Chronic tension-type headache: what is new?

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Tension-type headache (TTH) is the most common form of headache [1] and its chronic form (chronic tension-type headache: CTTH) is one of the most neglected [2] and difficult headaches to treat. This headache may cause substantial levels of disability not only to the patients and their families but also to the global society due to very high prevalence in the general population [3]. There has been an increasing interest in the pathogenesis of CTTH over the last decades but, despite several advances in aetiology, the pathogenesis is still not completely under-stood [4]. This review discusses current data on noso-logical boundaries related to diagnosis, pathophysiology (peripheral and central mechanisms) and therapeutic strategies (pharmacological and nonpharmacological).

What is new concerning the nosological

boundaries of tension-type headache?

TTH is an overarching syndrome of ‘featureless’ head-aches characterized by nothing but pain in the head.

Because of the variety of previously used terms to desig-nate this headache (muscular contraction, psychogenic, psychomyogenic, stress, nonmigrainous headache) and its presumed cause, the term ‘tension-type’ has been chosen by the International Headache Society (ICHD-II) [5] in order to offer a new heading underlining the uncertain pathogenesis, but indicating that some kind of mental or muscular tension may play a role. This ‘tabula rasa’ approach had the advantage of offering a single and accepted diagnosis, which could be submitted to further research, but the disadvantage of mixing in the same basket a number of head pain symptoms that have the same diagnostic criteria, but are far from being alike.

The differential diagnosis and boundary with migraine

There is evidence that the diagnostic criteria of the ICHD-II may classify patients with TTH as patients having a mild form of migraine without aura with mod-erate intensity and subtle or absent associated symptoms. Clinically, there is overlap between the symptoms of migraine and TTH. Migrainous features have been pre-viously reported in substantial proportions of TTH


Department of Physical Therapy, Occupational Therapy, Physical Medicine and Rehabilitation, b

Esthesiology Laboratory, Universidad Rey Juan Carlos, Alcorco´n, Madrid, Spain,c

Centre for Sensory-Motor Interaction (SMI), Department of Health Science and Technology, Aalborg University, Aalborg, Denmark anddHeadache Research Unit, Department of Neurology & Research Center for Neurobiology, Lie`ge University, Lie`ge, Belgium

Correspondence to Ce´sar Ferna´ndez-de-las-Pen˜as, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Avenida de Atenas s/n, 28922 Alcorco´n, Madrid, Spain

Tel: +34 91 488 88 84; fax: +34 91 488 89 57; e-mail:

Current Opinion in Neurology2009, 22:254–261


This review discusses current data on nosological boundaries related to diagnosis, pathophysiology and therapeutic strategies in chronic tension-type headache (CTTH). Recent findings

Diagnostic criteria of CTTH should be adapted to improve its sensitivity against migraine. It seems that mechanical pain sensitivity is a consequence and not a causative factor of CTTH. Recent evidence is modifying previous knowledge about relationships between muscle tissues and CTTH, suggesting a potential role of muscle trigger points in the genesis of pain. An updated pain model suggests that headache perception can be explained by referred pain from trigger points in the craniocervical muscles, mediated through the spinal cord and the trigeminal nucleus caudalis rather than only tenderness of the muscles themselves. Different therapeutic strategies, pharmacological, physical therapy, psychological and acupuncture, are generally used. The therapeutic efficacy of nonsteroidal anti-inflammatory drugs remains incomplete. The tricyclic antidepressants are the most used first-line therapeutic agents for CTTH. Surprisingly, few controlled studies have been performed and not all of them have found an efficacy superior to placebo. Further, there is insufficient evidence to support/refute the efficacy of physical therapy in CTTH.


Although there is an increasing scientific interest in CTTH, future studies incorporating subgroups of patients who will likely to benefit from a specific treatment (clinical prediction rules) should be conducted.


central sensitization, chronic tension-type headache, mechanical pain sensitivity, muscle trigger points, peripheral sensitization

Curr Opin Neurol 22:254–261

ß2009 Wolters Kluwer Health | Lippincott Williams & Wilkins 1350-7540


patients: aggravation by routine physical activity (27.7%), pulsating quality (17.5%), anorexia (18.2%), photophobia (10.6%), unilateral headache (10%) or nausea (4.2%) [6]. In children, even more so than in adults, migraine and TTH symptoms frequently cooccur. Out of 125 school-going children, from 10–17 years of age, with definite migraine, 58.4% reported TTH symptoms, whereas 68.1% out of 138 children with TTH had migraine symptoms [7]. Between preschool age (6 years) and puberty (13 years), the diagnosis changed to migraine in 52% of children initially diagnosed with TTH, whereas migraine became clinically TTH in 38% [8].

Even when a diagnosis of TTH is assigned from the history by a headache expert, patients often prove to have migraine on diary review. This was shown in the Spectrum Study in which the effectiveness of a triptan on migraine headaches of mild intensity was assessed [9], and in a recent trial of a combination analgesic in patients with migraine or TTH [10]. In these two studies, the initial diagnosis of TTH changed to migraine in 70 and 54% of the patients, respectively, after reviewing a pro-spectively filled in diary.

Some patients who present phenotypic TTH may display pathophysiological features generally found in migraine. One example is the induction of headache by nitrogly-cerin in CTTH [11] and its therapeutic response to an inhibitor of nitric oxide synthase [12], both features thought to characterize migraine patients. Further, the increase of blood calcitonin gene-related peptide (CGRP) levels in patients with CTTH complaining of pulsatile headaches [13] was initially described during migraine attacks.

Finally, treatments thought to be specific for migraine have shown some efficacy in TTH. A subcutaneous injection of sumatriptan provided relief in 75% of CTTH patients [14] and reduced pain scores by at least 50% in 67% of TTH episodes in an emergency ward [15]. In an open-label prospective trial, topiramate, an anticonvul-sant highly effective in migraine prevention, was able to reduce headache frequency in CTTH by more than 50% [16]. Moreover, biofeedback methods are effective in both migraine and TTH irrespective of biological modality used for feedback [17].

The common denominators with fibromyalgia

CTTH has also common clinical, therapeutic and patho-physiologic features with fibromyalgia (FMS), and both conditions are frequently comorbid [18]. Clinically, CTTH and FMS are more frequent in women, influ-enced by different trigger factors, including life events or hormonal changes, comorbid with depression or anxiety and genetically influenced [19]. There are also common denominators in the therapeutic strategies used in

CTTH and FMS: tricyclic antidepressants and physical therapy are, if combined, the most effective treatments, whereas acute pharmacotherapy is based on nonsteroidal anti-inflammatory drugs [20].

From a pathophysiologic point of view, hypersensitivity to various nociceptive stimuli is found in both conditions. In particular, increased peripheral and central sensitiz-ations are thought to play a role in CTTH and FMS [21]. For instance, the stimulus–response function for manual pressure over a tender muscle in FMS or trapezius muscle in CTTH is linear and thus qualitatively different from that of normal muscle [22,23]. The normal increase in pressure pain threshold levels induced by isometric con-traction of the underlying muscle is abolished over the temporalis muscle both in CTTH and FMS [24]. By contrast, it is also abolished over the flexor forearm muscles in FMS, but not in CTTH patients [25]. These results suggest that sensitization of central nociceptors plays a pivotal role in the pathophysiology of both FMS and CTTH. Nevertheless, in CTTH, sensitization seems to be more pronounced segmentally in the trigeminal system, whereas the sensitization involves diffusely spinal and brain stem levels in FMS patients. We can propose, therefore, a common pathophysiological hy-pothesis for both conditions, which can also include myofascial pain syndromes (Fig. 1).

Present knowledge and diagnostic tools are not sensitive enough to distinguish subgroups with a different patho-physiology in CTTH, in particular those patients with a migrainous pathophysiology. The controversy between advocates of the continuum theory, in which TTH would be a mild expression of migraine [26], and those who consider TTH and migraine as completely different headaches [27], is therefore, not settled. It is most likely Figure 1 A common pathophysiological hypothesis for chronic tension-type headache, fibromyalgia syndrome and regional myofascial pain


that mild ‘interval’ tension-type-like headaches in some migraine patients who have otherwise typical migraine attacks are in the majority mild migraine attacks and will respond to antimigraine treatment. By contrast, patients with TTH who never have migrainous features probably have a disorder which is pathophysiologically different from migraine [28], but comparable to FMS or myofascial pain syndromes.

What is new in pathophysiology?

CTTH is generally associated with changes in nocicep-tive pain perception in the central nervous system, particularly manifested as mechanical pain hypersensi-tivity. Whether this mechanical pain hypersensitivity is a primary (cause) or a secondary (consequence) phenom-enon to CTTH is under debate. Recent evidence answering this question and modifying previous concepts related to the relationship between muscle tissues and CTTH have emerged and will be reviewed.

Mechanical pain sensitivity: cause or consequence of chronic tension-type headache?

Recent studies have confirmed that the most prominent finding in CTTH patients is an increased tenderness to palpation of pericranial tissues, not only in muscles [29,30] but also in nerve tissues [31]. In a cross-sectional population study [32], the increase in the prevalence of TTH was associated with an increase in sensitivity to pericranial pain. It seems clear that increased tenderness to palpation of pericranial tissues is a clinical feature of CTTH. Additionally, patients with CTTH have lower pressure pain thresholds (PPT) in both cephalic and extracephalic locations [33,34]. Furthermore, it has been recently found that pressure pain sensitivity is not uniformly distributed over the temporalis muscle because topographical spatial changes in PPT are present throughout the cephalic region in patients with CTTH: the anterior part of the temporalis muscle is the most sensitive part of the muscle within patients but not in healthy controls [35].

Nevertheless, whether this mechanical pain hypersensi-tivity is a primary (cause) or a secondary (consequence) phenomenon to CTTH has been under debate. A 12-year follow-up longitudinal study [36] has demonstrated that individuals who later will develop CTTH showed normal tenderness scores and PPT levels before the beginning of the symptoms, which suggests that the mechanical hypersensitivity is rather a consequence than a risk factor for the development of CTTH.

Sensitization in chronic tension-type headache: interaction between peripheral and central mechanisms

These hyperalgesic and allodynic responses support the role of both peripheral and central mechanisms in the

development of the clinical picture of CTTH patients. It has been suggested that both hyperexcitability of the central nervous system [37], that is, central sensitization, and a reduction in inhibitory mechanisms [38,39] are mechanisms involved in nociception in CTTH. The most accepted theory is that the main problem in CTTH is the central sensitization process due to prolonged peripheral nociceptive inputs from muscle tissues [40]. Recent studies have confirmed the role of central sen-sitization in CTTH patients by studying nociceptive flexion reflex R3 component [41], suprathreshold single or repetitive electrical thresholds [42] and cortical poten-tial evoked by supraorbital laser heat stimulation [43]. CTTH patients have also shown a significant decrease in grey matter in structures involved in nociceptive pain processing, confirming hence a role of the brain stem in pain responses in these patients [44].

These data support the role of central mechanisms in CTTH patients. Nevertheless, as central sensitization is generated by prolonged nociceptive inputs from periph-eral structures [45] and dynamically influenced by activity and location of these nociceptive inputs [46], the role of peripheral mechanisms in the pathophysiology of CTTH is still a matter for debate. The existence of central sensitization mechanisms in different local pain syndromes, for example, repetitive strain injury [47], low-back pain [48], knee osteoarthritis [49], suggests that sustained peripheral nociceptive input to the central nervous system plays a role in the initiation or mainten-ance or both of central sensitization. This is also sup-ported by a study showing that the degree of sensitization in patients with chronic musculoskeletal pain is related to the severity of the musculoskeletal pain disorder [50]. Therefore, questions would be: Where is the peripheral nociceptive input in CTTH initiated? Which is the structure responsible for peripheral sensitization in CTTH? It seems that both bradykinin and serotonin are well known stimulants for muscle nociceptors [51]. It has been previously hypothesized that the central sensitization seen in CTTH would be provoked by peripheral drive initiated in tender muscle tissues [40]. Nevertheless, a study found no significant differences in interstitial concentration of chemical mediators (gluta-mate, bradykinin, prostaglandin E2, glucose or pyruvate) in tender tissues in patients with CTTH [52]. It has been recently demonstrated that active trigger points (TrPs), those TrPs for which a referred pain pattern reproduced symptoms [53], induced significantly higher levels of chemical mediators (bradykinin, CGRP, substance P, tumour necrosis factor-a, interleukin-1-b, serotonin or norepinephrine), not only locally [54], but also in distant pain-free regions [55], when compared with latent TrPs or non-TrP points. These studies confirm that active TrPs are responsible for the release of chemical


mediators and hence peripheral nociceptive barrage that can contribute to peripheral and central sensitization mechanisms in CTTH (readers are referred to other papers for a discussion about TrPs) [56,57].

Several clinical studies conducted by different research groups demonstrated the relevance of active TrPs in CTTH [58]. We have demonstrated that CTTH is associated with active TrPs in the suboccipital [59], upper trapezius [60], superior oblique [61], sternocleidomas-toid [62], temporalis [63] and lateral rectus [64] muscles (Fig. 2). Another group also found that 85% of the patients with CTTH had active TrPs in the upper trapezius muscle [65]. In addition, these studies also found that active TrPs were associated with more severe headache parameters, which may be considered as temporal integration of nociceptive inputs from active muscle TrPs [66]. With these data from clinical and basic studies, Ferna´ndez-de-las-Pen˜aset al.[67] formulated an updated pain model for CTTH involving both per-ipheral sensitization of nociceptors by active muscle TrPs and central sensitization: active muscle TrPs located in the musculature innervated by C1–C3 segments (upper trapezius, suboccipital, sternocleidomastoid) and by the trigeminal nerve (temporalis, masseter, extraocular) may be responsible for peripheral nociceptive inputs and may produce a continuous afferent barrage into the trigeminal nerve nucleus caudalis, sensitizing the central nervous system in CTTH. Therefore, according to this pain model, muscle tenderness is the consequence, whereas muscle TrPs (referred pain) is one of the main causes (but not the only one) of CTTH [68]. Nevertheless, there is no scientific evidence to claim a major role for peripheral or central sensitization in CTTH, as probably both sensitization mechanisms would be interconnected at the same time.

A muscle TrP role in CTTH does not negate the relevance of other perpetuating or promoting factors such

as forward head posture [69], muscle atrophy [70], altered muscle pattern recruitment [71] or psychological factor [72] in exacerbating these sensitization processes. For instance, avoidance behaviour and pain-related fear found in CTTH [73] may induce muscle disuse and, hence, muscle atrophy of the deep cervical extensor muscles [70], increasing muscle coactivation of the superficial cervical muscles [71]. This may overload the superficial musculature, particularly the upper trapezius [60] and sternocleidomastoid muscles [62], subsequently activating muscle TrPs [53], which could sensitize peripheral nociceptors [54], potentially contri-buting and driving to central sensitization [67]. In such a way, peripheral mechanisms may be a perpetuating factor of central sensitization processes.

What is new in therapeutic strategies?

Different possibly therapeutic strategies, pharmacologi-cal, physical therapy, psychological and acupuncture, are used for the management of CTTH. It seems that tricyclic antidepressants are the first-line therapeutic agents for CTTH, although few controlled studies have been performed. Further, although most patients with CTTH seek physical therapy management, there is insufficient evidence to support/refute the efficacy of physical therapy in CTTH.

Acute pharmacotherapy

Many controlled studies of simple analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) have been performed in TTH, using the headache attack as a model for acute pain. In most trials, simple analgesics were found inferior to the antirheumatic NSAIDs. At present, ibuprofen (800 mg) can probably be considered the first choice for acute TTH, followed by naproxen sodium (825 mg) because of the all-over better gastrointestinal tolerability [4]. The therapeutic efficacy of NSAIDs in TTH remains nevertheless incomplete, as shown by the Figure 2 Referred pain elicited from trigger points in the upper trapezius, superior oblique and suboccipital muscles simulating the pain pattern of chronic tension-type headache


relatively low proportion of patients becoming pain-free 2 h after dosing in most trials.

Although not recommended as first-line treatment, the combination of analgesics with caffeine, sedatives or tranquillisers may be more effective than simple analgesics or NSAIDs in some patients. It has been proven nonetheless in controlled trials that the adjunc-tion of caffeine (130 or 200 mg) significantly increases the efficacy of simple analgesics and of ibuprofen [74]. Unfortunately, few novel drugs have been studied. The most recent one is probably lumiracoxib, a cyclooxygenase 2 (COX-2) inhibitor, which was found effective for TTH at the 200 and 400 mg doses in a blind, double-dummy, placebo-controlled trial [75]. Until comparative trials are available, the possible advantage of the COX-2 inhibitors over the nonspecific NSAIDs remains ques-tionable.

Prophylactic pharmacotherapy

The tricyclic antidepressants are the most used first-line therapeutic agents for CTTH. Surprisingly, few con-trolled studies have been performed and not all of them have found an efficacy superior to placebo [4]. In a meta-analysis of all preventive drug trials on TTH, only marginal efficacy emerged for some of them, including tricyclic antidepressants [76]. One major problem that arises with those trials showing statistical differences between placebo and tricyclics is to evaluate whether the observed effect is clinically relevant. Nonetheless, in clinical practice, the tricyclic antidepressants remain the most useful prophylactic drugs for CTTH. Amitripty-line is the most frequently used, clomipramine may be slightly superior, but has more side effects. Nortriptyline has fewer side effects. Other antidepressants, for exam-ple doxepin, maprotiline or mianserin, can be used as a second choice [4].

Among the antidepressants inhibiting reuptake of serotonin and noradrenaline, several have been recently tested in TTH prevention. Mirtazapine was found effec-tive in CTTH at 15 – 30 mg per day [77]. Unfortunately, at this dosage mirtazapine often induces fatigue and weight gain, and a low dose of 4.5 mg/day was not effective [78]. Venlafaxine XR 150 mg/day has been studied in frequent episodic TTH but not in CTTH [79]. Further, it has been shown in an open-label trial that duloxetine at 60 mg/day significantly improved headache as well as depression in patients with major depression and chronic (migraine or tension-type) head-ache [80].

Overall, myorelaxants and antispastics are of no use in TTH. Some efficacy was found for tizanidine (6–18 mg/day), however, and combination at a 4 mg/day

dose with amitriptyline (20 mg/day) provided faster head-ache relief in CTTH than amitriptyline alone in an open randomized study [81].

As mentioned above, in an open study, topiramate, the anticonvulsant known to be effective in migraine pro-phylaxis, was effective in CTTH at 100 mg/day [16]. Again, this result needs to be confirmed in a randomized controlled trial.

Finally, in recent years, botulinum toxin has been popu-larized for the treatment of chronic headache, especially in North America. Beneficial effects reported in some open-label studies have not been confirmed in double-blind, placebo-controlled trials [82]. Nevertheless, con-tradictory results from different placebo-controlled trials continue to be published. For instance, Straubeet al.[83] found no effect of botulinum toxin A in CTTH for increasing headache-free days, but a significant reduction in headache duration and improvement in patient assess-ment scores were reported. By contrast, in another study, botulinum toxin significantly improved headache days, intensity and disability [84].

Nonpharmacological treatments: psychological and behavioural techniques

A recent meta-analysis of 53 trials has demonstrated the usefulness of relaxation and electromyography (EMG) biofeedback therapies in the management of TTH [85]. Meta-analytic integration resulted in a significant medium-to-large effect size [effect size¼ 0.73; 95% confidence interval (CI)¼0.61, 0.84] that proved stable over an average follow-up phase of 15 months. The strongest improvements resulted for frequency of headache episodes.

It has been shown some time ago that the combination of stress management therapy and a tricyclic antidepressant is more effective in CTTH than either behavioural or drug treatment alone [86]. At the present time, however, there is no study available that confirms this assertion.

Nonpharmacological treatments: physical treatments

Among nonpharmacological interventions proposed for the treatment of CTTH, physical/manual therapies are the most commonly used strategies [87]. Systematic reviews analysing the effects of physical/manual thera-pies on CTTH have concluded that there is insufficient evidence to support or refute the efficacy of physical therapy [88] or spinal manipulation [89,90] in CTTH patients. Nevertheless, spinal manipulation was found to be effective for the management of migraine [91] and cervicogenic headache [92], but not TTH [93]. Recent studies [94–96] have reported that physical therapy can be effective in reducing headache frequency, intensity and duration in CTTH patients.


Nevertheless, clinicians know that not all patients will benefit to the same degree from a specific intervention. Therefore, results from previous studies may be attrib-uted to the fact that previous studies did not identify subgroups of patients who are most likely to benefit from the analysed intervention [97]. Perhaps, identify-ing the clinical features of CTTH patients who are likely to benefit from a specific treatment (clinical prediction rules) prior to the carrying out of a random-ized clinical trial might lead to a strong effect size. We have elaborated a preliminary clinical prediction rule to identify patients with CTTH who experience a short-term success with a muscle TrP therapy approach [98]. A clinical prediction rule with four variables for immediate short-term (headache duration <8.5 h/day, headache frequency <5.5 days/week, bodily pain

<47, vitality <47.5) and two variables for 1-month (headache frequency <5.5 days/week and bodily pain

<47) follow-up was identified [98]. If all variables (positive likelihood ratio¼5.9) were present, the chance of experiencing immediate successful treatment im-proved from 54 to 87.4%. At 1-month follow-up, if both variables (positive likelihood ratio 4.6) were present, the probability of success increased from 54 to 84.4% [98]. Future studies incorporating subgroups of CTTH patients identified in clinical prediction rules are now needed.

Nonpharmacological treatments: acupuncture

Many available trials of acupuncture in TTH suffer from small sample sizes and controversial results. The con-troversy and methodological pitfalls are illustrated by the opposite conclusions in two recent meta-analyses. In one study [99], the majority of included trials comparing true acupuncture and sham acupuncture showed a trend in favour of acupuncture. The combined response rate in the acupuncture group was significantly higher compared with sham acupuncture either at the early follow-up period (risk ratio: 1.19, 95% CI: 1.08, 1.30) or late fol-low-up period (risk ratio: 1.22, 95% CI: 1.04, 1.43). Combined data also showed acupuncture was superior to medication therapy for headache intensity, headache frequency, physical function and response rate. By con-trast, a recent meta-analysis concluded that acupuncture compared with sham for TTH has limited efficacy for the reduction of headache frequency [100]. Further, there exists a lack of standardization of acupuncture points and treatment course among randomized, controlled trials and more research is further needed to investigate the treatment of specific TTH subtypes [100]. The major difference between the two meta-analyses is that the last one considered that only five published studies reached a sufficient methodological standard to be selected for the analysis [100], whereas the first one included 31 studies of which many have methodological shortcomings [99].


Diagnostic criteria of TTH should be adapted to improve its sensitivity against migraine. It seems that mechanical pain sensitivity is a consequence not a causative factor of CTTH. Recent evidence is modifying previous knowl-edge about relationships between muscle tissues and CTTH, suggesting a potential role of muscle TrPs and their referred pain in the genesis of head pain. Different therapeutic strategies such as pharmacological, physical and psychological therapies and acupuncture are gener-ally used. Future studies incorporating subgroups of patients who are likely to benefit from a specific treat-ment (clinical prediction rules) should be conducted.

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

of special interest

of outstanding interest

Additional references related to this topic can also be found in the Current World Literature section in this issue (pp. 325–326).

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Figure 1 A common pathophysiological hypothesis for chronic tension-type headache, fibromyalgia syndrome and regional myofascial pain

Figure 1

A common pathophysiological hypothesis for chronic tension-type headache, fibromyalgia syndrome and regional myofascial pain p.2
Figure 2 Referred pain elicited from trigger points in the upper trapezius, superior oblique and suboccipital muscles simulating the pain pattern of chronic tension-type headache

Figure 2

Referred pain elicited from trigger points in the upper trapezius, superior oblique and suboccipital muscles simulating the pain pattern of chronic tension-type headache p.4