Abstract
Objective
To investigate the association between trigger points (TrPs) and widespread pressure pain sensitivity in people with tension-type headache (TTH) and to determine if this association is different between frequent episodic (FETTH) or chronic (CTTH) headache.
Design
A cross-sectional study.
Methods
One hundred and fifty-seven individuals (29% male) with TTH participated. Clinical features of headache, i.e., intensity, duration, and frequency, were recorded in a headache diary. Active and latent TrPs were bilaterally explored in the temporalis, masseter, suboccipital, upper trapezius, sternocleidomastoid, and splenius capitis muscles. Pressure pain thresholds (PPT) were assessed over the trigeminal area (i.e., temporalis muscle), extra-trigeminal (i.e., C5/C6 zygapophyseal joint), and two distant pain-free points (i.e., second metacarpal and tibialis anterior muscle).
Results
Eighty (51%) patients were classified as FETTH, whereas 77 (49%) were classified as CTTH. No differences in the number of either active or latent TrPs (all p > 0.171) or widespread pressure pain sensitivity (all p > 0.351) were observed between FETTH and CTTH groups. The number of active and latent TrPs was significantly and negatively associated with PPTs: The higher the number of active or latent TrPs, the lower the widespread PPT, and the more generalized sensitization. This association was stronger within the FETTH group than the CTTH group.
Conclusions
This study found that the number of TrPs in head and neck/shoulder muscles was associated with widespread pressure hypersensitivity independently of the frequency of headache.
Introduction
Tension-type headache (TTH) is a common headache disorder, presenting an important burden for society (1). The global prevalence of TTH in an adult population is around 42% (2). The general costs in Europe in 2010 were €13.8 billion for headaches, including migraine and TTH (3).
Current research into the pathogenesis of TTH focuses on the role of muscle (4) and facilitation of nociceptive pain processing (5). In fact, it is argued that TTH has contributing muscle components (6), and that sensitization processes may play an important role in the transition from acute to chronic TTH (7). There is a consensus suggesting that subjects with TTH exhibit pressure pain hypersensitivity, i.e., lower pressure pain thresholds compared to healthy people, particularly in the trigeminal area (8). Further, data suggest that subjects with TTH exhibit widespread pressure hypersensitivity as a clinical sign of widespread sensitization (9,10).
There is evidence supporting the role of trigger points (TrPs) as contributors to TTH (11,12). A TrP is defined as “a hypersensitive spot in taut bands of skeletal muscle which elicit referred pain, autonomic, or motor symptoms when stimulated” (13). If any of the symptoms induced by stimulation of a TrP reproduces any of the patient’s symptoms, and the patient recognizes this symptom as a familiar/usual experience, the TrP is considered clinically active (13). Several studies reported that the referred pain elicited by TrPs in head, neck and shoulder muscles reproduces the headache pattern in TTH (14–17). In fact, it has been proposed that active TrPs can promote TTH pain by transmitting nociceptive inputs to the trigemino-cervical nucleus caudalis, thereby contributing to the generation of widespread sensitization observed in this headache disorder (18). Nevertheless, no study has previously investigated the relationship between the presence of TrPs and widespread pressure pain hypersensitivity in people with different severities of TTH.
Therefore, the objectives of the current study were to investigate the association between the number of TrPs and widespread pressure pain sensitivity in people with TTH, and to determine if this association is different between frequent episodic (FETTH) or chronic (TTH) headache. We hypothesized that active TrPs would be associated with widespread pressure pain sensitivity in TTH independently of the frequency of the headache.
Methods
Participants
Subjects with TTH were recruited from different university-based hospitals between January 2015 and April 2016. All diagnoses were performed according to the criteria of the International Classification of Headache Disorders, third edition (ICHD3 beta, 2013) down to third-digit level (codes 2.2, 2.3) by neurologists who were experts in the headache field (19). They performed a face-to-face interview followed by a general and neurological examination. To be included, patients had to describe all the pain features of TTH: Bilateral location, pressing and tightening pain, moderate intensity (≤6 on a 10-point numerical pain rate scale, NPRS) and no aggravation of pain during physical activity. Patients should report no more than one of photophobia, phonophobia or mild nausea, with no moderate or severe nausea or vomiting, as requested by the ICHD-III diagnostic criteria (19).
Key elements of the clinical history, including family headache history, headache features, temporal pattern, and intake medication were assessed. A headache diary kept for four weeks was used to substantiate the diagnosis and to record the headache’s clinical features (20,21). In this diary, subjects registered the number of days per week with headache, the duration of each headache attack (hours/day), and the headache intensity on an 11-point numerical pain rate scale (22) (NPRS, 0: no pain, 10: maximum pain).
Participants were excluded if they presented: 1, another primary/secondary headache; 2, medication overuse headache as defined by the ICHD-III; 3, history of cervical or head trauma (i.e., whiplash); 4, pregnancy; 5, a history of cervical herniated disk or cervical osteoarthritis on medical records; 6, systemic degenerative disease, e.g., rheumatoid arthritis, lupus erythematous; 7, comorbid diagnosis of fibromyalgia syndrome; 8, receiving anesthetic block within the previous six months; 9, receiving previous physical treatment in the neck/head the previous six months; or 10, regular consumption of caffeine (>300 mg/day), or other stimulating substances. A careful examination of each patient was conducted to determine inclusion and exclusion criteria. All subjects read and signed a consent form prior to participation. The study was approved by local Ethics Committees (URJC 23/2014, N20140063, CESU 5/2015).
All evaluations were conducted when all patients were headache-free or, in those with high frequency of headache, when the intensity of headache was ≤ 3 points. Participants were asked to avoid any analgesic or muscle relaxant 24 hours prior to the examination. No change was made to their prophylactic treatment.
Trigger point (TrP) examination
TrPs were explored bilaterally in the temporalis, masseter, suboccipital, upper trapezius, sternocleidomastoid, and splenius capitis musculature by a clinician with more than 10 years of experience in TrP diagnosis and blinded to FETTH or CTTH diagnosis. The order of examination was randomized between individuals, with a one minute rest period between muscles. TrPs diagnosis was performed as follows (13): 1, presence of a palpable taut band in the muscle; 2, presence of a painful tender spot in the taut band; 3, local twitch response on palpation of the taut muscle band; and 4, reproduction of referred pain. For the suboccipital muscles, TrP diagnosis was conducted when pressure applied on the suboccipital region for 10 seconds elicited referred pain, and contraction of the muscles in head extension increased the referred pain as previously described (14). In this study, active and latent TrPs were considered. A TrP was considered active when the referred pain elicited during examination reproduced at least part of the TTH pattern that the subject suffered from, and the pain was therefore recognized as a usual or familiar pain. A TrP was considered latent when the pain elicited during examination did not reproduce TTH features, and the elicited pain was therefore not recognized as a usual or familiar pain symptom (13).
Pressure pain sensitivity
The pressure pain threshold (PPT), i.e., the amount of pressure where a sensation of pressure first changes to pain, was bilaterally assessed with an electronic algometer (Somedic AB®, Farsta, Sweden) on the temporalis muscle (trigeminal point), C5/C6 zygapophyseal joint (extra-trigeminal point), second metacarpal, and tibialis anterior muscle (two pain-free distant points) by an assessor blinded to FETTH or CTTH diagnosis. The order of assessment was randomized between subjects. Subjects were instructed to press the “stop button” of the algometer as soon as the pressure resulted in the first sensation of pain. Pressure was increased at a rate of approximately 30 kPa/s. Participants were trained with a first trial on the wrist extensor muscles of the right forearm. The mean of three trials on each point was calculated and used for the analysis. A 30 second resting period was allowed between trials to avoid temporal summation (23). Pressure algometry has been found to be highly reliable (24,25).
Sample size calculation
The sample size was calculated using Ene 3.0® software (Autonomic University of Barcelona, Spain) and was based on detecting significant moderate correlations (r = 0.4) between the number of TrPs and PPTs with an alpha level (α) of 0.05, and a desired power (β) of 95%. This generated a sample size of 71 subjects in each group (FETTH or CTTH).
Statistical analysis
Data were analyzed with the SPSS statistical package (22.0 Version). Descriptive data were collected on all patients. The Kolmogorov-Smirnov test revealed that quantitative data exhibited a normal distribution (p > 0.05). Since no side-to-side differences in PPTs were found, the mean of both sides on each point was used in the analysis. Differences in clinical features (i.e., frequency, intensity or duration), the number of TrPs (active or latent), and PPTs between patients with FETTH or CTTH were assessed using the unpaired Student t-test. Several Pearson correlation tests (r) were used to determine the association between the number of TrPs, clinical variables relating to headache pain (frequency, intensity, duration) and PPT. Correlations were separately calculated for latent or active TrPs within the total sample, and FETTH or CTTH group. Correlations were considered weak when r < 0.3; moderate when 0.3 < r < 0.7, and strong when r > 0.7 (26). The statistical analysis was conducted at a 95% confidence level, and a p value less than 0.05 was considered statistically significant.
Results
Clinical data of the sample
Of 200 eligible subjects with headache who participated, 43 were excluded for the following reasons: Co-morbid migraine (n = 32), reporting previous neck trauma (n = 6), and fibromyalgia diagnosis (n = 5). A total of 157 subjects (29% male) with TTH were finally included. Eighty (51%) were classified as FETTH, whereas 77 (49%) were classified as CTTH accordingly to the ICHD-III beta 2013. Sixty-two (40%) were taking prophylactic drugs (i.e., amitriptyline) on a regular basis. Individuals with CTTH exhibited a significantly higher frequency and longer duration, but similar intensity, of headache attacks than those with FETTH (both p < 0.01). All individuals with FETTH were examined in a pain-free situation, whereas 40 (52%) patients with CTTH were examined when their headache attack was less than three points in intensity.
Clinical, demographic and neuro-physiological outcomes of patients with tension-type headache.
NPRS: Numerical Pain Rate Scale (0–10); FETTH: frequent episodic tension-type headache; CTTH: chronic tension-type headache
# Significant differences between patients with FETTH and CTTH (p < 0.05)
Trigger points and clinical features in tension-type headache
No associations were observed between the number of either active or latent TrPs and clinical pain features of TTH, such as the intensity, frequency or duration of the headache, in either the FETTH or CTTH group (all p > 0.508). Similarly, no association between the clinical pain features of TTH, such as intensity, frequency or the duration of the headache, and PPTs, was observed (all p > 0.276).
Trigger points and widespread pressure pain sensitivity in tension-type headache
The number of active TrPs was significantly and negatively associated with PPT in all the points assessed, considering the total sample (C5–C6 joint: r = −0.362, p < 0.001; temporalis muscle: r = −0.437, p < 0.001; second metacarpal: r = −0.318, p < 0.001; tibialis anterior muscle: r = −0.336, p < 0.001, Figure 1): The higher the number of active TrPs, the lower the widespread PPTs, that is, the greater the central sensitization. The number of latent TrPs also exhibited significant, but small, and negative associations with all PPTs (C5–C6 joint: r = −0.188, p = 0.019; temporalis muscle: r = −0.263, p = 0.001; second metacarpal: r = −0.299, p = 0.001; tibialis anterior: r = −0.188, p = 0.02, Figure 2): Again, the higher the number of latent TrPs, the higher the widespread pressure pain sensitivity.
Scatter plots of correlations between the number of active trigger points (TrPs) with pressure pain thresholds (PPT) over C5–C6 zygapophyseal joint (a), temporalis muscle (b), second metacarpal (c) and tibialis anterior muscle (d) in the total sample (n = 157). Note that several points are overlapping. A negative linear regression line is fitted to the data. Scatter plots of correlations between the number of latent trigger points (TrPs) with pressure pain thresholds (PPT) over C5–C6 zygapophyseal joint (a), temporalis muscle (b), second metacarpal (c) and tibialis anterior muscle (d) in the total sample (n = 157). Note that several points are overlapping. A negative linear regression line is fitted to the data.
Trigger points and widespread pressure pain sensitivity by frequency of headache
Within the CTTH group, the number of active (C5–C6 joint: r = −0.308, p = 0.007; temporalis muscle: r = −0.361, p = 0.001; second metacarpal: r = −0.253, p = 0.029; tibialis anterior muscle: r = −0.222, p = 0.025, Figure 3) but not the number of latent (C5–C6 joint: r = −0.191, p = 0.145; temporalis muscle: r = −0.139, p = 0.231; second metacarpal: r = −0.129, p = 0.241; tibialis anterior muscle: r = −0.156, p = 0.179, Figure 4) TrPs were associated with PPTs (the higher the number of active TrPs, the lower the PPT). On the contrary, within the FETTH group, all negative correlations were found between PPT values and the number of both active (C5–C6 joint: r = −0.425, p < 0.001; temporalis muscle: r = −0.527, p < 0.001; second metacarpal: r = −0.379, p = 0.001; tibialis anterior muscle: r = −0.455, p < 0.001, Figure 5) and latent (C5–C6 joint: r = −0.201, p = 0.045; temporalis muscle: r = −0.329, p = 0.003; second metacarpal: r = −0.348, p = 0.009; tibialis anterior muscle: r = −0.265, p = 0.018, Figure 6) TrPs, which were similar to those in the total sample.
Scatter plots of correlations between the number of active trigger points (TrPs) with pressure pain thresholds (PPT) over C5–C6 zygapophyseal joint (a), temporalis muscle (b), second metacarpal (c) and tibialis anterior muscle (d) in chronic tension-type headache (CTTH, n = 77). Note that several points are overlapping. A negative linear regression line is fitted to the data. Scatter plots of correlations between the number of latent trigger points (TrPs) with pressure pain thresholds (PPT) over C5–C6 zygapophyseal joint (a), temporalis muscle (b), second metacarpal (c) and tibialis anterior muscle (d) in chronic tension-type headache (CTTH, n = 77). Note that several points are overlapping. Scatter plots of correlations between the number of active trigger points (TrPs) with pressure pain thresholds (PPT) over C5–C6 zygapophyseal joint (a), temporalis muscle (b), second metacarpal (c) and tibialis anterior muscle (d) in frequent episodic tension-type headache (FETTH, n = 80). Note that several points are overlapping. A negative linear regression line is fitted to the data. Scatter plots of correlations between the number of latent trigger points (TrPs) with pressure pain thresholds (PPT) over C5–C6 zygapophyseal joint (a), temporalis muscle (b), second metacarpal (c) and tibialis anterior muscle (d) in frequent episodic tension-type headache (FETTH, n = 80). Note that several points are overlapping. A negative linear regression line is fitted to the data.
Discussion
The current study found that a greater number of TrPs in head and neck/shoulder muscles was associated with widespread pressure hypersensitivity in people with TTH. No differences in the presence of TrPs and widespread pressure sensitivity were observed between individuals with FETTH and CTTH.
There is supporting evidence that muscular factors may contribute, not only to the acute headache episode, but also to chronification of TTH (27). Previous studies have reported that active TrPs reproduce TTH pain features in patients with TTH (14–17). Additionally, the presence of pressure pain hypersensitivity has also been previously documented in TTH (8). The present study is the first one to investigate the relationship between the presence of TrPs and widespread pressure pain hypersensitivity. It has been postulated that sustained local contraction observed in the TrP can promote hypoxia and ischemia, elevating the concentrations of algogenic substances and chemical mediators, e.g., calcitonin gene-related peptide, substance P, bradykinin, serotonin, or histamine, among others, and consequently leading to peripheral nociceptive activation (28). This concept is mainly suggested for active TrPs, since they are associated with higher levels of these chemical mediators compared to latent TrPs (29). In such a scenario, peripheral nociception originating in active TrPs in the cranio-cervical muscles may contribute as a potential nociceptive driver into the trigemino-cervical nucleus caudalis by facilitating and contributing to the sensitization process (18). The association between TrPs and widespread pressure pain hyperalgesia was slightly higher in subjects with FETTH than those with CTTH, suggesting that peripheral mechanisms associated with TrPs may be more important during the development of FETTH compared to CTTH, where the more repeated attacks may maintain and perpetuate central sensitization.
The present study also observed that latent TrPs were also associated with pressure pain sensitivity, particularly within the FETTH subgroup. There has been an increasing research focus on latent TrPs in recent years (30). Preliminary evidence suggests that latent TrPs sensitize nociceptive and non-nociceptive nerve endings (31), and may also activate large-diameter myelinated muscle afferents (32). In addition, experimental stimulation of latent TrPs has been able to further facilitate sensitization (33), spatial pain propagation and widespread symptoms (34) in asymptomatic people. The fact that latent TrPs were not associated with widespread pressure pain sensitivity in subjects with CTTH could suggest that once the sensitization is established, the role of peripheral nociception drive may be less important to the consequent headache attacks . This could be relevant for clinicians, since early treatment of latent TrPs in individuals with FETTH may prevent or postpone the development of widespread pressure pain sensitivity in this subgroup of patients, and hence lower the pain amplification. Longitudinal clinical trials should explore this hypothesis.
Although the strengths of this study include a large sample size, the inclusion of both FETTH and CTTH groups and the use of the most up-to-date diagnostic criteria, we should recognize some potential limitations. First, individuals were recruited from tertiary care hospitals, therefore it is possible that they represent a specific subgroup of the general population with TTH. In fact, it has been recently suggested that TrPs may be relevant only for a subgroup of individuals with TTH (4). In fact, we do not know if these associations are specific to TTH, or whether it could also be observed in other headaches or pain syndromes. Secondly, we did not include a control group without headache, since asymptomatic subjects do not exhibit active TrPs. We believe that the inclusion of a control group without headache would not alter the direction of our findings. Third, the assessment and diagnosis of TrPs is still controversial due to the lack of golden clinical standards. The cross-sectional nature of the study does not permit the establishment of a cause and effect relationship between active TrPs and widespread pressure sensitivity. In fact, a bidirectional association between sensitization processes and TrPs is being debated (28). In addition, the role of other variables, for example anxiety, depression, and sleep disturbances, which may potentially influence the association between TrPs and widespread pressure sensitivity, should be explored in future studies.
Conclusions
This study found that the number of active TrPs in the head and neck/shoulder musculature was associated with widespread pressure pain sensitivity in subjects with TTH, regardless of whether the condition was chronic or episodic. Active TrPs were associated with widespread pressure sensitivity in both FETTH and CTTH, whereas latent TrPs were only associated with widespread pressure sensitivity within the FETTH group. Patients with FETTH and CTTH exhibited a similar number of TrPs and widespread pressure pain sensitivity.
Key findings
The number of TrPs and widespread pressure pain hyperalgesia were similar in individuals with frequent episodic or chronic tension-type headache. This study found that the higher the number of TrPs, the higher the widespread pressure sensitivity in individuals with tension-type headache. The association between TrPs and widespread pressure sensitivity was slightly higher in subjects with frequent episodic than in those with chronic tension-type headache.
Footnotes
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.