Tension - Type Headache

Lars Bendtsen, MD, PhD*, RigmorJensen, MD, PhD
KEYWORDS  Tension-type headache  Diagnosis  Disability  Mechanisms  Treatment

Tension-type headache (TTH) is the most costly and common form of headache and what many people consider a normal headache, in contrast to migraine. At the same time, it is the least studied type of headache, although scientific acceptance and interest have amplified within the past decade. Although TTH previously was considered primarily psychogenic, a neurobiologic basis has been demonstrated.1–3 Current epidemiologic and pathophysiologic knowledge and treatment strategies for TTH are reviewed.
DEFINITION

The recent second version of the International Headache Society classification4 distinguishes between three forms of TTH mainly on basis of headache frequency: (1) infrequent episodic TTH (fewer than 12 headache days per year), (2) frequent episodic TTH (between 12 and 180 days per year), and (3) chronic TTH (at least 180 days per year). Chronic TTH differs from the episodic forms not only in frequency but also with respect to pathophysiology, lack of effect to most treatment strategies, more medication overuse, more disability, and higher personal and socioeconomic costs.5 The infrequent episodic form has little impact on individuals and can be regarded as trivial and without need for medical attention. Patients who have frequent episodic or chronic TTH encounter considerable disability and warrant specific intervention.
DIAGNOSIS

TTH is characterized by a bilateral, pressing, tightening pain of mild to moderate intensity, occurring in short episodes of variable duration (episodic forms) or continuously (chronic form). The headache is not associated with the typical migraine features, such as vomiting, severe photophobia, and phonophobia. In the chronic form, only one of these accompanying symptoms is allowed and only mild nausea is accepted.4 Because of lack of accompanying symptoms and milder pain intensity, patients rarely are severely incapacitated by their pain. TTH is the most featureless of the primary

Danish Headache Center, Department of Neurology, University of Copenhagen, Glostrup Hospital, DK-2600 Glostrup, Denmark * Corresponding author. E-mail address: larben01@glo.regionh.dk (L. Bendtsen). Neurol Clin 27 (2009) 525–535 doi:10.1016/j.ncl.2008.11.010 neurologic.theclinics.com 0733-8619/08/$ – see front matter ª 2009 Elsevier Inc. All rights reserved.

7 Nevertheless. EPIDEMIOLOGY TTH varies considerably in frequency and duration. women are affected only slightly more than men. but the majority had episodic infrequent TTH (1 day a month or less) without specific need for medical attention. and 16% had unchanged or newly developed chronic TTH at follow-up. A general and neurologic examination and prospective follow-up using diagnostic headache diaries6 with registration of all consumed drugs are.9. 45% experienced remission.11 A recent review of the global prevalence and burden of headaches10 showed that the disability of TTH was greater than that of migraine. not being married.11 PATHOPHYSIOLOGY Headaches generally are reported to occur in relation to emotional conflict and psychosocial stress.3 to demonstrate a possible muscular factor for patients and to plan treatment strategy.11 decreasing with age. from rare. 39% had unchanged frequent episodic TTH. where physical training and relaxation therapy are important components. short-lasting episodes of discomfort to frequent. Two Danish studies have shown that the number of workdays missed in the population was 3 times higher for TTH than for migraine8. a diagnosis of TTH requires exclusion of other organic disorders. In a Danish epidemiologic follow-up study. long-lasting. A recent review16 concluded that there is no increase in anxiety or depression in patients who had infrequent TTH whereas frequent TTH was associated with higher rates of . therefore.14 The burden is particularly high for the minority who have substantial and complicating comorbidities. The lifetime prevalence of TTH was as high as 78% in a population-based study in Denmark. and 2% to 3% of the population had chronic TTH. 549 persons participated in the follow-up study. 10% had it weekly. usually lasting for the greater part of a lifetime. coexisting migraine. Poor outcome was associated with baseline chronic TTH.10 The average age of onset of TTH is higher than in migraine. because many secondary headaches may mimic TTH. indicating that the overall cost of TTH is greater than that of migraine.8 The female-to-male ratio of TTH is 5:4 indicating that. and sleeping few hours per night. therefore. the annual incidence for TTH was 14. There are no reliable specific paraclinical tests that are useful in differential diagnosis. In a 12-year longitudinal epidemiologic study from Denmark. unlike migraine. indirect costs of all headaches are several times higher than those of migraine alone.526 Bendtsen & Jensen headaches and.2 per 1000 person years for frequent TTH (female-to-male 3:1). Pooling these extremes in an overall prevalence. and sleeping problems.8 The prevalence peaks between ages 30 to 39 and decreases slightly with age.15 The prognosis of TTH has not been analyzed extensively.7.13 Also. Manual palpation of the pericranial muscles and their insertions should be done2. The incidence of developing headache de novo has been estimated only rarely. namely 25 to 30 years in cross-sectional epidemiologic studies.12 and a United States study also found that absenteeism resulting from TTH is considerable. indicating that the cost of nonmigraine headaches (mainly TTH) is higher than that of migraine. may be misleading. but the cause-and-effect relationship is not clear. Risk factors for developing TTH were poor self-rated health. Among 146 subjects who had frequent episodic TTH and 15 who had chronic TTH at baseline. or even continuous disabling headaches. inability to relax after work. 24% to 37% had TTH several times a month. of utmost importance to reach a diagnosis.

23 Moreover. As in other chronic pain disorders. pain detection thresholds have been reported decreased in patients who have frequent episodic TTH.16 In addition. ruling out muscle ischemia as a cause of the pain.17 The investigators suggested that depression may aggravate existing central sensitization (discussed later) in patients who have frequent headaches.Tension-Type Headache 527 anxiety and depression. it recently was demonstrated that depression increases vulnerability to TTH in patients who have frequent headaches during and after a laboratory stress test and that the induced headache was associated with elevated pericranial muscle tenderness.17 Thus. and that the tenderness is positively associated with the intensity and the frequency of TTH. To summarize. such as sensitization of second-order neurons at the level of the spinal dorsal horn/trigeminal nucleus.2 In contrast. pericranial myofascial pain sensitivity is increased in patients who have TTH and peripheral mechanisms most likely play a role in the pathophysiology of TTH. have reported normal or only slightly increased muscle activity in TTH.30 and pain detection and tolerance thresholds are found decreased in patients who had chronic TTH in all studies performed with sufficient sample size. there may be a bidirectional relationship between depression and frequent TTH.3.27 and it is possible that continuous activity in a few motor units over a long time could be sufficient for excitation or sensitization of peripheral nociceptors.2. The increased myofascial pain sensitivity in TTH also could be caused by central factors. The origin of pain in TTH traditionally has been attributed to increased contraction and ischemia of head and neck muscles.19–21 It also has been demonstrated that the consistency of pericranial muscles is increased22 and that patients who have TTH are more liable to develop shoulder and neck pain in response to static exercise than healthy controls.18 Many studies have consistently shown that the pericranial myofascial tissues are considerably more tender in patients who have TTH than in healthy subjects.24 and recent studies reported an increased number of active trigger points in pericranial muscles in patients who have frequent episodic TTH and in patients who have chronic TTH.2 Pain detection thresholds have been reported normal in patients who have episodic TTH in studies performed before the separation between the infrequent and frequent form was made. sensitization of supraspinal neurons.20. Peripheral sensitization of myofascial nociceptors could play a role in increased pain sensitivity but firm evidence for a peripheral abnormality is lacking. Many laboratory-based electromyographic (EMG) studies.30–32 The nociceptive hypersensitivity has been consistently found in response to different stimulus modalities in various tissues at cephalic and . catastrophizing and avoidance) seem to be common in TTH. however.29.2 Mork and colleagues28 infused a combination of endogenous substances into the trapezius muscle and reported that patients who had frequent episodic TTH developed more pain than healthy controls. Maladaptive coping strategies (eg.2 but this hypothesis was challenged by a study demonstrating normal interstitial concentrations of inflammatory mediators and metabolites in a tender point of patients who had chronic TTH. psychologic abnormalities in TTH may be viewed as secondary rather than primary. and decreased antinociceptive activity from supraspinal structures. Concomitant psychophysical measures indicated that a peripheral sensitization of myofascial sensory afferents was responsible for the muscular hypersensitivity in these patients.26 EMG activity has been reported increased in myofascial trigger points.25 The increased myofascial pain sensitivity in TTH could be the result of release of inflammatory mediators resulting in excitation and sensitization of peripheral sensory afferents.3 and it has been demonstrated that muscle lactate levels are normal during static muscle exercise in patients who have chronic TTH. infusion of hypertonic saline into various pericranial muscles elicits referred pain that is perceived as head pain in healthy subjects.

which may be explained by convergence of multiple peripheral sensory afferents onto sensitized spinal cord neurons. however. nitric oxide synthase inhibitors that reduce central sensitization in animal models of persistent pain also reduce headache and pericranial myofascial tenderness and hardness in patients who have chronic TTH.36. a previously reported increase in TTH prevalence over a 12-year period was related to increased pain sensitivity.39 Thus. whereas sensitization of pain pathways in the central nervous system resulting from prolonged nociceptive stimuli from pericranial myofascial tissues seems to be responsible for the conversion of episodic to chronic TTH (Fig. 1).1–3 . and that the results support that central sensitization plays an important role for the chronification of TTH. These data from clinical studies recently were confirmed in a population-based study demonstrating a close relation between altered pain perception and chronification of headache. whereas central nociceptive processing seems to be normal in patients who have infrequent episodic TTH. because peripheral sensitization would have more localized effects. This recently was provided in a 12-year follow-up study demonstrating that patients who developed episodic TTH had increased pericranial myofascial tenderness but normal general pain sensitivity at follow-up.34.up.2. deficient descending inhibition) also may contribute to the increased pain sensitivity in chronic TTH.5.37 Decreased antinociceptive activity from supraspinal structures (ie. whereas subjects who developed chronic TTH had normal pain sensitivity at baseline but developed increased central pain sensitivity at follow.2 Thus. it can be concluded that nociceptive processing in the central nervous system is increased in patients who have chronic TTH.32 Final evidence for the cause-and-effect relationship between frequent headache and central sensitization has to come from longitudinal studies.38 The hypothesis of central sensitization in TTH is supported further by clinical pharmacologic studies.33 The fact that chronic TTH patients are hypersensitive to stimuli applied at cephalic and at extracephalic.2 This hypothesis is supported further by a recent study demonstrating decrease in volume of gray matter brain structures involved in pain processing in patients who had chronic TTH.528 Bendtsen & Jensen extracephalic locations. is consistent with referred hyperalgesia. pericranial myofascial mechanisms probably are of importance in episodic TTH.40 Moreover. amitriptyline reduces headache and pericranial myofascial tenderness in patients who have chronic TTH. The widespread and unspecific nature of the hypersensitivity.36 This decrease was correlated positively with duration of headache and most likely a consequence of central sensitization generated by prolonged input from pericranial myofascial structures.41 To summarize. suggests that the central sensitization also involves supraspinal neurons. It has been hypothesized that the central sensitization could be caused by prolonged nociceptive input from tender pericranial myofascial tissues. This delineates two major targets for future treatment strategies: (1) identifying the source of peripheral nociception in order to prevent the development of central sensitization and thereby the conversion of episodic into chronic TTH and (2) reducing established central sensitization.40 The reduction of myofascial tenderness during treatment with amitriptyline may be caused by a segmental reduction of central sensitization in combination with an enhanced efficacy of noradrenergic or serotonergic descending inhibition.38 The investigators concluded that increased pain sensitivity is a consequence of frequent TTH. nonsymptomatic locations strongly indicates that synaptic transmission of nociceptive input within the central nervous system is increased in this group of patients. not a risk factor.35 The expansion of hypersensitivity to other tissues.19 In addition. such as skin.

Physicians taking this problem seriously may have a therapeutic effect. ultrasound. reduced or inappropriate physical exercise.46 A controlled study47 combined various techniques. relaxation.42 Significant comorbidities (eg. psychologic problems. The proposed pathophysiologic model of chronic TTH delineates two major aims for future research: (1) identifying the source of peripheral nociception in order to prevent the development of central sensitization in patients who have episodic TTH and thereby the conversion of episodic into chronic TTH and (2) reducing established central sensitization in patients who have chronic TTH.45 Physical therapy is the most used nonpharmacologic treatment of TTH and includes improvement of posture. brain tumor) and can be reassured by thorough examination.38 so that normally innocuous stimuli are perceived as painful. exercise programs. such as massage. relaxation. because avoidance of trigger factors may have a long-lasting effect. . A detailed analysis of trigger factors should be performed. Nonpharmacologic management should be considered for all patients who have TTH and is used widely. These treatments are described separately but should go hand in hand. Scientific evidence for efficacy of most treatment modalities. TREATMENT A correct diagnosis should be assured by means of a headache diary6 recorded over at least 4 weeks. high intake of coffee and other caffeinecontaining drinks. and it establishes a baseline against which to measure the efficacy of treatments.44 Most of triggers are selfreported and so far none of the triggers has been systematically tested. Identification of a high intake of analgesics is essential as other treatments largely are ineffective in the presence of medication overuse. It should be explained to patients that frequent TTH only seldom can be cured but a meaningful improvement can be obtained with the combination of nonpharmacologic and pharmacologic treatments. Muscle pain can lead to a disturbance of the brain’s pain-modulating mechanisms. hot and cold packs. is sparse. The diary also may reveal triggers and medication overuse. and variations during the female menstrual cycle and hormonal substitution. 1. dehydration. and found a modest effect.46 Active treatment strategies generally are recommended.43. The diagnostic problem encountered most often is discriminating between TTH and mild migraines. irregular or inappropriate meals. sleep disorders. and electrical stimulation. however. with secondary perpetuation of muscle pain and risk for anxiety and depression. and home-based exercises.2. The triggers reported most frequently for TTH are stress (mental or physical). Information about the nature of the disease is important. particularly if are patients are concerned about serious disease (eg. too much or too little sleep.Tension-Type Headache 529 Fig. anxiety or depression) should be identified and treated concomitantly.

This feedback helps the patients to develop control over pericranial muscle tension. simple analgesics are the mainstays in the acute therapy for TTH (Fig.57 The combination of analgesics with caffeine. The efficacy of the simple analgesics tends to decrease with increasing frequency of the headaches.54 The exact degree of effect of psychologic treatment strategies is difficult to estimate. naproxen sodium (375–550 mg). Cognitive-behavioral therapy (stress management) aims to teach patients to identify thoughts and beliefs that generate stress and aggravate headaches.42 Other interventions. such as nondrug treatments and prophylactic pharmacotherapy. The nonsteroidal anti-inflammatory drugs (NSAIDs). and chronification of the headache. or shoulders. codeine. patients are presented with an auditory or visual display of electrical activity of the muscles in the face.530 Bendtsen & Jensen It recently was reported that adding craniocervical training to classical physiotherapy was better than physiotherapy alone.58 Physicians should be aware of the risk for developing medication-overuse headache as a result of frequent and .55 Acute pharmacologic therapy refers to the treatment of individual attacks of headache in patients who have episodic and chronic TTH. and diclofenac potassium (50–100 mg) all have been demonstrated more effective than placebo in acute TTH. In patients who have chronic TTH. It is most likely that cognitive changes (ie. Most randomized placebo-controlled trials have demonstrated that aspirin (in doses of 500 mg and 1000 mg)56 and acetaminophen (1000 mg)56 are effective in the acute therapy for TTH. should be considered. 2). There is no consistent difference in efficacy between aspirin and acetaminophen.54 Relaxation training is a self-regulation strategy that provides patients with the ability to consciously reduce muscle tension and autonomic arousal that can precipitate and result from headaches. whereas a combination of the two treatments seemed more effective than either treatment alone. ketoprofen (25–50 mg).57 Combination analgesics. simple analgesics usually are ineffective but should be used with caution because of the risk for medication-overuse headache with a regular intake of simple analgesics more than 14 days a month or triptans or combination analgesics more than 9 days a month.48 Spinal manipulation has no effect on the treatment of episodic TTH.50 There are conflicting results regarding the efficacy of acupuncture for the treatment of TTH. anxiety. abuse. Acetaminophen (1000 mg) may be recommended as drug of first choice because of better gastric side-effect profile. and muscle relaxants have not been demonstrated effective in TTH. however. ibuprofen (200– 400 mg). and depression. ibuprofen (400 mg) may be recommended because of a favorable gastrointestinal side-effect profile compared with other NSAIDs.42 Triptans do not have a clinically relevant effect. comparative studies report that these NSAIDs are more effective than acetaminophen and aspirin.57 Most. neck. generally should be avoided because of the risk for dependency. Most headaches in patients who have episodic TTH are mild to moderate and the patients often can self-manage with simple analgesics.51–53 Psychologic treatment strategies have reasonable scientific support for effectiveness.49 Oromandibular treatment with occlusal splints often is recommended but has not yet been tested in trials of reasonable quality and cannot be recommended in general.57 To summarize. self-efficacy) rather than reductions in muscle tension account for the improvement in TTH with EMG biofeedback. sedatives. but cognitive-behavioral therapy has been found comparable with treatment with tricyclic antidepressants. but not all. or tranquilizers frequently is used and increased efficacy when adding caffeine to aspirin or ibuprofen has been reported.54 In EMG biofeedback.58 If acetaminophen is not effective. the headaches often are associated with stress.

and the tetracyclic antidepressants.59Antidepressants with action on serotonin and noradrenaline seem as effective as amitriptyline with the advantage that they are tolerated in doses needed for the treatment of concomitant depression. are reported as more effective than placebo. amitriptyline. and opioids do not have a role in the treatment of TTH. propranolol or valproic acid can not be recommended at present for the prophylactic treatment of TTH.42 Triptans. including patients who had not responded to amitriptyline. the initial approach to prophylactic pharmacotherapy for chronic TTH is through the use of amitriptyline (see Fig. muscle relaxants.60 It is advisable. is the only drug proved effective in several controlled trials in TTH. obstipation.55. mirtazapine .Tension-Type Headache 531 Fig. Tizanidine. 2. venlafaxine (150 mg/day).62 reduced headache days from 15 to 12 per month. mirtazapine (30 mg/day). Pharmacologic treatment paradigm for TTH.61 however.60 It is important that patients be informed that this is an antidepressant agent but has an independent action on pain. The side effects of amitriptyline include dry mouth. The tricyclic antidepressant. Prophylactic pharmacotherapy should be considered in patients who have chronic TTH who do not respond to nonpharmacologic treatment. and weight gain.59 To summarize. Concomitant use of daily analgesics should be avoided. clomipramine. Amitriptyline should be started at low dosages (10 mg/day) and titrated by 10 mg weekly until patients have good therapeutic effect or side effects are encountered. reduced headache index by 34% more than placebo in difficult-to-treat patients. maprotiline and mianserin. If patients do not respond to amitriptyline. A significant effect of amitriptyline may be observed in the first week on the therapeutic dose. excessive use of analgesics in acute therapy. the noradrenergic and specific serotonergic antidepressant. botulinum toxin.60. 2). drowsiness. The latter study62 is difficult to compare with the other studies discussed. Thus. to change to other prophylactic therapy if patients do not respond after 4 weeks on maintenance dose.61 The serotonin and noradrenaline reuptake inhibitor. The tricyclic antidepressant. because it was a small parallel group study performed in a mixed group of patients who had frequent episodic or chronic TTH.55. therefore.60 The effect is long lasting (at least 6 months)55 and not related to the presence of depression. dizziness.59 The two most recent studies reported that amitriptyline (75 mg per day) reduced headache index (duration  intensity) by 30% compared with placebo. The maintenance dose usually is 30 to 70 mg daily administered 1 to 2 hours before bedtime to help circumvent any sedative adverse effects. whereas the selective serotonin reuptake inhibitors (SSRIs) are not found effective.

whereas chronic TTH patients responded with 32%.19(6):602–21. Cephalalgia 2004. et al. and 33% in absence rate. Eur J Epidemiol 2005. 10. 9. 65(4):580–5. Cephalalgia 1992. et al. Rasmussen BK. Wittchen HU. Has the prevalence of migraine and tension-type headache changed over a 12-year period? A Danish population survey.24(Suppl 1):1–160.15(1):45–68. Lyngberg AC. Jorgensen T. Cephalalgia 2007. Lyngberg AC. Bendtsen L. 6. Physicians should keep in mind that the efficacy of preventive drug therapy for TTH often is modest and that the efficacy should outweigh the side effects. The global burden of headache: a documentation of headache prevalence and disability worldwide.12(Suppl 1):1–27. 8. Jensen R. 13.12(Suppl 1):59–62. Cephalalgia 1999. Central sensitization in tension-type headache—possible pathophysiological mechanisms. Ashina M. Jensen R. 4. It is reassuring. Epidemiology of headache. Bendtsen L. respectively. Discontinuation should be attempted every 6 to 12 months.63 REFERENCES 1.532 Bendtsen & Jensen could be attempted. Curr Opin Neurol 2006. Berg J. Jorgensen T. Rasmussen BK. Eur J Neurol 2005. 24(3):161–72. Lancet Neurol 2008. Tension-type headache: the most common. J Occup Environ Med 1997. Stovner LJ. Cost of disorders of the brain in Europe. 11. it usually is recommended to combine multiple strategies although proper evidence is lacking. Cephalalgia 2000. Cost of migraine and other headaches in Europe. et al. 15. therefore. et al. Eur J Neurol 2005.20(5):486–508. Stovner L.20(3):243–9. Jorgensen T. The international classification of headache disorders. headache disorder. but also the most neglected. et al. 14. 30%.19(3):305–9.63 Treatment results for all patients discharged within 1 year were evaluated. Patients who had episodic TTH demonstrated a 50% reduction in frequency. Jensen R. Secular changes in health care utilization and work absence for migraine and tension-type headache: a population based study. 75% reduction in intensity. Neurobiology of chronic tension-type headache. Neurology 2005. 39(4):320–7. Headache Classification Subcommittee of the International Headache Society. Andlin-Sobocki P. Hagen K.20(12):1007–14. Pathophysiological mechanisms of tension-type headache: a review of epidemiological and experimental studies.12(6):369–74. Lipton RB. Russell MB. that the first study that has evaluated the efficacy of a multidisciplinary headache clinic reports positive results. Epidemiology and comorbidity of headache. Jonsson B. Rasmussen BK. Lyngberg AC. Presentation of a new instrument: the diagnostic headache diary. if tricyclics or mirtazapine are not tolerated. As neither nonpharmacologic nor pharmacologic management is highly efficient. Cephalalgia 1995. Brennum J. 3. . Rasmussen BK. 2. 12.27(3): 193–210. Rasmussen BK. et al. Lost workdays and decreased work effectiveness associated with headache in the workplace. Stewart WF. Eur J Epidemiol 2005. Stovner LJ. 2nd edition. Venlafaxine or SSRIs could be considered in patients who have concomitant depression. and 40% reductions. Jensen R.7(4):354–61. 7. Cephalalgia 2004. 5. Prognosis of migraine and tension-type headache: a population-based follow-up study. Schwartz BS.

Cephalalgia 2007. et al. 30. In vivo evidence of altered skeletal muscle blood flow in chronic tension-type headache.5:4–11. Fernandez-De-Las-Penas C. 29.in vivo evidence in patients with chronic tension-type headache.27(2):145–52. 35. Eur J Neurol 2003. Abnormal modulatory influence of diffuse noxious inhibitory controls in migraine and chronic tension-type headache patients. et al. Pain and tension-type headache: a review of the possible pathophysiological mechanisms. et al.24(6):466–75. Cephalalgia 2007.10(6):439–47. Cephalalgia 2006. Bendtsen L.26(5):568–77. Pain 1999. chronicity and disability. Possible mechanisms of pain perception in patients with episodic tension-type headache.25(11):1061–7. Pain 2007. Holroyd KA. Cephalalgia 2005. Depression increases onset of tension-type headache following laboratory stress. Ashina M. et al. Increased pericranial tenderness. Lipchik GL.Tension-Type Headache 533 16. Ashina S. Sandrini G. et al. Holroyd KA. Berkoff GM. Buchgreitz L. Exteroceptive suppression periods and pericranial muscle tenderness in chronic tension-type headache: effects of psychopathology. J Headache Pain 2004. Svensson P. Bendtsen L. et al. et al. Cuadrado ML. Frequency of headache is related to sensitization: a population study. 18. Cuadrado ML. Bendtsen L.26(8):940–8.38(4):397–421. et al. Ashina M. Bendtsen L. Svensson P. Pain 2004. et al. Prog Neurobiol 1992. Milanov I. Spine 1993. Cephalalgia 2003. Fernandez-De-LAS-Penas C. Mork H.125:320–6. Curr Pain Headache Rep 2006. Jensen R.111(3):230–8. Bendtsen L. Myofascial trigger points show spontaneous needle EMG activity. et al. Tension-type headache and psychiatric comorbidity. Milanov I. Treede RD.20(7):638–46.129(1–2):113–21. Myofascial trigger points and sensitization: an updated pain model for tension-type headache. Increased muscle pain sensitivity in patients with tension-type headache. Romanek K. 34. 31. et al. Janke EA. et al. Clin J Pain 2007. et al. 26.10(3):249–56. Bogdanova D. Generalized hyperalgesia in patients with chronic tension-type headache. 21.27(5):383–93. 22. Schmidt-Hansen PT. Bendtsen L. Holroyd KA. Lyngberg A. and headache clinical parameters in chronic tension-type headache patients. Ashina M. Experimental induction of muscle tenderness and headache in tension-type headache patients. Buchgreitz L.26(7):782–9. 20. Mork H. Brain 2002. 24. Stallknecht B. Cephalalgia 2004. . et al. Ashina M. decreased pressure pain threshold. Cephalalgia 2000.123(1–2):19–27. Arendt-Nielsen L. Lyngberg AC. 17. Jensen TS. A new experimental model of myofascial pain. Induction of prolonged tenderness in patients with tension-type headache by means of a new experimental model of myofascial pain. Increased prevalence of tensiontype headache over a 12-year period is related to increased pain sensitivity. Arendt-Nielsen L. 23. Schmidt-Hansen PT. Patterns of experimentally induced pain in pericranial muscles. Ashina M. Bendtsen L. Cephalalgia 2006. Hubbard DR. 25.18(13):1803–7. Cephalalgia 2006. A population study. Rossi P. Ashina M. Pain 2006. Christensen M.23(4):346–52. Stallknecht B. Raja SN. Ashina M. 33. 28. et al. Bendtsen L. Meyer RA. Peripheral and central mechanisms of cutaneous hyperalgesia. Muscle hardness in patients with chronic tension-type headache: relation to actual headache state. Bendtsen L.23(2):109–16. Heckman BD.79(2–3): 201–5. 19. 32. Tender points are not sites of ongoing inflammation . 27. et al. Bendtsen L. O’Donnell FJ.

. Holroyd KA. Increased pain sensitivity is not a risk factor but a consequence of frequent headache: a population-based follow-up study. Voelker M. Philadelphia: Lippincott Williams Wilkins. Holroyd KA. Cephalalgia 2000.331(7513):376–82. Bendtsen L. 37. Ramadan N. Neurology 2005. Ulrich V. Bendtsen L. In: Olesen J. Endres HG. Curr Neurol Neurosci Rep 2006. Pain 2007 [-E-pub ahead of print]. 721–6. Lyngberg AC. Cephalalgia 2004.20(3):326–30. 3rd edition. Jensen R. Lange R. Tension-type headache. stress management therapy. Physiotherapy for tension-type headache: a controlled study.280(18):1576–9. 48. Curr Treat Options Neurol 2001. editors. Tension-type headache. Davis MA. 51. Goadsby PJ. Jensen R. Curr Opin Investig Drugs 2002. Ashina M. Hoppe A. The headaches. et al. Philadelphia: Lippincott Williams Wilkins. Acupuncture for tension-type headache: a multicentre. Cephalalgia 2006. Melchart D. p. Jensen R. Mathew NT. 285(17):2208–15. 38. Jensen R. randomised trial. Philadelphia: Lippincott Williams Wilkins. Roth JM. JAMA 2001. Lucas C. et al.534 Bendtsen & Jensen 36. Bowing G. Jensen R. Bendtsen L. O’Donnell FJ. Arch Neurol 1992. editors. et al. et al.9(8):667–77. Olesen J. Cephalalgia 2003. Schmidt-Wilcke T. 3rd edition. Martin PR. 56.65(9):1483–6. 2005. Streng A. et al. sham-controlled. Bove G. Spinal manipulation in the treatmentof episodic tension-type headache: a randomized controlled trial. Jensen R. J Pain 2008. Nash JM. The headaches. et al. 44. Aspirin in episodic tension-type headache: placebo-controlled dose-ranging comparison with paracetamol. In: Olesen J. JAMA 1998. 43. Medication-overuse headache: where are we now? Curr Opin Neurol 2007.24(1):29–36.20(6):603–10. 3rd edition. 711–9. Steiner TJ. 54. editors. Kononowech RW. 45. BMJ 2005. et al. Graff-Radford SB.49:914–8. Russell MB. Interrelations between migraine and tension-type headache in the general population. Goadsby PJ. Gray matter decrease in patients with chronic tension type headache. 2005. Nilsson N. J Headache Pain 2007. Ramadan N. Goadsby PJ. et al. Leinisch E. Rasmussen BK. 50. Psychological treatments of tension-type headache. controlled trials. 53. Buchgreitz L. p. 47. 42. Acupuncture in patients with tension-type headache: randomised controlled trial.26(8):983–91. A comparison of tension-type headache in migraineurs and in non-migraineurs: a population-based study. 41. 67(2–3):501–6. 49. Sensitization: its role in primary headache. et al. 39. Straube A. 55. Diener HC.6(2):100–5. In: Olesen J. Katsarava Z. Schroll M. 52. 46.23(1):59–66. Jensen R. van Ettekoven H. Efficacy of physiotherapy including a craniocervical training programme for tension-type headache. et al. Possible mechanisms of action of nitric oxide synthase inhibitors in chronic tension-type headache. Rolin SA. et al. Ramadan N.8(5):306–14.3(3):449–53. 1029–35. Acupuncture for tension-type headache: a meta-analysis of randomized. a randomized clinical trial. Amitriptyline reduces myofascial tenderness in patients with chronic tension-type headache. p. 2005. Jensen R. Torelli P. Headache attributed to orofacial/temporomandibular pathology. Pain 1996.3(2):169–80. patient-and observer-blinded. The headaches. Brain 1999. 40. Stensland M. Canavan DW. et al. and their combination: a randomized controlled trial.122(9):1629–35. Psysiotherapy of tension-type headaches. Management of chronic tensiontype headache with tricyclic antidepressant medication. Bendtsen L.

Cephalalgia 2007. A randomized. p. The headaches. Lancet 1994. Langman MJ. Vlaikidis N. 58. Mathew NT. Current and potential future drug therapies for tension-type headache. Harmoussi S. J Neurol Neurosurg Psychiatr 1996. Prophylactic pharmacotherapy of tension-type headache. 63. Jensen R. Weil J.25(12):1159–67. Olesen J. et al. 62.27(4):315–24. Ashina M. Olesen J. double-blind. 2005. A non-selective (amitriptyline). 343(8905):1075–8. Curr Pain Headache Rep 2003. Jensen R. 60. editors. 61. Philadelphia: Lippincott Williams Wilkins. et al. Mirtazapine is effective in the prophylactic treatment of chronic tension-type headache. Cephalalgia 2005. Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs. Goadsby PJ. . Zissis N. et al. 61(3):285–90. Bendtsen L. Neurology 2004.7(6):466–74.62(10):1706–11. Ramadan N. Wainwright P. Zeeberg P. Jensen R. serotonin reuptake inhibitor is effective in the prophylactic treatment of chronic tension-type headache. Ashina S.Tension-Type Headache 535 57. placebocontrolled study of venlafaxine XR in out-patients with tension-type headache. 735–41. but not a selective (citalopram). Efficacy of multidisciplinary treatment in a tertiary referral headache centre. 3rd edition. 59. In: Olesen J. Bendtsen L. Bendtsen L.