bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acceptance and commitment therapy for fibromyalgia: A randomized controlled trial
Authors: Olsson G.L. , Kemani M. , Jensen K. , Kosek E. , Kadetoff D. , Sorjonen K. , Ingvar M. , Wicksell R. 
Published: July 2012

Abstract

Background
Recent developments within cognitive behavior therapy (CBT) have emphasized the utility of acceptance and mindfulness strategies, contrasting interventions focused on reduction or control of symptoms. A study of fMRI changes after CBT in females with fibromyalgia (FM) has been performed and results are presented elsewhere (under review). The aim of the present study was evaluate the effectiveness of Acceptance and Commitment Therapy (ACT)-based intervention for patient diagnosed with FM in comparison with a wait-list control

Method
Female patients aged 18–55 years, fulfilling the American College of Rheumatology classification criteria for FM, and with a weekly self-reported average pain intensity of >40 (VAS 0–100) were considered eligible for inclusion. Participants completed a set of questionnaires prior to treatment, immediately following the treatment and at follow 3–4 months post treatment. Primaryoutcome variable was pain disability (PDI). FIQ, SF36, SES, STAI, pain intensity, BDI, PIPS (psychological inflexibility in pain scale) were also used. The ACT-intervention consisted of twelve weekly group sessions, ten with psychologist and two with pain physician. Treatment was evaluated and mediation analyses were performed.

Results
Primary outcome measure (PDI): A significant improvement in pain disability for ACT in relation to the control condition, p < 0.001. Secondary outcome measures: ACT showed significant improvement in mental health quality of life, self-efficacy, depression, and anxiety. Consistent with hypotheses, ACT did not result in significant changes in either physical quality of life or pain intensity. Mediation analyses: A decrease in psychological inflexibility from pre to post assessments significantly mediated the improvement in pain disability.

Conclusion
The present study supports the utility of using a relatively brief ACT intervention in a group format for women diagnosed with fibromyalgia, and data suggests a mediating function on improvements in psychological flexibility.
Sortilins in neuropathic pain
Authors: Richner M. , Bjerrum O.J. , Koninck Y. De , Nykjaer A. , Vaegter C.B. 
Published: July 2012

Abstract

Background/aims
The molecular mechanisms underlying neuropathic pain are incompletely understood, but recent data suggest that down-regulation of the chloride extruding co-transporter KCC2 in spinal cord sensory neurons is critical: Following peripheral nerve injury, activated microglia in the spinal cord release BDNF, which stimulates neuronal TrkB receptors and ultimately results in the reduction of KCC2 levels. Consequently, neuronal intracellular chloride ion concentration increases, impairing GABAA-receptor mediated inhibition. We have previously described how the receptor sortilin modulates neurotrophin signaling by facilitating anterograde transport of Trk receptors. Unpublished data further link SorCS2, another member of the Sortilins family of sorting receptors (sortilin, SorLA and SorCS1–3) to BDNF signaling by regulating presynaptic TrkB trafficking. The purpose of this study is to explore the involvement of Sortilins in neuropathic pain.

Methods
We subjected wild-type (wt), sortilin knockout (Sort1
-/-) and SorCS2 knockout (SorCS2
-/-) mice to the Spared Nerve Injury (SNI) model of peripheral nerve injury. Mechanical allodynia was measured by von Frey filaments using the up-down-up method and a 3-out-of-5 thresshold.

Results
As previously described by several groups, wt mice developed significant mechanical allodynia following SNI. Interestingly however, mice lacking sortilin or SorCS2 were fully protected from development of allodynia and did not display KCC2 down-regulation following injury. In addition, a single intrathecal injection of antibodies against sortilin or SorCS2 could delay or rescue mechanical allodynia in wt SNI mice for 2-3 days. Finally, neither sortilin nor SorCS2 deficient mice responded to intrathecal injection of BDNF, in contrast to wt mice which developed transient mechanical allodynia.

Conclusion
We hypothesize that sortilin and SorCS2 are involved in neuropathic pain development by regulating TrkB signaling. Alternatively, Sortilins may directly influence the regulation of KCC2 membrane levels following injury. Both hypotheses are currently being investigated by our group.
Glutamate attenuates nitric oxide release from isolated trigeminal ganglion satellite glial cells
Authors: Laursen J.C. , Somvanshi R. , Kumar U. , Cairns B.E. , Dong X.-D. , Arendt-Nielsen L. , Gazerani P. 
Published: July 2012

Abstract

Background/aims
Elevated concentrations of nitric oxide (NO) and glutamate (Glu) in the trigeminal ganglion (TG) may contribute to the development and maintenance of migraine headache. The role of satellite glial cells (SGC) and their pattern of substance release in relation to the pathophysiology of migraine are currently under investigation. In the present study, we investigated the release of NO from isolated trigeminal SGCs and its modulation by Glu.

Methods
SGCs from the TG of adult male Sprague-Dawley rats (n = 8) were isolated and maintained in culture until used. SGCs were treated with graded concentrations of Glu (0, 10, 100, 1000 μM) and samples were withdrawn after 48 h of incubation. In subsequent experiments, SGCs were treated with vehicle medium, 10 μM forskolin (FSK) alone, or 10 μM FSK in conjunction with 100 μM Glu and incubated for 48 h. The NO concentration was determined using the Griess Reagent System and data was subjected to a one-way repeated measures ANOVA analysis, where p <0.05 was considered statistically significant. All experimental procedures were performed at minimum in triplicate.

Results
The concentration of NO was 3.59 ± 0.04 M under baseline conditions. Application of 10 or 100 μM Glu resulted in a significant drop in NO concentration (2.92 ± 0.017 μM and 2.83 ± 0.012 M, respectively) compared to baseline, whereas treatment with 1000 μM Glu did not significantly alter NO release. Treatment of SGCs with 10 μM FSK significantly increased NO release (to 125.94 ± 3.90% of baseline) compared to baseline. Coapplication of 10 M FSK with 100 M Glu significantly decreased FSK-induced NO release (83.73 ± 2.29% of baseline), compared to both FSK-mediated NO release and baseline levels.

Conclusion
These findings suggest that one mechanism by which SGCs protect the TG from elevated Glu concentrations that may occur in response to prolonged noxious stimulation is to reduce the release of NO.
Dose and administration-period play a key role in the effect of ceftriaxone on neuropathic pain in CCI-operated rats
Authors: Frederiksen K.K. , Kristensen P. , Honoré P.H. , Gegelashvili G. , Bjerrum O.J. 
Published: July 2012

Abstract

Introduction
An unmet medical need for more effective therapies of neuropathic pain exits. Here modulation of the glutaminergic system represents an unexplored possibility. Down-regulation ofglutamate transporters potentiates pain transmission by delaying the removal of glutamate from the synapse. In the spinal cord, glutamate transporter 1 (GLT–1) is responsible for more than 90% of the glutamate uptake. Ceftriaxone, a β-lactam, is believed to induce the expression of GLT–1 through the transcriptional factor (NF-ºB) pathway, which results in induced promoter activity and thereby increased synthesis of GLT-1 protein.

Objectives
To evaluate the analgesic effect of ceftriaxone in the Chronic Constriction Injury (CCI) rat model of neuropathic pain and to investigate the pharmacodynamics of ceftriaxone in a chronic dosing regime.

Methods
In CCI rats, mechanical and thermal hypersensitivity, were determined with von Frey filaments and Hargreaves test, respectively. Groups of rats received ceftriaxone (200, 300 or 400 mg/kg, i.p.) once daily in 7–19 days and the control groups received vehicle.

Results
From a total of 24 CCI operated rats, 16 rats developed both mechanical (withdrawal threshold ≤3g) and thermal hypersensitivity (latency threshold ≤13 s.). Ceftriaxone alleviated mechanical allodynia and thermal hyperalgesia in CCI operated. Daily dosing of ceftriaxone 200, 300 and 400 mg/kg reached the same withdrawal threshold levels as before the CCI surgery, after 18, 12 and 7 days, respectively. This indicates that the dynamic effect of ceftriaxone is not only dependent of the dose, but also the duration of administration. Thus, it seems that dose exposure above a certain threshold is necessary to induce protein synthesis.

Conclusion
The CCI model is a useful model to evaluate the anti-nociceptive effects of ceftriaxone. Increased dose do not only elevate effect magnitude but also the rate of with which the effect appears.
Time-course of analgesic effects of botulinum neurotoxin type A (BoNTA) on human experimental model of pain induced by injection of glutamate into temporalis muscle
Authors: Bittencourt da Silva L. , Kulas D. , Karshenas A. , Cairns B.E. , Bach F.W. , Arendt-Nielsen L. , Gazerani P. 
Published: July 2012

Abstract

Background/aims
Analgesic effects of BoNTA develop within few hours in animal studies and within days in human studies. We have previously shown that BoNTA can block glutamate-induced mechanical sensitization and neurogenic vasodilation in rat temporalis muscle within 3 h. The present translational study was designed to explore the time-course of analgesic effects of BoNTA on pain, sensitization and vasomotor responses in a glutamateevoked human pain model.

Methods
BoNTA (5U) and saline were injected (30 min interval) into the left and right temporalis muscles of 12 healthy males (24.2° 2 years). Pressure pain threshold (PPT), skin temperature (thermo camera) and tissue perfusion (laser Doppler flowmetry) were measured every hour for 3 h. Afterwards, subjects received an intramuscular injection of glutamate (1M– 0.2 mL) into the left and right temporalis muscles. Pain intensity (VAS) was recorded for 10 min after injection and pain distribution was then mapped. PPT was measured at 15 and 30 min following the glutamate injections, while skin temperature and tissue perfusion were recorded at 5, 15 and 30 min.

Results
This preliminary data showed that BoNTA significantly reduced glutamate-evoked peak pain intensity compared with saline (P = 0.042). Expansion of pain area was also smaller in the muscles pretreated with BoNTA (P = 0.045). Glutamate-induced vasomotor reactions (elevated skin temperature and tissue perfusion) showed a tendency to decline in BoNTA-pretreated muscles. A similar pattern was seen in terms ofmuscle sensitivity with higher PPT values in BoNTA-pretreated muscles.

Conclusions
BoNTA induced a direct analgesic effect withi 3 h of its injection into the temporalis muscle. This phenomenon, at least in part, might be through BoNTA actions on nociceptors. Present data also indicated that BoNTA attenuated glutamateinduced muscle sensitization and vasomotor reactions. This finding may suggest additional effects of BoNTA on the pattern of release of substances which are involved in pain pathways.
The effect of nerve compression and capsaicin on contact heat evoked potentials (CHEPs) related to Aδ and C fibers
Authors: Madsen C.S. , Johnsen B. , Fuglsang-Frederiksen A. , Jensen T.S. , Finnerup N.B. 
Published: July 2012

Abstract

Background/aims
Brief noxious heat stimuli activate Aδ and C fibers, and contact heat evoked potentials (CHEPs) can be recorded from the scalp. Under standard conditions, late responses related to AS fibers can be recorded. This study examines C-fiber responses to contact heat stimuli.

Methods
A preferential A-fiber blockade by compression to the superficial radial nerve was applied in 22 healthy subjects. Quality and intensity of heat evoked pain (NRS, 0–10), and CHEPs were examined at baseline, during nerve compression, and during further nerve compression with topical capsaicin (5%).

Results
During the A-fiber blockade, 3 subjects had CHEPs with latencies below 400 ms, 8 subjects within 400–800 ms and 6 subjects later than 800 ms. Pain intensity to contact heat stimuli was reduced and fewer subjects reported the heat stimuli as stinging. Following acute capsaicin application, ultralate CHEPs with latencies >800 ms could be recorded in 13 subjects, pain intensity to the contact heat stimuli was increased (p <0.01) and more subjects reported the heat stimuli as being more warm/hot-burning.

Conclusion
The results indicate that following a compression to the superficial radial nerve, CHEPs compatible within complete A fibers or C fibers were recorded. Following sensitization with capsaicin, C-fiber responses were recorded in 62% of subjects.
Persistent pain, sensory disturbances and functional impairment after adjuvant chemotherapy for breast cancer
Authors: Andersen Kenneth Geving , Jensen Maj-Britt , Kehlet Henrik , Gärtner Rune , Eckhoff Lise , Kroman Niels 
Published: July 2012

Abstract

Background
Persistent pain after breast cancer treatment (PPBCT) is a considerable clinical problem affecting between 25 and 60% of breast cancer survivors [1]. Several risk factors have been proposed, among them nerve damage caused by adjuvant treatment [2]. Taxanes used in adjuvant therapy for breast cancer are neurotoxic, and thereby being a potential risk factor for PPBCT and sensory disturbances. However, the long term influence of taxanes on PPBCT is not well documented. Thus, the aim of this study was therefore to compare a nationwide cohort treated with cyclophosphamide and epirubicin + docetaxel (CE + T) versus a nationwide cohort treated with cyclophosphamide, epirubicin and fluoruracil (CEF), in order to assess differences in reporting of PPBCT, sensory disturbances in surgical area, symmetric peripheral sensory disturbances, and functional impairment.

Methods
A comparative nationwide cross-sectional questionnaire study on two cohorts treated with CEF respectively CE + T, based on the Danish Breast Cancer Cooperative Groups database. Inclusion criteria were identical i both cohorts: women treated with adjuvant chemotherapy for primary breast cancer, age 18–69 years, without recurrence. Exclusion criteria: bilateral or previous breast surgery, including reconstructive surgery. The same questionnaire [1] was used for both cohorts and contained detailed questions regarding pain intensity and frequency and sensory disturbances in the breast area, side of chest, axilla and arm, bilateral peripheral sensory disturbances in the hands and feet, and questions regarding daily activities.

Results
1241 patients treated with CEF in 2005-2006 and 1652 patients treated with CE + T in 2007–2008 were included. 664 (54%) with CEF and 861 (53%) patients with CE+T reported PPBCT. In the multivariate analysis including available risk factors, CE + T did not increase risk of PPBCT, adjusted OR 0.95 (95%C10.81–1.11), p = 0.52, compared to CEF. Patients treated with CE + T had a lower risk of sensory disturbances in the area of surgery compared with CEF, adjusted OR 0.75 (95%C1 0.62–0.90), p = 0.002. More CE+T patients reported peripheral sensory disturbances in the hands, adjusted OR 1.56 (95%C11.27–1.92), p < 0.0001, and in the feet, adjusted OR 2.0 (95%C1 1.66–2.42), p < 0.0001, compared to CEF. There was no difference in functional impairment (p = 0.62).

Conclusion
Docetaxcel as adjuvant treatment for breast cancer does not increase the risk of PPBCT, sensory disturbances in the surgical area or functional impairment, but increase the risk for peripheral sensory disturbances.
Influence of emotionally loaded visual and gustatory stimuli on pain perception
Authors: Horjales E. , Finnerup N.B. , Jensen T.S. , Svensson P. 
Published: July 2012

Abstract

Background/aims
Previous studies have focused on the effect of negative emotions generated by music, pictures or odours on pain perception. This study tested whether emotionally loaded visual and gustatory stimuli could influence experimental tonic jaw muscle pain in healthy subjects.

Methods
32 healthy subjects (16 men, 16 women; 18–39 years old) participated. In two sessions experimental jaw muscle pain was evoked by injection of 0.2 ml hypertonic saline into the masseter muscle. In the first session with each injection an emotion (positive, negative or neutral) was generated by visual stimuli (pictures taken from International Affective Picture System). In the second session, emotions were generated by gustatory stimuli (75% sucrose = sweet, 0.1% quinine = bitter, or tasteless gelatine). The participants continuously rated pain intensity (electronic visual analogue scale – VAS) as well as mood and unpleasantness/pleasantness of the conditioning stimuli (visual/ gustatory).

Results and conclusion
Hypertonic saline evoked moderate levels of pain in all subjects (mean peak VAS = 5.2 ± 2.4). During conditioning with negatively loaded pictures VAS pain scores were increased (19.3%) compared with neutral (p = 0.03) and positive emotions (p = 0.001). There was a linear relation between negative emotions and VAS pain scores (r = 0.40, p = 0.02). Although there was a tendency, no significant effect was observed during positive pictures in comparison with neutrals (p = 0.1). Surprisingly no effect on VAS pain scores was observed during neither negative (p = 0.1) nor positive (p = 0.2) gustatory stimuli. This may be due to failure of the gustatory stimuli to generate a change in emotions. These results suggest that not all conditioning stimuli are potent modifiers of emotions, which seem to be a prerequisite for effects on pain perception.
Modulating pain with augmented reality
Authors: Christoffersen G. , Petrini L. , Arendt-Nielsen L. 
Published: July 2012

Abstract

Background/aims
Being able to modulate pain through visual input raises the possibility that visually distorting body size also will reduce pain. The aim of the present study was to investigate whether experimental cold/heat pain could be modulated through a visual illusion of an increased/decreased hand size and whether pain perception correlated with the perceived sense of control of movement.

Methods
20 healthy right-handed volunteers were recruited. Hand sizes were modulated through an AR setting designed to act as a mirror. Four conditions were included: (1) No AR setting; (2) left/right hands were the same size; (3) left hand enlarged; (4) left hand decreased. Pain thresholds (PT) for both hands were alternately assessed using two thermodes, placed on each palmar side of the hands. After each condition subjects rated the following statement: “I could control the movements of my left/right hand”.

Results

Heat pain: no main effect for conditions or hands (left/right). Cold pain: Significant main effects for conditions, but not for hands – condition (2) is significantly more painful than all conditions. Control of movements when the left hand is stimulated: the more control subjects have of right hand in condition (4), the higher the cold PT for the left hand in conditions (1) and (2). Control of movements when the right hand is stimulated: the more control subjects have of the right hand in condition (4), the higher the heat PT in the right hand for condition (2).

Conclusions
Visual illusions can modulate pain, however the modulating factors do not only depend on the size of the limbs that are been viewed but also on how much control subjects feel they have of the movements in their hands-specifically the relationship to the right hand condition (4) seems to have an analgesic effect for cold pain and heat pain.
Pain following stroke: A prospective study
Authors: Hansen Anne P. , Marcussen Ninna S. , Klit Henriette , Kasch Helge , Jensen Troels S. , Finnerup Nanna B. 
Published: July 2012

Abstract

Background/aims
Pain following stroke is common and affects the quality of life in stroke survivors. The most common types of pain following stroke are headache, shoulder pain, other joint pain and central post-stroke pain (CPSP). The objectives of this study were to determine the prevalence of pain at stroke onset and 6 months after stroke and classify the different pain types.

Methods
All consecutively eligible patients admitted to the Stroke Unit at Aarhus University Hospital from February 1 to October 1, 2007 and from February 1 to August 1, 2008 were included. An interview on pain prior to and at stroke onset was conducted at admission followed by interviews on current pain by phone 3 and 6 months after the stroke.

Results
A total of 300 patients were included in the study, and 275 of them completed the 6-month follow-up. The mean age of the 275 patients was 65.9 years old and 55.2% was male. Pain prior to stroke was reported by 49.1% of patients at stroke onset and newly developed pain defined as pain not experienced prior to stroke was reported by 37.8% at stroke onset, 41.8% at the 3-month follow-up and 45.8% at the six month follow-up. The impact on daily life was moderate to severe in 36.4% and 33.6% of the patients with newly developed pain at the 3- and 6-month follow-up, respectively. More than one type of newly developed pain was experienced by 32.2% and 36.5% at the 3- and 6-month follow-up. Headache was reported by 33.5% at stroke onset and newly developed headache by 15.3% at 3-month follow-up and 13.1% at 6-month follow-up. Shoulder pain was reported by 1.5%, 13.1% and 16.4% at stroke onset, and the 3-and 6-month follow-up, respectively. Other joint pain was reported by 7.4% at 3-month and 11.7% at 6-month follow-up. Evoked pain was experienced by 3.6% at stroke onset and by 5.5% and 9.1% at the follow-up interviews.
Other types of pain were also reported; 7.3% at stroke onset, 18.9% at 3-month follow-up and 20.0% at 6-month follow-up. Possible CPSP was identified in 10.5% of patients from the different pain groups.

Conclusion
Pain following stroke is common and may have a considerable effect on the everyday life of the patient.
Sensory phenotypes in patients with peripheral neuropathic pain evaluated with quantitative sensory testing
Authors: Demant D. , Lund K. , Christensen B. , Segerdahl M. , Sjögren N. , Jensen T.S. , Sindrup S. , Finnerup N.B. 
Published: July 2012

Abstract

Background
In patients with neuropathic pain, Quantitative Sensory Testing (QST) can define different sensory phenotypes thought to be related to different underlying mechanisms. One phenotype with abnormal sensitization of cutaneous nociceptors has been termed irritable nociceptors.

Methods
This study is a part of a randomized, double-blind, placebo controlled, crossover trial with the anticonvulsant oxcarbazepine. The study is ongoing. In this report, baseline QST measures from patients with peripheral neuropathic pain due to either polyneuropathy (PNP) or peripheral nerve injury (PNI) are analyzed. QST evaluates thresholds for cold and heat detection (CDT, WDT), thermal pain (CPT, HPT), vibration (VDT), pin prick, mechanical detection and pressure pain. Furthermore, wind-up ratio and dynamic mechanical allodynia (DMA) are evaluated. Patients with irritable nociceptors are defined as patient with normal CDT and WDT and either mechanical or thermal allodynia or hyperalgesia.

Results
By March 2012, 28 patients with PNI and 24 with PNP were included. There was no difference in pain duration (66.2 (53.7) vs. 64.0 (43.3) months, p = 0.87) or pain intensity (NRS, 0 10) (6.6 (1.6) vs. 6.3 (1.7), p = 0.54), but patients with PNI were significantly younger (48.8 (15.1) years) compared to patients with PNP (62.4 (8.5) years), p < 0.001. The percentage of irritable nociceptors in the PNI group was 39.3% and in the PNP group 29.2% (p = 0.44). The percentage of patients with DMA was 39.3% and 33.3%, respectively (p = 0.66). Significantly more patients with PNI had thermal allodynia (28.6% vs. 0%, p = 0.005), 6 reported cold allodynia and 4 heat allodynia.

Conclusion
Preliminary results show that there was no significant difference in percentage of irritable nociceptors between the two groups, but more patients with PNI had thermal allodynia.