Quantitative Sensory Testing in Fibromyalgia Syndrome: A Scoping Review

1. Introduction

Characterized as a widespread chronic pain syndrome, Fibromyalgia Syndrome (FMS) has a complex multifactorial etiopathogenesis that remains not fully understood." [1,2] and affects 3 to 6% of global population [3]. FMS is often associated with impairments in mental health and quality of life [4,5,6,7].

Since 1980, various FMS diagnostic criteria have been developed to reduce subjective clinical judgment, most notably the American College of Rheumatology (ACR), which consider FMS diagnosis as a combined score of the Widespread Pain Index (WPI) and Symptom Severity Scale (SSS) [5]. In this context, Quantitative Sensory Testing (QST) has emerged to improve the precision of sensory deficit detection in FMS by assessing pain thresholds through a combination of static and dynamic protocols that allows the assessment of pain thresholds through isolated stimuli, measuring hyperalgesia or hypoalgesia in specific areas and the perception of pain.

QST is based on measurements of responses to calibrated, graded innocuous or noxious stimuli (generally mechanical or thermal) [8,9,10]. Despite its potential, its implementation can be complex due to cost and protocol selection [11,12]. In FMS, QST protocol variability combined with individual differences and comorbidities, can hinder the interpretation of evoked responses [13]. This lack of standardization impedes understanding, comparison of studies, and development of effective diagnostic and therapeutic strategies [10].

Equivalent difficulties have been observed in other chronic pain conditions, already postulated for previous reviews [14,15]. In brief, the use of QST for painful experiences demonstrated the need for a more standardized approach [14,15]. QST standardization issues, including test site variability and inconsistent definitions, have been reported in other chronic pain conditions like knee osteoarthritis [16] and pediatric populations [17], highlighting the need for consistent protocols to improve reproducibility and clinical applicability [17]. This heterogeneity compromises QST's potential in chronic pain research, including fibromyalgia [18].

Therefore, despite favorable evidence for QST application, there are no previous studies debating the implications of QST protocols in FMS. In this sense, this scoping review aims to clarify the complexities and variations inherent in QST methodologies in FMS. By examining QST protocols and identifying factors that influence their reliability as outcome measures, we believe it will be possible to develop more effective approaches for fibromyalgia syndrome (FMS).

2. Materials and Methods

This scoping review protocol was developed based on the Preferred Reporting Items for Systematic Reviews and Metanalysis Extension for Scoping Reviews, PRISMA-ScR [19] (Suppl. Material 1). The protocol was previously registered (DOI 10.17605/OSF.IO/UN69V).

2.1. Eligibility Criteria

This study considered studies where participants were adults, both sexes, aged 18+ with a clear diagnosis of Fibromyalgia Syndrome- FMS considering any of the ACR criteria. As we are looking for Quantitative Sensory Testing-QST measurement, studies with at least one measure of pain threshold or sensitivity (any study design), were selected. We excluded studies if they had less than 50% of the participants with FMS. Duplicates, reviews, and commentaries on findings from other studies or documents that were not the primary research (for example, conference abstracts) were also excluded.

2.2. Search

This review extracted studies from the following databases: Pubmed (n=508), Embase (n=817), and Web of Science (n=1187). We replicated the primary database search terms (Pubmed) for the others (see Supplementary Material 2). The search was not limited by language or year. The search was made up to June 31, 2024.

2.3. Selection of Sources of Evidence and Critical Appraisal

The quality of the included studies was assessed by two independent reviewers (AMC and VAS), and disagreements will be solved by a third reviewer (MGS). For the RCTs, the ROB 2 tool was used, and for the non-RCTs, the STROBE (see Suppl. Material 3 and 4).

2.4. Data Charting Process

The Rayyan software [20] was used to select studies by title and abstract. It was made by two independent reviewers (AMC and VAS) based on our previously established inclusion/exclusion criteria. The third reviewer (MGS) remained on standby if needed. After a full reading, data were extracted from papers by AMC and VAS using an extraction table developed by the reviewers, independently. In cases where it is not possible, we search for the data protocol or other similar studies made by the author/group, in order to clarify the information. In our study, it was not necessary to consult the authors.

2.5. Data items and Synthesis of Results

For extraction, we considered the study design, quality of the study, sample characteristics, age, sex, distribution, inclusion criteria, diagnosis, type of QST (static or dynamic), and methods applied by the studies. We also got information from other measurements and main conclusions. The data was tabulated and presented in a narrative way, answering the research objectives.

3. Results

The search (up to June 2024) yielded 2512 records, of which 1542 remained after duplicate removal. Following title/abstract screening and full-text review, 126 studies (39 RCTs, 87 non-RCTs) were included (Figure 1). Most participants were women aged 40-59. Participant characteristics (age, gender, study design, diagnostic criteria, QST) are shown in Table 1.

3.1. Quality Assessment

Only studies classified as having a low risk of bias or some concerns were considered, and 30(76.9%) RCTs and 59(67.81%) non RCT’s studies met this criterion. RCT limitations involved lack of information regarding the original protocol and data analysis plan (Supplementary Material 3). In terms of nonRCTs, limitations were related to sample (i.e., recruitment, inclusion, sample size calculation), generalizability and insufficient information regarding sample size and bias (Supplementary Material 4).

3.2. Narrative Synthesis of Quantitative Sensory Testing Methods

A total of 42.9% of studies included both static and dynamic QST assessments, offering a comprehensive approach to sensory evaluation. (Table 2). For those, we divided our results considering both assessments.

3.3. Static QST

Static QST methods comprised 76% of all assessments. Pressure pain thresholds/tolerances (PPTh/PPT) were the most frequently measured (n=84), predominantly at 18 tender points (n=24), hands (n=17), trapezius (n=8), and forearm (n=5), using primarily the Somac algometer (n=54). Mechanical detection/pain thresholds/sensitivity (MDTh/MPTh/MPS, n=10) were assessed mainly at the forearm (n=3) and hands (n=4), often with Von Frey monofilaments (n=5). Thermal pain thresholds/tolerances (TPTh/TPT, n=36) were typically measured at hands (n=9) and forearm (n=7), often with the TSA II Medoc.

3.4. Dynamic QST

Dynamic QST methods constituted 24% of assessments. Temporal Summation (TS, n=15) was primarily assessed at hands (n=7) and forearm (n=4). Conditioned Pain Modulation (CPM, n=26) was frequently tested at forearm (n=12) and hands (n=4), using PPT as the test stimulus and a cold water immersion as the conditioned stimulus.

4. Discussion

This scoping review examined how QST is used in FMS, a complex condition with widespread pain and variable symptom presentation, that per se makes diagnosis and measurement challenging[11,12]. While QST offers a potential surrogate measure to improve pain assessment reliability and validity, and understand neuropathic pain[4,21], this review revealed important methodological issues.

Although static QST is prevalent, variations in body location, stimulus duration, and intensity may affect results. González-Álvarez (2024) demonstrated PPT and CPM variability across test points, reflecting altered pain modulation in FMS. Given the diffuse pain and altered sensation characteristic of FMS, QST at remote sites may reinforce information regarding the central nervous system. The NeuPSIG consensus[10] reinforces the use of multiple test sites, or preferably standardizing test locations in order to improve the accuracy and interpretation by reducing variability and potentially revealing more consistent patterns of somatosensory dysfunction in FMS.

Given the scarcity of studies measuring QST both before and after interventions, QST stability in FMS remains poorly understood. No consistent information regarding the presence of other symptoms was controlled (e.g., sleep disturbances and other non-physical symptoms), neither the impact of psychological factors, the presence of psychopathology or neuropathic pain conditions[14,16]. There is an amount of literature available claiming for a more controlled information of those variables, once they are related to the severity of this disease[5,6,7]. Further research should explore how internal and external factors contribute to FMS progression[22]. Consequently, despite efforts to minimize bias, the generalizability of findings remains limited due to substantial methodological variation.

The diversity in test locations—from high muscle areas (e.g., trapezius, deltoid) to minimal muscle sites (e.g., wrist, thumbnail)—further adds to this heterogeneity. This inconsistency could limit the synthesis of findings across studies and impact the reliability of QST as a biomarker in FMS. Standardization in test locations and stimuli parameters could facilitate future meta-analyses and enhance the clinical applicability of QST.

Furthermore, QST modality definitions might be implicit. For example, while TS and CPM are often used as measures of central sensitization, they also involve the peripheral nervous system – the parameters of the sensitization analysis must be defined to each study. Additional limitations include variability in test parameters (number of tests, duration, rest intervals, stimulus intensity/increment) and equipment. Despite recommended protocols, application remains uncommon, hindering full standardization in this review.

Each of these factors can introduce variations between studies; despite there being recommended standardized protocols and methods, our findings show that their application is not yet common. In our review, even when controlling this information, it was not possible to standardize fully across studies.

Finally, as a strength, this is one of the first studies to recruit the state of art by considering QST measures in FMS. We hope that this scoping review might be able to summarize the need for a more standardized approach to measuring FMS, particularly considering the complex and unpredictable nature of endogenous pain inhibition mechanisms.

5. Conclusions

While promising for FMS assessment, QST's potential is hampered by significant lack of information regarding its validity and reliability. Future research should stratify studies by treatment modality (e.g., pharmacological vs. neuromodulatory) to elucidate treatment-specific effects and optimize patient care. Addressing these gaps promises to significantly advance FMS understanding and improve patient outcomes.