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.     

Amitriptyline Is Effective in Chronic But Not in Episodic Tension-Type Headache: Pathogenetic Implications

The tricyclic antidepressant amitriptyline, is an effective drug for the treatment of chronic tension-type headache and for other chronic pain syndromes, but it is also effective in the prophylaxis of an episodic type of headache such as migraine. However, its efficacy in episodic tension-type headache has not yet been clarified. We compared the efficacy of amitriptyline (25 mg/day) in 82 nondepressed patients with either chronic or episodic tension-type headache in an open-label study. Amitriptyline significantly reduced ( P <0.05) frequency and duration of headache as well as analgesic consumption in chronic, but not in episodic, tension-type headache. Further placebo-controlled trials, possibly with higher doses of amitriptyline, might confirm if the different pattern of response to amitriptyline can be explained in terms of different involvement of central nociception and of peripheral myofascial factors in the chronic and in the episodic forms of tension-type headache.     

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.     

Pain perception studies in tension-type headache

Tension-type headache (TTH) is a disorder with high prevalence and significant impact on society. Understanding of pathophysiology of TTH is paramount for development of effective treatments and prevention of chronification of TTH. Our aim was to review the findings from pain perception studies of pathophysiology of TTH as well as to review the research of pathophysiology of TTH. Pain perception studies such as measurement of muscle tenderness, pain detection thresholds, pain tolerance thresholds, pain response to suprathreshold stimulation, temporal summation and diffuse noxious inhibitory control (DNIC) have played a central role in elucidating the pathophysiology of TTH. It has been demonstrated that continuous nociceptive input from peripheral myofascial structures may induce central sensitization and thereby chronification of the headache. Measurements of pain tolerance thresholds and suprathreshold stimulation have shown presence of generalized hyperalgesia in chronic tension-type headache (CTTH) patients, while DNIC function has been shown to be reduced in CTTH. One imaging study showed loss of gray matter structures involved in pain processing in CTTH patients. Future studies should aim to integrate pain perception and imaging to confirm this finding. Pharmacological studies have shown that drugs like tricyclic anti-depressant amitriptyline and nitric oxide synthase inhibitors can reverse central sensitization and the chronicity of headache. Finally, low frequency electrical stimulation has been shown to rapidly reverse central sensitization and may be a new modality in treatment of CTTH and other chronic pain disorders.     

Chronic headache and nitric oxide inhibitors

Sensitization of myofascial pain pathways may play an important role in the pathophysiology of chronic headache. Animal studies have shown that sensitization of pain pathways may be caused by associated with activation of neuronal nitric oxide synthase (nNOS) and the generation of nitric oxide (NO). Furthermore, it has been shown that NOS inhibitors reduce central sensitization in animal models of persistent pain. On the basis of these findings, we investigated the analgesic effect of the NOS inhibitor, N-N ^G-methyl arginine hydrochloride, and demonstrated that this drug significantly reduced headache as well as myofascial factors in patients with chronic tension-type headache. In addition, we demonstrated that infusion of the NO donor, glyceryl trinitrate, induces headache in these patients, probably by enhancing the sensitizing effect of pre-existing myofascial input. These studies strongly indicate that NO plays a crucial role in the pathophysiology of tension-type headache. We suggested that the analgesic effect of NOS inhibition in patients with chronic tension-type headache is most likely due to reduction of central sensitization at the level of the spinal dorsal horn or trigeminal nucleus, or both. Furthermore, these data suggest that inhibition of NOS may become a novel means of future treatment of chronic headache. Received: 19 February 2001 / Accepted: 11 April 2001     

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.     

Initiating mechanisms of experimentally induced tension-type headache

To elucidate possible myofascial mechanisms of tension-type headache, the effect of 30 min of sustained tooth clenching (10% of maximal EMG-signal) was studied in 58 patients with tension-type headache and in 30 age- and sex-matched controls. Pericranial tenderness, mechanical and thermal pain detection and tolerance thresholds and FMG levels were recorded before and after the clenching procedure. Within 24 h, 69% of patients and 17% of controls developed a tension-type headache. Shortly after clenching, tenderness was increased in the group who subsequently developed headache, whereas tenderness was stable in the group of patients who remained headache free. Mechanical pain thresholds evaluated by pressure algometry remained unchanged in the group which developed headache, whereas thresholds increased in the group which did not develop headache Thermal pain detection and tolerance thresholds remained unchanged in both groups. These findings indicate that, though there may be several different mechanisms of tension-type headache, one of them is sustained muscle contraction. A peripheral mechanism of tension-type headache is therefore possible, whereas a secondary segmental central sensitization seems to be involved in subjects with frequent, tension-type headache. Finally, the increase in pressure pain thresholds in patients who did not develop headache suggested that clenching activated their antinociceptive system, whereas those developing headache were, unable to do so.     

Pressure pain threshold and needle acupuncture in chronic tension-type headache--a double-blind placebo-controlled study

In order to examine the role of muscular mechanisms in chronic tension-type headache a study with needle acupuncture was performed. Needle acupuncture could be of therapeutic value because it has shown some positive effects in myofascial pain syndromes. We performed a double-blind, placebo-controlled study with 39 patients (mean age 49.0 years, SD=14.8) fulfilling the International Headache Society criteria for chronic tension-type headaches. Participants were randomly assigned to verum or placebo condition. Six weeks after end of treatment no significant differences between placebo and verum could be observed with respect to visual analogue scale and frequency of headache attacks. Nevertheless, pressure pain thresholds significantly increased for the verum group. The findings of our study support the hypothesis that peripheral mechanisms - such as increased muscle tenderness - only play a minor role in the pathogenesis of chronic tension-type headache.     

Increased pain sensitivity is not a risk factor but a consequence of frequent headache: a population-based follow-up study

Altered pain sensitivity is believed to play an important role for chronification of headache. It has however mainly been evaluated in highly selected patients from headache clinics and never in longitudinal studies. The present study is a 12-year follow-up of a population-based study of primary headache disorders and pain perception, combining a diagnostic headache interview with examination of muscle tenderness and measurement of pressure pain thresholds in 1000 subjects drawn randomly from the general population in Denmark. The aim of the study was to explore the cause–effect relationship between the increased pain sensitivity and the development of headache. The pressure pain thresholds were normal at baseline but had decreased at follow-up in subjects who developed chronic tension-type headache over the 12-year period (p = 0.025). In subjects who developed frequent episodic tension-type headache the tenderness was normal at baseline but had increased at follow-up (p < 0.01) while the pain thresholds were normal both at baseline and at follow-up. The findings demonstrate that increased pain sensitivity is a consequence of frequent tension-type headache, not a risk factor, and support that central sensitization plays an important role for the chronification of tension-type headache.     

Pathophysiological mechanisms of tension-type headache: a review of epidemiological and experimental studies

In this present thesis I have discussed the epidemiology and possible pathophysiological mechanisms of tension-type headache. A population-based study of 1000 subjects randomly selected from a general population, two clinical studies, and a method study of EMG recordings, were conducted. Tension-type headache was the most prevalent form of headache, with a life-time prevalence of 78% in a general adult population. Thirty percent were affected more than 14 days per year and 3% were chronically affected, i.e. had headache at least every other day. Females were more frequently affected than males, and young subjects more frequently affected than older subjects. Females were more sensitive to mechanical pressure pain and revealed more tenderness from pericranial muscles and tendon insertions than males, and young subjects were more pain-sensitive than older subjects. Significantly higher tenderness in pericranial muscles was found in subjects with tension-type headache compared to migraineurs and to subjects without any experience of headache. Tenderness increased significantly with increasing frequency of tension-type headache in both males and females, whereas no such relation was found for mechanical pain thresholds. The applied EMG methodology was fairly reliable and nonpainful, but due to intersubject variability paired studies should be preferred. Subjects with chronic tension-type headache had slightly increased EMG levels during resting conditions and decreased levels during maximal voluntary contraction compared with headache-free subjects, indicating insufficient relaxation at rest and impaired recruitment at maximal activity. In a subsequent clinical, controlled study, the effect of 30 min of sustained tooth clenching was studied. Within 24 h, 69% of patients and 17% of controls developed a tension-type headache. Shortly after clenching, tenderness was increased in the group who subsequently developed headache, whereas tenderness was stable in the group of patients who remained headache-free, indicating that tenderness might be a causative factor of the headache. Likewise, psychophysical and EMG parameters were studied in 28 patients with tension-type headache, both during and outside of a spontaneous episode of tension-type headache. It was concluded that a peripheral mechanism of tension-type headache is most likely in the episodic subform, whereas a secondary, segmental central sensitization and/or an impaired supraspinal modulation of incoming stimuli seems to be involved in subjects with chronic tension-type headache. Prolonged nociceptive stimuli from myofascial tissue may be of importance for the conversion of episodic into chronic tension-type headache. The author emphasizes that tension-type headache is a multifactorial disorder with several concurrent pathophysiological mechanisms, and that extracranial myofascial nociception may constitute only one of them. The present thesis supplements the understanding of the balance between peripheral and central components in tension-type headache, and thereby, hopefully, leads us to a better prevention and treatment of the most prevalent type of headache.     

Treating chronic tension-type headache not responding to amitriptyline hydrochloride with paroxetine hydrochloride: a pilot evaluation

CONTEXT: In some individuals, chronic tension-type headache fails to respond to tricyclic antidepressant medications that often serve as first-line therapy. OBJECTIVE: To evaluate the clinical efficacy of paroxetine hydrochloride for chronic tension-type headache not responding to amitriptyline hydrochloride. DESIGN AND SETTING: Open-label trial of paroxetine conducted at 2 outpatient sites in Ohio. PARTICIPANTS AND INTERVENTION: Thirty-one adults (mean age, 37 years; 20 women) with chronic tension-type headache (mean, 25 headache days per month) who had failed to respond (less than 30% improvement) to treatment with either amitriptyline (n = 13) or matched placebo (n = 18). All participants were treated with paroxetine (up to 40 mg per day) in a 9-month protocol. OUTCOME MEASURES: Monthly headache index calculated as the mean of pain ratings (0 to 10 scale) recorded by participants in a diary 4 times per day, number of days per month with at least moderate pain (pain rating of 5 or greater), and analgesic medication use. RESULTS: In patients who had not responded to amitriptyline, paroxetine failed to reduce chronic tension-type headaches or analgesic medication use. In patients who had not responded to placebo, paroxetine produced modest reductions in chronic tension-type headaches and analgesic use. CONCLUSIONS: We found no evidence that chronic tension-type headaches that failed to respond to tricyclic antidepressant therapy with amitriptyline improved when subsequently treated with paroxetine. More support was found for the efficacy of paroxetine in patients with chronic tension-type headaches who had failed to respond to placebo.     

The Role of Muscles in Tension-Type Headache

The tenderness of pericranial myofascial tissues and number of myofascial trigger points are considerably increased in patients with tension-type headache (TTH). Mechanisms responsible for the increased myofascial pain sensitivity have been studied extensively. Peripheral activation or sensitization of myofascial nociceptors could play a role in causing increased pain sensitivity, but firm evidence for a peripheral abnormality still is lacking. Peripheral mechanisms are most likely of major importance in episodic TTH. Sensitization of pain pathways in the central nervous system due to prolonged nociceptive stimuli from pericranial myofascial tissues seem to be responsible for the conversion of episodic to chronic TTH. Treatment directed toward muscular factors include electromyography biofeedback, which has a documented effect in patients with TTH, as well as physiotherapy and muscle relaxation therapy, which are most likely effective. Future studies should aim to identify the source of peripheral nociception.     

Muscular disorders in tension-type headache

In order to evaluate the diagnostic criteria for muscular disorders in tension-type headache, pericranial muscle tenderness and pressure pain thresholds were studied in a random sample population of 735 adults aged 25–64. In addition, quantitative EMGs were recorded in 547 of these subjects. The correlation between the three diagnostic tests was assessed and the discriminality and cut-off points were analysed using Receiver Operating Characteristics analysis. Local tenderness from the temporal muscles was closely related to the total tenderness scores from 14 pairs of muscles. In chronic tension-type headache, tenderness was positively related to EMG and inversely related to pain thresholds. In the episodic form the total tenderness score was inversely related to pain thresholds, whereas no significant relation to EMG was noted. The Receiver Operating Characteristics curves indicated that tenderness recorded by manual palpation was the most specific and sensitive test, whereas EMG and pain thresholds were of limited diagnostic value. Eighty-seven percent of subjects with the chronic, and 66% of subjects with the episodic form were found to have a "muscular disorder" defined as increased tenderness recorded by either manual palpation or pressure algometry and/or increased EMG levels. However, muscle tenderness increased significantly during pain, so the headache state should be considered in future studies. Suggestions for revision of the present diagnostic criteria for muscular disorders are given.     

Amitriptyline treatment in chronic drug-induced headache: a double-blind comparative pilot study

OBJECTIVE: To assess the effects of amitriptyline and sudden analgesic withdrawal on headache frequency and quality of life in patients suffering from chronic daily headache related to analgesics abuse. METHODS: Seventeen nondepressed patients with chronic drug-induced headache were included in a 9-week, parallel-group, randomized, double-blind, placebo-controlled study. After abrupt analgesic withdrawal, amitriptyline or an active placebo (trihexyphenidyl) was started. The primary efficacy variable was headache frequency recorded on a headache diary in the last 4 weeks of each treatment. The secondary efficacy variable was quality of life (Nottingham Health Profile). RESULTS: Headache frequency decreased by 45% in the amitriptyline group and by 28% in the trihexyphenidyl group. Amitriptyline enhanced all the dimensions of quality of life and significantly improved emotional reaction and social isolation. CONCLUSION: This pilot study suggests a beneficial effect of amitriptyline on headache frequency and quality of life for patients with chronic drug-induced headache.     

Pathophysiology of tension-type headache

Tension-type headache is one of the most common primary headache disorders. Advances in basic pain and clinical research have improved our understanding of pathophysiologic mechanisms of tension-type headache. Increased excitability of the central nervous system generated by repetitive and sustained pericranial myofascial input may be responsible for the transformation of episodic tension-type headache into the chronic form. Studies of nitric oxide (NO) mechanisms suggest that NO may play a key role in the pathophysiology of tension-type headache and that the antinociceptive effect of nitric oxide synthase inhibitors may become a novel principle in the future treatment of chronic headache. Future studies should focus on investigation of the source of peripheral nociception, the role of descending pain modulation, and the development of an animal model of tension-type headache to support the pathophysiologic importance of central sensitization in tension-type headache.     

Dynamic assessment of abnormalities in central pain transmission and modulation in tension-type headache sufferers

OBJECTIVE: To examine and compare central pain processing and modulation in young tension-type headache sufferers with that of matched healthy controls using an induced headache "challenge" paradigm. BACKGROUND: Recent research has suggested that abnormalities in central pain processing and descending pain modulation may contribute to chronic tension-type headache. These abnormalities, if they contribute to headache pathogenesis, should be present in young adult tension-type headache sufferers. Recent research using static measures of physiological variables, such as muscle tenderness and exteroceptive suppression, has identified chronic muscle tenderness as a characteristic of young tension-type headache sufferers, but other central nervous system functional abnormalities may require a dynamic "challenge" to be observed. METHODS: Twenty-four young women meeting the International Headache Society diagnostic criteria for tension-type headache (headache-prone) and a matched group of 24 healthy women who reported fewer than 10 problem headaches per year (control) participated in a double-blind, placebo-controlled, crossover study. Subjects completed jaw clenching and a placebo condition on different days in counterbalanced order. Pericranial muscle tenderness, pressure-pain thresholds on the temporalis, and exteroceptive suppression periods were assessed before and after each procedure. Head pain was recorded for 12 to16 hours following each condition. RESULTS: Headache-prone subjects were more likely than controls to experience headaches after both the jaw clenching and placebo procedures, but neither group was significantly more likely to experience headaches following jaw clenching than placebo. In pretreatment measurements, headache-prone subjects exhibited greater muscle tenderness than controls, but pressure-pain detection thresholds and exteroceptive suppression periods did not differ in the two groups. Control subjects showed increases in muscle tenderness and exteroceptive suppression periods following both the clenching and placebo procedures, whereas headache-prone subjects exhibited no significant changes in any of the physiological measures following either experimental manipulation. CONCLUSIONS: These results confirm previous findings indicating abnormally high pericranial muscle tenderness in young tension headache sufferers even in the headache-free state. In addition, the results suggest that the development of headaches following noxious stimulation is more strongly related to headache proneness and associated abnormalities in central pain transmission or modulation (indexed by pericranial muscle tenderness and exteroceptive suppression responses) than muscle strain induced by jaw clenching.     

Pressure pain thresholds and thermal nociceptive thresholds in chronic tension-type headache

The nociceptive thresholds to mechanical and thermal stimuli in patients with chronic tension-type headache were compared. Palpation of pericranial tenderness was performed in 50 patients and a total tenderness score (TTS) was calculated. Palpation was repeated, and pressure pain thresholds (PPTs) were determined with a pressure algometer in the temporal and occipital regions. In 32 of the patients, pain thresholds for heat and cold and limens for detection of non-painful temperature changes were determined in the hands and the temporal regions. Twenty-four healthy volunteers served as controls. Scores obtained by manual palpation (TTS) at the first and second visit were positively correlated. A negative correlation between headache severity and PPT was found in the temporal region. A positive correlation between PPT in the temporal and occipital region was found, and PPT and TTS were negatively correlated. Thermal pain thresholds were consistently less extreme in patients compared to controls, and patients reporting severe headache on the examination day were those most sensitive to thermal pain. No difference was found between patients and controls with respect to detection of temperature changes. A correlation was found between PPT and the corresponding cold pain thresholds, but no correlation could be demonstrated between TTS and thermal pain thresholds. In conclusion, headache patients had decreased pain perception thresholds. Chronic tension-type headache might be a result of dysmodulation of nociceptive impulses, but it is likely that sensitized nociceptors also play a role.     

Pressure-controlled palpation: a new technique which increases the reliability of manual palpation

The objective of the present study was to investigate whether the reliability of tenderness evaluation can be increased by using a new technique called "pressure-controlled palpation" (pcp). The technique has been made possible by a newly invented piece of equipment called a palpometer, with which a pressure-sensitive plastic film attached to the index finger records the pressure exerted. In 15 patients with chronic tension-type headache and in 15 healthy volunteers, 2 investigators studied myofascial tenderness using conventional palpation and pressure-controlled palpation. Tenderness was scored on a 4-point scale in each of the examined pericranial regions. The sum of tenderness scores recorded by two observers using conventional palpation differed significantly ( p = 0.0003), while results did not differ between observers using pressure-controlled palpation ( p = 0.89). During palpation with seven different pressure intensities a positive and linear relation between pressure and pain intensity was found ( p = 0.00006). Pain intensity reported by the subjects correlated highly with tenderness scored by the observer ( r_s = 0.95, p < 0.0001). These results demonstrate for the first time that tenderness scores can be compared between observers if palpation pressure is controlled. Pressure-controlled palpation represents a major improvement on current palpation techniques and should be standard in future research on myofascial pain disorders.     

Efficacy and tolerability of amitriptylinoxide in the treatment of chronic tension-type headache: a multi-centre controlled study

Amitriptyline is the medication of first choice in the treatment of chronic tension-type headache. In 197 patients with chronic tension-type headache (87M and 110F with a mean age of 38 ±13 (18–68)) efficacy and tolerability of 60–90 mg amitriptylinoxide (AO) were compared with 50–75 mg amitriptyline (AM) and placebo (PL) in a double-blind, parallel-group trial consisting of a four weeks' baseline phase and 12 weeks of treatment. The primary study endpoint was a reduction of at least 50% of the product of headache duration and frequency and a reduction of at least 50% in headache intensity. Statistics used were Fisher's exact test and analysis of variance. No significant difference emerged between AO, AM and PL with respect to the primary study endpoint. Treatment response occurred in 30.3% of the AO, 22.4% of the AM and 21.9% of the PL group. A reduction in headache duration and frequency of at least 50% was found in 39.4% on AO, in 25.4% on AM and in 26.6% on PL (P_AO-PL = .1384, P_AM-PL = 1.000, P_AO-AM = .0973). A reduction in headache intensity of at least 50% was found in 31.8% on AO, in 26.9% on AM and in 26.6% on PL (P_AO-PL = .5657, P_AM-PL = 1.000, P_AO-AM = .5715). Trend analysis with respect to a significant reduction of headache intensity ( p < 0.05) and the product of headache duration and frequency revealed a superior effect of AO. Adverse events occurred in 75.8% on AO, 82.1% on AM and 76.6% on PL (P_AO-PL = 1.000, P_AM-PL =.5188, P_AO-AM = .4017). Neither depressive symptoms, measured by the SCL-90-R, nor study drug-related adverse events had any influence on the results.     

Muscle tenderness in pericranial and neck-shoulder region in children with headache. A controlled study

Increased pericranial muscle tenderness is connected with tension-type headache in adults. In children, the importance of muscle tenderness in the pericranial or neck-shoulder region in the pathogenesis of different types of headache is unknown. The present study evaluated muscle tenderness in the pericranial and neck-shoulder region in children with migraine, those with tension-type headache and those without headache. An unselected population-based questionnaire study concerning headache was carried out in 1135 Finnish schoolchildren aged 12 years. Of them, 183 children were randomly selected for a face-to-face interview and a clinical examination. Muscle tenderness was recorded by manual palpation and dolorimeter. Children with migraine had increased overall tenderness, recorded by manual palpation, compared with those without headache. They also self-reported tenderness in the neck-shoulder region during daily activities more often than the children of the other groups. Muscle tenderness was not associated with paediatric tension-type headache. The mean pressure pain thresholds did not differ among the three groups. However, a negative correlation between the total tenderness score and the dolorimeter score was found in each group. In conclusion, children with migraine had increased muscle tenderness at palpation of the pericranial and neck-shoulder muscles and they also reported pain symptoms in the neck-shoulder region most frequently. Instead, increased pericranial and neck-shoulder muscle tenderness was not associated with tension-type headache in children.