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Biomedical subjects

L Bendtsen

Publications and source records attributed to L Bendtsen.

At least 19 recordsLinked to original sources

Frequency of headache is related to sensitization: a population study.

Central sensitization is thought to play an important role in the chronification of tension-type headache and in the maintenance and exacerbation of the migraine attack. It has, however, almost exclusively been studied in highly selected patients from headache clinics. The aim of the present study was to evaluate pain perception in primary headaches in the general population. Stimulus-response functions for pressure versus pain, tenderness and pressure pain thresholds were studied in a random sample of 523 adults from the general population. All results were controlled for the effects of age and gender. The area under the stimulus-response function was increased in chronic- and frequent episodic tension-type headache compared with subjects without headache (p<0.001, p<0.001) and in chronic tension-type headache compared with migraine (p=0.01). Increasing slope (p<0.0001) and displacement towards lower pressures was found in the following order: no headache, migraine, frequent episodic tension-type headache, chronic tension-type headache. The displacement of the stimulus-response function was closely associated with frequency of headache. Finally, the stimulus-response function tended to be qualitatively altered in patients with frequent headache. The findings demonstrate, for the first time in a population-based study, a close relation between altered pain perception and chronification of headache, which most likely can be explained by central sensitization.

Adult↗

Generalized hyperalgesia in patients with chronic tension-type headache.

Increased pain sensitivity in the central nervous system may play an important role in the pathophysiology of chronic tension-type headache (CTTH). Previous studies using pain thresholds as a measure of central pain sensitivity have yielded inconsistent results and only a few studies have examined perception of muscle pain without involvement of adjacent tissues. It has been suggested that suprathreshold testing might be more sensitive than threshold measurements in evaluation of central hyperexcitability in CTTH. The aim of the study was to compare pain ratings to suprathreshold single and repetitive (2 Hz) electrical stimulation of muscle and skin in cephalic (temporal and trapezius) and extracephalic (anterior tibial) regions between patients with CTTH and healthy subjects. In addition, we aimed to examine gender differences in pain ratings to suprathreshold stimulation and degree of temporal summation of pain between patients and controls. Pain ratings to both single and repetitive suprathreshold stimulation were higher in patients than in controls in both skin and muscle in all examined cephalic and extracephalic regions (P < 0.04). Pain ratings to both single and repetitive suprathreshold electrical stimulation were significantly higher in female compared with male patients (P < 0.001) and in female compared with male controls (P < or = 0.001). The degree of temporal summation of muscular and cutaneous pain tended to be higher in patients than in controls but the differences were not statistically different. This study provides evidence for generalized increased pain sensitivity in CTTH and strongly suggests that pain processing in the central nervous system is abnormal in this disorder. Furthermore, it indicates that suprathreshold stimulation is more sensitive than recording of pain thresholds for evaluation of generalized pain perception.

Adult↗

A prospective, open-label, long-term study of the efficacy and tolerability of topiramate in the prophylaxis of chronic tension-type headache.

This open study evaluates the effectiveness and safety of topiramate for the prophylaxis of chronic tension-type headache. Fifty-one patients were enrolled, of whom 46 completed 24 weeks of treatment with topiramate. Daily dosing was titrated from 25 mg to 100 mg by treatment week 4. The primary efficacy parameter was headache frequency at weeks 13-24 compared with baseline. Headache frequency declined from 23.50 +/- 5.32 days (baseline, mean, SD) to 12.58 +/- 6.28 days at weeks 13-24 (P < 0.0001), with frequency of severe headaches dropping from 8.18 to 3.14 days (P < 0.0001). The average headache intensity dropped from 6.13 to 2.07 on the visual analogue scale (P < 0.0001). These parameters were not significantly reduced at weeks 5-12. A 50% reduction in headache frequency was achieved in 73% of patients at weeks 13-24. Also improved were mood, sleep, quality of life (all parameters, P < 0.0001) as well as the Beck Depression Inventory-II (P < 0.0001). In addition, a highly significant weight loss of 2.14 kg (mean) was observed between baseline (71.64 +/- 10.65 kg) and week 24 [69.50 +/- 10.04 kg (SD)] (P < 0.0001). There were only few side-effects, none of these rated severe. The results provide preliminary confirmation of the efficacy and tolerability of topiramate in the prophylaxis of chronic tension-type headache.

Adolescent↗

Increased muscular and cutaneous pain sensitivity in cephalic region in patients with chronic tension-type headache.

Increased excitability of the central nervous system generated by repetitive and sustained pericranial myofascial nociception may be responsible for transformation of episodic tension-type headache into chronic form. We aimed to compare mechanical and electrical (intramuscular and cutaneous) pain thresholds in trapezius and anterior tibial regions between 20 patients with chronic tension type headache and 20 healthy controls. Pain thresholds to three types of electrical stimulation (single pulse, 2 and 100 Hz) were significantly lower in patients than in controls in trapezius muscle (P < 0.02) and in skin overlying the trapezius muscle (P < 0.05), whilst electrical pain thresholds did not differ between groups in anterior tibial muscle and skin. Quantitative sensory testing revealed increased pain sensitivity in patients as assessed by pressure-controlled manual palpation (local tenderness score, LTS; P < 0.01) and by pressure algometry (mechanical pain thresholds; P < 0.05) in test areas over the trapezius muscle, but not the anterior tibial muscle. In summary, this study demonstrates lower pain thresholds in muscle and skin of the cephalic region but not in lower limb muscle and skin in patients with chronic tension-type headache than in healthy controls. Increased sensitivity in nociceptive pathways from cephalic region may be of importance in the pathophysiology of chronic tension type headache.

Adult↗

Experimental induction of muscle tenderness and headache in tension-type headache patients.

The aim of the present study was to investigate the impact of static contraction of the shoulder and neck muscles on muscle tenderness and headache in patients with tension-type headache. Twenty patients with frequent episodic tension-type headache and 20 healthy age- and sex-matched controls were examined using a placebo-controlled cross-over design. The subjects performed static contraction of the trapezius muscles (active procedure) or the anterior tibial muscles (placebo procedure) with 10% of maximal force for 30 min. Total tenderness score, local tenderness score and headache intensity were evaluated before and after the static work. Changes in headache intensity were followed for 24 h. Pericranial tenderness increased significantly more in patients than in controls after the active procedure (P = 0.04). The increase in pericranial tenderness tended to be higher after the active procedure than after the placebo procedure in patients (P = 0.08) and in controls (P = 0.07). Sixty per cent of the patients and 20% of the healthy controls developed headache after the active procedure. Fifty per cent of the patients and none of the controls developed headache after the placebo procedure. There was no significant difference in headache development between the active and the placebo procedure in patients or controls. These findings demonstrate that tension-type headache patients are more liable to develop shoulder and neck pain in response to static exercise than healthy controls.

Adult↗

Possible mechanisms of pain perception in patients with episodic tension-type headache. A new experimental model of myofascial pain.

A new experimental human model of myofascial pain using intramuscular infusion of a combination of bradykinin, serotonin (5-hydroxytryptamine), histamine, and prostaglandin E2 was applied to patients with episodic tension-type headache (ETTH) in order to examine pain perception. Fifteen patients with ETTH and 15 healthy controls completed the randomized, balanced, double-blinded, placebo-controlled study. Pain intensity, punctate hyperalgesia and allodynia, and pain quality were recorded. The combination induced a moderate and prolonged pain in both patients (median 51 min) (P = 0.001) and controls (median 22 min) (P = 0.001). Patients reported more pain than controls both after the combination (P = 0.045) and after placebo (P < 0.001). The McGill pain score [PRI(R)] was significantly higher in patients (P = 0.002) and in controls (P = 0.001), whereas pain quality and hyperalgesia were similar after the combination compared with placebo in the two groups. Due to side-effects nine subjects did not complete the study. The increased pain response, but similar qualitative pain perception, in ETTH patients may be explained by sensitization of peripheral nociceptors even though central mechanisms may also be involved.

Adult↗

Glyceryl trinitrate may trigger endogenous nitric oxide production in patients with chronic tension-type headache.

Experimental studies in humans have shown that nitric oxide (NO) may play an important role in initiation of primary headaches. It has been proposed that activation of L-arginine-NO pathway and increased endogenous production of NO may be responsible for NO induced headache. NO is synthesized from L-arginine and that reaction also yields citrulline. In the present study we aimed to investigate plasma levels of citrulline and arginine as markers of NO production after infusion of the NO donor, glyceryl trinitrate (GTN). We recruited 16 patients with chronic tension-type headache and 16 healthy controls. The subjects were randomly allocated to receive 0.5 microg/kg/min GTN or placebo over 20 min. Patients were examined on headache free days. Blood samples were collected at baseline and 60 min after start of infusion. Both patients and controls developed stronger immediate headache on the GTN day than on the placebo day (P = 0.008). The headache was more pronounced in patients than in controls (P = 0.02). Plasma levels of citrulline increased significantly 60 min after start of GTN infusion compared to placebo infusion in patients (P = 0.01) but not in controls (P = 0.50). Plasma levels of arginine were unchanged in both patients (P = 0.12) and controls (P = 0.18). We suggest that GTN administration may trigger endogenous production of NO in patients with chronic tension-type headache resulting in activation of perivascular sensory afferents.

Adult↗

Induction of prolonged tenderness in patients with tension-type headache by means of a new experimental model of myofascial pain.

Tenderness is the most prominent abnormal finding in patients with tension-type headache (TTH). Recently we developed a model of myofascial tenderness using intramuscular infusion of a combination of bradykinin, serotonin, histamine and prostaglandin E2. We aimed to examine tenderness after this combination in patients with episodic TTH (ETTH). Fifteen patients and 15 healthy controls completed the study. Participants received the combination into the non-dominant trapezius muscle in a randomized, double-blinded and placebo-controlled design. Local tenderness and stimulus-response functions, mechanical pain thresholds (PPDT) in the temporal region and on the finger, and total tenderness score (TTS) were recorded. A local, prolonged, and mild to moderate tenderness was reported both in patients (P = 0.001) and in controls (P = 0.001) after the combination compared with the placebo. The response to the combination tended to be increased in patients. The stimulus-response function was leftward shifted after the combination, compared with baseline in both groups. No changes in PPDT or TTS were found after the infusions, whereas baseline PPDTs were decreased in ETTH compared with controls (PPDTfinger: P = 0.033; PPDTtemporal: P = 0.015). Intramuscular infusion of a combination of endogenous substances induced prolonged tenderness in both patients with episodic TTH and healthy subjects. The present results suggest an increased excitability of peripheral muscle afferents in TTH.

Adult↗

Tender points are not sites of ongoing inflammation -in vivo evidence in patients with chronic tension-type headache.

Increased muscle tenderness is the most prominent finding in patients with tension-type headache, and it has recently been shown that muscle blood flow is diminished in response to static exercise in tender points in these patients. Although tenderness has been ascribed to local inflammation and release of inflammatory mediators, the interstitial concentration of inflammatory mediators has not previously been studied in tender muscles of patients with tension-type headache. The aim of the present study was to investigate in vivo concentrations of prostaglandin E2 (PGE2), adenosine 5'-triphosphate (ATP), glutamate, bradykinin and other metabolites in a tender point of patients with chronic tension-type headache, in the resting state as well as in response to static exercise, and to compare findings with measurements in a matched non-tender point of healthy controls. We recruited 16 patients with chronic tension-type headache and 17 healthy control subjects. Two microdialysis catheters were inserted into the trapezius muscle and dialysates were collected at rest, 15 and 30 min after start of static exercise (10% of maximal force) and 15 and 30 min after end of exercise. All samples were coded and analysed blindly. There was no difference in resting concentration of any inflammatory mediators or metabolites between tender patients and non-tender controls (P > 0.05). We also found no difference in change in interstitial concentration of ATP, PGE2, glutamate, glucose, pyruvate and urea from baseline to exercise and post-exercise periods between patients and controls (P > 0.05). The present study provides in vivo evidence of normal interstitial levels of inflammatory mediators and metabolites in tender trapezius muscle in patients with chronic tension-type headache during both rest and static exercise. Thus, our data suggest that tender points in these patients are not sites of ongoing inflammation.

Adult↗

Placebo response in clinical randomized trials of analgesics in migraine.

The objective was to assess the placebo response in randomized clinical trials of analgesics in the treatment of migraine attacks. We included placebo-controlled studies that used the criteria of the International Headache Society for the diagnosis of migraine and headache response as the primary efficacy parameter. In the 11 studies that qualified for inclusion, headache response occurred after placebo treatment in 7-50% of the migraineurs with an average placebo response rate of 30% (95% confidence interval (CI) 23-36). Two hours after treatment with placebo an average of 9% (95% CI 7-12, range 7-17%) of the patients were found to be pain free. In conclusion, the average headache response rate to placebo was 30% in randomized clinical trials of analgesics in migraine with a tremendous variation among studies. Placebo response rates vary with the choice of primary efficacy measure as well as patient characteristics and study design.

Analgesics↗

Pain sensitivity in pericranial and extracranial regions.

Chronic myofascial pain is very common in the general population. The pain is most frequently located in the shoulder and neck regions, and nociceptive input from these regions may play an important role for tension-type headache. The mechanisms leading to the frequent occurrence of muscle pain in the shoulder and neck regions are largely unknown. It is possible that the pain is caused by increased sensitivity of muscle nociceptors or by central sensitization induced by nociceptive input from muscle. The primary aim of the present study was to compare muscle pain sensitivity in the trapezius and anterior tibial muscles. The secondary aim was to investigate whether temporal summation, a clinical correlate of wind-up, is more pronounced in muscle than in skin and, if so, whether such a difference is more pronounced in the trapezius than in the anterior tibial region. Sixteen healthy subjects were included. Pressure-pain thresholds and electrical cutaneous and intramuscular pain thresholds were measured at standard anatomical points in the trapezius and anterior tibial regions. Temporal summation was assessed by repetitive electrical stimulation. Pressure-pain thresholds (P = 0.005) and intramuscular electrical pain thresholds (P = 0.006) were significantly lower in trapezius than in anterior tibial muscle. Temporal summation was present in skin and muscle of both regions (P < 0.001). The degree of temporal summation was significantly higher in muscle than in skin in the trapezius region (P = 0.02), but not in the anterior tibial region (P = 0.47). In conclusion, we found that muscle pain sensitivity was higher in the trapezius than in the anterior tibial muscle. We also demonstrated that temporal summation could be induced in both muscle and skin and, importantly, that temporal summation was significantly more pronounced in muscle than in skin in the trapezius but not in the anterior tibial region. These data may help to explain why chronic muscle pain most frequently is located in the shoulder and neck regions.

Adult↗

In vivo evidence of altered skeletal muscle blood flow in chronic tension-type headache.

Painful impulses from tender pericranial muscles may play a major role in the pathophysiology of chronic tension-type headache. Firm evidence for peripheral muscle pathology as a cause of muscle pain and chronic headache is still lacking. Using a microdialysis technique, we aimed to estimate in vivo blood flow and interstitial lactate concentrations in the trapezius muscle at rest and during static exercise in patients with chronic tension-type headache and in healthy subjects. We recruited 16 patients with chronic tension-type headache and 17 healthy control subjects. Two microdialysis catheters were inserted into the trapezius muscle (on the non-dominant side) of subjects, and dialysates were collected at rest, 15 and 30 min after the start of static exercise (10% of maximal force) and 15 and 30 min after the exercise was completed. All samples were coded and analysed blind. The primary endpoints were to detect a difference between patients and controls in changes of muscle blood flow and the interstitial lactate concentration from baseline to exercise and post-exercise periods. The increase in muscle blood flow from baseline to exercise and post-exercise periods was significantly lower in patients than controls (P = 0.03). There was no difference in resting blood flow between patients and controls (P = 0.43). Resting interstitial concentration of lactate did not differ between patients (2.51 +/- 0.18 mM; mean +/- standard error of the mean) and controls (2.35 +/- 0.23 mM, P = 0.57). There was no difference in change in interstitial lactate from baseline to exercise and post-exercise periods between patients and controls (P = 0.38). The present study provides in vivo evidence of decreased blood flow in response to static exercise in a tender muscle in patients with chronic tension-type headache. We suggest that, because of increased excitability of neurones in the CNS, the central interpretation and response to normal sensory input are altered in patients with chronic tension-type headache. This may lead to enhanced sympathetically mediated vasoconstriction and thereby a decreased blood flow in response to static exercise.

Adolescent↗

Calcitonin gene-related peptide levels during nitric oxide-induced headache in patients with chronic tension-type headache.

It has been proposed that nitric oxide (NO) induced headache in primary headaches may be associated with release of calcitonin gene-related peptide (CGRP). In the present study we aimed to investigate plasma levels of CGRP during headache induced by the NO donor glyceryl trinitrate (GTN) in 16 patients with chronic tension-type headache and 16 healthy controls. The subjects were randomly allocated to receive 0.5 microg/kg/min GTN or placebo over 20 min on two headache-free days. Blood samples were collected at baseline, 10, 20 and 60 min after start of infusion. Both patients and controls developed significantly stronger immediate headache on the GTN day than on the placebo day and the headache was significantly more pronounced in patients than in controls. There was no difference between the area under the CGRP curve (AUCCGRP) on GTN vs. placebo day in either patients (P=0.65) or controls (P=0.48). The AUCCGRP recorded on the GTN day did not differ between patients and controls (P=0.36). Both in patients and controls, CGRP levels changed significantly over time, on both the GTN and placebo days (P < 0.05). The present study indicates that NO-induced immediate headache is not associated with release of CGRP.

Adult↗

Plasma levels of calcitonin gene-related peptide in chronic tension-type headache.

BACKGROUND: Calcitonin gene-related peptide (CGRP) is involved in the pathophysiology of migraine and cluster headache. Whether CGRP has any role in chronic tension-type headache is unknown. OBJECTIVES: To compare interictal plasma levels of CGRP between patients with chronic tension-type headache and healthy control subjects, to investigate plasma CGRP in relation to headache state, and to compare plasma CGRP between the peripheral and the cranial circulation. METHODS: Blood from the antecubital vein was drawn from 30 patients with chronic tension-type headache and 34 healthy control subjects. In addition, blood samples from the consecutive first 15 patients and from the consecutive first 20 healthy control subjects were also collected from the external jugular vein. RESULTS: CGRP levels measured in the peripheral circulation in patients on days without headache, 63+/-5 pmol/L, tended to be higher than CGRP levels in control subjects, 53+/-3 pmol/L (p = 0.06). In patients, no differences were found between CGRP levels assessed ictally and interictally in either the cranial (p = 0.91) or the peripheral (p = 0.62) circulation. Plasma CGRP level was higher in the external jugular vein than in the antecubital vein on days without headache (p = 0.03) but not on days with headache (p = 0.82). In control subjects, CGRP levels in the cranial circulation did not differ from CGRP levels in the peripheral circulation (p = 0.92). Exploratory analyses showed that 8 patients whose usual headache quality was throbbing had a higher interictal plasma CGRP level than control subjects (p = 0.002), whereas plasma CGRP level was normal in 22 patients with pressing headaches (p = 0.36). CONCLUSIONS: Plasma levels of CGRP are normal in patients with chronic tension-type headache and are unrelated to headache state. Interictal plasma CGRP was increased in patients with a pulsating pain quality. Because the authors have previously shown a similar increase of interictal CGRP levels in migraine, this study suggests that headaches with symptoms that fulfill International Headache Society criteria for tension-type headache may be pathophysiologically related to migraine, if the headache has a pulsating quality.

Adult↗

[Inhibition of nitric oxide synthase has an analgesic effect in chronic pain].

The efficacy of the inhibitor of nitric oxide synthase, NG-monomethyl-L-arginine hydrochloride (L-NMMA), was tested in 16 patients with chronic tension-type chronic headache. The study was designed as a randomized double-blind, crossover trial. Patients were assigned intravenous infusion of 6 mg/kg L-NMMA or placebo on two days separated by at least one week in a randomized order. Headache intensity was measured on a 100 mm visual analogue scale at baseline and at 30 min, 60 min, and 120 min after start of treatment. L-NMMA reduced pain intensity 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). The present study demonstrates that inhibition of NOS has an analgesic effect in chronic tension-type headache.

Adult↗

Evidence for increased plasma levels of calcitonin gene-related peptide in migraine outside of attacks.

Although calcitonin gene-related peptide (CGRP) has been shown to be elevated in jugular venous blood of adult migraineurs during acute migraine attacks, it remains unknown whether CGRP is increased outside of attacks in jugular or cubital venous blood. The aim of the present study was to compare interictal plasma levels of CGRP in adult migraine patients and in healthy controls. Twenty patients with a diagnosis of migraine with or without aura and 20 healthy controls were included. In blood from the cubital vein, CGRP levels were significantly higher in patients (75+/-8 pmol/l (mean+/-SEM)) than in controls (49+/-3 pmol/l) (P=0.005). The subgroup of patients suffering exclusively from migraine without aura (n=14) also had significantly higher levels of CGRP (82+/-10 pmol/l) than controls (n=20; 49+/-3 pmol/l) (P=0.001). The findings could not be explained by confounding factors such as age, sex or use of contraceptive pills. We therefore conclude that CGRP is increased in cubital venous blood of migraineurs outside of attack. It is hypothesized that this finding may reflect a long-lasting or permanent abnormal neurogenic vascular control in patients with migraine.

Adult↗

Central sensitization in tension-type headache--possible pathophysiological mechanisms.

The aim of the present thesis was to investigate the pathophysiology of chronic tension-type headache with special reference to central mechanisms. Increased tenderness to palpation of pericranial myofascial tissues is the most apparent abnormality in patients with tension-type headache. A new piece of equipment, a so-called palpometer, that makes it possible to control the pressure intensity exerted during palpation, was developed. Thereafter, it was demonstrated that the measurement of tenderness could be compared between two observers if the palpation pressure was controlled, and that the Total Tenderness Scoring system was well suited for the scoring of tenderness during manual palpation. Subsequently, it was found that pressure pain detection and tolerance thresholds were significantly decreased in the finger and tended to be decreased in the temporal region in chronic tension-type headache patients compared with controls. In addition, the electrical pain threshold in the cephalic region was significantly decreased in patients. It was concluded that the central pain sensitivity was increased in the patients probably due to sensitization of supraspinal neurones. The stimulus-response function for palpation pressure vs. pain was found to be qualitatively altered in chronic tension-type headache patients compared with controls. The abnormality was related to the degree of tenderness and not to the diagnosis of tension-type headache. In support of this, the stimulus-response function was found to be qualitatively altered also in patients with fibromyalgia. It was concluded that the qualitatively altered nociception was probably due to central sensitization at the level of the spinal dorsal horn/trigeminal nucleus. Thereafter, the prophylactic effect of amitriptyline, a non-selective serotonin (5-HT) reuptake inhibitor, and of citalopram, a highly selective 5-HT reuptake inhibitor, was examined in patients with chronic tension-type headache. Amitriptyline reduced headache significantly more than placebo, while citalopram had only a slight and insignificant effect. It was concluded that the blockade of 5-HT reuptake could only partly explain the efficacy of amitriptyline in tension-type headache, and that also other actions of amitriptyline, e.g. reduction of central sensitization, were involved. Finally, the plasma 5-HT level, the platelet 5-HT level and the number of platelet 5-HT transporters were found to be normal in chronic tension-type headache. On the basis of the present and previous studies, a pathophysiological model for tension-type headache is presented. According to the model, the main problem in chronic tension-type headache is central sensitization at the level of the spinal dorsal horn/trigeminal nucleus due to prolonged nociceptive inputs from pericranial myofascial tissues. The increased nociceptive input to supraspinal structures may in turn result in supraspinal sensitization. The central neuroplastic changes may affect the regulation of peripheral mechanisms and thereby lead to, for example, increased pericranial muscle activity or release of neurotransmitters in the myofascial tissues. By such mechanisms the central sensitization may be maintained even after the initial eliciting factors have been normalized, resulting in the conversion of episodic into chronic tension-type headache. Future basic and clinical research should aim at identifying the source of peripheral nociception in order to prevent the development of central sensitization and at ways of reducing established sensitization. This may lead to a much needed improvement in the treatment of chronic tension-type headache and other chronic myofascial pain conditions.

Central Nervous System↗

Amitriptyline reduces myofascial tenderness in patients with chronic tension-type headache.

The tricyclic anti-depressant amitriptyline is widely used in the treatment of chronic tension-type headache. The aim of the present study was to investigate whether the analgesic effect is caused by a reduction of muscle pain or by a general reduction of pain sensitivity. Thirty-three non-depressed patients with chronic tension-type headache were treated with amitriptyline 75 mg/day and with the highly selective serotonin reuptake inhibitor citalopram 20 mg/day in a 32-week, double-blind, placebo-controlled, three-way crossover study. At the end of each treatment period, actual headache intensity and pericranial myofascial tenderness were recorded, pressure pain detection and tolerance thresholds were measured in the finger and in the temporal region and the electrical pain threshold was measured at the labial commissure. Amitriptyline reduced tenderness and headache intensity significantly more than placebo (P=0.01 and P=0.04, respectively). The reduction in tenderness could be ascribed solely to the group of patients who responded to amitriptyline treatment by at least 30% reduction in headache while tenderness was unchanged in non-responders. Amitriptyline did not affect pressure or electrical pain thresholds at any of the examined locations. Citalopram had no significant effect on any of the examined parameters. These findings indicate that amitriptyline elicits its analgesic effect in chronic myofascial pain by reducing the transmission of painful stimuli from myofascial tissues rather than by reducing overall pain sensitivity. We suggest that this effect is caused by a segmental reduction of central sensitization in combination with a peripheral anti-nociceptive action.

Adult↗