Biomedical subjects

Lars Arendt-Nielsen

Publications and source records attributed to Lars Arendt-Nielsen.

At least 19 recordsLinked to original sources

PubMed2007

Managing chronic whiplash associated pain with a combination of low-dose opioid (remifentanil) and NMDA-antagonist (ketamine).

The aim was to investigate the efficacy of a combination of low-dose remifentanil (REMI) and ketamine (KET) compared to the single drugs and placebo (P) on whiplash associated pain (WAD) in a double-blind, randomized, placebo-controlled, cross-over study. Twenty patients with chronic (>1 year) WAD were included. Four different drug combinations were tested in four sessions: placebo/placebo (P/P), placebo/remifentanil (P/REMI), ketamine/placebo (KET/P) and ketamine/remifentanil (KET/REMI). Target concentrations were 1 and 2ng/ml (stepwise) for remifentanil and 100ng/ml for ketamine. Habitual pain intensity was assessed on a visual analogue scale (VAS). Experimental pain was assessed with electrical stimulation (single and repeated) of tibialis anterior (TA) muscle, pressure pain algometry applied over infraspinatus (IS) and TA muscles and VAS scores after intramuscular hypertonic saline infusion in TA. KET/REMI significantly reduced habitual pain. KET/REMI infused at low REMI target concentration (1ng/ml) significantly elevated electrical intramuscular pain thresholds (single and repeated). Pain thresholds to electrical stimulation were similarly increased by both P/REMI and KET/REMI at 2ng/ml target concentration. Pressure pain thresholds were increased by both KET/REMI and P/REMI. VAS-scores after intramuscular saline were also similarly decreased by both REMI combinations. Seven out of 20 subjects were non-responders (<50% pain relief). No correlation was found between effects on spontaneous pain and experimental pain. KET/REMI showed an analgesic effect on habitual pain. Experimental pain was attenuated by both combinations containing the opioid, however, KET seemed to enhance the effect of REMI on electrical pain thresholds when a low REMI target concentration was used.

Adult↗

PubMed2006

Roles of capsaicin-sensitive primary afferents in differential rat models of inflammatory pain: a systematic comparative study in conscious rats.

To characterize the role of capsaicin-sensitive primary afferents in inflammatory pain, the effects of subcutaneous (s.c.) injection of 0.15% capsaicin on different chemical irritants-induced pathological nociception including persistent spontaneous nociception, primary thermal and mechanical hyperalgesia, and inflammatory response were systematically investigated in unanesthetized conscious rats. Four different animal models of inflammatory pain: the bee venom (BV) test, the formalin test, the carrageenan model, and the complete Freund's adjuvant (CFA) model, were employed and compared. Local pre-treatment with capsaicin produced a significant inhibition on the s.c. BV and formalin induced long-lasting persistent spontaneous nociception. However, this capsaicin-induced inhibitory effect on spontaneous nociception in the BV test was only found within the late phase (tonic nociception; 11-60 min), but not the early phase (acute nociception; 0-10 min). A complete preventing effect of capsaicin on the decreased thermal paw withdrawal latency was found in the BV, carrageenan, and CFA models. Nevertheless, pre-treatment with capsaicin only produced complete blocking effects on the decreased mechanical paw withdrawal threshold in the BV and carrageenan models, but not in the CFA model. For inflammatory response, a significant inhibition of the BV-elicited paw swelling was found following capsaicin treatment. In marked contrast, capsaicin did not produce any effects on the paw inflammation during exposure to carrageenan, CFA, and formalin. These data suggest that capsaicin-sensitive primary afferents may play differential roles in the induction and development of pathological nociception in differential inflammatory pain models. In contrast to other chemical irritants, BV-induced long-term spontaneous nociception, facilitated nociceptive behavior, and inflammation are modulated by peripheral capsaicin-sensitive afferents.

Analgesics, Non-Narcotic↗

PubMed2006

Reversibility of central neuronal changes in patients recovering from gallbladder stones or acute cholecystitis.

AIM: To investigate the referred pain area in patients 2-7 years after cholecystectomy in order to test the hypothesis that neuroplastic changes could give rise to post cholecystectomy pain. METHODS: Forty patients were tested. Twenty five were cholecystectomized due to uncomplicated gallbladder stones and 15 because of acute cholecystitis. Sensitivity to pinprick, heat, cold, pressure and single and repeated electrical stimulation was studied both in the referred pain area and in the control area on the contra lateral side of the abdomen. RESULTS: Five patients still intermittently suffered from pain. But in the objective test of the 40 patients, no statistical significant difference was found between the referred pain area and the control area. CONCLUSION: This study does not support the hypothesis that de novo neuroplastic changes could develop several years after cholecys-tectomy.

Adult↗

PubMed2006

The change in spatial distribution of upper trapezius muscle activity is correlated to contraction duration.

The aim of the study was to confirm the hypothesis that the longer a contraction is sustained, the larger are the changes in the spatial distribution of muscle activity. For this purpose, surface electromyographic (EMG) signals were recorded with a 13 x 5 grid of electrodes from the upper trapezius muscle of 11 healthy male subjects during static contractions with shoulders 90 degrees abducted until endurance. The entropy (degree of uniformity) and center of gravity of the EMG root mean square map were computed to assess spatial inhomogeneity in muscle activation and changes over time in EMG amplitude spatial distribution. At the endurance time, entropy decreased (mean+/-SD, percent change 2.0+/-1.6%; P<0.0001) and the center of gravity moved in the cranial direction (shift 11.2+/-6.1mm; P<0.0001) with respect to the beginning of the contraction. The shift in the center of gravity was positively correlated with endurance time (R(2)=0.46, P<0.05), thus subjects with larger shift in the activity map showed longer endurance time. The percent variation in average (over the grid) root mean square was positively correlated with the shift in the center of gravity (R(2)=0.51, P<0.05). Moreover, the shift in the center of gravity was negatively correlated to both initial and final (at the endurance) entropy (R(2)=0.54 and R(2)=0.56, respectively; P<0.01 in both cases), indicating that subjects with less uniform root mean square maps had larger shift of the center of gravity over time. The spatial changes in root mean square EMG were likely due to spatially-dependent changes in motor unit activation during the sustained contraction. It was concluded that the changes in spatial muscle activity distribution play a role in the ability to maintain a static contraction.

Adult↗

PubMed2006

Experimental muscle pain changes the spatial distribution of upper trapezius muscle activity during sustained contraction.

OBJECTIVE: To investigate the effect of local excitation of nociceptive muscle afferents on the spatial distribution of muscle activity. METHODS: Surface electromyographic (EMG) signals were recorded from the upper trapezius muscle of 10 healthy volunteers with a 5 x 13 electrode grid during 90-s isometric contractions before, during, 15 and 30 min after intramuscular injection of hypertonic (painful) or isotonic (non-painful) saline. From the multi-channel EMG recordings, two-dimensional maps of root mean square and mean power frequency were obtained. The centre of gravity of the root mean square map was used to quantify global changes in the spatial distribution of muscle activity. RESULTS: During sustained contractions, average root mean square increased, average mean frequency decreased and the centre of gravity moved cranially. During experimental muscle pain, compared to before injection, the average root mean square decreased and there was a caudal shift of the centre of gravity. Fifteen minutes after the painful injection the centre of gravity returned to its original position. CONCLUSIONS: Short-term dynamic reorganization of the spatial distribution of muscle activity occurred in response to nociceptive afferent input. SIGNIFICANCE: The study furnishes an extension of the pain adaptation model indicating heterogeneous inhibition of muscle activity.

Adult↗

PubMed2006

Nociceptive withdrawal reflexes evoked by uniform-temperature laser heat stimulation of large skin areas in humans.

Nociceptive withdrawal reflexes (NWR) were evoked by brief (200 ms) painful CO(2) laser stimulation at five intensities (1.2, 1.4, 1.6, 1.8, and 2.0 x pain threshold) applied to nine sites (2 cm(2)) separated by 1.7 cm on the dorsal side of the foot and anterior part of the lower leg of 14 healthy volunteers. The purpose of the study was to investigate the characteristics of NWRs evoked by a natural stimulation modality. The reflexes were measured as the electromyographic response from the iliopsoas (ILI), quadriceps vastus lateralis (QVL), biceps femoris (BF), tibialis anterior (TA), and soleus (SOL) muscles. Stimulus-response relationships between heat intensity and the reflex magnitude and correlation between perceived pain intensity and reflex magnitude were observed in the ILI, QVL, BF, and TA but not the SOL. No significant differences in reflex magnitude were found between the stimulation sites. NWRs were evoked more often in flexor muscles than extensor muscles, indicating a non-site-specific reflex organization. The paper presents a new method to evoke NWRs by uniform-temperature laser heat stimulation of large skin areas in humans. These heat evoked reflexes had a stimulus-response relationship.

Adult↗

PubMed2006

Psychophysical 'perceptual maps' of heat and pain sensations by direct localization of CO2 laser stimuli on the skin.

Brain activation patterns derived from neurofunctional methods are often implicitly regarded as being directly related to subjective perceptual experience in an iso- or at least homomorph manner, neglecting the operational differences between these two dimensions. This paper (a) introduces a method for assessing 'perceptual maps' of stimulation patterns presented to the body surface, providing a means to parametrically relate neural representation and subjective percept, and (b) applies this method to demonstrate the existence of 'somatotopic maps' of hot and painful stimulus patterns independent from mechanoceptive co-activation. Brief (90 ms) CO2 laser pulses were presented in an array of multiple stimulation sites on the dorsal forearms (N. radialis area, C7 dermatome) of healthy subjects. Perceived locations were indicated with a 3D tracker without touching the skin, and (mis-)localizations in distal-proximal direction were analyzed. Stimuli were localized with overall mean errors of 22 mm (SD: 16 mm) toward the wrist and 24 mm (SD: 18 mm) toward the elbow. Somatotopic representation of thermal-nociceptive stimuli could be demonstrated in all subjects, independent from mechanoceptive co-activation. The perceptual maps revealed striking individual (mis-)localization patterns, many subjects exhibiting 'stretched', some 'condensed' somatotopic representations. In estimating the mapping parameters from physical to perceptual space linear regressions generally provided a good fit (adj. R2>0.80 in 10 out of 12 subjects). Nonlinear models were advantageous in some subjects only. Our method can be useful in assessing inter-individual differences or experimentally induced shifts in somatotopic processing.

Adult↗

PubMed2006

Modulation of heat evoked nociceptive withdrawal reflexes by painful intramuscular conditioning stimulation.

Convergence between cutaneous heat nociceptors and muscles afferents was investigated by applying a phasic, conditioning electrical stimulus to the tibialis anterior muscle (a train of five 1 ms pulses over 21 ms) at varying time intervals relative to a thermal test stimulus used for evoking the withdrawal reflex in humans. The 200 ms thermal stimulus was applied on the dorsum of the foot at an intensity of two times the pain threshold. The conditioning electrical stimulus was applied at an intensity of two times the pain threshold via a set of intramuscular needle electrodes. The conditioning-test interval was varied between -400 ms and 8,000 ms at 17 different intervals. The mean reflex onset latency of reflexes evoked by thermal stimuli alone was 354 +/- 9 ms. A facilitation of the reflex was seen when the conditioning stimulus was applied 275 ms (174 +/- 30% compared to control) and 300 ms (162 +/- 32% compared to control) after the test stimulus onset indicating sensory convergence between muscle afferents (group I-III) and cutaneous Adelta heat nociceptors arriving simultaneously at the spinal cord.

Adult↗

PubMed2006

Referred pain from trapezius muscle trigger points shares similar characteristics with chronic tension type headache.

Referred pain and pain characteristics evoked from the upper trapezius muscle was investigated in 20 patients with chronic tension-type headache (CTTH) and 20 age- and gender-matched controls. A headache diary was kept for 4 weeks in order to confirm the diagnosis and record the pain history. Both upper trapezius muscles were examined for the presence of myofascial trigger points (TrPs) in a blinded fashion. The local and referred pain intensities, referred pain pattern, and pressure pain threshold (PPT) were recorded. The results show that referred pain was evoked in 85% and 50% on the dominant and non-dominant sides in CTTH patients, much higher than 55% and 25% in controls (P<0.01). Referred pain spread to the posterior-lateral aspect of the neck ipsi-lateral to the stimulated muscle in both patients and controls, with additional referral to the temple in most patients, but none in controls. Nearly half of the CTTH patients (45%) recognized the referred pain as their usual headache sensation, i.e. active TrPs. CTTH patients with active TrPs in the right upper trapezius muscle showed greater headache intensity and frequency, and longer headache duration than those with latent TrPs. CTTH patients with bilateral TrPs reported significantly decreased PPT than those with unilateral TrP (P<0.01). Our results showed that manual exploration of TrPs in the upper trapezius muscle elicited referred pain patterns in both CTTH patients and healthy subjects. In CTTH patients, the evoked referred pain and its sensory characteristics shared similar patterns as their habitual headache pain, consistent with active TrPs. Our results suggest that spatial summation of perceived pain and mechanical pain sensitivity exists in CTTH patients.

Adult↗

PubMed2006

Effects of subcutaneous administration of glutamate on pain, sensitization and vasomotor responses in healthy men and women.

The present study aimed to investigate if (1) subcutaneous injection of glutamate induces pain, sensitization and vasomotor responses in humans and (2) if sex differences exist in these responses. Thirty healthy volunteers (men-15 and women-15) were included. Each subject received four subcutaneous injections (0.1ml; glutamate 100, 10, 1mM and isotonic saline 0.9%) into the forehead skin in two sessions separated by one week. Assessments of pain intensity (VAS), quality, distribution; area of pinprick hyperalgesia; pressure pain threshold (PPT) at the injection site; surface skin temperature and local blood flow were performed at predetermined time points. The highest concentration of glutamate evoked the highest pain intensity, the longest duration of pain and the largest pain area under the VAS-time curve (P<0.001) in both men and women, although responses in women were larger than in men (P<0.05). The face-chart pain area was the largest for the highest concentration of glutamate (P<0.001) and women drew a larger pain area than men (P=0.024). The area of pinprick hyperalgesia was the largest for glutamate 100mM (P<0.001) and women indicated a larger area than men (P<0.001). Concentration-dependent local vasomotor responses were found following the subcutaneous injection of glutamate but there was no sex difference in this effect. Glutamate 100mM significantly reduced the PPT values (P<0.001) without sex-related differences. The present study demonstrates for the first time that subcutaneous injection of glutamate evokes pain, vasomotor responses and pinprick hyperalgesia in human volunteers and that there are sex-related differences in some of these responses.

Adult↗

PubMed2006

Ultrasonographic study of mechanosensory properties in human esophagus during mechanical distension.

AIM: To study the esophageal geometry and mechanosensation using endoscopic ultrasonography during volume-controlled ramp distensions in the distal esophagus. METHODS: Twelve healthy volunteers underwent distension of a bag. During distension up to moderate pain the sensory intensity was assessed on a visual analogue scale (VAS). The esophageal deformation in terms of multidimensional stretch ratios and strains was calculated at different volumes and VAS levels. Distensions were done before and during administration of the anti-cholinergic drug butylscopolamine. RESULTS: The stimulus-response (volume-VAS) curve did not differ without or with the administration of butylscopolamine. Analysis of stretch ratios demonstrated tensile stretch in circumferential direction, compression in radial direction and a small tensile stretch in longitudinal direction. A strain gradient existed throughout the esophageal wall with the largest circumferential deformation at the mucosal surface. The sensation intensity increased exponentially as function of the strains. CONCLUSION: The method provides information of esophageal deformation gradients that correlate to the sensation intensity. Hence, it can be used to study mechanosensation in the human esophagus. Further studies are needed to determine the exact deformation stimulus for the esophageal mechanoreceptors.

Adult↗

PubMed2006

Correlation and cluster analysis of sensory, pain, and reflex thresholds to various stimulus modalities in symptom-free subjects.

OBJECTIVE: In order to evaluate the possible relation between the psychophysical response and a motor reflex, sensory and pain thresholds to various stimuli were analyzed in combination with the occurrence threshold of the late masseteric exteroceptive suppression (ES2) period. METHODS: Twenty men and 20 women participated. The tactile detection threshold and the filament-prick pain detection threshold were measured on the cheek skin overlying the left masseter muscles. The pressure pain threshold and pressure pain tolerance threshold were measured at the left masseter muscle. The surface EMG was recorded from the left masseter muscle, while electrical stimuli with 13 fixed intensities were applied to the skin above the left mental nerve. The stimulation intensity at which the ES2 appeared for the first time and the lowest stimulus intensity at which the subjects reported to be painful were defined as the ES2 and pain threshold, respectively. RESULTS: There were significant positive correlations between the tactile detection threshold and the pain thresholds determined using the different stimulus modalities, and the ES2 threshold was also significantly correlated with the pain thresholds (P<0.05). Cluster analysis could significantly discriminate two distinct groups with high versus low tactile, pain and ES2 thresholds (P<0.05). CONCLUSIONS: The present findings suggested that the ES2 reflex response has a relation with the individual sensory and pain sensitivity in symptom-free subjects. SIGNIFICANCE: Combined examination of sensory, pain, and ES2 thresholds might provide complementary information on the pathophysiology underlying orofacial pain.

Adult↗

PubMed2006

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

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

Chronic Disease↗

PubMed2006

Gender effects on trapezius surface EMG during delayed onset muscle soreness due to eccentric shoulder exercise.

The purpose of this study was to investigate gender-specific motor control strategies during eccentric exercise and delayed onset muscle soreness (DOMS) in the shoulder region. Twelve healthy males and females participated in the study. Eccentric shoulder exercises were conducted on the dominant shoulder while the other side served as control. The exerted force, range of shoulder elevation, rating of perceived exertion, pain intensity, and surface electromyography (EMG) from the trapezius muscles were recorded and analyzed. A significant decrease in exerted force during exercise was only found in males despite similar rating of perceived exertion among genders. During eccentric exercise: males showed increasing root mean square (RMS) of the EMG while a decrease occurred for females, no difference between genders in mean power frequency of the EMG were seen. During static and dynamic contractions: no differences between genders in pain intensity or RMS were observed; RMS of the exercised side were lower than that of the control side (P<0.05) at 24 h after exercise. The results indicated a more prominent muscle fatigue resistance in females compared with males and mobilization of different muscle activation strategies during eccentric exercise. A protective adaptation to DOMS, i.e. decrease in RMS values was found with no gender differences.

Adaptation, Physiological↗

PubMed2006

Sympathetic facilitation of hyperalgesia evoked from myofascial tender and trigger points in patients with unilateral shoulder pain.

OBJECTIVE: To provide evidence for the sympathetic-sensory interaction within a trigger point, which may contribute to local and referred pain and sympathetic symptoms in myofascial pain syndrome. METHODS: Pressure pain threshold (PPT) was measured from a trigger point in the painful side, from a tender point in the non-painful side in the infraspinatus muscles, and from a normal control point in the tibialis anterior muscle in 21 patients with unilateral shoulder pain. In addition, pressure threshold for eliciting referred pain (referred pain threshold, PTRP) was determined, then the intensity was measured of local and referred pain evoked by a pressure equal to 1.5 times PRPT, applied at the trigger point, in 11 patients. All measurements were taken during normal respiration and elevated intrathoracic pressure (EITP). RESULTS: PPT was significantly lower at the trigger than tender points during normal respiration (P=0.001). PPT decreased significantly at both the tender and trigger points during EITP compared with normal respiration (P<0.001). Significant decreases in referred pain threshold and increases in local and referred pain intensities were seen during EITP than normal respiration (all, P<0.01). CONCLUSIONS: These results provide evidence of sympathetic facilitation of mechanical sensitization and the local and referred muscle pain. SIGNIFICANCE: Sympathetic hyperactivity needs to be considered during the clinical evaluation and management of myofascial pain syndrome.

Adult↗

PubMed2006

A comparison between mechanomyographic condenser microphone and accelerometer measurements during submaximal isometric, concentric and eccentric contractions.

The aim of this study was to compare mechanomyogram (MMG) recorded by a condenser microphone (MIC) and an accelerometer (ACC) during submaximal isometric, concentric and eccentric contractions in 14 males. The maximal voluntary force (MVC) of the biceps brachii was measured. The subjects were asked to do short duration isometric, concentric and eccentric contraction at 10%, 30%, 50%, 70% MVC twice. For the concentric and eccentric contraction, the subject bent his arm for 3s (concentric) then held it for 3s and extended (eccentric) during 3s. The normalized root mean square (RMS) and mean power frequency (MPF) increased linearly with increased force for both transducers. There was a correlation between MIC MPF and ACC MPF at 10%, 30%, 50% MVC, and between MIC RMS and ACC RMS at 30% MVC during isometric contractions. There was significantly higher MPF for the ACC than for the MIC in concentric and eccentric modes, while the RMS did not differ among transducers in the three contraction modes. The RMS and MPF values coefficient of variations were significantly larger during anisometric contractions compared with isometric contractions and were lower for the accelerometer than for the microphone. The present results obtained during isometric, concentric and eccentric contractions of increased intensity showed that the information contained in microphone- and accelerometer-based MMG signals is different despite similar trends. It can be concluded that at low-moderate movement velocity, concentric contractions can be investigated by means of accelerometer and microphone.

Adult↗

PubMed2006

Experimental human pain models in gastro-esophageal reflux disease and unexplained chest pain.

Methods related to experimental human pain research aim at activating different nociceptors, evoke pain from different organs and activate specific pathways and mechanisms. The different possibilities for using mechanical, electrical, thermal and chemical methods in visceral pain research are discussed with emphasis of combinations (e.g., the multimodal approach). The methods have been used widely in assessment of pain mechanisms in the esophagus and have contributed to our understanding of the symptoms reported in these patients. Hence abnormal activation and plastic changes of central pain pathways seem to play a major role in the symptoms in some patients with gastro-esophageal reflux disease and in patients with functional chest pain of esophageal origin. These findings may lead to an alternative approach for treatment in patients that does not respond to conventional medical or surgical therapy.

Central Nervous System↗

PubMed2006

Effects of muscle fatigue induced by low-level clenching on experimental muscle pain and resting jaw muscle activity: gender differences.

The purpose of this study was to investigate the effects of jaw-muscle fatigue evoked by low-level tooth-clenching followed by the induction of experimental muscle pain by injection of glutamate on the perception of fatigue and pain and on the resting electromyographic (EMG) activity. In addition, the role of gender on these interactions was studied. The EMG activities of bilateral masseter (MAL, MAR) and temporalis (TAL, TAR) muscles in 11 healthy young women and 12 men were measured before (Baseline) and after tooth-clenching for 30 min at 10% of maximal force (Post1), after subsequent glutamate (Glu) or isotonic saline (Iso) injection into the MAL following the tooth-clenching (Post2) and 60 min after tooth-clenching (Post3). The intensities of fatigue, fatigue-related muscle pain and headache-like symptoms were scored on 0-10 cm visual analog scales (VAS). The glutamate-evoked pain was continuously scored on an electronic VAS. Sustained low-level tooth-clenching consistently produced fatigue sensation, fatigue-related muscle pain and headache-like symptoms in both genders with significantly higher fatigue VAS scores in men than in women, while the accompanying increase in the resting EMG activity appears higher in women than in men in the masseter muscles. In this study no gender differences were found for the perceived amount of experimental pain induced by glutamate injection. Additional increases of the resting EMG activity after injections occurred only in men in the injected masseter muscle and non-injected temporalis muscles. The present findings provide new information on the complex influence of gender on sensory-motor integration in the trigeminal system which may contribute to differences in susceptibility to develop musculoskeletal pain problems.

Adult↗