bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the ability of non-rectangular electrical pulse forms to preferentially activate nociceptive fibers by comparing perception thresholds
Authors: Hugosdottir R. , Mørch C.D. , Andersen O.K. , Helgason T. , Arendt-Nielsen L. 
Published: August 2017

Abstract

Aims
Selective activation of nociceptive fibers is difficult using electrical stimulation as the activation threshold is higher than for non-nociceptive fibers. It remains unclear to what extent accommodation of non-nociceptive fibers during slowly rising electrical pulses can be utilized to reverse this activation order. The aim of this study was to evaluate the ability of different pulse forms to activate nociceptive fibers with minimal co-activation of non-nociceptive fibers by comparing subjective perception thresholds (PT).

Methods
Electrical pulses were applied on the volar forearm of 25 subjects with (1) small diameter pin electrodes providing high current density in the skin epidermis, where primarily nociceptive fibers terminate and (2) standard patch electrodes (2.63 cm2). PTs were obtained for exponential current increase, linear current increase, increasing form of exponential current decay (ED), and standard rectangular current pulses. All pulse forms were tested at two relatively long durations (5 and 50 ms). The PT ratio between patch- and pin electrode was calculated as an estimate of the ability of a pulse form to preferentially activate nociceptive fibers. The short form McGill pain questionnaire (SF-MPQ) was used to assess perceived quality of pain for all pulse forms.

Results
For the pin electrode, PT tended to decrease with increasing pulse area. Patch electrode PT tended to increase for increasing pulse area for non-rectangular 50 ms pulses, in contrast to 5 ms pulses, indicating accommodation of non-nociceptive fibers. Largest PT ratio was obtained for the 50 ms ED. SF-MPQ scores were higher for the pin- compared to the patch electrode. Pin electrode pain qualities were mainly described as stabbing and sharp. SF-MPQ scores did not differ between pulse forms.

Conclusions
Long duration ED pulses seem to activate nociceptive fibers better than regular, short duration pulses; most likely reflecting accommodation of non-nociceptive fibers.
Acute muscle pain alters corticomotor output of the affected muscle stronger than a synergistic, ipsilateral muscle
Authors: Larsen Dennis Boye , Graven-Nielsen Thomas , Hirata Rogerio Pessoto , Boudreau Shellie A. 
Published: August 2017

Abstract

Aims
Muscle pain affects corticomotor areas representing the affected muscle, by changing the size of representation and reduces the corticospinal output as assessed by transcranial magnetic stimulation (TMS). Less work has been done to understand how pain in one muscle group may affect synergistic ipsilateral muscles distal to the pain. This study aimed to explore the effects of acute extensor carpi radialis (ECR) muscle pain on TMS motor-evoked potentials (MEPs) of the ECR and the first dorsal interosseus (FDI) muscle, which are known to strongly overlap within the corticomotor area.

Methods
Eight healthy volunteers (1 woman) were injected with hypertonic saline (5.8%, 0.5 mL) into the ECR muscle. Pain intensity was assessed by the visual analogue scale (VAS) every minute for 10 min. TMS was applied at 120% of ECR resting motor threshold, and MEPs were acquired from the ECR and the FDI muscles. At baseline, 10 TMS pulses were delivered. Temporal mapping of ECR and FDI MEPs over 10 min duration was performed by delivering 100 single-pulses of TMS, at 6 s interstimulus-interval. The MEPs for each muscle were averaged at baseline, peak-pain (1 –2 min epoch), and 10 min post-injection

Results
Pain intensity reduced significantly at 10 min postinjection as compared to peak-pain (P = 0.011). Further, one-way repeated measures analysis of variance revealed that ECR MEPs were altered at peak-pain compared to baseline (P > 0.05), but not 10 min post-injection (P > 0.05). Baseline and 10 min post-injection of ECR MEPs did not differ significantly (P = 0.67). The MEPs of the FDI muscle did not show a similar alteration over time (P = 0.1).

Conclusions
Despite the overlap between ECR and FDI representations, acute muscle pain of the ECR only significantly altered cortical excitability of the ECR muscle representation.
The size of pain referral patterns from a tonic painful mechanical stimulus is increased in women
Authors: Liu Q.G. , Palsson T.S. , Sørensen L.B. , Graven-Nielsen T. 
Published: August 2017

Abstract

Aims
The purpose of this study was to investigate potential gender differences in pain referral patterns induced by a tonic painful mechanical stimulus.

Methods
Forty-five healthy adults (22 women) participated in this study. Pressure pain thresholds (PPTs) were assessed at the infraspinatus, the brachioradialis and the gastrocnemius muscles on the dominant side, using handheld algometry. Following this, painful pressure at the infraspinatus muscle was induced using the algometer by rapidly increasing the pressure until it reached the level of 7 cm on VAS (PVAS7). This pressure was kept constant for 60s. Upon release, the subject was asked to indicate the area of the pressure-induced pain on a digital body chart. PPT values, PVAS7 and the pain area (number of pixels) were extracted for data analysis.

Results
No gender differences were found in PPT values (P >0.05). The pressure needed to reach 7 cm on the VAS was significantly lower in the female group (687.4±50.5 kPa) compared with males (971.0 ± 49.6 kPa; unpaired t-test: P < 0.05). The size of the pain area following PVAS7 stimulation for 60 s was significantly larger in the female group (12,578.5 ± 17,280.3 pixels) compared with the male group (6175.0 ± 9518.5 pixels; Mann–Whitney-U; P < 0.05).

Conclusions
Despite comparable PPT values, women demonstrated larger pain areas compared with men although the standardized painful stimulus which intensity was perceived similarly as 7 cm on the VAS scale in both groups. These findings suggest that there are gender-specific differences in pain distribution and referred pain but it is unclear through which mechanism they are mediated.
Topical allyl-isothiocyanate (mustard oil) as a TRPA1-dependent human surrogate model of pain, hyperalgesia, and neurogenic inflammation – A dose response study
Authors: Andersen H.H. , Lo Vecchio S. , Gazerani P. , Arendt-Nielsen L. 
Published: August 2017

Abstract

Aims
Transient receptor potential ion channel A1 (TRPA1) has been shown to play a pathoetiological role in several painful and inflammatory conditions and therefore several new drug candidates, targeting TRPA1 are currently being developed [1]. While the natural TRPA1-agonist allyl-isothiocyanate (AITC, known as “mustard oil”) is an exceedingly common animal pain model, it has only been sparsely investigated as a potential human surrogate model of pain and neurogenic inflammation. This study aimed to evaluate dose-response features of AITC as a sensitizing, algogenic irritant in human skin.

Methods
Three concentrations of AITC (10%, 50%, 90%) and vehicle (100% paraffin) were applied for 5 min to 3 cm × 3 cm areas on the volar forearms in 14 healthy volunteers, and evoked pain (visual analog scale 0–100 mm) and pain quality were assessed. Following the application, a battery of quantitative sensory tests was conducted including assessment of mechanical and thermal sensitivity. Neurogenic inflammation was evaluated using Laser Perfusion Imaging (FLPI). Erythema and pigmentation were assessed before, immediately after and≈64 h after AITC exposure.

Results
Topical application of AITC induced significant dose-dependent, moderate-to-severe spontaneous pain mostly described as burning as well as mechanical and heat hyperalgesia (p < 0.05). The model also produced robust dynamic mechanical allodynia (p < 0.05). Only modest increases in pain hypersensitivity were observed between the 50% and 90% concentrations. Neurogenic inflammation was evoked by all concentrations and assessments by FLPI demonstrated a significant dose dependent increase from 10% to 50% ATIC, with a ceiling effect from 50% to 90%.

Conclusions
Topical AITC-application evokes dose-dependent rapid pain and somatosensory sensitization with optimal concentrations recommended to be above 10% and equal to or below 50%. The model is translatable and could be useful in pharmacological proof-of-concept studies of TRPA1-antagonists, analgesics and anti-inflammatory compounds or for exploratory clinical purposes (e.g. loss- or gain-of-function in peripheral neuropathies).
Combined electric and pressure cuff pain stimuli for assessing conditioning pain modulation (CPM)
Authors: Tsukamoto M. , Petersen K.K. , Mørch C.D. , Arendt-Nielsen L. 
Published: August 2017

Abstract

Aims
Traditionally, conditioning pain modulation (CPM) can be assessed by applying a test stimulus (TS) before and after application of a conditioning stimulus (CS), which is normally applied extra-segmental. Currently, no studies have attempted to apply the TS and CS to the same site using different stimuli modalities. The aim of this study was to evaluate electrical TS and cuff pressure CS applied to the same experimental site for studying CPM.

Methods
20 male volunteers participated in this study, which consisted of stimulations applied by a cuff-algometer (NociTech and Aalborg University, Denmark) and current stimulator (Digitimer DS5, UK), through two Ag/AgCl electrodes (Ambu® Neuroline 700, Denmark). The cuff was wrapped around the lower leg and stimulation electrodes were placed under the cuff and to the same location on the contralateral leg. Electrical TS were applied to the non-dominant leg with or without cuff pressure CS on the dominant (CS1) or the same (non-dominant) leg (CS2, electrode under cuff). The subjects were instructed to rate the electrical evoked pain intensity on a 10-cm continuous visual analog scale (VAS, “0” represented “no pain”, and “10” represented “maximal pain”). The pain detection threshold (PDT) was defined as “1” on the VAS scale.

Results
There was no significant deference in PDT for neither CS1 nor CS2. A median split subanalysis on CPM-responders versus CPM-nonresponders to the TS + CS1 combination. Using this grouping, there was significant increase in PDT when comparing TS to TS + CS1 or TS + CS2 (4.0 mA vs 5.6 mA; P < 0.05, 4.0 mA vs 5.1 mA; P < 0.05).

Conclusions
The study indicates that CPM can be evoked in a subgroup of subjects by applying the electrical test stimulus and cuff pressure conditioning stimuli to the same experimental site.
The effect of facilitated temporal summation of pain, widespread pressure hyperalgesia and pain intensity in patients with knee osteoarthritis on the responds to Non-Steroidal Anti-Inflammatory Drugs – A preliminary analysis
Authors: Petersen K.K. , Simonsen O. , Andersen M.M. , Olesen A.E. , Arendt-Nielsen L. 
Published: August 2017

Abstract

Background
Non-Steroidal Anti-Inflammatory Drug (NSAID) treatment is recommended as the first step in the treatment of knee osteoarthritis (KOA). Due to the risk of side-effects of NSIADs and low responds rate, methods for selection of NSAID responders are highly warranted. Recent studies suggest that pain sensitization in KOA might be predictive for the effect of surgical treatment, why the purpose of the present study was to evaluated whether quantitative sensory testing (QST) could be predictive for the effect of NSAID treatment in KOA.

Material and methods
100 patients were enrolled and assessed using temporal summation of pain (TSP), pressure pain thresholds (PPT) and pain intensity (visual analog scale, VAS; 0: no pain and 10: worst imaginable pain) before and 8 weeks after daily treatment of Ibuprofen 400 mg × 3, Paracetamol 1 g × 3 and Pantoprazole 20 mg × 1. TSP was assessed by the difference in pain scores to one PinPrick stimulus followed by 10 PinPrick stimuli. PPT was assessed at the extensor carpi radialis longus muscle. Responders were categorized as decrease in pain intensity of at least three VAS-points.

Results
80 patients had complete data at follow-up. 28 patients were categorized as responders and 52 patients as non-responders. Pre-treatment pain intensity (responders: 7.5 (SD: 1.6) vs. nonresponders: 6.5 (SD: 2.3), P < 0.03) and TSP (responders: 1.9 (SD: 2.5) vs. non-responders: 1.0 (SD: 1.5), P < 0.05) were significantly higher in responders compared with non-responders. Pre-treatment PPT at the arm trended towards significantly lower in responders (293 kPa (SD: 85)) compared with no responders (339 kPa (SD: 124), P < 0.06).

Conclusions
This preliminary analysis indicate that KOA patients with high pain intensities, facilitated TSP and widespread pressure hyperalgesia respond to NSAIDs.
How to obtain the biopsychosocial record in multidisciplinary pain clinic? An action research study
Authors: Sejling L.B. , Svensson L. , Jensen P.F. , Pawlak W.Z. 
Published: August 2017

Abstract

Background
Patients with complicated chronic non-malignant pain (CCNMP) should be referred to the multidisciplinary treatment based on the biopsychosocial pain model. This is not a trivial task to obtain the biopsychosocial record (BPSR) during the first visit in multidisciplinary pain center – some important data can be missing, but it is difficult to choose the right questions.

Purpose
To find the optimal method for obtaining of BPSR in patients with CCNMP.

Methods
The action research methodology is used. First, the literature search was done. Second, the meetings between therapists were hold. Third, the patients are asked about their experiences with obtaining of BPSR.

Results
The following area of interest were identified: (1) patient’s demographic data, (2) lifestyle factors, (3) previous diseases, (4) concurrent diseases, (5) previous pain treatments, (6) pain intensity and effect of the actual pain treatment, (7) general activity, (8) mood, (9) walking activity, (10) work ability, (11) home activities, (12) relations with other people, (13) sleep, (14) enjoyment of life, (15) patients expectations from treatment, and (16) treatment goals. Patients are asked about those variables. Either Visual Analogue Scale or Numeric Rating Scale is used for assessment of pain intensity and pain influence on variables (7) to (14). First, data about variables (1) to (6) are collected by the physician. Next, data about variables (7) to (15) are gathered under interview with the nurse. Last, the physician and the nurse keep the meeting on treatment goals and treatment course. Up to date (February 2017), 8 patients were asked about their experience with obtaining of BPSR. All but one patient were very satisfied.

Conclusions
The method presented above seems to be promising approach to obtaining of BPSJ in patients with CCNMP. The study is ongoing and updated results will be presented at the conference.
Prevalence and pattern of helmet-induced headache among Danish military personnel
Authors: Rahmani Z. , Kochanek A. , Astrup J.J. , Poulsen J.N. , Gazerani P. 
Published: August 2017

Abstract

Aims
Headache is a leading reason to seek medical care. Several subtypes of headaches have been defined, one of which is external compression headache. This headache is due to an external physical compression applied on the head. It affects approximately 4% of the general population; however, certain populations for example construction workers and military personnel with particular needs of headwear or helmet are at higher risk for development of this type of headache. Generally, external compression headache is poorly studied and there is no report on helmet-induced headache among Danish military personnel. This survey-based study was designed to investigate prevalence and pattern of helmet-induced external compression headache among these personnel.

Methods
Questionnaires were carefully developed and delivered to a total of 279 participants who use helmets in the Danish military service. The military of the Northern Jutland region of Denmark facilitated recruitment of study participants. Questionnaires were delivered on paper and anonymous answers were collected and used for further analysis. Data were handled using descriptive statistics.

Results
Up to 30% of the participants reported headache in relation to wearing the military helmet. Headache was defined as moderate intensity with pressing pain quality mostly located in front of the head. Two types of helmets in this study were different in the weight and padding of the inner part and delivered different pattern of pressure; while one evenly delivered pressure on multiple head regions, the other delivered pressure mostly on the sides and top of the head. This suggests that helmet pressure and headache location might be associated.

Conclusions
This study was first to demonstrate prevalence and pattern of helmet-induced headache among military personnel in North Jutland, Denmark. Findings of this study call for further attention to helmet-induced headache and strategies to minimize the burden, for example by design of appropriate helmets.
Aquaporin 4 expression on trigeminal satellite glial cells under normal and inflammatory conditions
Authors: Riccio D. , Magni G. , Ceruti S. , Arendt-Nielsen L. , Gazerani P. 
Published: August 2017

Abstract

Aims
Limited information is currently available for the expression and role of Aquaporin 4 (AQP4) (AQ4) in the peripheral nervous system (PNS). It has been demonstrated that AQP4 is expressed in sensory ganglia. Immunohistochemistry has revealed that satellite glial cells (SGCs) surrounding the cell bodies of the primary afferent sensory neurons in these sensory ganglia exclusively express AQP4 at a considerably lower level than what is seen in astrocytes. The pathophysiological relevance of AQP4 in peripheral nociception; however, remains unclear. Hence, this study aimed at investigating AQP4 expression in trigeminal neurons and SGCs under normal and inflammatory conditions relevant to craniofacial pain conditions.

Methods
Rat trigeminal ganglia (TG) were isolated from adult male Sprague-Dawley rats subjected to a model of trigeminal inflammation evoked by unilateral complete Freund’s adjuvant (CFA) injection in temporomandibular joint. Immunohistochemistry was performed on TG sections of CFA-treated animals. NeuN and GS markers were used for identification of neurons and SGCs, respectively. AQP4 expression was investigated in both ipsilateral and contralateral TG sections. The study protocol was approved by the local ethics committee.

Results
Co-localization of NeuN-AQP4 and GS-AQP4 were identified in both ipsi and contralateral trigeminal ganglia of the CFA-treated rats. However, we did not detect any difference between the ipsi- and contralateral side in terms of alteration in AQP4 receptor expression.

Conclusions
AQP4 was expressed both on trigeminal neurons and SGCs and CFA did not cause a remarkable change in AQP4 expression, when ipsilateral and contralateral TG of the test animals was compared. Previously, it has been shown that in a neuropathic pain model no difference is detectable between wild type and AQP4-deficient mice, for mechanical and thermal perception; however, in formalin pain model AQP4-deficient mice have higher thermal pain thresholds. Further investigation is required to clarify role of AQP4 in pain.
Biomarkers alterations in trapezius muscle after an acute tissue trauma: A human microdialysis study
Authors: Sørensen L.B. , Gazerani P. , Wåhlén K. , Ghafouri N. , Gerdle B. , Ghafouri B. 
Published: August 2017

Abstract

Aims
Alteration in muscle milieu has been proposed as one of the main contributors underlying chronic musculoskeletal pain (CMP). Microdialysis (MD) provides real-time information on release of pain and metabolic biomarkers in muscle. However, insertion of MD probe causes a local tissue trauma, which may affect the tissue milieu. Whether an acute tissue trauma alter pain and metabolite biomarkers in trapezius muscle of patients with CMP is not known. Hence, this study investigated changes in muscle metabolites following MD probe insertion in patients with CMP in comparison with healthy controls.

Methods
Nineteen patients (11 women and 8 men; 41.4 years) with CMP and 20 pain-free volunteers (10 women and 10 men; 36.5 years) were recruited (project approval number: 2013/151- 31). Baseline pressure pain thresholds (PPT) at trapezius muscle were obtained bilaterally with a reference point at the tibialis muscle. Pain questionnaires were used for determining levels of anxiety and depression and catastrophizing impact. Interstitial samples were collected from trapezius muscles by aid of MD (20 kDa cut-off) during a period of 40 min. Collected dialysates at 2 time-points of 20 and 40 min were stored at −70 °C until analysis. Concentrations of glucose, lactate, pyruvate, glycerol, and glutamate were analyzed by ISCUSSflex. P ≤ 0.05 was considered significant.

Results
No potential case with respect to anxiety, depression or catastrophizing impact was found. Lower PPTs were found in CMP group (P ≤ 0.05). Significantly lower levels of pyruvate were found in CMP group at both 20 min (P = 0.003) and 40 min (P = 0.006). Gender-based analysis indicated higher concentrations of glutamate in female patients with CMP.

Conclusions
This study was first to demonstrate metabolite alterations during trauma phase of MD in trapezius muscles of CPM compared with healthy controls. This model proved beneficial for investigating pain and metabolic biomarkers during acute phase of MD.
Drugs that can cause respiratory depression with concomitant use of opioids
Authors: Sigmarsdottir B.D. , Gudmundsdottir Th.K. , Zoäga S. , Gunnarsson P.S. 
Published: August 2017

Abstract

Aims
Respiratory depression is a serious life threatening condition and a known adverse event of opioids. Little is known about the use of the opioid antidote naloxon in Iceland, and the additive effects of other potentially respiratory depressive drugs administered with opioids. The aim of the study was to review the literature on drugs that may cause respiratory depression and to assess medication use in patients receiving parenteral naloxone in Landspítali University Hospital.

Methods
A review and analysis of drugs that can cause respiratory depression based on information from the scientific literature, medicine databases and clinical guidelines. A retrospective study was performed using data collected from the electronic medical records system of Landspítali University Hospital for all patients, 18 years and older that had parenteral naloxon administered in the years 2010–2014. Information about the type of opioid and other respiratory depressive drugs was collected and the data was further investigated in regards to age, gender, and type of service.

Results
The most potential drugs and drug classes that can cause respiratory depression when used concomitantly with opioids are benzodiazepines and other anxiolytics, hypnotics and sedatives, antipsychotics, antiepileptics, antihistamins and anesthetics. When use was examined (N=138) morphine was the most frequent opioid given (49%). Concomitant use of opioids and other respiratory depressive drugs was seen in 63% of cases, and benzodiazepines were the most frequent drugs given with opioids (33%).

Conclusions
The concomitant use of benzodiazepines and other sedative drugs with opioids is frequent, despite the known risk of additive respiratory depression as described in the literature. Other patient risk factors such as medical condition, general health and consciousness should be considered in context with drugs used.