain Self-Efficacy of Patients with Chronic Pain

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Sara Saedi

2016-11-01

Full Text Available Chronic pain is one of the most common reasons for visit to primary medical centers. Evidences show that cognitive-behavioral therapy is the effective therapy in chronic pains. The present study evaluates the effectiveness of cognitive-behavioral therapy on alexithymia and pains self-efficacy of patients with chronic pain. For this purpose, in a quasi-experimental plan and pre-test and post-test kind with control group, 45 patients with chronic musculoskeletal pain who visited to the therapeutic-sanitary centers in Ahwaz city were selected by using the available sampling method and they were assigned randomly in two experimental and control groups. Groups were tested in terms of alexithymia and self-effectiveness of pain at first. Then behavioral-cognitive training was presented in the time of 8 sessions of 90 minutes to the group and after ending the training program and three month consistency period, both groups were tested in terms of alexithymia and self-efficacy of pain. analyzing data by multivariate covariance method showed that the behavioral-cognitive therapy has been effective on alexithymia and pain intensity of patients with chronic musculoskeletal pain and these effects remain on patients in the high amount in the consistency stage, too. According to the results, behavioral-cognitive therapy causes to increasing the self-efficacy of pain and reducing the alexithymia and harmful effects of pain to the least level by changing nonefficiency behaviors, correction of adverse cognitions and destructive emotions related to pain.

Central representation of muscle pain and mechanical hyperesthesia in the orofacial region: a positron emission tomography study

DEFF Research Database (Denmark)

Kupers, Rron; Svensson, Peter; Jensen, Troels Staehlin

2004-01-01

Functional neuroimaging studies of the human brain have revealed a network of brain regions involved in the processing of nociceptive information. However, little is known of the cerebral processing of pain originating from muscles. The aim of this study was to investigate the cerebral activation...... pattern evoked by experimental jaw-muscle pain and its interference by simultaneous mechanical stimuli, which has been shown to evoke hyperesthesia. Ten healthy subjects participated in a PET study and jaw-muscle pain was induced by bolus injections of 5% hypertonic saline into the right masseter muscle....... Repeated von Frey hair stimulation (0.5 Hz) of the skin above the masseter muscle was used as the mechanical stimulus. Hypertonic saline injections caused strong muscle pain spreading to adjacent areas. von Frey stimulation was rated as non-painful but produced hyperesthesia during jaw-muscle pain. Jaw...

Pain-related anxiety influences pain perception differently in men and women: a quantitative sensory test across thermal pain modalities.

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Thibodeau, Michel A; Welch, Patrick G; Katz, Joel; Asmundson, Gordon J G

2013-03-01

The sexes differ with respect to perception of experimental pain. Anxiety influences pain perception more in men than in women; however, there lacks research exploring which anxiety constructs influence pain perception differentially between men and women. Furthermore, research examining whether depression is associated with pain perception differently between the sexes remains scant. The present investigation was designed to examine how trait anxiety, pain-related anxiety constructs (ie, fear of pain, pain-related anxiety, anxiety sensitivity), and depression are associated with pain perception between the sexes. A total of 95 nonclinical participants (55% women) completed measures assessing the constructs of interest and participated in quantitative sensory testing using heat and cold stimuli administered by a Medoc Pathway Pain and Sensory Evaluation System. The findings suggest that pain-related anxiety constructs, but not trait anxiety, are associated with pain perception. Furthermore, these constructs are associated with pain intensity ratings in men and pain tolerance levels in women. This contrasts with previous research suggesting that anxiety influences pain perception mostly or uniquely in men. Depression was not systematically associated with pain perception in either sex. Systematic relationships were not identified that allow conclusions regarding how fear of pain, pain-related anxiety, and anxiety sensitivity may contribute to pain perception differentially in men and women; however, anxiety sensitivity was associated with increased pain tolerance, a novel finding needing further examination. The results provide directions for future research and clinical endeavors and support that fear and anxiety are important features associated with hyperalgesia in both men and women. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Symptoms of Fibromyalgia According to the 2016 Revised Fibromyalgia Criteria in Chronic Pain Patients Referred to Multidisciplinary Pain Rehabilitation: Influence on Clinical and Experimental Pain Sensitivity

DEFF Research Database (Denmark)

Plesner, Karin Bruun; Vaegter, Henrik Bjarke

2018-01-01

Fibromyalgia is a condition with chronic widespread pain and signs of generalized pain hypersensitivity. FM has previously been classified according to the ACR1990 criteria, where the presence of hypersensitivity is estimated by a tender point examination. Due to the limitations of these classifi......Fibromyalgia is a condition with chronic widespread pain and signs of generalized pain hypersensitivity. FM has previously been classified according to the ACR1990 criteria, where the presence of hypersensitivity is estimated by a tender point examination. Due to the limitations...... of these classification criteria, new diagnostic criteria have been proposed, abandoning this examination. This cross-sectional study investigated the prevalence of FM according to the revised 2016 FM criteria in a large cohort of chronic pain patients. Pain drawings, the Fibromyalgia Symptom Severity Scale...

Multimodal distribution of human cold pain thresholds.

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Lötsch, Jörn; Dimova, Violeta; Lieb, Isabel; Zimmermann, Michael; Oertel, Bruno G; Ultsch, Alfred

2015-01-01

It is assumed that different pain phenotypes are based on varying molecular pathomechanisms. Distinct ion channels seem to be associated with the perception of cold pain, in particular TRPM8 and TRPA1 have been highlighted previously. The present study analyzed the distribution of cold pain thresholds with focus at describing the multimodality based on the hypothesis that it reflects a contribution of distinct ion channels. Cold pain thresholds (CPT) were available from 329 healthy volunteers (aged 18 - 37 years; 159 men) enrolled in previous studies. The distribution of the pooled and log-transformed threshold data was described using a kernel density estimation (Pareto Density Estimation (PDE)) and subsequently, the log data was modeled as a mixture of Gaussian distributions using the expectation maximization (EM) algorithm to optimize the fit. CPTs were clearly multi-modally distributed. Fitting a Gaussian Mixture Model (GMM) to the log-transformed threshold data revealed that the best fit is obtained when applying a three-model distribution pattern. The modes of the identified three Gaussian distributions, retransformed from the log domain to the mean stimulation temperatures at which the subjects had indicated pain thresholds, were obtained at 23.7 °C, 13.2 °C and 1.5 °C for Gaussian #1, #2 and #3, respectively. The localization of the first and second Gaussians was interpreted as reflecting the contribution of two different cold sensors. From the calculated localization of the modes of the first two Gaussians, the hypothesis of an involvement of TRPM8, sensing temperatures from 25 - 24 °C, and TRPA1, sensing cold from 17 °C can be derived. In that case, subjects belonging to either Gaussian would possess a dominance of the one or the other receptor at the skin area where the cold stimuli had been applied. The findings therefore support a suitability of complex analytical approaches to detect mechanistically determined patterns from pain phenotype data.

Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling

OpenAIRE

Vetter, Irina; Touska, Filip; Hess, Andreas; Hinsbey, Rachel; Sattler, Simon; Lampert, Angelika; Sergejeva, Marina; Sharov, Anastasia; Collins, Lindon S; Eberhardt, Mirjam; Engel, Matthias; Cabot, Peter J; Wood, John N; Vlachová, Viktorie; Reeh, Peter W

2012-01-01

Ciguatoxins derived from fish lead to cold allodynia in humans, the perception of intense burning pain in response to mild cooling. A novel mouse model of ciguatoxin-induced cold allodynia reveals that ciguatoxin activates the TRPA1 thermosensitive ion channel to mediate pain perception.

Acute pain induces an instant increase in natural killer cell cytotoxicity in humans and this response is abolished by local anaesthesia

DEFF Research Database (Denmark)

Greisen, J.; Hokland, Marianne; Grøfte, Thorbjørn

1999-01-01

We have investigated the effect of pain without tissue injury on natural killer (NK) cell activity in peripheral blood in humans and the effect of local anaesthesia on the response. Ten subjects were investigated during two sessions. First, self-controlled painful electric stimulation was applied...

Pain and psycho-affective disorders.

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Broggi, Giovanni

2008-06-01

The subject of human pain can be subdivided into two broad categories: physical pain and psychological pain. Since the dawn of human consciousness, each of these two forms of pain-one clearly physical, the other having more to deal with the mind-have played a central role in human existence. Psychological pain and suffering add dimensions that go far beyond the boundaries of its physical counterpart. In the past 50 years, one of the more remarkable accomplishments of medical science has been to increasingly enable the clinician to impact, as never before, each of these critical realms of human existence. Our intention is, therefore, to initially describe a few of the many exciting neuroscientific and neurosurgical advances that have been made in the treatment of various types of pain and to speculate on some of the emergent questions that we believe need to be addressed. After this is accomplished, we will then use this information as a kind of two-pronged philosophical entrance into questions of the mind, brain, and soul that we feel are necessary to bring back into the sphere of the modern physician's practice. The goal of this article is two-fold: 1) to share some of our exciting research and 2) to renew the interest in timeless questions, such as that of the mind-brain and the brain-mind, in the conversation of the modern neurosurgeon. The International Association for the Study of Pain divides pain into two broad functions and anatomical categories. In this framework, "nociceptive" pain is defined as the kind of physical pain that results when the tissue is damaged. Given this perspective, such pain is usually considered a consequence of one's defense against one's environment. The other pain is the "neuropathic" one resulting from a lesion or a dysfunction of the human nervous system. As such, we will take the risk of crossing beyond the boundaries of neurosurgery and venture into boundaries that, at another time, might seem more natural to the discipline of

Post-operative pain prevalence, predictors, management practices ...

African Journals Online (AJOL)

MWASHAMBWA

developing countries however, the prevalence of post-operative pain is relatively very high and pain control strategies ... Keywords: post-operative pain, prevalence, predictors, pain management, satisfaction, Tanzania. Introduction ..... perception and patterns of cerebral activation during noxious heat stimulation in humans.

Experimentally induced masseter-pain changes masseter but not sternocleidomastoid muscle-related activity during mastication.

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Pasinato, Fernanda; Santos-Couto-Paz, Clarissa C; Zeredo, Jorge Luis Lopes; Macedo, Sergio Bruzadelli; Corrêa, Eliane C R

2016-12-01

The aim of this study was to verify the effects of induced masseter-muscle pain on the amplitude of muscle activation, symmetry and coactivation of jaw- and neck-muscles during mastication. Twenty-eight male volunteers, mean age±SD 20.6±2.0years, participated in this study. Surface electromyography of the masseter and sternocleidomastoid (SCM) muscles was performed bilaterally during mastication of a gummy candy before and after injections of monosodium glutamate solution and isotonic saline solution. As a result, we observed a decrease in the amplitude of activation of the masseter muscle on the working side (p=0.009; d=0.34) and a reduction in the asymmetry between the working and the balancing side during mastication (p=0.007; d=0.38). No changes were observed either on the craniocervical electromyographic variables. In conclusion, experimentally induced pain reduced the masseter muscle activation on the working side, thereby reducing the physiological masseters' recruitment asymmetry between the two sides during mastication. No effects on SCM activity were detected. These results may partly explain the initial maladaptative changes underlying TMD conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Influence of exercise on visceral pain

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van Weerdenburg, Laura Jgm; Brock, Christina; Drewes, Asbjørn Mohr

2017-01-01

Background and objectives: Contradictory results have been found about the effect of different exercise modalities on pain. The aim of this study was to investigate the early effects of aerobic and isometric exercise on different types of experimental pain, including visceral pain, compared...... intervention, psychophysical tests were performed, including electrical stimulation of the esophagus, pressure pain thresholds and the cold pressor test as a measure for conditioned pain modulation. Participants completed the Medical Outcome Study Short-Form 36 and State- Trait Anxiety Inventory prior...

The necessity of animal models in pain research.

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Mogil, Jeffrey S; Davis, Karen D; Derbyshire, Stuart W

2010-10-01

There exists currently a fair degree of introspection in the pain research community about the value of animal research. This review represents a defense of animal research in pain. We discuss the inherent advantage of animal models over human research as well as the crucial complementary roles animal studies play vis-à-vis human imaging and genetic studies. Finally, we discuss recent developments in animal models of pain that should improve the relevance and translatability of findings using laboratory animals. We believe that pain research using animal models is a continuing necessity-to understand fundamental mechanisms, identify new analgesic targets, and inform, guide and follow up human studies-if novel analgesics are to be developed for the treatment of chronic pain. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Depression and Pain in Asian and White Americans With Knee Osteoarthritis.

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Ahn, Hyochol; Weaver, Michael; Lyon, Debra; Choi, Eunyoung; Fillingim, Roger B

2017-10-01

Few studies have examined the underlying psychosocial mechanisms of pain in Asian Americans. Using the biopsychosocial model, we sought to determine whether variations in depression contribute to racial group differences in symptomatic knee osteoarthritis pain between Asian Americans and non-Hispanic white Americans. The sample consisted of 100 participants, including 50 Asian Americans (28 Korean Americans, 9 Chinese Americans, 7 Japanese Americans, 5 Filipino Americans, and 1 Indian American) and 50 age- and sex-matched non-Hispanic white Americans with symptomatic knee osteoarthritis pain. The Centers for Epidemiologic Studies Depression Scale was used to assess symptoms of depression, and the Western Ontario and McMaster Universities Osteoarthritis Index and the Graded Chronic Pain Scale were used to measure clinical pain. In addition, quantitative sensory testing was used to measure experimental sensitivity to heat- and mechanically-induced pain. The results indicated that higher levels of depression in Asian Americans may contribute to greater clinical pain and experimental pain sensitivity. These findings add to the growing literature regarding ethnic and racial differences in pain and its associated psychological conditions, and additional research is warranted to strengthen these findings. This article shows the contribution of depression to clinical pain and experimental pain sensitivity in Asian Americans with knee osteoarthritis. Our results suggest that Asian Americans have higher levels of depressive symptoms and that depression plays a relevant role in greater clinical pain and experimental pain sensitivity in Asian Americans. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

Electronic Gaming as Pain Distraction

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Eleanor Jameson

2011-01-01

Full Text Available The current study investigated whether active distraction reduces participants’ experience of pain more than passive distraction during a cold pressor task. In the first experiment, 60 participants were asked to submerge their hand in cold (2°C water for as long as they could tolerate. They did this with no distraction, and then with active (electronic gaming system and passive (television distraction, in randomly assigned order. Tolerance time, pain intensity ratings and task absorption ratings were measured for each condition. A second experiment attempted to control for participants’ expectations about the effects of distraction on pain. Forty participants underwent the same experimental procedure, but were given verbal suggestions about the effects of distraction by the experimenter before each distraction condition. Participants in both experiments had a significantly higher pain tolerance and reported less pain with the active distraction compared with passive or no distraction. Participants reported being more absorbed, and were significantly more willing to do the task again when they had the active distraction compared with both passive distraction and no distraction. They also had more enjoyment, less anxiety and greater reduction in pain with active distraction than with passive distraction. There was no effect of suggestion. These experiments offer further support for the use of electronic games as a method of pain control.

Doubling Your Payoff: Winning Pain Relief Engages Endogenous Pain Inhibition1,2,3

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Kwan, Saskia; Schweinhardt, Petra

2015-01-01

Abstract When in pain, pain relief is much sought after, particularly for individuals with chronic pain. In analogy to augmentation of the hedonic experience (“liking”) of a reward by the motivation to obtain a reward (“wanting”), the seeking of pain relief in a motivated state might increase the experience of pain relief when obtained. We tested this hypothesis in a psychophysical experiment in healthy human subjects, by assessing potential pain-inhibitory effects of pain relief “won” in a wheel of fortune game compared with pain relief without winning, exploiting the fact that the mere chance of winning induces a motivated state. The results show pain-inhibitory effects of pain relief obtained by winning in behaviorally assessed pain perception and ratings of pain intensity. Further, the higher participants scored on the personality trait novelty seeking, the more pain inhibition was induced. These results provide evidence that pain relief, when obtained in a motivated state, engages endogenous pain-inhibitory systems beyond the pain reduction that underlies the relief in the first place. Consequently, such pain relief might be used to improve behavioral pain therapy, inducing a positive, perhaps self-amplifying feedback loop of reduced pain and improved functionality. PMID:26464995

Forebrain Mechanisms of Nociception and Pain: Analysis through Imaging

Science.gov (United States)

Casey, Kenneth L.

1999-07-01

Pain is a unified experience composed of interacting discriminative, affective-motivational, and cognitive components, each of which is mediated and modulated through forebrain mechanisms acting at spinal, brainstem, and cerebral levels. The size of the human forebrain in relation to the spinal cord gives anatomical emphasis to forebrain control over nociceptive processing. Human forebrain pathology can cause pain without the activation of nociceptors. Functional imaging of the normal human brain with positron emission tomography (PET) shows synaptically induced increases in regional cerebral blood flow (rCBF) in several regions specifically during pain. We have examined the variables of gender, type of noxious stimulus, and the origin of nociceptive input as potential determinants of the pattern and intensity of rCBF responses. The structures most consistently activated across genders and during contact heat pain, cold pain, cutaneous laser pain or intramuscular pain were the contralateral insula and anterior cingulate cortex, the bilateral thalamus and premotor cortex, and the cerebellar vermis. These regions are commonly activated in PET studies of pain conducted by other investigators, and the intensity of the brain rCBF response correlates parametrically with perceived pain intensity. To complement the human studies, we developed an animal model for investigating stimulus-induced rCBF responses in the rat. In accord with behavioral measures and the results of human PET, there is a progressive and selective activation of somatosensory and limbic system structures in the brain and brainstem following the subcutaneous injection of formalin. The animal model and human PET studies should be mutually reinforcing and thus facilitate progress in understanding forebrain mechanisms of normal and pathological pain.

Effect of experimental stress in 2 different pain conditions affecting the facial muscles.

Science.gov (United States)

Woda, Alain; L'heveder, Gildas; Ouchchane, Lemlih; Bodéré, Céline

2013-05-01

Chronic facial muscle pain is a common feature in both fibromyalgia (FM) and myofascial (MF) pain conditions. In this controlled study, a possible difference in the mode of deregulation of the physiological response to a stressing stimulus was explored by applying an acute mental stress to FM and MF patients and to controls. The effects of the stress test were observed on pain, sympathetic variables, and both tonic and reflex electromyographic activities of masseteric and temporal muscles. The statistical analyses were performed through a generalized linear model including mixed effects. Painful reaction to the stressor was stronger (P < .001) and longer (P = .011) in FM than in MF independently of a higher pain level at baseline. The stress-induced autonomic changes only seen in FM patients did not reach significance. The electromyographic responses to the stress test were strongest for controls and weakest for FM. The stress test had no effect on reflex activity (area under the curve [AUC]) or latency, although AUC was high in FM and latencies were low in both pain groups. It is suggested that FM is characterized by a lower ability to adapt to acute stress than MF. This study showed that an acute psychosocial stress triggered several changes in 2 pain conditions including an increase in pain of larger amplitude in FM than in MF pain. Similar stress-induced changes should be explored as possible mechanisms for differentiation between dysfunctional pain conditions. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

Equal pain – Unequal fear response: Enhanced susceptibility of tooth pain to fear conditioning

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Michael Lukas Meier

2014-07-01

Full Text Available Experimental fear conditioning in humans is widely used as a model to investigate the neural basis of fear learning and to unravel the pathogenesis of anxiety disorders. It has been observed that fear conditioning depends on stimulus salience and subject vulnerability to fear. It is further known that the prevalence of dental-related fear and phobia is exceedingly high in the population. Dental phobia is unique as no other body part is associated with a specific phobia. Therefore, we hypothesized that painful dental stimuli exhibit an enhanced susceptibility to fear conditioning when comparing to equal perceived stimuli applied to other body sites. Differential susceptibility to pain-related fear was investigated by analyzing responses to an unconditioned stimulus (UCS applied to the right maxillary canine (UCS-c versus the right tibia (UCS-t. For fear conditioning, UCS-c and USC-t consisted of painful electric stimuli, carefully matched at both application sites for equal intensity and quality perception. UCSs were paired to simple geometrical forms which served as conditioned stimuli (CS+. Unpaired CS+ were presented for eliciting and analyzing conditioned fear responses. Outcome parameter were 1 skin conductance changes and 2 time-dependent brain activity (BOLD responses in fear-related brain regions such as the amygdala, anterior cingulate cortex, insula, thalamus, orbitofrontal cortex and medial prefrontal cortex.A preferential susceptibility of dental pain to fear conditioning was observed, reflected by heightened skin conductance responses and enhanced time-dependent brain activity (BOLD responses in the fear network. For the first time, this study demonstrates fear-related neurobiological mechanisms that point towards a superior conditionability of tooth pain. Beside traumatic dental experiences our results offer novel evidence that might explain the high prevalence of dental-related fears in the population.

Is the Experience of Thermal Pain Genetics Dependent?

Directory of Open Access Journals (Sweden)

Emilia Horjales-Araujo

2015-01-01

Full Text Available It is suggested that genetic variations explain a significant portion of the variability in pain perception; therefore, increased understanding of pain-related genetic influences may identify new targets for therapies and treatments. The relative contribution of the different genes to the variance in clinical and experimental pain responses remains unknown. It is suggested that the genetic contributions to pain perception vary across pain modalities. For example, it has been suggested that more than 60% of the variance in cold pressor responses can be explained by genetic factors; in comparison, only 26% of the variance in heat pain responses is explained by these variations. Thus, the selection of pain model might markedly influence the magnitude of the association between the pain phenotype and genetic variability. Thermal pain sensation is complex with multiple molecular and cellular mechanisms operating alone and in combination within the peripheral and central nervous system. It is thus highly probable that the thermal pain experience is affected by genetic variants in one or more of the pathways involved in the thermal pain signaling. This review aims to present and discuss some of the genetic variations that have previously been associated with different experimental thermal pain models.

Genes contributing to pain sensitivity in the normal population

DEFF Research Database (Denmark)

Williams, Frances M.K.; Scollen, Serena; Cao, Dandan

2012-01-01

Sensitivity to pain varies considerably between individuals and is known to be heritable. Increased sensitivity to experimental pain is a risk factor for developing chronic pain, a common and debilitating but poorly understood symptom. To understand mechanisms underlying pain sensitivity and to s...

Complex Regional Pain Syndrome (CRPS/RSD and Neuropathic Pain: Role of Intravenous Bisphosphonates as Analgesics

Directory of Open Access Journals (Sweden)

Jennifer Yanow

2008-01-01

Full Text Available Neuropathic pain is a sequela of dysfunction, injuries, or diseases of the peripheral and/or central nervous system pain pathways, which has historically been extremely difficult to treat. Complex regional pain syndrome (CRPS types 1 and 2 are neuropathic pain conditions that have a long history in the medical literature but whose pathophysiology remains elusive and whose available treatment options remain few. While an exact animal model for CRPS doesn't yet exist, there are several animal models of neuropathic pain that develop behaviors of hypersensitivity, one of the hallmark signs of neuropathic pain in humans.

Night-shift work is associated with increased pain perception.

Science.gov (United States)

Matre, Dagfinn; Knardahl, Stein; Nilsen, Kristian Bernhard

2017-05-01

Objectives The aim of the present study was to determine whether shift workers exhibit increased perception of experimentally induced pain after working night shifts. Methods The study was a paired cross-over design with two sleep conditions, after at least two nights of habitual sleep and after two consecutive night shifts at work. Fifty-three nurses in rotating shift work participated. The sensitivity to electrically induced pain, heat pain, cold pain, pressure pain and pain inhibition was determined experimentally in each sleep condition. Sleepiness and vigilance were also assessed. Results Night-shift work (NSW) increased the sensitivity to electrically induced pain and heat pain (P≤0.001). Relative to habitual sleep, electrically induced pain increased by 22.3% and heat pain increased by 26.5%. The sensitivity to cold and pressure pain did not change, changes relative to habitual sleep was 0.5). Pain inhibition was 66.9% stronger after NSW versus after habitual sleep (Peffect sizes and may be an important marker for studies comparing the physiological effects of different shift work schedules. Explanations for the differential effect on different pain modalities should be a focus for future studies.

The role of executive functioning in children's attentional pain control: an experimental analysis.

Science.gov (United States)

Verhoeven, Katrien; Dick, Bruce; Eccleston, Christopher; Goubert, Liesbet; Crombez, Geert

2014-02-01

Directing attention away from pain is often used in children's pain treatment programs to control pain. However, empirical evidence concerning its effectiveness is inconclusive. We therefore sought to understand other influencing factors, including executive function and its role in the pain experience. This study investigates the role of executive functioning in the effectiveness of distraction. School children (n=164) completed executive functioning tasks (inhibition, switching, and working memory) and performed a cold-pressor task. One half of the children simultaneously performed a distracting tone-detection task; the other half did not. Results showed that participants in the distraction group were engaged in the distraction task and were reported to pay significantly less attention to pain than controls. Executive functioning influenced distraction task engagement. More specifically, participants with good inhibition and working memory abilities performed the distraction task better; participants with good switching abilities reported having paid more attention to the distraction task. Furthermore, distraction was found to be ineffective in reducing pain intensity and affect. Executive functioning did not influence the effectiveness of distraction. However, a relationship was found between executive functioning and pain affect, indicating that participants with good inhibition and working memory abilities experienced the cold-pressor task as less stressful and unpleasant. Our findings suggest that distraction as a process for managing pain is complex. While it appears that executive function may play a role in adult distraction, in this study it did not direct attention away from pain. It may instead be involved in the overall pain experience. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Operant conditioning of enhanced pain sensitivity by heat-pain titration.

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Becker, Susanne; Kleinböhl, Dieter; Klossika, Iris; Hölzl, Rupert

2008-11-15

Operant conditioning mechanisms have been demonstrated to be important in the development of chronic pain. Most experimental studies have investigated the operant modulation of verbal pain reports with extrinsic reinforcement, such as verbal reinforcement. Whether this reflects actual changes in the subjective experience of the nociceptive stimulus remained unclear. This study replicates and extends our previous demonstration that enhanced pain sensitivity to prolonged heat-pain stimulation could be learned in healthy participants through intrinsic reinforcement (contingent changes in nociceptive input) independent of verbal pain reports. In addition, we examine whether different magnitudes of reinforcement differentially enhance pain sensitivity using an operant heat-pain titration paradigm. It is based on the previously developed non-verbal behavioral discrimination task for the assessment of sensitization, which uses discriminative down- or up-regulation of stimulus temperatures in response to changes in subjective intensity. In operant heat-pain titration, this discriminative behavior and not verbal pain report was contingently reinforced or punished by acute decreases or increases in heat-pain intensity. The magnitude of reinforcement was varied between three groups: low (N1=13), medium (N2=11) and high reinforcement (N3=12). Continuous reinforcement was applied to acquire and train the operant behavior, followed by partial reinforcement to analyze the underlying learning mechanisms. Results demonstrated that sensitization to prolonged heat-pain stimulation was enhanced by operant learning within 1h. The extent of sensitization was directly dependent on the received magnitude of reinforcement. Thus, operant learning mechanisms based on intrinsic reinforcement may provide an explanation for the gradual development of sustained hypersensitivity during pain that is becoming chronic.

Neuronal Plasticity Associated with Burn Injury and Its Relevance for Perception and Management of Pain in Burn Patients

Directory of Open Access Journals (Sweden)

Terence J Coderre

2000-01-01

Full Text Available Through the introduction of the gate control theory and various subsequent works, Ronald Melzack has inspired many investigators worldwide to realize two important facts about pain. First, incoming pain messages are subject to both negative and positive modulation, which significantly affect its perception. Second, the progression of knowledge about the basic mechanisms underlying persistent and chronic pain is critically dependent on the increased understanding of the complexity of the symptoms experienced by pain patients. The present paper examines these two very important issues in an effort to understand better the mechanisms that underlie the pain suffered by burn patients. The physiological responses to burn injury involve many different mediators and mechanisms, all of which contribute to pain perception and development of neuronal plasticity underlying short and long term changes in pain sensitivity. While experimental burn injuries in humans and animals are typically well controlled and mild, in burn victims, the severity is much more variable, and clinical care involves repeated traumas and manipulations of the injured sites. Recurrent inputs from damaged and redamaged tissue impinge on a nervous system that becomes an active participant in the initiation of changes in sensory perception and maintenance of long term sensory disturbances. Recently acquired experimental evidence on postburn hyperalgesia, central hyperexcitability and changes in opioid sensitivity provides strong support that burn patients need an analgesic approach aimed at preventing or reducing the 'neural' memory of pain, including the use of more than one treatment modality. Burn injuries offer a unique opportunity to combine experimental and clinical research to understand pain mechanisms better. Over the years, Ronald Melzack has insisted that one of the most laudable enterprises in research is to span the gap between these two often separate worlds.

Person-centred pain management for the patient with acute abdominal pain

DEFF Research Database (Denmark)

Avallin, Therese; Muntlin Athlin, Åsa; Sorensen, Erik Elgaard

2018-01-01

AIMS: To explore and describe the impact of the organizational culture on and the patient-practitioner patterns of actions that contribute to or detract from successful pain management for the patient with acute abdominal pain across the acute care pathway. BACKGROUND: Although pain management...... is a recognised human right, unmanaged pain continues to cause suffering and prolong hospital care. Unanswered questions about how to successfully manage pain relate to both organizational culture and individual practitioners' performance. DESIGN: Focused ethnography, applying the Developmental Research Sequence...... and the Fundamentals of Care framework. METHODS: Participant observation and informal interviews (92 hours) were performed at one emergency department and two surgical wards at a University Hospital during April - November 2015. Data includes 261 interactions between patients, aged ≥18 years seeking care for acute...

The effects of music therapy on pain in patients with neuropathic pain.

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Korhan, Esra Akın; Uyar, Meltem; Eyigör, Can; Hakverdioğlu Yönt, Gülendam; Çelik, Serkan; Khorshıd, Leyla

2014-03-01

The aim of this study was to investigate the effect of relaxing music on pain intensity in patients with neuropathic pain. A quasi-experimental study, repeated measures design was used. Thirty patients, aged 18-70 years, with neuropathic pain and hospitalized in an Algology clinic were identified as a convenience sample. Participants received 60 minutes of music therapy. Classical Turkish music was played to patients using a media player (MP3) and headphones. Participants had pain scores taken immediately before the intervention and at the 30th and 60th minutes of the intervention. Data were collected over a 6-month period in 2012. The patients' mean pain intensity scores were reduced by music, and that decrease was progressive over the 30th and 60th minutes of the intervention, indicating a cumulative dose effect. The results of this study implied that the inclusion of music therapy in the routine care of patients with neuropathic pain could provide nurses with an effective practice for reducing patients' pain intensity. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Conditioned pain modulation is minimally influenced by cognitive evaluation or imagery of the conditioning stimulus

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Bernaba M

2014-11-01

Full Text Available Mario Bernaba, Kevin A Johnson, Jiang-Ti Kong, Sean MackeyStanford Systems Neuroscience and Pain Laboratory, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USAPurpose: Conditioned pain modulation (CPM is an experimental approach for probing endogenous analgesia by which one painful stimulus (the conditioning stimulus may inhibit the perceived pain of a subsequent stimulus (the test stimulus. Animal studies suggest that CPM is mediated by a spino–bulbo–spinal loop using objective measures such as neuronal firing. In humans, pain ratings are often used as the end point. Because pain self-reports are subject to cognitive influences, we tested whether cognitive factors would impact on CPM results in healthy humans.Methods: We conducted a within-subject, crossover study of healthy adults to determine the extent to which CPM is affected by 1 threatening and reassuring evaluation and 2 imagery alone of a cold conditioning stimulus. We used a heat stimulus individualized to 5/10 on a visual analog scale as the testing stimulus and computed the magnitude of CPM by subtracting the postconditioning rating from the baseline pain rating of the heat stimulus.Results: We found that although evaluation can increase the pain rating of the conditioning stimulus, it did not significantly alter the magnitude of CPM. We also found that imagery of cold pain alone did not result in statistically significant CPM effect.Conclusion: Our results suggest that CPM is primarily dependent on sensory input, and that the cortical processes of evaluation and imagery have little impact on CPM. These findings lend support for CPM as a useful tool for probing endogenous analgesia through subcortical mechanisms.Keywords: conditioned pain modulation, endogenous analgesia, evaluation, imagery, cold presser test, CHEPS, contact heat-evoked potential stimulator

Effects of noxious stimulation and pain expectations on neuromuscular control of the spine in patients with chronic low back pain.

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Henchoz, Yves; Tétreau, Charles; Abboud, Jacques; Piché, Mathieu; Descarreaux, Martin

2013-10-01

Alterations of the neuromuscular control of the lumbar spine have been reported in patients with chronic low back pain (LBP). During trunk flexion and extension tasks, the reduced myoelectric activity of the low back extensor musculature observed during full trunk flexion is typically absent in patients with chronic LBP. To determine whether pain expectations could modulate neuromuscular responses to experimental LBP to a higher extent in patients with chronic LBP compared with controls. A cross-sectional, case-control study. Twenty-two patients with nonspecific chronic LBP and 22 age- and sex-matched control participants. Trunk flexion-extension tasks were performed under three experimental conditions: innocuous heat, noxious stimulation with low pain expectation, and noxious stimulation with high pain expectation. Noxious stimulations were delivered using a contact heat thermode applied on the skin of the lumbar region (L4-L5), whereas low or high pain expectations were induced by verbal and visual instructions. Surface electromyography of erector spinae at L2-L3 and L4-L5, as well as lumbopelvic kinematic variables were collected during the tasks. Pain was evaluated using a numerical rating scale. Pain catastrophizing, disability, anxiety, and fear-avoidance beliefs were measured using validated questionnaires. Two-way mixed analysis of variance revealed that pain was significantly different among the three experimental conditions (F2,84=317.5; plow back extensor musculature during full trunk flexion was observed in the high compared with low pain expectations condition at the L2-L3 level (F2,84=9.5; ppain catastrophizing in patients with chronic LBP (r=0.54; p=.012). Repeated exposure to pain appears to generate rigid and less variable patterns of muscle activation in patients with chronic LBP, which attenuate their response to pain expectations. Patients with high levels of pain catastrophizing show higher myoelectric activity of lumbar muscles in full flexion

Nursing Home - Pain - Percentage of Residents Reporting Pain

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U.S. Department of Health & Human Services — Adequate pain management is an important indicator of quality of care and quality of life. Nursing home staff should check patients regularly to see if they are...

Report on first certificate course on applied physiology of pain, analgesia, anesthesia, and euthanasia for laboratory animals held in Sri Lanka.

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Gunatilake, Mangala

2018-06-01

Similar to human beings, pain is an unpleasant sensation experienced by animals as well. There is no exception when the animals are subjected to experimental procedures. Our duty as researchers/scientists is to prevent or minimize the pain in animals so as to lessen their suffering and distress during experimental procedures. The basics of the physiology of pain and pain perception, analgesia, anesthesia, and euthanasia of laboratory animals were included to complete the program, before the practical part was attempted and before advanced topics, such as comparison of anesthetic combinations, were discussed. Therefore, this course was organized in Sri Lanka for the first time in collaboration with the Comparative Biology Centre of Newcastle University, UK. During this course, we were able to demonstrate how an anesthesia machine could be used in laboratory animal anesthesia for the first time in the country. None of the animal houses in the country were equipped with an anesthesia machine at the time of conducting the course.

[Pain and emotional dysregulation: Cellular memory due to pain].

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Narita, Minoru; Watanabe, Moe; Hamada, Yusuke; Tamura, Hideki; Ikegami, Daigo; Kuzumaki, Naoko; Igarashi, Katsuhide

2015-08-01

Genetic factors are involved in determinants for the risk of psychiatric disorders, and neurological and neurodegenerative diseases. Chronic pain stimuli and intense pain have effects at a cellular and/or gene expression level, and will eventually induce "cellular memory due to pain", which means that tissue damage, even if only transient, can elicit epigenetically abnormal transcription/translation and post-translational modification in related cells depending on the degree or kind of injury or associated conditions. Such cell memory/transformation due to pain can cause an abnormality in a fundamental intracellular response, such as a change in the three-dimensional structure of DNA, transcription, or translation. On the other hand, pain is a multidimensional experience with sensory-discriminative and motivational-affective components. Recent human brain imaging studies have examined differences in activity in the nucleus accumbens between controls and patients with chronic pain, and have revealed that the nucleus accumbens plays a role in predicting the value of a noxious stimulus and its offset, and in the consequent changes in the motivational state. In this review, we provide a very brief overview of a comprehensive understanding of chronic pain associated with emotional dysregulation due to transcriptional regulation, epigenetic modification and miRNA regulation.

Pain evaluation in self and others in autism spectrum disorder

DEFF Research Database (Denmark)

Thaler, Hanna; Skewes, Joshua; Gebauer, Line

The picture of pain sensation in autism and its relationship with perception of pain in others is currently far from clear. A common observation in case studies is that autistic individuals are more pain insensitive. However, this hypothesis has recently been challenged by experimental evidence...... indicating that physiological sensitivity in autism may even be enhanced. Evaluation of own pain might also relate to one’s ability to evaluate pain in others. There is some experimental evidence indicating that people generally tend to underestimate how much pain another person feels. Our study investigated...... whether this underestimation bias is stronger in individuals with autism and how this evaluation may be associated with one’s individual pain sensitivity. Using electric pain stimulation, we tested whether autistic and non-autistic male adults (n = 16 in each group) rated the intensity and unpleasantness...

The Fear of Movement/Pain in Musculoskeletal Pain-A Review

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Behnam Akhbari

2012-07-01

Full Text Available Objective: To investigate and review psychological influences of pain such as kinesiophobia and pain-related fear on patients with musculoskeletal pain and on rehabilitation outcomes. Materials & Methods: Fear is a universal and powerful emotion and, as a result, it can have a profound impact on human behavior. the fear-motivated behavior has the potential to adversely impact rehabilitation outcomes for patients with musculoskeletal pain. cross-sectional studies consistently documented a positive association between elevated pain-related fear and increased pain intensity and disability. in addition, several longitudinal studies indicated that elevated pain-related fear is a precursor to poor clinical outcomes. existence of catastrophizing in patients effect on the fear of movement/ (reinjury. this fear contributes to avoidance behaviors and subsequent disuse, depression, and disability. it has been established that kinesiophobia plays a negative role in the outcome of the rehabilitation of acute and chronic low back pain, chronic fatigue syndrome and fibromyalgia syndrome. Results: The recent studies suggest that physical therapists should consider the role of pain-related fear and avoidance behaviors in patients' function and they should assess these cognitive and behavioral factors. or (physical therapists should assess pain-related fear when rehabilitating certain individuals with musculoskeletal pain. currently, there is a lot of evidence for the assessment of pain-related fear in patients with musculoskeletal pain. self-report questionnaires are readily available for assessment and investigation of pain-related fear and several studies have found support for their validity and reliability. recent research indicated that besides fear-avoidance responses, endurance-related responses lead to chronic pain via physical overload. the existence of mental kinesiophobia has been established in patients with chronic stress complaints, and this

The biologic effects of grounding the human body during sleep as measured by cortisol levels and subjective reporting of sleep, pain, and stress.

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Ghaly, Maurice; Teplitz, Dale

2004-10-01

Diurnal cortisol secretion levels were measured and circadian cortisol profiles were evaluated in a pilot study conducted to test the hypothesis that grounding the human body to earth during sleep will result in quantifiable changes in cortisol. It was also hypothesized that grounding the human body would result in changes in sleep, pain, and stress (anxiety, depression, irritability), as measured by subjective reporting. Twelve (12) subjects with complaints of sleep dysfunction, pain, and stress were grounded to earth during sleep for 8 weeks in their own beds using a conductive mattress pad. Saliva tests were administered to establish pregrounding baseline cortisol levels. Levels were obtained at 4-hour intervals for a 24-hour period to determine the circadian cortisol profile. Cortisol testing was repeated at week 6. Subjective symptoms of sleep dysfunction, pain, and stress were reported daily throughout the 8-week test period. Measurable improvements in diurnal cortisol profiles were observed, with cortisol levels significantly reduced during night-time sleep. Subjects' 24-hour circadian cortisol profiles showed a trend toward normalization. Subjectively reported symptoms, including sleep dysfunction, pain, and stress, were reduced or eliminated in nearly all subjects. Results indicate that grounding the human body to earth ("earthing") during sleep reduces night-time levels of cortisol and resynchronizes cortisol hormone secretion more in alignment with the natural 24-hour circadian rhythm profile. Changes were most apparent in females. Furthermore, subjective reporting indicates that grounding the human body to earth during sleep improves sleep and reduces pain and stress.

Antinociceptive Interaction of Tramadol with Gabapentin in Experimental Mononeuropathic Pain.

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Miranda, Hugo F; Noriega, Viviana; Prieto, Juan Carlos; Zanetta, Pilar; Castillo, Rodrigo; Aranda, Nicolás; Sierralta, Fernando

2016-08-01

Neuropathic pain is the result of injury to the nervous system, and different animal models have been established to meet the manifestations of neuropathy. The pharmacotherapy for neuropathic pain includes gabapentin and tramadol, but these are only partially effective when given alone. The aim of this study was to assess the antinociceptive interaction between both drugs using the isobolographic analysis and changes of the IL-1β concentration in a mouse model of neuropathic pain (partial sciatic nerve ligation or PSNL). The i.p. administration of gabapentin (5-100 mg/kg) or tramadol (12.5-100 mg/kg) displayed a dose-dependent antinociception in the hot plate assay of PSNL mice, and effects induced by gabapentin with tramadol were synergistic. Administration of gabapentin or tramadol reversed significantly the increase in the concentration of IL-1β induced by PSNL after either 7 or 14 days and their combination was significantly more potent in reversing the elevated concentration of IL-1β. The synergism obtained by the co-administration of gabapentin and tramadol is proposed to result from action on different mechanisms in pain pathways. Gabapentin or tramadol or their combination modulates the expression of pro-inflammatory cytokine, IL-1β, in a model of mice PSNL which could be due to an inhibition of glial function. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Endogenous Pain Modulation Induced by Extrinsic and Intrinsic Psychological Threat in Healthy Individuals.

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Gibson, William; Moss, Penny; Cheng, Tak Ho; Garnier, Alexandre; Wright, Anthony; Wand, Benedict M

2018-03-01

Many factors interact to influence threat perception and the subsequent experience of pain. This study investigated the effect of observing pain (extrinsic threat) and intrinsic threat of pain to oneself on pressure pain threshold (PPT). Forty socially connected pairs of healthy volunteers were threat-primed and randomly allocated to experimental or control roles. An experimental pain modulation paradigm was applied, with non-nociceptive threat cues used as conditioning stimuli. In substudy 1, the extrinsic threat to the experimental participant was observation of the control partner in pain. The control participant underwent hand immersion in noxious and non-noxious water baths in randomized order. Change in the observing participant's PPT from baseline to mid- and postimmersion was calculated. A significant interaction was found for PPT between conditions and test time (F 2,78  = 24.9, P Extrinsic and intrinsic threat of pain, in the absence of any afferent input therefore influences pain modulation. This may need to be considered in studies that use noxious afferent input with populations who show dysfunctional pain modulation. The effect on endogenous analgesia of observing another's pain and of threat of pain to oneself was investigated. Extrinsic as well as intrinsic threat cues, in the absence of any afferent input, increased pain thresholds, suggesting that mere threat of pain may initiate analgesic effects in traditional noxious experimental paradigms. Copyright © 2017 The American Pain Society. Published by Elsevier Inc. All rights reserved.

Extensibility and stiffness of the hamstrings in patients with nonspecific low back pain.

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Halbertsma, J P; Göeken, L N; Hof, A L; Groothoff, J W; Eisma, W H

2001-02-01

To investigate the extensibility and stiffness of the hamstrings in patients with nonspecific low back pain (LBP). An experimental design. A university laboratory for human movement analysis in a department of rehabilitation medicine. Forty subjects, a patient group (20) and a healthy control group (20). Subjects laid supine on an examination table with a lift frame, with left leg placed in a sling at the ankle. Straight leg raising, pulling force, and activity of hamstring and back muscles were recorded with electrodes. Patients indicated when they experienced tension or pain. The lift force, leg excursion, pelvic-femoral angle, first sensation of pain, and the electromyogram of the hamstrings and back muscles measured in an experimental straight-leg raising set-up. The patient group showed a significant restriction in range of motion (ROM) and extensibility of the hamstrings compared with the control group. No significant difference in hamstring muscle stiffness can be assessed between both groups. The restricted ROM and the decreased extensibility of the hamstrings in patients with nonspecific LBP is not caused by increased muscle stiffness of the hamstrings, but determined by the stretch tolerance of the patients.

Pain relief by touch: a quantitative approach.

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Mancini, Flavia; Nash, Thomas; Iannetti, Gian Domenico; Haggard, Patrick

2014-03-01

Pain relief by touch has been studied for decades in pain neuroscience. Human perceptual studies revealed analgesic effects of segmental tactile stimulation, as compared to extrasegmental touch. However, the spatial organisation of touch-pain interactions within a single human dermatome has not been investigated yet. In 2 experiments we tested whether, how, and where within a dermatome touch modulates the perception of laser-evoked pain. We measured pain perception using intensity ratings, qualitative descriptors, and signal detection measures of sensitivity and response bias. Touch concurrent with laser pulses produced a significant analgesia, and reduced the sensitivity in detecting the energy of laser stimulation, implying a functional loss of information within the ascending Aδ pathway. Touch also produced a bias to judge laser stimuli as less painful. This bias decreased linearly when the distance between the laser and tactile stimuli increased. Thus, our study provides evidence for a spatial organisation of intrasegmental touch-pain interactions. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Disentangling opposing effects of motivational states on pain perception

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Geuter, Stephan; Cunningham, Jonathan T.; Wager, Tor D.

2016-01-01

Abstract Introduction: Although the motivation to avoid injury and pain is central to human and animal behavior, this goal compete priority with other homeostatic goals. Animal studies have shown that competing motivational states, such as thirst, reduce pain. However, such states may also induce negative mood, which in humans has been found to increase pain. These opposing effects complicate study of the effects of motivational states in humans. Objectives: To evaluate concurrent effects of motivational state competition and mood on pain ratings. Methods: We compared a thirst challenge against a control group and measured thirst and mood as potential mediators. Pain induced through contact heat stimulation on the left forearm and was tested at 3 time points: before group randomization, after thirst induction, and after rehydration. Results: Overall, the thirst group reported more pain when thirsty compared with baseline and controls. Mediation analyses showed evidence for two opposing effects. First, the thirst challenge increased negative mood and thirstiness, which was related to increased pain. Second, the thirst challenge produced a direct, pain-reducing effect. Conclusion: Competing motivational states reduce pain but also induce concurrent mood changes that can mask motivational state-related effects. PMID:27747310

The effects of anger and sadness on clinical pain reports and experimentally-induced pain thresholds in women with and without fibromyalgia.

NARCIS (Netherlands)

Middendorp, H. van; Lumley, M.A.; Jacobs, J.W.G.; Bijlsma, J.W.J.; Geenen, R.

2010-01-01

OBJECTIVE: Negative emotions are commonly experienced in fibromyalgia and may affect pain. This study examined the effects of anger and sadness on clinical pain reports and on pain threshold and tolerance in response to electrical stimulation in women with and without fibromyalgia. METHODS: In an

Contextual influences on pain communication in couples with and without a partner with chronic pain.

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Gagnon, Michelle M; Hadjistavropoulos, Thomas; MacNab, Ying C

2017-10-01

This is an experimental study of pain communication in couples. Despite evidence that chronic pain in one partner impacts both members of the dyad, dyadic influences on pain communication have not been sufficiently examined and are typically studied based on retrospective reports. Our goal was to directly study contextual influences (ie, presence of chronic pain, gender, relationship quality, and pain catastrophizing) on self-reported and nonverbal (ie, facial expressions) pain responses. Couples with (n = 66) and without (n = 65) an individual with chronic pain (ICP) completed relationship and pain catastrophizing questionnaires. Subsequently, one partner underwent a pain task (pain target, PT), while the other partner observed (pain observer, PO). In couples with an ICP, the ICP was assigned to be the PT. Pain intensity and PO perceived pain intensity ratings were recorded at multiple intervals. Facial expressions were video recorded throughout the pain task. Pain-related facial expression was quantified using the Facial Action Coding System. The most consistent predictor of either partner's pain-related facial expression was the pain-related facial expression of the other partner. Pain targets provided higher pain ratings than POs and female PTs reported and showed more pain, regardless of chronic pain status. Gender and the interaction between gender and relationship satisfaction were predictors of pain-related facial expression among PTs, but not POs. None of the examined variables predicted self-reported pain. Results suggest that contextual variables influence pain communication in couples, with distinct influences for PTs and POs. Moreover, self-report and nonverbal responses are not displayed in a parallel manner.

The Animal Model of Spinal Cord Injury as an Experimental Pain Model

OpenAIRE

Nakae, Aya; Nakai, Kunihiro; Yano, Kenji; Hosokawa, Ko; Shibata, Masahiko; Mashimo, Takashi

2011-01-01

Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of patholo...

The human factors and the safety of experimentation reactors

International Nuclear Information System (INIS)

Jeffroy, F.; Delaporte-Normier, M.L.

2007-01-01

Inside IRSN (Institute for Radiological protection and Nuclear Safety), the mission of the Human Factors Group is to assess the way operators of nuclear installations take into account the risks related to human activities. In the last few years, IRSN has been involved in the safety analysis of different installations where Cea develops research programs, in particular experimental reactors. The first part of this article presents the methodology used by IRSN to evaluate how operators take into account risks related to human activities. This methodology is made up of 4 steps: 1) the identification of the human activities that convey a risk for the installation nuclear safety (safety-sensitive activities), for instance in the case of the Masurca reactor, it has been shown that errors made during the manufacturing of fuel tubes can lead to a criticality accident; 2) listing all the dispositions or arrangements taken to make human safety-sensitive activities more reliable; 3) checking the efficiency of such dispositions or arrangements; and 4) assessing the ability of the operators to generate the adequate dispositions or arrangements. The second part highlights the necessity to develop inside these research installations an organisation that facilitates cooperation between experimenters and operators

Effects of a home-exercise therapy programme on cervical and lumbar range of motion among nurses with neck and lower back pain: a quasi-experimental study.

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Freimann, Tiina; Merisalu, Eda; Pääsuke, Mati

2015-01-01

Cervical and lumbar range of motion limitations are usually associated with musculoskeletal pain in the neck and lower back, and are a major health problem among nurses. Physical exercise has been evaluated as an effective intervention method for improving cervical and lumbar range of motion, and for preventing and reducing musculoskeletal pain. The purpose of this study was to investigate the effects of a home-exercise therapy programme on cervical and lumbar range of motion among intensive care unit nurses who had experienced mild to moderate musculoskeletal pain in the neck and or lower back during the previous six months. A quasi-experimental study was conducted among intensive care unit nurses at Tartu University Hospital (Estonia) between May and July 2011. Thirteen nurses who had suffered musculoskeletal pain episodes in the neck and or lower back during the previous six months underwent an 8-week home-exercise therapy programme. Eleven nurses without musculoskeletal pain formed a control group. Questions from the Nordic Musculoskeletal Questionnaire and the 11-point Visual Analogue Scale were used to select potential participants for the experimental group via an assessment of the prevalence and intensity of musculoskeletal pain. Cervical range of motion and lumbar range of motion in flexion, extension, lateral flexion and (cervical range of motion only) rotation were measured with a digital goniometer. A paired t-test was used to compare the measured parameters before and after the home-exercise therapy programme. A Student's t-test was used to analyse any differences between the experimental and control groups. After the home-exercise therapy, there was a significant increase (p cervical range of motion in flexion, extension, lateral flexion and rotation, and in lumbar range of motion in lateral flexion. Cervical range of motion in flexion was significantly higher (p cervical and lumbar range of motion among intensive care nurses. Further studies are

A review of the evidence regarding associations between attachment theory and experimentally induced pain.

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Meredith, Pamela Joy

2013-04-01

Theoretical and empirical evidence suggests that adult attachment and pain-related variables are predictably and consistently linked, and that understanding these links may guide pain intervention and prevention efforts. In general, insecure attachment has been portrayed as a risk factor, and secure attachment as a protective factor, for people with chronic pain conditions. In an effort to better understand the relationships among attachment and pain variables, these links have been investigated in pain-free samples using induced-pain techniques. The present paper reviews the available research linking adult attachment and laboratory-induced pain. While the diverse nature of the studies precludes definitive conclusions, together these papers offer support for associations between insecure attachment and a more negative pain experience. The evidence presented in this review highlights areas for further empirical attention, as well as providing some guidance for clinicians who may wish to employ preventive approaches and other interventions informed by attachment theory.

Comparing the Effectiveness of Cognitive Behavioral Therapy and Hypnosis Therapy Pain Self-Efficacy and Pain Severity in Girls with Primary Dysmenorrhea

OpenAIRE

F Farshbaf Manei Sefat; A Abolghasemi; U Barahmand; N Hajloo

2017-01-01

ABSTRACT   Background & aim: Menstruation as an important issue in adolescence and menstrual pain is a common problem in adolescents. Regarding the relationship between pain severity and  pain self-efficacy, this study aimed to investigate and compare the efficacy of cognitive-behavioral therapy and hypnosis therapy on pain and pain self-efficacy in girls with primary dysmenorrhea.   Methods: The method of research is Quasi experimental and research design is pretes...

Usefulness of the Pain Tracking Technique in Acute Mechanical Low Back Pain

Directory of Open Access Journals (Sweden)

Tania Bravo Acosta

2015-01-01

Full Text Available Objective. To evaluate the usefulness of the pain tracking technique in acute mechanical low back pain. Method. We performed an experimental prospective (longitudinal explanatory study between January 2011 and September 2012. The sample was randomly divided into two groups. Patients were assessed at the start and end of the treatment using the visual analogue scale and the Waddell test. Treatment consisted in applying the pain tracking technique to the study group and interferential current therapy to the control group. At the end of treatment, cryotherapy was applied for 10 minutes. The Wilcoxon signed-rank test and the Mann Whitney test were used. They were performed with a predetermined significance level of p≤0.05. Results. Pain was triggered by prolonged static posture and intense physical labor and intensified through trunk movements and when sitting and standing. The greatest relief was reported in lateral decubitus position and in William’s position. The majority of the patients had contracture. Pain and disability were modified with the rehabilitation treatment in both groups. Conclusions. Both the pain tracking and interferential current techniques combined with cryotherapy are useful treatments for acute mechanical low back pain. The onset of analgesia is faster when using the pain tracking technique.

Central sensitization: implications for the diagnosis and treatment of pain.

Science.gov (United States)

Woolf, Clifford J

2011-03-01

Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the

Mindfulness meditation-related pain relief: Evidence for unique brain mechanisms in the regulation of pain

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Zeidan, F.; Grant, J.A.; Brown, C.A.; McHaffie, J.G.; Coghill, R.C.

2013-01-01

The cognitive modulation of pain is influenced by a number of factors ranging from attention, beliefs, conditioning, expectations, mood, and the regulation of emotional responses to noxious sensory events. Recently, mindfulness meditation has been found attenuate pain through some of these mechanisms including enhanced cognitive and emotional control, as well as altering the contextual evaluation of sensory events. This review discusses the brain mechanisms involved in mindfulness meditation-related pain relief across different meditative techniques, expertise and training levels, experimental procedures, and neuroimaging methodologies. Converging lines of neuroimaging evidence reveal that mindfulness meditation-related pain relief is associated with unique appraisal cognitive processes depending on expertise level and meditation tradition. Moreover, it is postulated that mindfulness meditation-related pain relief may share a common final pathway with other cognitive techniques in the modulation of pain. PMID:22487846

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

Science.gov (United States)

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

2015-01-01

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

Penis pain

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Pain - penis ... Bites, either human or insect Cancer of the penis Erection that does not go away (priapism) Genital herpes Infected hair follicles Infected prosthesis of the penis Infection under the foreskin of uncircumcised men ( balanitis ) ...

Pharmacology of human experimental anxiety

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F.G. Graeff

2003-04-01

Full Text Available This review covers the effect of drugs affecting anxiety using four psychological procedures for inducing experimental anxiety applied to healthy volunteers and patients with anxiety disorders. The first is aversive conditioning of the skin conductance responses to tones. The second is simulated public speaking, which consists of speaking in front of a video camera, with anxiety being measured with psychometric scales. The third is the Stroop Color-Word test, in which words naming colors are painted in the same or in a different shade, the incongruence generating a cognitive conflict. The last test is a human version of a thoroughly studied animal model of anxiety, fear-potentiated startle, in which the eye-blink reflex to a loud noise is recorded. The evidence reviewed led to the conclusion that the aversive conditioning and potentiated startle tests are based on classical conditioning of anticipatory anxiety. Their sensitivity to benzodiazepine anxiolytics suggests that these models generate an emotional state related to generalized anxiety disorder. On the other hand, the increase in anxiety determined by simulated public speaking is resistant to benzodiazepines and sensitive to drugs affecting serotonergic neurotransmission. This pharmacological profile, together with epidemiological evidence indicating its widespread prevalence, suggests that the emotional state generated by public speaking represents a species-specific response that may be related to social phobia and panic disorder. Because of scant pharmacological data, the status of the Stroop Color-Word test remains uncertain. In spite of ethical and economic constraints, human experimental anxiety constitutes a valuable tool for the study of the pathophysiology of anxiety disorders.

The Effect of Positive Affect on the Memory of Pain.

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Bąbel, Przemysław

2017-06-01

The aim of the study was to assess the accuracy of the memory of experimentally induced pain and the affect that accompanies experimentally induced pain. Sixty-two healthy female volunteers participated in the study. In the first phase of the study, the participants received three pain stimuli and rated pain intensity, pain unpleasantness, state anxiety, and their positive and negative affect. About a month later, in the second phase of the study, the participants were asked to rate the pain intensity, pain unpleasantness, state anxiety, and the emotions they had felt during the first phase of the study. Both recalled pain intensity and recalled pain unpleasantness were found to be underestimated. Although the positive affect that accompanied pain was remembered accurately, recalled negative affect was overestimated and recalled state anxiety was underestimated. Experienced pain, recalled state anxiety, and recalled positive affect accounted for 44% of the total variance in predicting recalled pain intensity and 61% of the total variance in predicting recalled pain unpleasantness. Together with recent research findings on the memory of other types of pain, the present study supports the idea that pain is accompanied by positive as well as negative emotions, and that positive affect influences the memory of pain. Copyright © 2017 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Lumbopelvic Core Stabilization Exercise and Pain Modulation Among Individuals with Chronic Nonspecific Low Back Pain.

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Paungmali, Aatit; Joseph, Leonard H; Sitilertpisan, Patraporn; Pirunsan, Ubon; Uthaikhup, Sureeporn

2017-11-01

Lumbopelvic stabilization training (LPST) may provide therapeutic benefits on pain modulation in chronic nonspecific low back pain conditions. This study aimed to examine the effects of LPST on pain threshold and pain intensity in comparison with the passive automated cycling intervention and control intervention among patients with chronic nonspecific low back pain. A within-subject, repeated-measures, crossover randomized controlled design was conducted among 25 participants (7 males and 18 females) with chronic nonspecific low back pain. All the participants received 3 different types of experimental interventions, which included LPST, the passive automated cycling intervention, and the control intervention randomly, with 48 hours between the sessions. The pressure pain threshold (PPT), hot-cold pain threshold, and pain intensity were estimated before and after the interventions. Repeated-measures analysis of variance showed that LPST provided therapeutic effects as it improved the PPT beyond the placebo and control interventions (P pain intensity under the LPST condition was significantly better than that under the passive automated cycling intervention and controlled intervention (P pain threshold under the LPST condition also showed a significant trend of improvement beyond the control (P pain threshold were evident. Lumbopelvic stabilization training may provide therapeutic effects by inducing pain modulation through an improvement in the pain threshold and reduction in pain intensity. LPST may be considered as part of the management programs for treatment of chronic low back pain. © 2017 World Institute of Pain.

Experimental evidence of human recreational disturbance effects on bird-territory establishment.

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Bötsch, Yves; Tablado, Zulima; Jenni, Lukas

2017-07-12

The worldwide increase in human outdoor activities raises concerns for wildlife. Human disturbances, even at low levels, are likely to impact species during sensitive periods of the annual cycle. However, experimental studies during the putative sensitive period of territory establishment of birds which not only investigate low disturbance levels, but which also exclude the effect of habitat modification (e.g. walking trails) are lacking. Here, we experimentally disturbed birds in forest plots by walking through twice a day during territory establishment. Later we compared the breeding bird community of experimentally disturbed plots with that of undisturbed control plots. We discovered that the number of territories (-15.0%) and species richness (-15.2%) in disturbed plots were substantially reduced compared with control plots. Species most affected included those sensitive to human presence (assessed by flight-initiation distances), open-cup nesters and above-ground foragers. Long-distance migrants, however, were unaffected due to their arrival after experimental disturbance took place. These findings highlight how territory establishment is a sensitive period for birds, when even low levels of human recreation may be perceived as threatening, and alter settlement decisions. This can have important implications for the conservation of species, which might go unnoticed when focusing only on already established birds. © 2017 The Author(s).

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

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

2007-12-05

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

Common brain activations for painful and non-painful aversive stimuli

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Hayes Dave J

2012-06-01

Full Text Available Abstract Background Identification of potentially harmful stimuli is necessary for the well-being and self-preservation of all organisms. However, the neural substrates involved in the processing of aversive stimuli are not well understood. For instance, painful and non-painful aversive stimuli are largely thought to activate different neural networks. However, it is presently unclear whether there is a common aversion-related network of brain regions responsible for the basic processing of aversive stimuli. To help clarify this issue, this report used a cross-species translational approach in humans (i.e. meta-analysis and rodents (i.e. systematic review of functional neuroanatomy. Results Animal and human data combined to show a core aversion-related network, consisting of similar cortical (i.e. MCC, PCC, AI, DMPFC, RTG, SMA, VLOFC; see results section or abbreviation section for full names and subcortical (i.e. Amyg, BNST, DS, Hab, Hipp/Parahipp, Hyp, NAc, NTS, PAG, PBN, raphe, septal nuclei, Thal, LC, midbrain regions. In addition, a number of regions appeared to be more involved in pain-related (e.g. sensory cortex or non-pain-related (e.g. amygdala aversive processing. Conclusions This investigation suggests that aversive processing, at the most basic level, relies on similar neural substrates, and that differential responses may be due, in part, to the recruitment of additional structures as well as the spatio-temporal dynamic activity of the network. This network perspective may provide a clearer understanding of why components of this circuit appear dysfunctional in some psychiatric and pain-related disorders.

Human embryonic stem cell lines model experimental human cytomegalovirus latency.

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Penkert, Rhiannon R; Kalejta, Robert F

2013-05-28

Herpesviruses are highly successful pathogens that persist for the lifetime of their hosts primarily because of their ability to establish and maintain latent infections from which the virus is capable of productively reactivating. Human cytomegalovirus (HCMV), a betaherpesvirus, establishes latency in CD34(+) hematopoietic progenitor cells during natural infections in the body. Experimental infection of CD34(+) cells ex vivo has demonstrated that expression of the viral gene products that drive productive infection is silenced by an intrinsic immune defense mediated by Daxx and histone deacetylases through heterochromatinization of the viral genome during the establishment of latency. Additional mechanistic details about the establishment, let alone maintenance and reactivation, of HCMV latency remain scarce. This is partly due to the technical challenges of CD34(+) cell culture, most notably, the difficulty in preventing spontaneous differentiation that drives reactivation and renders them permissive for productive infection. Here we demonstrate that HCMV can establish, maintain, and reactivate in vitro from experimental latency in cultures of human embryonic stem cells (ESCs), for which spurious differentiation can be prevented or controlled. Furthermore, we show that known molecular aspects of HCMV latency are faithfully recapitulated in these cells. In total, we present ESCs as a novel, tractable model for studies of HCMV latency.

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

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

2017-01-01

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

Melittin, the Major Pain-Producing Substance of Bee Venom.

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Chen, Jun; Guan, Su-Min; Sun, Wei; Fu, Han

2016-06-01

Melittin is a basic 26-amino-acid polypeptide that constitutes 40-60% of dry honeybee (Apis mellifera) venom. Although much is known about its strong surface activity on lipid membranes, less is known about its pain-producing effects in the nervous system. In this review, we provide lines of accumulating evidence to support the hypothesis that melittin is the major pain-producing substance of bee venom. At the psychophysical and behavioral levels, subcutaneous injection of melittin causes tonic pain sensation and pain-related behaviors in both humans and animals. At the cellular level, melittin activates primary nociceptor cells through direct and indirect effects. On one hand, melittin can selectively open thermal nociceptor transient receptor potential vanilloid receptor channels via phospholipase A2-lipoxygenase/cyclooxygenase metabolites, leading to depolarization of primary nociceptor cells. On the other hand, algogens and inflammatory/pro-inflammatory mediators released from the tissue matrix by melittin's pore-forming effects can activate primary nociceptor cells through both ligand-gated receptor channels and the G-protein-coupled receptor-mediated opening of transient receptor potential canonical channels. Moreover, subcutaneous melittin up-regulates Nav1.8 and Nav1.9 subunits, resulting in the enhancement of tetrodotoxin-resistant Na(+) currents and the generation of long-term action potential firing. These nociceptive responses in the periphery finally activate and sensitize the spinal dorsal horn pain-signaling neurons, resulting in spontaneous nociceptive paw flinches and pain hypersensitivity to thermal and mechanical stimuli. Taken together, it is concluded that melittin is the major pain-producing substance of bee venom, by which peripheral persistent pain and hyperalgesia (or allodynia), primary nociceptive neuronal sensitization, and CNS synaptic plasticity (or metaplasticity) can be readily induced and the molecular and cellular mechanisms

Phonetic characteristics of vocalizations during pain

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Niebuhr, Oliver; Lautenbacher, Stefan; Salinas-Ranneberg, Melissa

2017-01-01

” (central vowel, sounding like a darker “e” as in hesitations like “ehm”)—as experimental approximations to natural vocalizations. Methods: In 50 students vowel production and self-report ratings were assessed during painful and nonpainful heat stimulation (hot water immersion) as well as during baseline......Introduction and Objectives: There have, yet, been only few attempts to phonetically characterize the vocalizations of pain, although there is wide agreement that moaning, groaning, or other nonverbal utterance can be indicative of pain. We studied the production of vowels “u,” “a,” “i”, and “schwa...... pain. Furthermore, changes from nonpainful to painful stimulations in these parameters also significantly predicted concurrent changes in pain ratings. Conclusion: Vocalization characteristics of pain seem to be best described by an increase in pitch and in loudness. Future studies using more specific...

Effects of Tobacco Smoking on Measures of Cold-Induced Pain

National Research Council Canada - National Science Library

Spillane, Erica L; Szewczyk, Robert P; McDonald, James D

2005-01-01

Nicotine's effect on human pain perception is uncertain. This study's purpose was to determine whether pain thresholds, pain tolerances, or ratings of pain intensity differ among smokers (S), non-smokers (NS...

The use of ginger (Zingiber officinale) for the treatment of pain: a systematic review of clinical trials.

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Terry, Rohini; Posadzki, Paul; Watson, Leala K; Ernst, Edzard

2011-12-01

  Zingiber officinale (Z. officinale), commonly known as ginger, has been widely used traditionally for a variety of medicinal purposes, one of which is for the treatment of pain. The aim of this systematic review was to evaluate the evidence from all human participant clinical trials that have assessed the efficacy of ginger for the treatment of any type of pain.   Following a protocol, multiple databases were sought using comprehensive search strategies for Z. officinale and pain together with a trial filter for randomized or controlled clinical trials. Trials testing the efficacy of Z. officinale, used as a sole oral treatment against a comparison condition in human adults suffering from any pain condition, were included.   Seven published articles, reporting a total of eight trials (481 participants), were included in the review. Six trials (two for osteoarthritis, one for dysmenorrhea, and three for experimentally induced acute muscle pain) found that the use of Z. officinale reduced subjective pain reports. The methodological quality of the included articles was variable. When assessed using the Jadad scale, which allows a score of between 0 and 5 to be given, included articles obtained Jadad ratings ranging from 2 to 5.   Due to a paucity of well-conducted trials, evidence of the efficacy of Z. officinale to treat pain remains insufficient. However, the available data provide tentative support for the anti-inflammatory role of Z. officinale constituents, which may reduce the subjective experience of pain in some conditions such as osteoarthritis. Further rigorous trials therefore seem to be warranted. Wiley Periodicals, Inc.

[Nursing intervention and evaluation of postoperative pain in preschool children with cleft lip and palate].

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Gong, Caixia; Yan, Miao; Jiang, Fei; Chen, Zehua; Long, Yuan; Chen, Lixian; Zheng, Qian; Shi, Bing

2014-06-01

This study aimed to observe the postoperative pain rate and degree of pain in preschool children with cleft lip and palate, and investigate the effect of nursing intervention on pain relief. A total of 120 hospitalized cases of three- to seven-year-old preschool children with cleft lip and palate were selected from May to October 2011. The subjects were randomly divided into the control group and experimental groups 1, 2, and 3. The control group used conventional nursing methods, experimental group 1 used analgesic drug treatment, experimental group 2 used psychological nursing interventions, and experimental group 3 used both psychological nursing intervention and analgesic drug treatment. After 6, 12, 24, and 48 h, pain self-assessment, pain parent-assessment, and pain nurse-assessment were calculated for the four groups using the pain assessment forms, and their ratings were compared. The postoperative pain rates of the four groups ranged from 50.0% to 73.3%. The difference among the four groups was statistically significant (P palate is common. Psychological nursing intervention with analgesic treatment is effective in relieving postoperative pain.

IMMEDIATE EFFECT OF CERVICAL MANIPULATION ON PAIN AND RANGE OF MOTION IN PATIENTS WITH CHRONIC MECHANICAL NECK PAIN

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Kabir Isah Mayana

2017-06-01

Full Text Available Background: Neck pain has been reported as a prevalent musculoskeletal disorder globally with more than half of the general population being affected once or more within their life span. Methods: A randomized clinical trial research design was used which investigated the immediate effect of cervical manipulation on neck pain and cervical range of motion among patients with chronic mechanical neck pain. 20 male and female participants between the ages of 26 to 60 years with chronic mechanical neck pain attending physiotherapy clinics were recruited. They were randomly assigned into two groups (A and B of 10 patients each. Group A received soft tissue massage, and cervical manipulation and group B served as the control group, and they received only soft tissue massage. There were two outcomes measured; Pain intensity was rated using visual analog scale (VAS before and immediately after the intervention. Pre and Post intervention measurements of cervical spine range of motion using Goniometer were also taken. Results: Findings of the study revealed significant immediate improvement of pain and Cervical Range of Motions (p<0.05 in all dimensions in the experimental group while Pain, flexion and right side Cervical flexion significantly improved in the control group. It was also found out after comparing the outcomes between the two groups that, the experimental group had significantly (p<0.05 better improvement than the control group in post-intervention pain, cervical flexion, cervical extension and cervical (right and left lateral rotations. Conclusion: Cervical manipulation is effective in immediate pain relief and improvement in cervical range of motion in patients with mechanical neck pain

The Pathobiology of the Meniscus: A Comparison Between the Human and Dog

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Olga Krupkova

2018-04-01

Full Text Available Serious knee pain and related disability have an annual prevalence of approximately 25% on those over the age of 55 years. As curative treatments for the common knee problems are not available to date, knee pathologies typically progress and often lead to osteoarthritis (OA. While the roles that the meniscus plays in knee biomechanics are well characterized, biological mechanisms underlying meniscus pathophysiology and roles in knee pain and OA progression are not fully clear. Experimental treatments for knee disorders that are successful in animal models often produce unsatisfactory results in humans due to species differences or the inability to fully replicate disease progression in experimental animals. The use of animals with spontaneous knee pathologies, such as dogs, can significantly help addressing this issue. As microscopic and macroscopic anatomy of the canine and human menisci are similar, spontaneous meniscal pathologies in canine patients are thought to be highly relevant for translational medicine. However, it is not clear whether the biomolecular mechanisms of pain, degradation of extracellular matrix, and inflammatory responses are species dependent. The aims of this review are (1 to provide an overview of the anatomy, physiology, and pathology of the human and canine meniscus, (2 to compare the known signaling pathways involved in spontaneous meniscus pathology between both species, and (3 to assess the relevance of dogs with spontaneous meniscal pathology as a translational model. Understanding these mechanisms in human and canine meniscus can help to advance diagnostic and therapeutic strategies for painful knee disorders and improve clinical decision making.

Effect of Pain Neuroscience Education Combined With Cognition-Targeted Motor Control Training on Chronic Spinal Pain: A Randomized Clinical Trial.

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Malfliet, Anneleen; Kregel, Jeroen; Coppieters, Iris; De Pauw, Robby; Meeus, Mira; Roussel, Nathalie; Cagnie, Barbara; Danneels, Lieven; Nijs, Jo

2018-04-16

Effective treatments for chronic spinal pain are essential to reduce the related high personal and socioeconomic costs. To compare pain neuroscience education combined with cognition-targeted motor control training with current best-evidence physiotherapy for reducing pain and improving functionality, gray matter morphologic features, and pain cognitions in individuals with chronic spinal pain. Multicenter randomized clinical trial conducted from January 1, 2014, to January 30, 2017, among 120 patients with chronic nonspecific spinal pain in 2 outpatient hospitals with follow-up at 3, 6, and 12 months. Participants were randomized into an experimental group (combined pain neuroscience education and cognition-targeted motor control training) and a control group (combining education on back and neck pain and general exercise therapy). Primary outcomes were pain (pressure pain thresholds, numeric rating scale, and central sensitization inventory) and function (pain disability index and mental health and physical health). There were 22 men and 38 women in the experimental group (mean [SD] age, 39.9 [12.0] years) and 25 men and 35 women in the control group (mean [SD] age, 40.5 [12.9] years). Participants in the experimental group experienced reduced pain (small to medium effect sizes): higher pressure pain thresholds at primary test site at 3 months (estimated marginal [EM] mean, 0.971; 95% CI, -0.028 to 1.970) and reduced central sensitization inventory scores at 6 months (EM mean, -5.684; 95% CI, -10.589 to -0.780) and 12 months (EM mean, -6.053; 95% CI, -10.781 to -1.324). They also experienced improved function (small to medium effect sizes): significant and clinically relevant reduction of disability at 3 months (EM mean, -5.113; 95% CI, -9.994 to -0.232), 6 months (EM mean, -6.351; 95% CI, -11.153 to -1.550), and 12 months (EM mean, -5.779; 95% CI, -10.340 to -1.217); better mental health at 6 months (EM mean, 36.496; 95% CI, 7.998-64.995); and better physical

Effects of a pain program on nurses' pharmacological pain management

NARCIS (Netherlands)

Francke, AL; Dingemans, WA; Borg, PAJ; Luiken, JB; Grypdonck, M; Abu-Saad, HH

1999-01-01

Surgical nurses from five Dutch general hospitals participated in a continuing education program on pain assessment and management. Effects of the program were measured in a pretest-post-test control group design, in which nursing wards were randomly allocated to the experimental condition (program)

Neurodynamic treatment did not improve pain and disability at two weeks in patients with chronic nerve-related leg pain: a randomised trial

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Giovanni Ferreira

2016-10-01

Full Text Available Question: In people with nerve-related leg pain, does adding neurodynamic treatment to advice to remain active improve leg pain, disability, low back pain, function, global perceived effect and location of symptoms? Design: Randomised trial with concealed allocation and intention-to-treat analysis. Participants: Sixty participants with nerve-related leg pain recruited from the community. Interventions: The experimental group received four sessions of neurodynamic treatment. Both groups received advice to remain active. Outcome measures: Leg pain and low back pain (0, none, to 10, worst, Oswestry Disability Index (0, none, to 100, worst, Patient-Specific Functional Scale (0, unable to perform, to 30, able to perform, global perceived effect (–5 to 5 and location of symptoms were measured at 2 and 4 weeks after randomisation. Continuous outcomes were analysed by linear mixed models. Location of symptoms was assessed by relative risk (95% CI. Results: At 2 weeks, the experimental group did not have significantly greater improvement than the control group in leg pain (MD –1.1, 95% CI –2.3 to 0.1 or disability (MD –3.3, 95% CI –9.6 to 2.9. At 4 weeks, the experimental group experienced a significantly greater reduction in leg pain (MD –2.4, 95% CI –3.6 to –1.2 and low back pain (MD –1.5, 95% CI –2.8 to –0.2. The experimental group also improved significantly more in function at 2 weeks (MD 5.2, 95% CI 2.2 to 8.2 and 4 weeks (MD 4.7, 95% CI 1.7 to 7.8, as well as global perceived effect at 2 weeks (MD 2.5, 95% CI 1.6 to 3.5 and 4 weeks (MD 2.9, 95% CI 1.9 to 3.9. No significant between-group differences occurred in disability at 4 weeks and location of symptoms. Conclusion: Adding neurodynamic treatment to advice to remain active did not improve leg pain and disability at 2 weeks. Trial registration: NCT01954199. [Ferreira G, Stieven F, Araujo F, Wiebusch M, Rosa C, Plentz R, et al. (2016 Neurodynamic treatment did not improve

Nutraceuticals and osteoarthritis pain.

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Wang, Angela; Leong, Daniel J; Cardoso, Luis; Sun, Hui B

2018-02-24

Arthritis is a chronic disease of joints. It is highly prevalent, particularly in the elderly, and is commonly associated with pain that interferes with quality of life. Because of its chronic nature, pharmacological approaches to pain relief and joint repair must be safe for long term use, a quality many current therapies lack. Nutraceuticals refer to compounds or materials that can function as nutrition and exert a potential therapeutic effect, including the relief of pain, such as pain related to arthritis, of which osteoarthritis (OA) is the most common form. Of interest, nutraceuticals have recently been shown to have potential in relieving OA pain in human clinical trials. Emerging evidence indicates nutraceuticals may represent promising alternatives for the relief of OA pain. In this paper, we will overview OA pain and the use of nutraceuticals in OA pain management, focusing on those that have been evaluated by clinical trials. Furthermore, we discuss the biologic and pharmacologic actions underlying the nutraceutical effects on pain relief based on the potential active ingredients identified from traditional nutraceuticals in OA pain management and their potential for drug development. The review concludes by sharing our viewpoints that future studies should prioritize elucidating the mechanisms of action of nutraceuticals in OA and developing nutraceuticals that not only relieve OA pain, but also mitigate OA pathology. Copyright © 2018 Elsevier Inc. All rights reserved.

Healthy volunteers can be phenotyped using cutaneous sensitization pain models.

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Mads U Werner

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

Study on Bee venom and Pain

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Hyoung-Seok Yun

2000-07-01

Full Text Available In order to study Bee venom and Pain, We searched Journals and Internet. The results were as follows: 1. The domestic papers were total 13. 4 papers were published at The journal of korean acupuncture & moxibustion society, 3 papers were published at The journal of korean oriental medical society, Each The journal of KyoungHee University Oriental Medicine and The journal of korean sports oriental medical society published 1 papers and Unpublished desertations were 3. The clinical studies were 4 and the experimental studies were 9. 2. The domestic clinical studies reported that Bee venom Herbal Acupuncture therapy was effective on HIVD, Subacute arthritis of Knee Joint and Sequale of sprain. In the domestic experimental studies, 5 were related to analgesic effect of Bee vnom and 4 were related to mechanism of analgesia. 3. The journals searched by PubMed were total 18. 5 papers were published at Pain, Each 2 papers were published at Neurosci Lett. and Br J Pharmacol, and Each Eur J Pain, J Rheumatol, Brain Res, Neuroscience, Nature and Toxicon et al published 1 paper. 4. In the journals searched by PubMed, Only the experimental studies were existed. 8 papers used Bee Venom as pain induction substance and 1 paper was related to analgesic effects of Bee venom. 5. 15 webpage were searched by internet related to Bee Venom and pain. 11 were the introduction related to arthritis, 1 was the advertisement, 1 was the patient's experience, 1 was the case report on RA, 1 was review article.

Pharmacokinetic-Pharmacodynamic Modelling of the Analgesic and Antihyperalgesic Effects of Morphine after Intravenous Infusion in Human Volunteers

DEFF Research Database (Denmark)

Ravn, Pernille; Foster, David J. R.; Kreilgaard, Mads

2014-01-01

Using a modelling approach, this study aimed to (i) examine whether the pharmacodynamics of the analgesic and antihyperalgesic effects of morphine differ; (ii) investigate the influence of demographic, pain sensitivity and genetic (OPRM1) variables on between-subject variability of morphine...... pharmacokinetics and pharmacodynamics in human experimental pain models. The study was a randomized, double-blind, 5-arm, cross-over, placebo-controlled study. The psychophysical cutaneous pain tests, electrical pain tolerance (EPTo) and secondary hyperalgesia areas (2HA) were studied in 28 healthy individuals (15...

Pain anticipation: an activation likelihood estimation meta-analysis of brain imaging studies.

Science.gov (United States)

Palermo, Sara; Benedetti, Fabrizio; Costa, Tommaso; Amanzio, Martina

2015-05-01

The anticipation of pain has been investigated in a variety of brain imaging studies. Importantly, today there is no clear overall picture of the areas that are involved in different studies and the exact role of these regions in pain expectation remains especially unexploited. To address this issue, we used activation likelihood estimation meta-analysis to analyze pain anticipation in several neuroimaging studies. A total of 19 functional magnetic resonance imaging were included in the analysis to search for the cortical areas involved in pain anticipation in human experimental models. During anticipation, activated foci were found in the dorsolateral prefrontal, midcingulate and anterior insula cortices, medial and inferior frontal gyri, inferior parietal lobule, middle and superior temporal gyrus, thalamus, and caudate. Deactivated foci were found in the anterior cingulate, superior frontal gyrus, parahippocampal gyrus and in the claustrum. The results of the meta-analytic connectivity analysis provide an overall view of the brain responses triggered by the anticipation of a noxious stimulus. Such a highly distributed perceptual set of self-regulation may prime brain regions to process information where emotion, action and perception as well as their related subcategories play a central role. Not only do these findings provide important information on the neural events when anticipating pain, but also they may give a perspective into nocebo responses, whereby negative expectations may lead to pain worsening. © 2014 Wiley Periodicals, Inc.

Human parallels to experimental myopia?

DEFF Research Database (Denmark)

Fledelius, Hans C; Goldschmidt, Ernst; Haargaard, Birgitte

2014-01-01

acquiring new and basic knowledge, the practical object of the research is to reduce the burden of human myopia around the world. Acquisition and cost of optical correction is one issue, but associated morbidity counts more, with its global load of myopia-associated visual loss and blindness. The object......Raviola and Wiesel's monkey eyelid suture studies of the 1970s laid the cornerstone for the experimental myopia science undertaken since then. The aim has been to clarify the basic humoral and neuronal mechanisms behind induced myopization, its eye tissue transmitters in particular. Besides...... serve as inspiration to the laboratory research, which aims at solving the basic enigmas on a tissue level....

Chenopodium ambrosioides L. Reduces Synovial Inflammation and Pain in Experimental Osteoarthritis.

Directory of Open Access Journals (Sweden)

Gustavo P Calado

Full Text Available The chronicity of osteoarthritis (OA, characterized by pain and inflammation in the joints, is linked to a glutamate receptor, N-methyl-D-aspartate (NMDA. The use of plant species such as Chenopodium ambrosioides L. (Amaranthaceae as NMDA antagonists offers a promising perspective. This work aims to analyze the antinociceptive and anti-inflammatory responses of the crude hydroalcoholic extract (HCE of C. ambrosioides leaves in an experimental OA model. Wistar rats were separated into six groups (n = 24: clean (C, negative control (CTL-, positive control (CTL+, HCE0.5, HCE5 and HCE50. The first group received no intervention. The other groups received an intra-articular injection of sodium monoiodoacetate (MIA (8 mg/kg on day 0. After six hours, they were orally treated with saline, Maxicam plus (meloxicam + chondroitin sulfate and HCE at doses of 0.5 mg/kg, 5 mg/kg and 50 mg/kg, respectively. After three, seven and ten days, clinical evaluations were performed (knee diameter, mechanical allodynia, mechanical hyperalgesia and motor activity. On the tenth day, after euthanasia, synovial fluid and draining lymph node were collected for cellular quantification, and cartilage was collected for histopathological analysis. Finally, molecular docking was performed to evaluate the compatibility of ascaridole, a monoterpene found in HCE, with the NMDA receptor. After the third day, HCE reduced knee edema. HCE5 showed less cellular infiltrate in the cartilage and synovium and lower intensities of allodynia from the third day and of hyperalgesia from the seventh day up to the last treatment day. The HCE5 and HCE50 groups improved in forced walking. In relation to molecular docking, ascaridole showed NMDA receptor binding affinity. C. ambrosioides HCE was effective in the treatment of OA because it reduced synovial inflammation and behavioral changes due to pain. This effect may be related to the antagonistic effect of ascaridole on the NMDA receptor.

Painful tonic heat stimulation induces GABA accumulation in the prefrontal cortex in man

DEFF Research Database (Denmark)

Kupers, Ron; Danielsen, Else R; Kehlet, Henrik

2009-01-01

Relatively little is known on pain-induced neurotransmitter release in the human cerebral cortex. We used proton magnetic resonance spectroscopy (1H-MRS) during tonic painful heat stimulation to test the hypothesis of increases in both glutamate and GABA, two neurotransmitters with a key role...... that GABA is released in the human cerebral cortex during painful stimulation. The results are in line with animal findings on the role of GABA in pain processing and with studies in humans showing analgesic efficacy of GABA-related drugs in clinical pain conditions....... in pain processing. Using a 3T MR scanner, we acquired spectra from the rostral anterior cingulate cortex (rACC) in 13 healthy right-handed subjects at rest and during painful heat stimulation. The painful stimulus consisted of a suprathreshold painful tonic heat pulse, which was delivered to the right...

Production of consistent pain by intermittent infusion of sterile 5% hypertonic saline, followed by decrease of pain with cryotherapy.

Science.gov (United States)

Long, Blaine C; Knight, Kenneth L; Hopkins, Ty; Parcell, Allen C; Feland, J Brent

2012-08-01

It is suggested that postinjury pain is difficult to examine; thus, investigators have developed experimental pain models. To minimize pain, cryotherapy (cryo) is applied, but reports on its effectiveness are limited. To investigate a pain model for the anterior knee and examine cryo in reducing the pain. Controlled laboratory study. Therapeutic modality laboratory. 30 physically active healthy male subjects who were free from any lower extremity orthopedic, neurological, cardiovascular, or endocrine pathologies. Perceived pain was measured every minute. Surface temperature was also assessed in the center of the patella and the popliteal fossa. There was a significant interaction between group and time (F68,864 = 3.0, P = .0001). At the first minute, there was no difference in pain between the 3 groups (saline/cryo = 4.80 ± 4.87 mm, saline/sham = 2.80 ± 3.55 mm, no saline/cryo = 4.00 ± 3.33 mm). During the first 5 min, pain increased from 4.80 ± 4.87 to 45.90 ± 21.17 mm in the saline/cryo group and from 2.80 ± 3.55 to 31.10 ± 20.25 mm in the saline/sham group. Pain did not change within the no-saline/cryo group, 4.00 ± 3.33 to 1.70 ± 1.70 mm. Pain for the saline/sham group remained constant for 17 min. Cryo decreased pain for 16 min in the saline/cryo group. There was no difference in preapplication surface temperature between or within each group. No change in temperature occurred within the saline/sham. Cooling and rewarming were similar in both cryo groups. Ambient temperature fluctuated less than 1°C during data collection. Intermittent infusion of sterile 5% hypertonic saline may be a useful experimental pain model in establishing a constant level of pain in a controlled laboratory setting. Cryotherapy decreased the induced anterior knee pain for 16 min.