Prevalence, Incidence, Localization, and Pathophysiology of Myofascial Trigger Points in Patients With Spinal Pain: A Systematic Literature Review

PREVALENCE, INCIDENCE, LOCALIZATION, AND PATHOPHYSIOLOGY OF MYOFASCIAL TRIGGER POINTS IN PATIENTS WITH SPINAL PAIN: A SYSTEMATIC LITERATURE REVIEW Enrique Lluch, PT, a Jo Nijs, PhD, b c Margot De Kooning, PhD, b d Dries Van Dyck, PT, e

Rob Vanderstraeten, PT, e Filip Struyf, PhD, f g h and Nathalie Anne Roussel, PhD f i j ABSTRACT

Objective: A systematic review was performed to evaluate the existing evidence related to the prevalence, incidence, localization, and pathophysiology of myofascial trigger points (MTrPs) in patients with spinal (back and neck) pain. Methods: A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed in 2 electronic databases (PubMed and Web of Science) using predefined keywords regarding MTrPs and spinal pain. A “PICOS” questionnaire was used to set up the search strategies and inclusion criteria. Full-text reports concerning MTrPs in patients with back or neck pain, which described their prevalence, incidence, location, or underlying physiopathology were included and screened for methodological quality by 3 independent researchers. Each study was assessed for risk of bias using a checklist derived from the Web site of the Dutch Cochrane Centre. Results: Fourteen articles were retrieved for quality assessment and data extraction. Studies reporting the incidence of MTrPs in patients with spinal pain were lacking. Within spinal pain, patients with neck pain were found to have the highest prevalence rates of MTrPs. The trapezius descendens, levator scapulae, and suboccipitales muscles were the most prevalent locations for active MTrPs in patients with neck pain. Latent MTrPs were present in asymptomatic people, but no significant differences were found in the prevalence rate of latent MTrPs between patients with spinal (neck) pain and healthy controls. The only study investigating prevalence of MTrPs in different localizations of the same muscle reported no significant differences in prevalence between active and latent MTrPs within the trapezius descendens muscle. Studies examining pathophysiological mechanisms underlying MTrPs demonstrated an acidic environment, high concentration of algogenic/inflammatory substances, stiffer muscle tissue, retrograde diastolic blood flows, spontaneous muscle activity at rest, and loss of muscle contractibility in muscles with MTrPs. Altered central processing was also found to play a role in the development of MTrPs. Conclusions: Myofascial trigger points are a prevalent clinical entity, especially in patients with neck pain. Evidence was not found to support or deny the role of MTrPs in other spinal pain. Compelling evidence supports local mechanisms underlying MTrPs. Future research should unravel the relevance of central mechanisms and investigate the incidence of MTrPs in patients with spinal pain. (J Manipulative Physiol Ther 2015;xx:1-14) Key Indexing Terms: Trigger Points; Myofascial Pain Syndromes; Systematic Review; Neck Pain; Low Back Pain

a Professor, Department of Physical Therapy, University of Valencia, Valencia, Spain. b Professor, Pain in Motion Research Group, Departments of Human Physiology and Physiotherapy, Faculty of Physical Education & Rehabilitation, Vrije Universiteit Brussel, Belgium. c Physiotherapist, Department of Physical Medicine and Physiotherapy, University Hospital, Brussels, Belgium. d Physiotherapist, Department of Physical Medicine and Physiotherapy, University Hospital, Brussels, Belgium. e Physiotherapist, Department of Physiotherapy and Rehabilitation Sciences (REVAKI), Faculty of Medicine and Health Sciences, University of Antwerp, Belgium. f Professor, Department of Health Sciences, Artesis University College Antwerp, Antwerp, Belgium. g Professor, Pain in Motion Research Group, Departments of Human Physiology and Physiotherapy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Belgium.

h Professor, Division of Musculoskeletal Physiotherapy, Department of Health Sciences, Artesis University College Antwerp, Antwerp, Belgium. i Professor, Pain in Motion Research Group, Departments of Human Physiology and Physiotherapy, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Belgium. j Professor, Division of Musculoskeletal Physiotherapy, Department of Health Sciences, Artesis University College Antwerp, Antwerp, Belgium. Submit requests for reprints to: Enrique Lluch, PT, Department of Physical Therapy, University of Valencia, Gascó Oliag 5, 46010 Valencia, Spain. (e-mail: [email protected]). Paper submitted May 12, 2015; in revised form June 15, 2015; accepted June 15, 2015. 0161-4754 Copyright © 2015 by National University of Health Sciences. http://dx.doi.org/10.1016/j.jmpt.2015.08.004

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yofascial trigger points (MTrPs) are a common source of (regional) pain in patients presenting with musculoskeletal pain, 1,2 with a lifetime prevalence of up to 85% in the general population. 3 An MTrP is a taut band of skeletal muscle, which is painful on compression that, when stimulated (ie, by compression, percussion, or needling), can evoke a characteristic pattern of referred pain and related autonomic responses. 4 Clinically, MTrPs are either being classified as active or latent. Active and latent MTrPs have similar physical findings, except that latent MTrPs do not elicit spontaneous symptoms and the local and referred pain reproduced by stimulating them is not recognizable as familiar to the patient. 4 The prevalence of MTrPs has been studied in healthy people 5 and different painful conditions such as patellofemoral pain, 6 cervical radiculopathy, 7 shoulder impingement syndrome, 8 chronic tension-type headache, 9 complex regional pain syndrome 10 or lateral epicondylalgia. 11 All the aforementioned studies show a high prevalence of MTrPs. However, the prevalence of MTrPs in patients with spinal pain is unknown. Some studies have investigated the incidence of MTrPs in different pain populations. For example, Torres Lacomba et al 12 assessed the incidence of MTrPs prospectively over a 12-month period after breast cancer surgery. Interestingly, almost half of the women who underwent breast cancer surgery developed MTrPs. Another incidence study showed a significant correlation between carpal tunnel syndrome and MTrPs of the M. trapezius descendens. 13 The cause of MTrPs is still a matter of speculation, and several hypothetical models have tried to explain the formation of MTrPs. The integrated hypothesis provides the most prominent and accepted explanation for MTrPs. 14 However, other alternative models have been also developed such as the central modulation hypothesis, 15 the neurogenic hypothesis, 16,17 the neurophysiological hypothesis, 18 or the radiculopathy hypothesis. 19 Results from several evaluation techniques looking at MTrP physiopathology such as microdialysis, 20,21 magnetic resonance elastography imaging, 22,23 or vibration sonoelastography 24,25 seem to support at least part of those theories. All the aforementioned studies provide independent data about possible underlying mechanisms of MTrPs. However, to date, no study has systematically reviewed the scientific literature to ascertain the physiopathological mechanisms potentially involved in MTrP formation in patients with spinal pain. The primary aim of this study was to systematically review the current knowledge regarding the prevalence, incidence, and localization of MTrPs in patients with spinal pain (study objective A). As a secondary aim, pathophysiological mechanisms underlying MTrP formation in patients with spinal pain were thoroughly investigated (study objective B).

M

Journal of Manipulative and Physiological Therapeutics Month 2015

METHODS Search Strategy This systematic review was written in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. 26 To identify relevant articles concerning the study objectives, a systematic search was performed in 2 electronic databases (PubMed and Web of Science [WoS]) between the 25th of October and the 5th of November 2013. The search strategies and inclusion criteria were based on keywords derived after making a “PICOS” questionnaire. Specifically, “P” (patients) made reference to subjects with spinal (back or neck) pain; “I” (intervention), assessment of MTrPs; “C” (comparison), healthy subjects; “O” (outcome study objective A), prevalence, incidence, and localization of MTrPs or “O” (outcome study objective B), etiological, (patho)physiological, biochemical, nociceptive, inflammatory, electrical, or homeostatic mechanisms of MTrPs; and “S” (study design), randomized controlled trials, case-control, cohort, cross-sectional studies. Two search strategies were built, 1 for each study objective (A and B). Two groups of keywords were combined, and for each study objective, a third group of keywords was added as detailed in Table 1. Two filters were activated (ie, human and English) in PubMed for both search strategies. Relevant hand-searched articles were also included to obtain as complete information as possible. No authors were contacted to obtain additional studies.

Study Selection Articles were eligible for this systematic review if they fulfilled the following inclusion criteria: (I) the authors studied MTrPs in patients with spinal (back or neck) pain without a central neurological cause; (II) studies were published in English; (III) articles were full-text reports of original studies; and (IV for the study objective A) studies had to describe the prevalence, incidence, or the localization of MTrPs or (IV for the study objective B) studies had to investigate the underlying etiological, (patho)physiological, biochemical, nociceptive, inflammatory, electrical, or homeostatic mechanisms of MTrPs. If any of these inclusion criteria were not fulfilled, the article was excluded from the literature search.

Study Process After performing the literature search, duplicate articles were removed. Eligibility assessment was performed based on title and abstract. The full-text article was searched and analyzed when the article seemed to fulfill the inclusion criteria. When there was uncertainty regarding the content of the article based on title and abstract, the full text was read and evaluated against the inclusion criteria. Screening was performed by 2 researchers independently (DVD and RV). The researchers were holders of a bachelor of science

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Table 1. Search Strategy Keywords AND

Lluch et al Myofascial Trigger Points in Spinal Pain

Table 2. Methodological Scoring Case-Control Studies Included for Study Objective A

(“back pain” OR “spinal pain” OR “neck pain”) (“myofascial pain syndromes” OR “Myofascial Pain Syndrome” OR “Pain Syndrome, Myofascial” OR “Pain Syndromes, Myofascial” OR “Syndrome, Myofascial Pain” OR “Syndromes, Myofascial Pain” OR “Myofascial Trigger Point Pain” OR “Trigger Point Pain, Myofascial” OR “myofascial trigger point” OR “myofascial trigger points” OR “trigger point” OR “trigger points” OR “soft tissue pain” OR “repetitive nerve stimulation” OR “pressure pain threshold” OR “dry needling” OR “local twitch response” OR “twitch response” OR “pressure pain”) (localization OR prevalence OR incidence)

AND (study objective A) (“etiology” OR “biochemical phenomena” OR AND (study objective B) “Adaptation, Physiological” OR “Electrophysiological Processes” OR “homeostasis” OR “Physiology” OR pathophysiolog* OR physiopatholog* OR “blood flow” OR “biochemical substances” OR “biochemical substance” OR nociceptor OR nociceptors OR “inflammatory mediator” OR “inflammatory mediators” OR “endplate potential” OR “endplate potentials” OR “electrical activity” OR “electrical activities” OR hypercontraction OR vitamins)

degree in rehabilitation sciences and physiotherapy. A consensus meeting was organized to discuss potential disagreements. When consensus could not be reached, a third opinion was provided by a trained experienced researcher (NAR). The full-text versions of all articles that met the inclusion criteria were retrieved for methodological quality assessment and data extraction.

Quality Assessment Three independent researchers (DVD, RV, and NAR) assessed the risk of bias of the included studies using a checklist derived from the Web site of the Dutch Cochrane Centre. Seven items from this checklist were assessed for a case-control study, related to (1) description of the patient group, (2) description of the control group, (3) selection bias, (4) exposure, (5) blinded measurement of the exposure, (6) confounders, and (7) results. Items 2 and 5 were not scored for the cross-sectional studies (Table 2). However, the quality assessment was only done by assessing risk of bias at study level, not at outcome level. Each item was scored “1” if the answer on that item was positive or “0” if negative. If a study did not provide sufficient information to score a particular item, a score “0” was given. The reviewers reached a definitive score during a consensus meeting, resulting in a final quality score.

Data Extraction To examine the prevalence, incidence, and localization of MTrPs in patients with spinal pain, 2 authors

Reference

1 2 3 4 5 6 7 Total

Barbero et al 201327 Fernandez-de-las-Peñas et al 200728 Fernandez-Perez et al 201229 Munoz-Munoz et al 201230 Sari et al 20127 Zapata et al 200631

1 1 1 1 1 0

1 1 1 1 1 1

0 0 0 0 0 0

1 1 1 1 1 0

0 1 1 1 0 1

0 1 1 1 1 1

0 1 1 1 1 0

3/7 6/7 6/7 6/7 5/7 3/7

Case-Control and Cross-Sectional Studies Included for Study Objective B Reference

1 2 3 4 5 6 7 Total

Audette et al 200432 Ballyns et al 201133 Ballyns et al 201234 Shah et al 200521 Shah et al 200820 Sikdar et al 201035 Turo et al 201336 Wytrazek et al 201137

1 0 1 0 0 1 1 1

1 0 0 1 0 0 0 0 0 0 1 0 1 0

1 1 1 1 1 1 1 1

0 0 0 1 0 0 0 0 0 0 1 1 1 0

1 1 1 1 1 1 1 1

4/7 2/5 5/7 2/7 2/7 3/5 6/7 5/7

Result of the assessment of risk of bias of the included studies using the checklist for case-control studies derived from the Web site of the Dutch Cochrane Centre. Seven items were assessed for a case-control study, related to (1) description of the patient group, (2) description of the control group, (3) selection bias, (4) exposure, (5) blinded measurement of the exposure, (6) confounders, and (7) results. Items 2 and 5 were not scored for the cross-sectional studies.33,35

extracted for each included study information about the following: study characteristics (no. of participants, age, sex, characteristics of the participants, criteria for identification of MTrPs, and outcome); specific localization of MTrPs; prevalence and incidence of MTrPs in specific muscles; and prevalence of MTrPs in different populations. To examine the pathophysiological mechanisms underlying MTrP formation in patients with spinal pain, 2 authors extracted for each included study information about the type of intervention, the outcome measures, and the results.

RESULTS Study Selection The selection process of the articles is presented in Figure 1A and B. The initial search resulted in 498 hits (112 for study objective A [63 in PubMed and 49 in WoS] and 386 for study objective B [313 in PubMed and 73 in WoS]). One additional reference was retrieved in the study objective A from the reference lists of the selected articles. In total, 466 studies were excluded based on title and abstract evaluation; and 19, after examining the full-text reports. A consensus could not be reached for 5 studies, so a third opinion was required. Fourteen articles were finally retrieved for quality assessment and data extraction.

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Study Characteristics Of the 14 selected studies for objectives A and B, most were categorized as case-control (n = 12) or cross-sectional studies (n = 2). Tables 3 and 4 show the study characteristics of the included articles for both study objectives. Eleven studies used Travell and Simons' criteria 4 for identification of MTrPs. One study used incomplete Travell and Simons' criteria for MTrP identification, 32 and 2 articles did not explain how they identified MTrPs in the methods section, 21,37 although they both included the reference of Travell and Simons in their introduction. The original Travell and Simons' diagnostic criteria reported to be essential for the diagnosis of MTrPs are tenderness within a taut band, a predictable pattern of referred pain with palpation of the taut band, and a painful limited range of movement. 4,38

Study Characteristics Prevalence, Incidence, and Localization (Study Objective A). Five studies investigated patients with neck pain, and 1 study examined adolescents with low back pain/upper limb pain. The exact characteristics of the studied populations are specified in Table 3. Five studies investigated both active and latent MTrPs. 7,27-30 One study examined the prevalence of myofascial pain syndrome based on the presence of active MTrPs. 31

Study Characteristics (Patho)Physiology (Study Objective B). The selected studies examined patients with neck pain, 20,21,32-36 or both low back and neck pain caused by spinal overloading. 37 All except 3 studies 34,36,37 investigated both active and latent MTrPs. Details of the included studies examining the (patho)physiology of MTrPs in patients with spinal pain can be found in Table 4.

A Potentially relevant citations identified:

Additional potentially relevant citations (hand searching):

112

Based on title and abstract evaluation, citations excluded: Reasons: Population Intervention Outcome Design Language Animal Double

1

Studies retrieved for more detailed evaluation:

24 15 15 25 0 0 13

21

Based on full text evaluation, studies excluded: Reasons: Population Intervention Outcome Design Language Animal Double

Relevant studies:

92

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Fig 1. A, Flow chart study objective A. B, Flow chart study objective B.

15 2 9 3 1 0 0 0

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B

Additional potentially relevant citations (hand searching):

Potentially relevant citations identified:

386

Based on title and abstract evaluation, citations excluded: Reasons: Population Intervention Outcome Design Language Animals Double

0

Studies retrieved for more detailed evaluation:

64 123 78 89 0 1 19

12

Based on full text evaluation, studies excluded: Reasons: Population Intervention Outcome Design Language Animals Double

Relevant studies:

374

4 1 3 0 0 0 0 0

8

Fig 1. (continued)

Risk of Bias of Individual Studies Each article was scored individually for risk of bias. The results of the risk of bias assessment are presented in Table 2. Five studies 20,21,27,31,33 scored less than 50%, whereas 4 studies 28 -30,36 scored more than 80%. The case-control studies by Shah et al 20,21 obtained the highest risk of bias score. They only gave proper information about the exposure and method for evaluating this exposure (question 4) and results (question 7). All studies lost points on questions regarding selection bias (question 3), and 8 studies scored 0 for the confounders (question 6).

Results of Individual Studies Prevalence, Incidence, and Localization of MTrPs in Patients With Spinal Pain. None of the included studies investigated the incidence rate of MTrPs in patients with spinal pain. The prevalence of active MTrPs in several muscles in patients with neck pain is presented in Figure 2 and Table 5. The 4

studies 7,28-30 examining active MTrPs in patients with neck pain reported a wide variation in prevalence rates. The prevalence of active MTrPs varied between 14% and 47% and between 0% and 65% in the M. trapezius descendens and M. levator scapulae, respectively. A high prevalence rate (ie, 50%) of active MTrPs was observed in the Mm. suboccipitales in patients with neck pain. 28 Prevalence of active MTrPs in the M. splenius capitis, M. semispinalis capitis, Mm. scalene, Mm. multifidi, Mm. rhomboidei, and M. sternocleidomastoideus did not exceed 30%. Significant differences were found in the prevalence of active MTrPs between patients with neck pain and asymptomatic subjects, with the former presenting significantly more active MTrPs than the latter (0%). 28,29 All the studies examining the prevalence of active MTrPs related to spinal pain included patients with neck pain (Fig 2). Only 1 study 31 investigated the prevalence of myofascial pain syndrome, based on active MTrPs in subjects with low back/upper limb pain. However, this

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Table 3. Study Characteristics (Study Objective A) Reference

Study Design

Barbero et al 201327 Case control

Participants

Age (y), Mean ± SD (Min, Max)

P1: 18 P2: 6 C: 24

Not reported

Characteristics of the Participants

P1: chronic (N 3 mo) mechanical neck pain and an aMTrP in the right upper trapezius P2: chronic (N 3 mo) mechanical neck pain and an lMTrP in the right upper trapezius C: pain-free subjects with lMTrPs P: 28 ± 7 (20-44) P: mechanical neck pain (N4 mo) C: 29 ± 9 (20-50) C: no neck pain during the last 6 mo P: 28.7 ± 12.4 P: acute WAD neck pain (motor C: 29.1 ± 12.2 vehicle accident b 1 mo ago), classified as Quebeck Task Force WAD II C: healthy people without current pain, and without history of pain during the last 6 mo P: 39 ± 8 (33-43) P: mechanical neck pain C: 40 ± 7 (33-43) (mean duration 3.3 y) C: healthy subjects without neck pain or shoulder pain during the previous year P: 44.6 ± 10.3 (20-65) P: cervical radiculopathy C:43.8 ± 9.8 C: no neck pain during the last 6 mo

Fernandez-de-lasPeñas et al 200728 Fernandez-Perez et al 201229

Case control Case control

P:20 (7 M) C:20 (10 M) P: 20 (10 M) C: 20 (10 M)

Munoz-Munoz et al 201230

Case control

P:15 (3 M) C:12 (3 M)

Sari et al 20127

Case control

Zapata et al 200631

Case control

P: 244 (116 M) C: 122 (matched for sex) P: 126 P + C:14.04 C: 233

P: adolescent students with pain in back/upper limbs C: no pain

Criteria for Identification of MTrPs

Outcome

Travell and aMTrPs Simons' criteria lMTrPs

Travell and Simons' criteria Travell and Simons' criteria

aMTrPs lMTrPs aMTrPs lMTrPs

Travell and aMTrPs Simons' criteria lMTrPs

Travell and aMTrPs Simons' criteria lMTrPs Travell and MPS (based Simons' criteria on aMTrPs)

aMTrPs, active myofascial trigger points; C, control subjects; lMTrPs, latent myofascial trigger points; M, number of male subjects (if specified); MPS, myofascial pain syndrome; MTrPs, myofascial trigger points; P, patients; SD, standard deviation.

study only reported a percentage rate of 5%, without any further specification regarding the MTrPs. The prevalence of latent MTrPs in patients with spinal pain vs asymptomatic subjects is represented in Figure 3 and Table 5. The prevalence of latent MTrPs in M. sternocleidomastoideus, Mm. rhomboidei, Mm. suboccipitales, and Mm. scalene was higher in patients with neck pain as compared to healthy controls. The contrary was found for latent MTrPs of the M. trapezius descendens, M. levator scapulae, and Mm. multifidi. Prevalence of latent MTrPs in the M. splenius capitis, M. semispinalis capitis, Mm. rhomboidei, and Mm. multifidi did not exceed 30% in either group. A large variation of prevalence was found for latent MTrPs located in the M. trapezius descendens, M. levator scapulae, M. sternocleidomastoideus, and Mm. scaleni. The 4 studies examining the presence of latent MTrPs 7,28-30 found no significant differences in the prevalence rate of latent MTrPs between patients with neck pain and healthy controls. Only 1 study investigated the prevalence of MTrPs in different localizations of the same muscle (ie, M. trapezius descendens). 27 Most MTrPs were found in the lower medial quadrant (93%) followed by the upper medial quadrant (7%) of the M. trapezius descendens, but none in the lateral

quadrants. However, they observed no significant differences in prevalence between active and latent MTrPs within this muscle.

(Patho)Physiological Mechanisms of MTrPs in Patients With Spinal Pain. Different diagnostic interventions were used to investigate the pathophysiology of MTrPs (Table 6). Three studies 20,21,33 evaluated pressure pain thresholds (PPTs) in muscles containing MTrPs. Although 2 studies found lower PPTs in active MTrPs when compared to latent MTrPs and normal tissue, 20,21 differences were not significant. In contrast, 1 study 33 reported significant differences in PPTs between active MTrPs, latent MTrPs, and muscles without MTrPs. However, these 3 studies had poor methodological quality. The only study examining pain intensity reported by patients with MTrP stimulation observed higher pain scores in the visual analog scale (VAS) in active MTrPs compared to latent MTrPs and normal sites. 20 Two studies by the same group 20,21 used a microdialysis technique 39 to investigate the biochemical milieu of M. trapezius descendens MTrPs and remote sites in patients with cervical pain. Active M. trapezius descendens MTrPs were found to have a more acidic environment (lower micro-pH) and higher concentrations of different algogenic

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Table 4. Study Characteristics (Study Objective B) Reference

Study Design

Participants

Age (y), Mean ± SD Characteristics of the Participants (Min, Max)

Audette et al 200432

Case control

P: 13 C: 8

P and C: (19, 71)

Ballyns et al 201133

Cross sectional P: 44

Ballyns et al 201234

Case control

Shah et al 200521

Case control

Shah et al 200820

Case control

P: 3 C1: 3 C2: 3

Not specified

Sikdar et al 201035

Cross sectional P: 16

Not specified

Turo et al 201336

Case control

P: 14 (4 M) C: 15 (9 M)

P: 36 ± 12 C: 28 ± 8

Wytrazek et al 201137 Case control

P: 30 (7 M) C:30 (16 M)

P: (34, 67) C: (19, 54)

P: (22, 57)

P: 13 (5 M) P: 41 ± 13 (from which 7 C: 30 ± 5 acute and 6 chronic) C: 9 (6 M) P1: 3 Not specified C1: 3 C2: 3

Criteria for Identification of MTrPs

Outcome

P: unilateral neck pain N6 mo and a palpable aMTrP C: pain free at rest + a palpable lMTrP P: acute cervical pain and either aMTrP or lMTrP in Upper Trapezius P: cervical pain b 3 mo (acute) or N 3 mo (chronic) and a palpable aMTrP C: no pain and no palpable MTrPs

Travell and Simons' criteria (except referred pain) Travell and Simons' criteria

aMTrPs lMTrPs

Travell and Simons' criteria

aMTrPs

P1: idiopathic cervical pain (b3 mo) and aMTrP C1: no cervical pain but lMTrPs C2: healthy subjects without lMTrPs P1: idiopathic cervical pain (b3 mo) and aMTrP C1: no cervical pain but lMTrPs C2: healthy subjects without lMTrPs P: acute (b 3 mo) neck pain with aMTrPs P: N 3 mo chronic cervical pain and palpable aMTrPs C: no pain and no palpable MTrPs P: N3 mo nonspecific cervical or low back muscle pain caused by spine overloading P1: aMTrPs P2: chronic pain with no aMTrPs P3: transient pain with no aMTrPs C: no pain

Not specified

aMTrPs lMTrPs

Travell and Simons' criteria

aMTrPs lMTrPs

Travell and Simons' criteria Travell and Simons' criteria

aMTrPs lMTrPs aMTrPs

Not specified

aMTrPs

aMTrPs lMTrPs

aMTrPs, active myofascial trigger points; C, control subjects; lMTrPs, latent myofascial trigger points; M, number of male subjects (if specified); m, months; MTrPs, myofascial trigger points; P, patients.

and proinflammatory substances (ie, calcitonin gene–related factor, substance P), than latent MTrPs and normal sites. The concentration of these biochemical substances was also higher in a remote pain-free area (ie, M. gastrocnemius medialis) of individuals with active MTrPs compared to those with latent MTrPs or normal muscle tissue. 20 In addition, immediately after a local twitch response (LTR), concentrations of nociceptive substances dropped locally, although they did not quite reach the level of normal tissue. However, these studies were performed in very small samples and reach low scores on methodological quality assessment. Ultrasound images were used to investigate MTrPs in patients with neck pain in 4 studies. 33-36 A lower entropy level, 36 band-like hypoechoic regions, and increase in fiber alignment heterogeneity 34 were identified in active MTrP regions as compared to normal tissue. A hypoechoic region may be indicative of contraction knots resulting from increased muscle fiber contraction, local injury, or localized regions of ischemia. 35 Evaluation of the area of nonvibrating regions revealed a

significant difference between active MTrPs, latent MTrPs, and normal tissue, meaning that MTrPs consist of a larger area of stiffer tissue. 33,36 Ballyns et al 34 found differences in shear wave speeds and phase plots in active MTrPs, indicating that the soft tissue milieu of active MTrPs is substantially stiffer and more heterogeneous than normal muscle tissue. Some studies used a Doppler ultrasound to examine the vascular environment of MTrPs. 33,35 They found a significant greater retrograde diastolic blood flow in active and latent MTrPs as compared to normal tissue. 33 Blood flow velocities were investigated through pulsatility index and resistivity index, to establish exactly the cause of this retrograde diastolic blood flow. Resistivity index was the same for normal tissue and active and latent MTrPs, indicating that observed differences in diastolic blood flow were not due to vasculature bed resistance changes. In contrast, the pulsatility index was significantly higher in active MTrPs when compared to latent MTrPs and normal tissue, which means that the retrograde diastolic flow observed in active MTrPs is due to an increase in vascular volume.

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Fig 2. Prevalence of active MTrPs in several muscles in patients and asymptomatic subjects. The gray boxes represent the patients; black boxes represent the healthy control subjects. LS, levator scapulae (7, 30, 31, 32); MF, multifidus (7); Sca, scalenus (31, 32); SCM, sternocleidomastoid (30, 31, 32); SO, suboccipital muscles (30); SPC, splenius capitis (7, 32); SSC, semispinalis capitis (32); Rho, rhomboids minor/major (7); UT, upper trapezius (7, 30, 31, 32, 33).

Table 5. Prevalence Rate of Both Active and Latent MTrPs in Patients With Neck Pain and Healthy Control Subjects Muscle

Active MTrPs Patients With Neck Pain

Upper trapezius → lower medial quadrant → upper medial quadrant

Levator scapulae

Splenius capitis Semispinalis capitis Scaleni Rhomboideus Multifidus Suboccipital muscles Sternocleidomastoideus

35%-40% 30%-35% 33%-47% 14% 93% 7% 0%-15% 55%-65% 13%-27% 16% 7%-13% 15% 7% 20%-30% 7% 10%-14% 9% 50% 15%-25% 5%-30% 7%

Latent MTrPs

Reference

Healthy Control Subjects

Patients With Neck Pain

Healthy Control Subjects

0% 0% 0%

25%-35% 30%-40% 20%-27% 33%

40%-50% 10%-15% 25% 40%

0% 0% 0%

15%-30% 15%-20% 7%-13% 27% 0% 17% 0%-7% 45%-50% 20%-33% 9%-25% 8% 40% 50%-60% 45%-60% 7%

0%-35% 20%-25% 0%-25% 34% 0%-8% 16% 0%-8% 10%-20% 8% 7%-21% 17% 25% 5%-20% 20%-25% 0%

0% 0% 0% 0%

0% 0% 0% 0%

Fernandez-de-las-Peñas et al 200728 Fernandez-Perez et al 201229 Munoz-Munoz et al 201230 Sari et al 20127 Barbero et al 201327 Barbero et al 201327 Fernandez-de-las-Peñas et al 200728 Fernandez-Perez et al 201229 Munoz-Munoz et al 201230 Sari et al 20127 Munoz-Munoz et al 201230 Sari et al 20127 Munoz-Munoz et al 201230 Fernandez-Perez et al 201229 Munoz-Munoz et al 201230 Sari et al 20127 Sari et al 20127 Fernandez-de-las-Peñas et al 200728 Fernandez-de-las-Peñas et al 200728 Fernandez-Perez et al 201229 Munoz-Munoz et al 201230

MTrPs, myofascial trigger points.

Two studies 32,37 investigated MTrP pathophysiology with electromyography (EMG). They found different amplitudes and duration of motor unit potentials and asynchronous spontaneous activity at rest between muscles with MTrPs and normal muscles, by using surface 37 and needle EMG. 32 This was interpreted as a reflection of more spontaneous electrical activity in MTrPs at rest. Wytrazek et al 37 found lower signal amplitude in patients with MTrPs compared with controls, due to a muscle strength decrease (ie, weakness) during maximal voluntary contraction. One study 32 demonstrated the existence of bilaterally evoked

LTRs after dry needling in 61.5% of active MTrPs located in the M. trapezius descendens and M. levator scapulae. Dry needling of latent MTrPs resulted only in unilateral LTRs. Detailed information about results of the different studies investigating pathophysiological mechanisms of MTrPs can be found in Table 6.

DISCUSSION To the best of our knowledge, this is the first study that has systematically reviewed the prevalence, incidence,

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Lluch et al Myofascial Trigger Points in Spinal Pain

Fig 3. Prevalence of latent MTrPs in patients with spinal pain and asymptomatic subjects. The gray boxes represent the patients; black boxes represent the healthy control subjects. LS, levator scapulae (7, 30, 31, 32); MF, multifidus (7); Sca, scalenus (31, 32); SCM, sternocleidomastoid (30, 31, 32); SO, suboccipital muscles (30); SPC, splenius capitis (7, 32); SSC, semispinalis capitis (32); Rho, rhomboids minor/major (7); UT, upper trapezius (7, 30, 31, 32, 33).

localization, and underlying (patho)physiological mechanisms of MTrPs in patients with spinal pain. Based on the results of this review, it is concluded that the incidence of MTrPs remains unexplored in patients with spinal pain. Regarding the prevalence, most of the studies were focused on the cervical spine and showed that active (but not latent) MTrPs are significantly more prevalent in patients with cervical pain than in asymptomatic subjects. Studies examining MTrPs' physiopathology used different assessment methodologies, which revealed both peripheral (ie, local inflammation, stiffness, and weakness) and central phenomena associated with MTrPs. Studies examining the prevalence, incidence, localization, and underlying mechanisms of low back pain are essentially lacking.

Prevalence, Incidence, and Localization of MTrPs in Patients With Spinal Pain. This systematic review adds new information regarding the epidemiology of MTrPs in spinal pain population. Only the prevalence of active MTrPs was found to be higher in people with spinal (cervical) pain than asymptomatic subjects. This finding seems logical if considering that asymptomatic people have—per definition—no active MTrPs. 28-30 However, latent MTrPs can exist in asymptomatic people, as confirmed in this review, and might be converted to active MTrPs by continuous detrimental stimuli. 40,41 The prevalence of MTrPs in patients with spinal pain was found to vary when considering specific pathologies. This finding agrees with other studies, which showed a specific distribution of MTrPs in patients with spinal (cervical) pain depending on the pathology. 42,43 The current review showed that, in a population without specific pathologies (eg,

adolescent students 31), myofascial pain syndromes appear in 5%. Active MTrPs of the Mm. suboccipitales were very prominent (ie, 50%) in patients with mechanical pain, 28 whereas acute whiplash patients had a higher prevalence of active MTrPs in the M. levator scapulae. 29 Regarding patients with cervical radiculopathy, no particular muscle was found to have a high prevalence rate for active MTrPs. 7 A widespread spectrum of prevalence rates was reported by this review for active and latent MTrPs within different pain populations, potentially caused by the lack of consensus about the criteria used for identification of MTrPs. 38 Tough et al 38 found that only 12 of 57 articles analyzed in their systematic review used diagnostic criteria as defined by Travell and Simons. All studies included in the current study about prevalence of MTrPs in spinal pain used Travell and Simons' criteria. In fact, a high number of studies with vague criteria when describing identification of MTrPs were excluded. Future studies should investigate the prevalence of MTrPs, in general population and within the context of different populations, using a uniform operational definition for MTrPs. As no literature is available about the incidence rate of MTrPs in patients with spinal pain, further investigation in that regard is recommended as well. This would add to unravel the clear cause for MTrP development. The only study 27 retrieved examining the specific localization of MTrPs within a single muscle concluded that MTrP prevalence could vary depending on the region of the muscle. M. trapezius descendens MTrPs were located proximal to, but not completely overlapping, the innervation zones of this muscle (and, consequently, endplate zones). 27 This conclusion raises the question as to whether specific

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Table 6. Table of Evidence (Study Objective B) Reference

Methodology Used for MTrP Examination

Outcome Measures

Results

LS UT

-nEMG in both sites (MTrPs and contralateral site) and searching for LTR in taut band

-Motor unit potentials

Ballyns et al 201133

UT

-Vibration elastography -Color Doppler variance image -Physical examination

-Area of nonvibrating regions -Blood flow velocity (PI, RI) -PPT

Ballyns et al 201234

UT

-US images: B-mode -Vibration elastography

-Analyze echoic regions -Phase plots -Shear wave speeds

Shah et al 200521

UT

-Physical examination: PPT in UT -Microdialysis technique in UT before (pre) and after (post) LTR measures: -immunoaffinity capillary electrophoresis -capillary electrochromatography -micro pH

-PPT, H +, bradykinin, SP, CGRP, tumor necrosis factor α, interleukin 1β, serotonin, norepinephrine

-Larger amplitude and duration of motor unit potentials in aMTrPs (in P) compared to lMTrPs (C) -Contralateral motor potentials are only evoked in subjects with aMTrPs, not in subjects with lMTrPs -aMTrPs and lMTrPs N normal sites a aMTrPs N lMTrPs a -Retrograde diastolic blood flow: 55% aMTrPs, 40% lMTrP, 31% normal sites a PI: aMTrPs N normal sites a RI: aMTrPs = lMTrPs = normal sites -PPT: aMTrPs and lMTrPs b normal sites a aMTrPs b lMTrPs a -aMTrPs: band-like hypoechoic region and increase in fiber alignment heterogeneity -aMTrPs: difference in overall phase lag + localized shear wave disruption -Variability at N100 Hz aMTrPs N normal sites a variability at 350 Hz aMTrPs = normal sites -PPT: aMTrPs b lMTrPs and normal site -pH: aMTrPs b lMTrPs and normal site a other substances: aMTrPs N lMTrPs and normal site a -Peak values of CGRP: aMTrPs N lMTrPs N normal site a -After LTR: post SP and CGRP b pre-SP and CGRP a

Audette et al 2004

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Muscles 32

UT gastroc

Sikdar et al 201035

UT

Turo et al 201336

Wytrazek et al 201137

-Physical examination: PPT in UT -Pain intensity -Microdialysis technique in UT and gastrocnemius before (pre) and after (post) LTR measures: -immunoaffinity capillary electrophoresis -capillary electrochromatography -micro pH -US images -Doppler US

-PPT, VAS, H+, bradykinin, SP, CGRP, tumor necrosis factor α, interleukin 1β, interleukin 6, interleukin 8, serotonin, norepinephrine

UT

-US images: B-mode imaging -Vibration elastography

-Entropy -Area of nonvibrating regions

UT GM TFL LES

-Physical examination: muscle strength in UT, GM, TFL, LES -ENG of motor fibers in suprascapular or femoral nerve -sEMG of UT, GM, TFL, LES -nEMG in muscles with aMTrPs and in chronic painful muscles without MTrPs

-Muscle strength -Changes in resting potential (sEMG) -Amplitude during maximal contraction (sEMG) -Motor fiber transmission -Spontaneous activity (sEMG)

-Flow velocities: PSF, MDV, RI, PI, AT, TAPV

-In UT and gastroc overall VAS: aMTrPs N lMTrPs and normal site a PPT: aMTrPs b lMTrPs and normal site pH: aMTrPs b lMTrPs and normal site a Other substances: aMTrPs N lMTrPs and normal site a -In UT and gastroc: After LTR: post SP and CGRP b pre-SP and CGRP a PSF: aMTrPs N lMTrPs and normal sites a MDV: aMTrPs b lMTrPs and normal sites a PI: aMTrPs N lMTrPs and normal sites a no other significant differences -aMTrPs b normal sites a lMTrPs = aMTrPs -aMTrPs N normal sites a -P b C a in UT, LES, GM, TFL -Greater amplitudes P1 N P2/3 N normal sites a greatest difference P1 and C for UT, LES, GM a -P1 b P2 b P3 a different measures between P and C a -No changes in P and C -aMTrPs exclusively asynchronous

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Shah et al 200820

aMTrPs, active myofascial trigger points; AT, acceleration time; C, controls; CGRP, calcitonine gene-related peptide; gastroc, gastrocnemius muscle; GM, gluteus medius; lMTrPs, latent myofascial trigger points; LES, lumbar erector spinae; LS, levator scapulae muscle; LTR, local twitch response; MDV, median diastolic velocity; MTrPs, myofascial trigger points; nEMG, needle EMG; P, patients; PI, pulsatility index; PPT, pressure pain threshold; PSF, peak systolic flow; RI, resistivity index; SP, substance P; TAPV, time-averaged peak velocity; TFL, tensor fascia latae; US, ultrasound; UT, upper trapezius muscle; VAS, visual analogue scale. a Statistical significant difference.

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MTrP locations for each muscle, supposed to be in the endplate zones and described with a (X) in numbered sequences based on their approximate order of appearance, 4 can be established. In fact, some authors state that MTrPs have no specific predetermined or fixed locations but may theoretically form anywhere in the muscle belly. 44 To shed light on this important issue, future research should expand the study of MTrPs' localization to other muscles besides the M. trapezius descendens and M. triceps surae. 5

(Patho)Physiological Mechanisms of MTrPs in Patients With Spinal Pain. Different methodologies were used to examine the underlying pathophysiological processes related to MTrPs, making it difficult to compare the results of the selected studies. Nevertheless, the current review revealed both local/peripheral and central alterations in relation to MTrPs located in spinal muscles, particularly in active MTrPs. Regarding local phenomena, MTrPs were found to be a focus of peripheral sensitization confirmed by the presence of pressure hypersensitivity, 33 an acidic milieu and high concentration of different algogenic/inflammatory substances, especially in the vicinity of active MTrPs. 21 Interestingly, results from the study by Shah et al may supply a solid histochemical base for some aspects of the feedback loop suggested in the integrated hypothesis 45 and for the clinical distinction (ie, pressure sensitivity) between active and latent MTrPs reported by Ballyns et al. 33 However, these results should be viewed with caution as the study by Shah et al was performed in a very small sample, without giving much information about the patient group, and had a high risk of bias and poor methodological quality. In addition, the reduction of concentration of nociceptive substances after LTRs was observed during approximately 10 minutes, before they appeared to slowly rise again. Therefore, it is unknown whether the concentrations stabilized or increased again over time. Besides these findings derived from microdialysis studies, other local alterations such as increased muscular tension (ie, stiffness 33,34,36), spontaneous muscle activity at rest, 32,37 blood flow deviations, 33,35 and muscle weakness, 37 were documented in spinal muscles harboring MTrPs. Reported stiffness and increased resting activity could be underneath the formation of MTrPs taut bands. Taut bands, in turn, may be responsible of capillary compression and ischemia 14 and alterations in the vascular environment of MTrPs detected by means of Doppler ultrasound. 33,35 Muscles harboring MTrPs are often weak, without atrophy, 4 which was confirmed by a single study in this review. 37 Others reported muscle weakness associated to animal taut bands 46 and MTrPs in patients with neck pain. 47 Debate about whether MTrPs are a peripheral or central phenomenon is continuous. 48 Some results from this review indicate that MTrPs could lead to nociceptive changes in the central nervous system (ie, central sensitization). For instance, concentrations of algogenic/inflammatory substances are not locally limited to MTrPs but are also higher in remote pain-free areas of patients with active MTrPs as

Journal of Manipulative and Physiological Therapeutics Month 2015

compared to those with latent MTrPs or normal muscle tissue. 20 In addition, Audette et al 32 found that nociceptive information originating from active MTrPs was enhanced at the spinal cord in comparison to latent MTrPs. This finding was interpreted as reflecting greater altered central pain processing with active than latent MTrPs. However, no firm conclusions about the link between MTrPs and central sensitization can be extracted based solely on these 2 studies. Scoring on methodological quality was low in the study by Shah et al, 20 and authors only looked at 1 distant pain-free site (ie, M. gastrocnemius medialis). In addition, that study was also performed in a very small sample. Further work needs to be done to establish the relevance of central manifestations accompanying MTrPs.

Limitations The results of this review should be seen in light of some methodological limitations. First, the review was focused on spinal muscles and patients with spinal pain. Specifically, the interest of this review was on back and neck pain, and consequently, keywords related to thoracic pain were not included. Therefore, relevant articles investigating pathophysiological mechanisms of MTrPs in the thoracic spine and other body parts were not included. However, even retrieval of identified research related to back and neck pain might have been incomplete. Second, a broad selection of key words was used to include potential studies examining MTrPs physiopathology. However, given the variety of methodologies used, studies using other pathophysiological mechanisms may have been missed. Lack of consensus about MTrP definition may have also influenced prevalence results extracted from this review. Third, only 2 databases were searched. Fourth, the risk of bias/methodological quality of the cross-sectional studies was derived from only 5 criteria, and articles with poor methodological quality were also included, as relevant studies for some study aims were scarce. In addition, the risk of bias was only assessed at the level of the study, not at outcome level. Finally, this systematic review was not registered in PROSPERO, which is an international database of prospectively registered systematic reviews in health and social care. 49

CONCLUSION Based on the results of this systematic review, MTrPs can be viewed as a prevalent clinical entity in people with neck pain. Besides neck pain, evidence to support or deny the role of MTrPs in other spinal pain is insufficient. Compelling evidence supports local mechanisms underlying MTrPs in spinal muscles, but more studies are needed to unravel the relevance of central manifestations associated with MTrPs. Studies examining the prevalence, incidence, localization, and underlying mechanisms of MTrPs in people with low back pain are essentially lacking. Future

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research should use standard criteria for MTrP diagnosis and investigate the incidence of MTrPs in patients with spinal pain.

FUNDING SOURCES AND POTENTIAL CONFLICTS OF INTEREST No funding sources or conflicts of interest were reported for this study.

CONTRIBUTORSHIP INFORMATION Concept development (provided idea for the research): E.L.L., J.N., M.D.K., D.V.D., R.V., F.S., N.A.R. Design (planned the methods to generate the results): E.L.L., J.N., M.D.K., D.V.D., R.V., F.S., N.A.R. Supervision (provided oversight, responsible for organization and implementation, writing of the manuscript): E.L.L., J.N., M.D.K., F.S., N.A.R. Data collection/processing (responsible for experiments, patient management, organization, or reporting data): E.L.L., J.N., M.D.K., D.V.D., R.V., F.S., N.A.R. Analysis/interpretation (responsible for statistical analysis, evaluation, and presentation of the results): M.D.K., D.V.D., R.V., N.A.R. Literature search (performed the literature search): M.D.K., D.V.D., R.V., N.A.R. Writing (responsible for writing a substantive part of the manuscript): E.L.L., J.N., M.D.K., D.V.D., R.V., F.S., N.A.R. Critical review (revised manuscript for intellectual content, this does not relate to spelling and grammar checking): E.L.L., J.N., M.D.K., F.S., N.A.R.

Practical Applications • This systematic review provided evidence that MTrPs are a prevalent clinical entity in people with neck pain. • Evidence was not found to support or deny the role of MTrPs in other spinal pain. • The incidence of MTrPs in patients with spinal pain is currently unknown. • Studies examining the prevalence, incidence, localization, and underlying mechanisms of MTrPs in low back pain are essentially lacking. • Both local and central mechanisms underlie MTrP development in spinal muscles, although further studies should unravel the relevance of central manifestations associated with MTrPs.

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