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Biomedical subjects

L Bendtsen

Publications and source records attributed to L Bendtsen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Possible mechanisms of glyceryl-trinitrate-induced immediate headache in patients with chronic tension-type headache.

Nitric oxide (NO) plays an important role in the pathophysiology of primary headaches including chronic tension-type headache (CTTH). Thus, a NO synthase inhibitor reduces headache and muscle hardness while the NO donor glyceryl trinitrate (GTN) causes more headache in patients than in healthy controls. Sensitization of myofascial pain pathways is important in CTTH, and the aim of the present study was to investigate if such mechanisms may also explain GTN-induced immediate headache in patients with CTTH. In a randomized, double-blind, crossover study 16 patients with CTTH and 16 healthy subjects received intravenous infusion of GTN (0.5 microg/kg per min for 20 min) or placebo on two headache-free days separated by at least 1 week. Muscle hardness, myofascial tenderness, mechanical and heat pain thresholds were measured at baseline and at 60 min and 120 min after start of infusion. In patients, GTN infusion resulted in a biphasic response with immediate headache and more pronounced delayed headache. A similar but less pronounced response was seen in controls. There was no difference between GTN and placebo regarding muscle hardness, myofascial tenderness or pressure and heat pain thresholds in either patients or controls (P>0.05). The unchanged sensitivity of pericranial myofascial pain pathways indicates that peripheral and central sensitization is not involved in the mechanisms of GTN-induced immediate headache.

Adult↗
PubMed2000

Nitric oxide-induced headache in patients with chronic tension-type headache.

An experimental model of headache offers unique possibilities to study the mechanisms responsible for head pain. Using the glyceryl trinitrate [GTN; nitric oxide (NO) donor] model of experimental headache, we studied the intensity, quality and time profile of headache after infusion of GTN in 16 patients with chronic tension-type headache and in 16 healthy controls. Subjects were randomized to receive intravenous infusion of GTN (0.5 microg/kg per minute for 20 min) or placebo on two headache-free days separated by at least 1 week. Headache intensity was measured on a 10-point verbal rating scale during 2 h of observation and for the next 10 h after discharge from hospital. The primary endpoints were the difference between the area under the curve (AUC-intensities x duration) for headache recorded on the day of GTN treatment and on the day of placebo treatment in patients, and in patients and controls on the days of GTN treatment. In patients, the AUC on a GTN day [2221 (1572-3704); median with quartiles in parentheses], was significantly greater than on a placebo day [730 (60-1678), P: = 0. 008]. On the GTN day, the AUC in patients [2221 (1572-3704)] was significantly higher than in controls [43 (0-972), P: = 0.0001]. In patients, peak pain intensity occurred 8 h after infusion of GTN, whereas in controls it occurred 20 min after the start of infusion. The present study demonstrates that an NO-induced biphasic response with an immediate and a delayed headache is common to chronic tension-type headache and migraine. Furthermore, the NO-induced delayed headache has the characteristics of the primary headache disorder. This suggests that NO contributes to the mechanisms of several types of primary headaches and that NO-related central sensitization may be an important common denominator in the pain mechanisms of primary headaches.

Adult↗
PubMed1999

Effect of inhibition of nitric oxide synthase on chronic tension-type headache: a randomised crossover trial.

BACKGROUND: Studies in animals have shown that nitric oxide plays an important part in central sensitisation and that inhibitors of nitric oxide synthase (NOS) decrease sensitisation in models of persistent pain. The efficacy of inhibitors of NOS has not been tested in patients with tension-type chronic headache. We aimed to show whether N(G)-monomethyl-L-arginine hydrochloride (L-NMMA), an inhibitor of NOS, is effective in relieving pain in such patients. METHODS: We undertook a randomised double-blind, crossover trial of 16 patients with chronic-tension-type headache. Patients were assigned intravenous infusion of 6 mg/kg L-NMMA or placebo on 2 days separated by at least 1 week in a randomised order. Headache intensity was measured on a 100 mm visual analogue scale, and on a verbal rating scale at baseline and at 30 min, 60 min, and 120 min after start of treatment. The primary endpoint was reduction of pain intensity on the visual analogue scale by the active treatment compared with placebo. FINDINGS: L-NMMA reduced pain intensity on the visual analogue scale significantly more than placebo: 120 min after start of treatment, the mean pain score was decreased from 49 to 33 with L-NMMA and from 44 to 40 with placebo (p=0.01). Pain intensity on the verbal rating scale was also significantly lower for treatment with L-NMMA than for treatment with placebo (p=0.02). INTERPRETATION: Inhibition of NOS had an analgesic effect in chronic tension-type headache. Further tests are required before clinical application.

Adult↗
PubMed1999

Muscle hardness in patients with chronic tension-type headache: relation to actual headache state.

It has recently been reported that the pericranial muscles in patients with chronic tension-type headache are harder, i.e. have a higher consistency, than in controls. The primary aim of the present study was to investigate whether muscle hardness is influenced by the presence or absence of actual headache and whether hardness is correlated to tenderness. The secondary aim was to compare muscle hardness between patients and healthy controls. Hardness of the trapezius muscle was measured with a hardness meter in 20 patients with chronic tension-type headache and in 20 healthy controls. The patients were examined on 2 days, 1 day with headache and 1 day without headache. Pericranial myofascial tenderness was recorded with manual palpation. In addition, muscle hardness was measured in another five patients out-side headache and in 30 healthy controls. The muscle hardness recorded in patients (n = 20) on days with headache, 98 +/- 26 kPa/cm, did not differ significantly from the muscle hardness recorded on days without headache, 100 +/- 21 kPa/cm, (P = 0.62). The muscle hardness was positively correlated to the local tenderness score recorded from the trapezius muscle both on days with headache (R = 0.52, P = 0.02) and on days without headache (R = 0.53, P = 0.02). The total tenderness score (TTS) recorded in patients on days with headache, 23 +/- 10, was significantly higher than the TTS recorded on days without headache, 15 +/- 11, (P = 0.0001). There was a significant difference between the TTS recorded in patients without headache, 15 +/- 11, and in controls, 4 +/- 4, (P = 0.002). The muscle hardness was significantly higher in patients on days without headache (n = 25), 97 +/- 20 kPa/cm, than in controls (n = 30), 87 +/- 16 kPa/cm (P = 0.03). On basis of previous and present results, we suggest that muscle hardness and muscle tenderness are permanently altered in chronic tension-type headache and not only a consequence of actual pain. In addition, the positive correlation between muscle hardness and tenderness supports the common clinical observation that tender muscles are harder than normal muscles.

Adult↗
PubMed1999

Plasma levels of substance P, neuropeptide Y and vasoactive intestinal polypeptide in patients with chronic tension-type headache.

Animal and human studies have shown that substance P (SP), neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) are involved in the pathophysiology of acute and chronic pain conditions. The primary aim of the present study was to compare plasma levels of SP, NPY and VIP in external jugular vein between patients with chronic tension-type headache and healthy controls. The secondary aim was to examine plasma levels of these neuropeptides in relation to headache state. In addition, we wanted to study the relation between cranial circulation (jugular vein) and peripheral circulation (antecubital vein). Blood from the external jugular and antecubital vein was drawn from 20 patients with chronic tension-type headache and 20 healthy controls. Plasma SP in patients, 2.0 (1.4-2.2) pmol/l, did not differ significantly from plasma SP in controls, 1.7 (1.1-2.1) pmol/l, (P=0.44). No significant differences were found between SP levels on days with headache, 1.5 (0.3-1.7) pmol/l, and SP levels on days without headache, 1.7 (1.1-1. 9) pmol/l, (P=0.06). Plasma NPY in patients, 118+/-3 pmol/l, did not differ significantly from plasma NPY in controls, 113+/-5 pmol/l, (P=0.40). There was no difference between NPY levels on days with headache, 120+/-3 pmol/l, and on days without headache, 118+/-3 pmol/l, (P=0.73). VIP levels in patients, 6 (4-7) pmol/l, did not differ significantly from VIP levels in controls, 5 (5-7) pmol/l, (P=0.50). No significant differences were found between VIP levels measured on days with headache, 5 (4-6) pmol/l, and VIP levels measured on days without headache, 6 (4-7) pmol/l, (P=0.81). Plasma levels of SP, NPY and VIP did not significantly differ between the peripheral and the cranial circulation neither in patients nor in controls (0.05). In summary, the present study indicates that plasma levels of SP, NPY and VIP are normal in chronic tension-type headache patients and largely unrelated to headache state.

Adult↗
PubMed1999

Familial occurrence of chronic tension-type headache.

Chronic tension-type headache (CTTH) assessed by proband report was evaluated in a family study of CTTH. A clinical interview of first-degree relatives by a physician was used as index of validity. Familial occurrence of CTTH in first-degree relatives was also investigated. Patterns of familial aggregation of CTTH were assessed by calculating the population relative risk. A neurological resident carried out all the interviews of probands and their first-degree relatives. The operational diagnostic criteria of the International Headache Society were used. The 122 probands had 377 first-degree relatives. Sensitivity, specificity, predictive values, and chance-corrected agreement rate for the diagnosis CTTH were 68%, 86%, 53% (PVpos), 92% (PVneg), and 0.48, respectively. The low sensitivity of CTTH assessed by proband report indicates that a clinical interview by a physician is necessary in family studies of CTTH. Clinically interviewed parents, siblings, and children had a 2.1 to 3.9-fold significantly increased risk of CTTH compared with the general population. The gender of the probands did not influence the risk of CTTH among first-degree relatives. The significantly increased familial risk of CTTH and no increased risk of CTTH in spouses suggest that a genetic factor is involved in CTTH.

Adolescent↗
PubMed1999

Possible mechanisms of action of nitric oxide synthase inhibitors in chronic tension-type headache.

It has been demonstrated recently that nitric oxide synthase (NOS) inhibition has an analgesic effect in patients with chronic tension-type headache. The aim of the present study was to investigate the influence of the NOS inhibitor, L-N(G) methyl arginine hydrochloride (L-NMMA), on two of the most prominent features of chronic tension-type headache, i.e. increased muscle hardness and increased myofascial tenderness. In a double blind, crossover designed trial, 16 patients with chronic tension-type headache were randomized to receive intravenous infusion of 6 mg/kg L-NMMA or placebo on 2 days separated by at least 1 week. Muscle hardness of the trapezius muscle was measured with a hardness meter. Myofascial tenderness in the pericranial region was evaluated by manual palpation with standardized and validated methodology. All parameters were recorded at baseline and at 60 and 120 min after start of infusion. Compared with baseline, muscle hardness, 107 +/- 17 kPa/cm and tenderness, 18 +/- 11 were significantly reduced at 60 and 120 min to: hardness, 101 +/- 17 kPa/cm and 101 +/- 17 kPa/cm, respectively; tenderness, 15 +/- 11 and 14 +/- 11, respectively, after treatment with L-NMMA (P < 0.05 and P < 0.01, respectively), while there was no significant reduction at any time after treatment with the placebo. Compared with the placebo, the summary score of muscle hardness was significantly reduced (P = 0.04), while tenderness showed a non-significant reduction (P = 0.11) following treatment with L-NMMA. Since increased muscle hardness in patients with chronic tension-type headache may reflect sensitization of second order neurons due to prolonged nociceptive input from myofascial tissues, we suggest that the decrease in muscle hardness following treatment with L-NMMA may be caused by reduction of central sensitization.

Adult↗
PubMed1998

The platelet serotonin transporter in primary headaches.

Serotonin (5-HT) plays a major role in the pathophysiology of primary headaches. The presynaptic 5-HT uptake mechanism, which is important for the regulation of 5-HT levels in the neuronal synapses, can be examined indirectly by measuring the number of 5-HT transporters in membranes from platelets. The aim of the present study was to investigate the platelet 5-HT transport system in patients with primary headache disorders. Bmax, an index of the number of platelet 5-HT transporters, was measured in 40 patients with chronic tension-type headache, in 30 patients with migraine without aura, and in 40 healthy controls using a binding analysis with tritiated paroxetine as the ligand. The Bmax was 664 (589-846) (median (quartiles)) fmol/mg protein in patients with tension-type headache and 662 (534-781) fmol/mg protein in healthy controls, P = 0.40. The Bmax was 675 (558-747) fmol/mg protein in patients with migraine, which was not significantly different from the Bmax in controls, P = 0.94. In conclusion, the present results indicate that the number of platelet 5-HT transporters is normal in patients with chronic tension-type headache and in patients with migraine without aura.Copyright Lippincott-Raven Publishers

Journal Article↗
PubMed1998

Measurement of muscle hardness: a methodological study.

The aim of the present study was to determine the intra- and interobserver variation during measurement of muscle hardness with a new instrument, a so-called hardness meter. In addition, we investigated the factors which may influence the recording of muscle hardness and whether the hardness differs within the same muscle. Hardness was measured at a standardized point on the trapezius muscle in 20 volunteers by 2 observers in random order and again by 1 of the observers after 30 min. Muscle hardness was then measured at 3 different locations on the trapezius muscle. In addition, the muscle hardness at the standard point was measured in 10 volunteers by both observers at 3 different speeds of the applied pressure. The intraobserver variation was 10% and the interobserver variation was 12% for recording of muscle hardness. There was no significant difference in hardness values from time to time within the same observer (p=0.12), while there was a significant difference in hardness measurements between observers (p=0.007). Muscle hardness differed significantly among the 3 anatomical locations (p=0.03). For both observers, there was a significant difference among hardness recordings obtained at 3 different speeds (p=0.01 and p=0.0001). In conclusion, we have shown that the hardness meter can measure muscle hardness reliably if the same observer is used throughout a study. The speed factor was a major source of variability In addition, we have demonstrated that muscle hardness differs within the same muscle. We suggest that the muscle hardness meter will be an important tool in future research of the mechanisms leading to myofascial pain.

Adult↗
PubMed1998

Muscular factors are of importance in tension-type headache.

Recent studies have indicated that muscular disorders may be of importance for the development of increased pain sensitivity in patients with chronic tension-type headache. The objective of the present study was to investigate this hypothesis by examining the pain perception in tension-type headache with and without muscular disorders defined as increased tenderness. We examined 28 patients with episodic tension-type headache, 28 patients with chronic tension-type headache, and 30 healthy controls. Pericranial myofascial tenderness was recorded with manual palpation, and pressure pain detection and tolerances in cephalic and extracephalic locations with an electronic pressure algometer. In addition, thermal pain sensitivity and electromyographic activity were recorded. The main result was significantly lower pressure pain detection thresholds and tolerances in all the examined locations in patients with chronic tension-type headache with a muscular disorder compared to those without a muscular disorder. There were no such differences in any of the examined locations when the two subgroups of patients with episodic tension-type headache were compared. Thermal pain sensitivity did not differ between patients with and without a muscular disorder, while electromyographic activity levels were significantly higher in patients with chronic tension-type headache with than in those without a muscular disorder. Our results strongly indicate that prolonged nociceptive stimuli from the pericranial myofascial tissue sensitize the central nervous system and, thereby, lead to an increased general pain sensitivity. Muscular factors may, therefore, be of major importance for the conversion of episodic into chronic tension-type headache. The present study complements the understanding of the important interactions between peripheral and central factors in tension-type headache and may lead to a better prevention and treatment of the most prevalent type of headache.

Adult↗
PubMed1997

[Decreased pain threshold and tolerance in patients with chronic tension headache].

Nociceptive processing was studied in 40 patients with chronic tension-type headache and in 40 healthy controls. We found that pericranial tenderness recorded by manual palpation was considerably higher in patients than in controls (p < or = 0.0002). Pressure pain detection and tolerance thresholds recorded in the finger, by means of a pressure algometer, were significantly lower in patients than in controls (p < or = 0.0009), and a non-significant similar trend was observed in the temple (p < or = 0.12). Detection and tolerance thresholds were decreased to a similar degree in patients compared with controls, and pain thresholds recorded in the finger and in the temple were highly correlated (r = 0.84, p < 0.0001). The electrical pain threshold at the labial commissure, by means of an electrical stimulator, was significantly decreased in patients compared with controls (p = 0.03). All of the examined pain thresholds were significantly correlated to the pericranial tenderness recorded by palpation (r = -0.35 to -0.53, p < or = 0.03). We conclude that the present finding of a general hypersensitivity to pain stimuli in chronic tension-type headache indicates that central factors play an important role in the pathogenesis of this disorder.

Adolescent↗
PubMed1997

Evidence of qualitatively altered nociception in patients with fibromyalgia.

OBJECTIVE: To investigate the perception of pain in tender muscles of patients with fibromyalgia. METHODS: Twenty-five women with fibromyalgia and 25 healthy women were examined. Seven different pressure intensities were used to palpate a highly tender muscle and a largely normal muscle. Subjects then recorded their response to induced pain on a visual analog scale. The examiner was blinded to each subject's response. RESULTS: The stimulus-response function for pressure versus pain recorded for normal muscle was well described by a power function. For highly tender muscle, the stimulus-response function was displaced toward lower pressures and, more importantly, it was linear, i.e., qualitatively different from that of normal muscle. CONCLUSION: This study demonstrates that nociception is qualitatively altered in patients with fibromyalgia, which is consistent with recent findings in other patients with tender muscles. The data strongly indicate that fibromyalgic pain, at least in part, is due to aberrant central pain mechanisms.

Adult↗
PubMed1997

Serotonin metabolism in chronic tension-type headache.

Serotonergic neurons play a major role in the regulation of pain and may therefore also be involved in the pathophysiology of tension-type headache. Platelets are important in the regulation of the free serotonin level in plasma and may be a model of serotonergic neurons. The aim of the present study was to investigate the peripheral serotonin (5HT) metabolism in patients with chronic tension-type headache. The 5HT levels in platelets and in plasma, the beta-thromboglobulin (beta-TG) levels in plasma, and the urinary excretion of 5-hydroxyindoleacetic acid (5HIAA) were measured in 40 patients with chronic tension-type headache and in 40 healthy controls. The platelet uptake index was calculated as the ratio between platelet 5HT and plasma 5HT levels. There were no significant differences in platelet 5HT, plasma 5HT, beta-TG, or 5HIAA between patients and controls. The platelet uptake index was significantly lower in patients 243 (136-367) than in controls 352 (202-508), p=0.03. Our results indicate that the peripheral 5HT metabolism is largely normal in patients with chronic tension-type headache.

Adult↗
PubMed1996

Decreased pain detection and tolerance thresholds in chronic tension-type headache.

OBJECTIVE: To study nociceptive processing in patients with chronic tension-type headache. METHODS: Forty patients with chronic tension-type headache and 40 healthy controls were examined. Pericranial tenderness was recorded by manual palpation, pressure pain detection and tolerance thresholds were recorded with an electronic pressure algometer, and the relative (pain detection minus sensory detection) electrical pain threshold was recorded with a constant current stimulator. RESULTS: Patients were considerably more tender than controls at all the locations examined by manual palpation (P<.001). Pressure pain detection and tolerance thresholds recorded in the finger were significantly lower in patients than in controls (P<.001). A nonsignificant similar trend was observed in the temple (P < or =.12). Detection and tolerance thresholds were decreased to a similar degree in patients compared with controls, and pain thresholds recorded in the finger and in the temple were highly correlated (r=.84, P<.001). The relative electrical pain threshold recorded at the labial commissure was significantly decreased in patients compared with controls (P=.03). All of the examined pain thresholds were significantly correlated to the pericranial tenderness recorded by palpation (r=-.35 to -.53, P < or = .03). CONCLUSION: The present finding of a general hypersensitivity to pain stimuli in chronic tension-type headache indicates that central factors play an important role in the pathogenesis of this disorder.

Adult↗
PubMed1996

Exteroceptive suppression of temporal muscle activity is normal in chronic tension-type headache and not related to actual headache state.

The aim of the present study was to compare the late exteroceptive suppression period (ES2) of temporalis muscle activity between patients with chronic tension-type headache and healthy controls, and to investigate the influence, if any, of actual headache on ES2. ES2 was recorded in 55 patients and in 55 controls with a previously evaluated methodology and analysed by a blinded observer. The first 20 patients were randomly studied on 2 additional days, 1 day with and 1 day without headache. The duration of ES2 did not differ between patients and controls and did not differ on days with headache compared with days without headache. ES2 duration was not related to the frequency of headache, headache intensity, age, pericranial muscle tenderness or electrical pain threshold. Our results strongly indicate that ES2 is normal in chronic tension-type headache and therefore may not be related to the pathophysiology of this disorder.

Adult↗
PubMed1996

311C90 (Zolmitriptan), a novel centrally and peripheral acting oral 5-hydroxytryptamine-1D agonist: a comparison of its absorption during a migraine attack and in a migraine-free period.

The oral absorption of a 10-mg oral dose of the novel 5-hydroxytryptamine (5HT1D) agonist, 311C90, was compared during a moderate or severe migraine headache and in a migraine-free period in an open, two-period study. The safety and efficacy of 311C90 in acute migraine were also assessed. Twenty patients attended the clinics during a moderate or severe migraine attack and 18 patients returned for a second dose in a migraine-free period. 311C90 was less rapidly absorbed during a migraine attack compared to the migraine-free period, consistent with gastric stasis during a migraine attach. The median area under the curve (AUC) was 15.7 ng/mlh lower during a migraine (median AUC: 18.4 ng/ml.h, range: 0-60.8 ng/ml.h) compared to the migraine-free period (median AUC: 33.4 ng/ml.h, range 9.4-79.5 ng/ml.h) (95% confidence interval: 6.9, 25.3) and the time to reach maximum plasma concentration was delayed (n = 18). Eleven out of 20 patients experienced a significant improvement in migraine headache intensity at 2 h post-dose. Plasma 311C90 concentrations were generally higher in those patients who responded to treatment with 311C90 in the plasma, but there was one patient with no quantifiable 311C90 in the plasma whose headache improved. Minor adverse experiences were reported in 11 out of 20 patients during a migraine attack and in 11 out of 18 patients outside an attack. They occurred shortly following drug administration and were of short duration, but their occurrence did not appear to be related to plasma 311C90 concentration. There were no clinically significant changes in blood pressure or 12-lead ECG during the assessment period.

Adolescent↗