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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Clinical and pathophysiological observations in migraine and tension-type headache explained by integration of vascular, supraspinal and myofascial inputs.

A vascular-supraspinal-myogenic (VSM) model for pain in migraine based on our previous clinical and pathophysiological observations is proposed. According to the model, perceived pain (headache) intensity is determined by the sum of nociception from cephalic arteries and pericranial myofascial tissues converging upon the same neurons and integrated with supraspinal effects (usually facilitating). Vascular input predominates over myofascial input in migraine, whereas significance of supraspinal facilitation is difficult to estimate. The importance of these 3 effects may vary between patients and in the same individual with time. The model is in accordance with recent experimental studies showing convergence of somatovisceral afferents upon n. caudalis neurons. Also, long term potentiation due to nociceptive activation and sensitization of neurons to input from wider areas and non-nociceptive stimuli are relevant to our model. In tension-type headache, nociception is primarily myofascial, but vascular input cannot be disregarded. Supraspinal facilitation probably plays a large, sometimes dominant role (the MSV model). The model explains much of the complexity of the clinical picture of these disorders as well as their tendency to overlap and to change into one another. Also, a number of pathophysiological observations such as why muscles are tender during migraine, why trigger-point injection may cure migraine attacks and why chronic tension-type headache is often associated with episodes of pulsating pain, can be explained. The model gives a rational explanation of empirically developed, internationally accepted, multimodal treatment strategies for migraine and tension-type headache. It may thus serve a useful purpose in explaining the disorder to patients. Finally, the model points to several avenues of future research in animals and man.     

Myofascial trigger points and sensitization: an updated pain model for tension-type headache

Present pain models for tension-type headache suggest that nociceptive inputs from peripheral tender muscles can lead to central sensitization and chronic tension-type headache (CTTH) conditions. Such models support that possible peripheral mechanisms leading to pericranial tenderness include activation or sensitization of nociceptive nerve endings by liberation of chemical mediators (bradikinin, serotonin, substance P). However, a study has found that non-specific tender points in CTTH subjects were not responsible for liberation of algogenic substances in the periphery. Assuming that liberation of algogenic substances is important, the question arising is: if tender muscle points are not the primary sites of on-going neurogenic inflammation, which structure can be responsible for liberation of chemical mediators in the periphery? A recent study has found higher levels of algogenic substances, and lower pH levels, in active myofascial trigger point (TrPs) compared with control tender points. Clinical studies have demonstrated that referred pain elicited by head and neck muscles contribute to head pain patterns in CTTH. Based on available data, an updated pain model for CTTH is proposed in which headache can at least partly be explained by referred pain from TrPs in the posterior cervical, head and shoulder muscles. In this updated pain model, TrPs would be the primary hyperalgesic zones responsible for the development of central sensitization in CTTH.     

Heat pain thresholds and cerebral event-related potentials following painful CO2 laser stimulation in chronic tension-type headache

Current opinion concerning the pathophysiology of tension-type headache (TTH) and its related pericranial muscle tenderness proposes a primary role of central sensitization at the level of dorsalhorn/trigeminal nucleus as well as the supraspinal level. Investigation of these phenomena can be conducted using laser-evoked potentials (LEPs), which are objective and quantitative neurophysiological tools for the assessment of pain perception. In the present study we examined features of LEPs, as well as cutaneous heat-pain thresholds to laser stimulation, in relation to the tenderness of pericranial muscles in chronic TTH resulting from pericranial muscle disorder, during a pain-free phase. Twelve patients with TTH and 11 healthy controls were examined using the Total Tenderness Scoring (TTS) system. The stimulus was a laser pulse generated by a CO(2) laser. The dorsum of the hand and the cutaneous zones corresponding to pericranial muscles were stimulated. Subjective perception of stimulus intensity was assessed by a visual analogue scale. Two responses, the earlier named N2a and the last named P2, were considered; the absolute latency was measured at the highest peak of each response. The N2a-P2 components' peak-to-peak amplitude was detected. The heat pain threshold was similar in TTH patients and controls at the level of both the hand and pericranial skin. The TTS scores at almost all pericranial sites were higher in TTH patients than in normal controls. The amplitude of the N2a-P2 complex elicited by stimulation of the pericranial zone was greater in TTH patients than in controls; the amplitude increase was significantly associated with the TTS score. Our findings suggest that pericranial tenderness may be a primary phenomenon that precedes headache, and is mediated by a greater pain-specific hypervigilance at the cortical level.     

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.     

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.     

Sleep features and central sensitization symptoms in primary headache patients

Background

Association between sleep disorders and headache is largely known. The aim of the present study was to evaluate sleep quality and quantity in a large cohort of primary headache patients, in order to correlate these scores with symptoms of central sensitization as allodynia, pericranial tenderness and comorbidity with diffuse muscle-skeletal pain.

Methods

One thousand six hundreds and seventy primary headache out patients were submitted to the Medical Outcomes Study (MOS) within a clinical assessment, consisting of evaluation of frequency of headache, pericranial tenderness, allodynia and coexistence of fibromyalgia syndrome (FM).

Results

Ten groups of primary headache patients were individuated, including patients with episodic and chronic migraine and tension type headache, mixed forms, cluster headache and other trigeminal autonomic cephalalgias. Duration but not sleep disturbances score was correlated with symptoms of central sensitization as allodynia and pericranial tenderness in primary headache patients. The association among allodynia, pericranial tenderness and short sleep characterized chronic migraine more than any other primary headache form. Patients presenting with FM comorbidity suffered from sleep disturbances in addition to reduction of sleep duration.

Conclusion

Self reported duration of sleep seems a useful index to be correlated with allodynia, pericranial tenderness and chronic headache as a therapeutic target to be assessed in forthcoming studies aiming to prevent central sensitization symptoms development.     

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.     

Central mechanisms in tension-type headaches

Although tension-type headache is the most frequent primary headache, little is known about its pathophysiology. It is a matter of debate if the pain in tension-type headache originates from myofascial tissues or from central mechanisms in the brain. This article presents a summary of available data on the pathophysiology of tension-type headache and proposes a pathogenic model. From experimental research and clinical studies, it appears that myofascial nociception is important in episodic tension-type headache; however, central mechanisms (ie, central sensitization) are preponderant in the pathophysiology of the chronic form. Understanding the mechanisms of this central sensitization could allow for more efficient prophylactic treatments to emerge.     

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     

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.     

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.