Efficacy of Dry Needling and Acupuncture in Patients with Fibromyalgia: A Systematic Review and Meta-Analysis

Fibromyalgia (FM) is a syndrome that involves chronic pain, fatigue, sleep disturbance and impaired quality of life and daily functioning. In addition to medical and psychological therapies, other therapies including acupuncture and dry needling aim to reduce pain and disability in patients with FM. The aim of this study was to investigate the efficacy of dry needling and acupuncture in patients with FM regarding pain, function and disability in both the short and the long term. MEDLINE, PubMed, SCOPUS and Web of Science databases were systematically searched for randomized controlled trial studies evaluating efficacy data of dry needling or/and acupuncture treatments to improve pain, fatigue, sleep disturbance and impaired quality of life and/or daily function. A qualitative analysis including the methodological quality and a systematic data synthesis was performed. A total of 25 studies addressed the selection criteria. Most studies had an acceptable methodological quality. Four studies assessed the effect of dry needling, and twenty-one studies assessed the effect of acupuncture. In general, both interventions improved pain, anxiety, depression, fatigue, stiffness, quality of sleep and quality of life. However, both techniques were not compared in any study. Acupuncture and dry needling therapies seems to be effective in patients with FM, since both reduced pain pressure thresholds, anxiety, depression, fatigue, sleep disturbances and disability in the short term. It is still required to compare both techniques and their application in the long term.


Introduction
Fibromyalgia (FM) is a condition that involves generalized chronic pain [1] associated with fatigue, sleep disturbance, depression and cognitive impairments [2,3]. This disease can affect people at different ages, but FM is most frequently found in middle-aged women [4]. In addition to gender and age, prior family history of FM increases the risk of suffering this condition. Therefore, this suggests a mixed genetic and lifestyle etiology [5], but the exact etiology is still unknown. Previous studies assessed the altered pain perception reporting a chronic and increased pain response to a painful stimulus (hyperalgesia) and pain caused by a stimulus which normally should not cause pain (allodynia) [6][7][8]. Gender differences were found in the intensity, frequency, duration and locations, female patients being more affected than male patients. Although pain perception is conditioned

Study Eligibility Criteria
Studies were eligible for inclusion if they evaluated the application of dry needling and/or acupuncture in adult patients with FM for the pain, disability, function and/or quality of life management and were published during the last 10 years in the English, Portuguese or Spanish languages. Animal studies, cadaveric studies, published proceedings, abstracts and studies with a sample size lower than 30 subjects were excluded for review. All included studies must have obtained approval from an ethics committee or institutional review board.

Study Appraisal and Synthesis Methods
The Mendeley Desktop v. 1.19.4 for Mac OS (Glyph & Cog, LLC 2008) program was used to insert the search hits from the databases. First, the duplicates were removed. Second, title/abstracts of the articles were screened for potential eligibility by two authors. Third, the full text was analyzed to identify potentially eligible studies. Reviewers were required to agree in the inclusion/exclusion decision. In case of discrepancy between the initial two reviewers, a third reviewer participated in the process to reach the consensus for including the study in the systematic review or not.
A standardized data extraction form containing questions on study design, sample size, objectives, interventions, outcomes assessed, results and conclusions was used, following the main structure reported by Shokraneh et al. [24]. The methodological quality of the included studies was assessed using the PEDro scale, which consists of a checklist of 10 scored yes-or-no questions pertaining to the internal validity and the statistical information provided. Reported cut-offs for the scale interpretation are as follows: 0-3 score was interpreted as poor quality; 4-5 as fair quality; and 6-10 as high quality [25].

Level of Evidence
The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to evaluate the level of evidence [26]. The level of evidence was classified as high, moderate, low or very low based on study limitations, indirectness of evidence, unexplained heterogeneity, imprecision of the results and high probability of publication bias [27]. High-quality evidence was scored when all items were negative; moderate quality was scored when one item included serious risk, low quality was scored if two items showed serious risk or one item showed very serious risk; or very low quality was scored when three or more items had serious risk or two or more had very serious risk. This process was also performed by two authors, with the participation of a third one if disagreement occurred.

Data Analysis
Data analysis was performed with Review Manager statistical software (RevMan version 5.3). Data synthesis was presented by groups according to comparative groups, such as sham/control/placebo; manual therapy or other physical therapy intervention; and by follow-up, such as short-(0 to 3 months) and mid-term (>3months to <6 months), since long-term (≥6 months) data were not available. No other subgroup analysis was prespecified a priori.
Data extraction for the data analysis included sample size, means and standard deviations of the outcomes. When the trial reported standard errors, they were converted to standard deviations. Mean and standard deviations were estimated from graphs when needed. If data were expressed as median and interquartile range, they were converted to mean and standard deviation as needed [28].
The between-groups mean difference (MD) with the 95% confidence interval (CI) was calculated for those outcomes assessed with the same instrument, e.g., pain intensity and pressure pain thresholds. Between-groups mean differences were converted to SMD when different instruments were used for the same outcome, e.g., pain-intensity. A random-effects model was used to determine the effect sizes (SMD). An effect size (SMD) of ≥0.8 was considered large, between 0.5 and 0.8 was considered moderate and between 0.2 and 0.5 was considered small [29]. p-values < 0.05 were considered statistically significant.
Finally, when two subgroups included the same intervention, e.g., dry needling, the sample size was adjusted by dividing the sample size as the Cochrane textbook recommends for avoiding duplication in the overall effect [30].

Study Selection
The electronic searches identified 695 potential studies for review. After removing 214 duplicated studies, 481 studies remained. Four hundred forty-six (n = 446) studies were excluded based on examination of their titles or abstracts, leaving 35 articles for full-text analysis. Eleven articles were excluded because they were not published in English or Spanish languages (n = 8), were protocols (n = 1) or had a case series design (n = 2) or retrospective observational design (n = 1). A total of twenty-four studies were included in this systematic review [6,. The included articles investigated dry needling (n = 4) or acupuncture (n = 20), but none compared both techniques directly in the same study ( Figure 1).

Methodological Quality Assessment
The methodological quality scores measured using the PEDro scale ranged from 5 to 9 (mean: 6.8; SD: 1.1) out of a maximum of 10 points (Table 1). The most consistent flaws were the blinding of all therapists administering the therapy (n = 22 studies out of 25), the blinding of the subjects to discriminate if they had or did not have the treatment (n = 19 out of 25), the concealed allocation (n = 10 out of 25) and the blinding of all assessors who measured at least one key outcome (n = 10 out of 25).
Overall, most of the studies specified the eligibility criteria (n = 25), allocated the subjects randomly to the groups (n = 23), had balanced group at baseline regarding the most important prognostic indicators (n = 21), obtained data from more than 85% of the subjects initially allocated in the groups (n = 20), participants received the treatment or control condition as allocated (n = 18), statistical comparisons between groups were 5 of 32 reported (n = 25) and both point measures and measures of variability provided (n = 25). The methodological quality of studies assessing dry needling was higher (mean: 7.2; SD: 1.7) than that of acupuncture (mean: 6.6; SD: 1.0). Table 2 summarizes the four studies investigating the efficacy of dry needling in patients with FM. Just one study applied the technique in Tender Points (TP) [36] while three applied dry needling in MTrPs [6,42,50]. Comparative interventions selected for these studies were their ordinary medical treatment [30], taping applications [42], manual myofascial release techniques [6], and Transcutaneous Electrical Nerve Stimulation (TENS) [50]. The included studies had a total sample size of 312 patients with FM (35 men and 277 women).

Methodological Quality Assessment
The methodological quality scores measured using the PEDro scale ranged from 5 to 9 (mean: 6.8; SD: 1.1) out of a maximum of 10 points (Table 1). The most consistent flaws were the blinding of all therapists administering the therapy (n = 22 studies out of 25), the blinding of the subjects to discriminate if they had or did not have the treatment (n = 19 out of 25), the concealed allocation (n = 10 out of 25) and the blinding of all assessors who measured at least one key outcome (n = 10 out of 25).
Overall, most of the studies specified the eligibility criteria (n = 25), allocated the subjects randomly to the groups (n = 23), had balanced group at baseline regarding the most important prognostic indicators (n = 21), obtained data from more than 85% of the subjects  1: Eligibility criteria were specified; 2: Subjects were randomly allocated to groups; 3: Allocation was concealed; 4: The groups were similar at baseline regarding the most important prognostic indicators; 5: There was blinding of all subjects; 6: There was blinding of all therapists who administered the therapy; 7: There was blinding of all assessors who measured at least one key outcome; 8: Measures of at least one key outcome were obtained from more than 85% of the subjects initially allocated to groups; 9: All subjects for whom outcome measures were available received the treatment or control condition as allocated or, where this was not the case, data for at least one key outcome was analyzed by "intention to treat"; 10: The results of between-group statistical comparisons are reported for at least one key outcome; 11: The study provides both point measures and measures of variability for at least one key outcome. +: Yes; −: No.  Patients severely affected by fibromyalgia can obtain short-term improvements following weekly dry needling for 6 weeks.   Pain intensity Heart rate variability Galvanic skin response Oxygen saturation Photoplethysmography Significant differences between groups were found for the sensory dimension of pain, affective dimension of pain, total dimension of pain, visual analogue scale (VAS) and present pain intensity (PPI) (p = 0.001). In addition, significant differences between groups were achieved for very low frequency power of heart rate variability (p = 0.008) and low frequency power (p = 0.033). There were no significant differences in dry needling versus TENS groups on the spectral analysis of the photoplethysmography and oxygen saturation. Although pain was a common outcome in all the included studies [6,36,42,50], the measurement instruments were not consistent in all the designs. Visual Analogue Scale (VAS) of pain was used in two studies [36,50], Pain Pressure Thresholds (PPTs) were reported in three of the studies for both TPs [36] and MTrPs [6,42] and McGill Pain Questionnaire and myalgic score in just one study [30]. In addition to pain outcomes, quality of life was assessed in two studies, including questionnaires, sleep quality, impact of fibromyalgia and fatigue [6,36]; psychological outcomes including depression and anxiety were assessed in one study [6]; spinal mobility was assessed in one study [42]; and finally, autonomic function including heart rate variability, galvanic skin response, oxygen saturation (SpO 2 ) and photoplethysmography was assessed in one study [50].
In general, dry needling is shown to induce improvements in short-term subjective pain perception, pain pressure thresholds, mobility, fatigue, quality of life, physical function, physical role, general health, vitality, social function, emotional role and mental health.
In general, acupuncture and scalp acupuncture showed to be effective in the treatment of fibromyalgia for reducing pain and disability in the short term if combined with other treatments, reducing the adverse effects and treatment costs. Although the placebo effect seems to play a relevant role in these improvements since sham acupuncture demonstrated significant reduction in pain and disability, real treatment seems to be more effective. The application of TCDT together with acupuncture is an effective measure to improve the therapeutic approach, although acupuncture produced the greatest improvements. The scalp acupuncture group showed significant differences in all variables compared to the other two groups after 6 months; particularly, the pain scale values decreased by 28.23% and those of the VAS by 20%. No differences were found on the FIQ in any of the groups. There were significant differences (p < 0.01) after 6 months in analgesic use, favoring moxibustion over acupuncture.
The scalp acupuncture protocol used showed notably more effectiveness than the moxibustion protocol and acupuncture treatment after syndromic diagnosis in the management of fibromyalgia. All groups showed a significant improvement in FIQ and HAQ scores at the evaluation after the intervention. The complete group exhibited the best result on both the FIQ and HAQ (p < 0.001), and the improvement in HAQ score was significant (p < 0.004).
The placebo effect in FM may be substantial. However, comparison between groups revealed that the complete group had the greatest reduction in both FIQ and HAQ, with a significant improvement in HAQ, suggesting that the combined use of music and vibration exerts a greater effect on FM symptoms. There was no significant improvement in pain or reduction in tender points in any of the groups studied, at the end of the eighth session. Significant improvement in quality of life was perceived in vitality (after acupuncture treatment) and in mental health (after electroacupuncture and moxibustion treatments). The baseline serum NPY levels of the patients were higher than those of the controls. They had significantly increased by the end of the treatment, when there was also a statistically significant reduction in pain, the number of tender points numbers and the clinimetric scores.
These findings confirm the analgesic properties of acupuncture as a complementary treatment in FM and indicate that NPY could play a role in pain modulation. Acupuncture efficacy in fibromyalgia may be underestimated, and a more personalized treatment for fibromyalgia may also be possible. Serum serotonin values increased significantly after treatment in EG and SG1 (p < 0.001 and p < 0.01, respectively). The increase in the EG was also different from both of the other groups (p < 0.01). While substance p levels decreased in the EG, they increased in the SG2 (p = 0.001). In the EG, significant improvements were found in almost all clinical outcomes after treatment. These usually continued for three months. In the SG1, there were also significant changes in the NTP, VAS, FIQ and BDI scores after treatment. Improvements in the NTP and FIQ scores lasted for three months.
In the SG, significant improvements were found only in the NTP, VAS and BDI scores after treatment.
Acupuncture, rather than sham or placebo acupuncture, may lead to long-term improvements in clinical outcomes and pain neuromediator values.
Changes in serum serotonin and substance P levels may be a valuable explanation for acupuncture mechanisms in fibromyalgia treatment.  In the TENS group, after the treatment, an increase was observed in the alpha power of the left anterior region as well as a decrease in pain scores. In the acupuncture group, an increase was determined in the alpha power of the right and left posterior regions as well as a decrease in pain score after the treatment. The power of low-and moderate-frequency waves on resting EEG was decreased in the patients with fibromyalgia. Decreased pain and increased inhibitor activity were found on EEG after TENS and acupuncture applications.
TENS and acupuncture applications seem to be beneficial in fibromyalgia patients.

SF-MPQ VAS of pain FIQ
There was a reduction in all SF-MPQ domains and FIQ scores after treatment in both the physical therapy and acupuncture groups. There was no difference in pre-and post-treatment scores between the two groups.
Physical therapy modalities and acupuncture can be effectively used in the treatment of fibromyalgia. Even though one treatment option was not found to be more beneficial than the other, longer post-treatment follow-up may help determine the superior treatment option. The results showed statistically significant improvements in the acupuncture and physiotherapy groups vs. the control group at week 6 regarding Berg Balance Scale (p = 0.00, both groups), timed up and go test (p = 0.00 and p = 0.01, respectively) and 10 m walk test at comfortable speed (p = 0.02 and p = 0.03, respectively). The 10 m walk test at maximum speed showed significance when comparing the physiotherapy and control group (p = 0.03). However, no significant differences were found between the physiotherapy and the acupuncture groups. In relation to functional capacity, the improvements achieved after the treatments were not statistically significant.
Core stability-based physiotherapy and acupuncture improve dynamic balance and postural control in women with fibromyalgia. However, these improvements were not statistically significant.
Core-stability-based physiotherapy and acupuncture showed non-significant improvements in quality of life, pain, joint stiffness, difficulty to work and depression in women with fibromyalgia.

Level of Evidence
The risk of bias, inconsistency of the results, indirectness of evidence, imprecision of results and publication bias for determining the level of evidence according to GRADE assessment are detailed in Table 4. The serious/very serious inconsistency of the results

Level of Evidence
The risk of bias, inconsistency of the results, indirectness of evidence, imprecision of results and publication bias for determining the level of evidence according to GRADE assessment are detailed in Table 4. The serious/very serious inconsistency of the results (heterogeneity) downgraded the evidence level of dry needling and acupuncture to low or moderate for most of the outcomes assessed, except for the pressure pain threshold in the short-term (with moderate to high quality evidence, especially for dry needling).

Discussion
The main findings of this meta-analysis were that dry needling could induce a shortterm improvements in pain, quality of life, vitality, social function, psychological and severity in patients with FM in comparison with other techniques (e.g., manual myofascial release, cross tape) and that acupuncture, if combined with other treatments, is also an effective technique to reduce the ingestion of analgesics and to improve pain perception, quality of life, pain perception, depression and anxiety from the short-term to up to 12 months. Recent studies highlighted the importance of these outcomes in FM severity [55][56][57][58][59][60][61][62][63]. However, we could not find any study comparing the effectiveness of both techniques within the same research. Although the blinding process in studies including needling techniques is not always possible, the studies included in this review did not consider important methodological aspects regarding allocation concealing, the representative sample size or the inclusion of a proper comparator group, furthering the blinding of therapists, patients and assessors. Therefore, future studies should consider reducing methodological flaws including a greater patient recruitment to correct the patients lost during follow-up, especially in those with large follow-up times, and the inclusion of a blinded assessor to perform the measurements.
Although this is not the first meta-analysis comparing the application of dry needling and acupuncture for reducing pain and disability in patients with FM [64], the existing literature included a minor number of articles (including 14 studies for qualitative synthesis and 8 in the quantitative synthesis) and outcomes (i.e., FIQ, PPT and quality of life) in their analyses compared with this one, despite all types of invasive techniques being compared in their analyses.
One likely reason that could explain the limited number of studies applying dry needling in this population could be that dry needling focuses on MTrPs rather than tender points. MTrPs are defined as hyperirritable spots in skeletal muscles that are associated with hypersensitive palpable and painful nodules in a taut band that can induce referred pain, tenderness, motor dysfunction and autonomic phenomena, probably caused by the ischemia and hypoxia produced by the capillary vessels' compression in these taut bands, and producing peripheral sensitization [65]. Low blood oxygen levels result in a significative pH reduction, an activation of acid-sensing ion channel receptors, acetylcholinesterase inhibition, ATP stimulation, bradykinin, tumor necrosis factor alfa, interleukins, serotonin, noradrenaline, P substance and calcitonin gen-related peptide [66]. On the other hand, tender points were defined by the American College of Rheumatology assessing the hypersensitivity of 18 specific locations to confirm the clinical diagnosis of FM [67].
Based on available literature to date, we found that dry needling induces a global subjective, pain, quality of life and disability improvement in the short-term up to 6 weeks after the treatment [36,50], reporting better results than TENS [50], manual myofascial release treatment [6] and cross tape for all the measured outcomes, except spinal mobility after cross tape treatment [42]. However, further research is needed to confirm these findings due to the lack of studies, the limited comparator groups and the limited follow-up time.
We also found that acupuncture is also an effective and safe tool for managing patients with FM if combined with other therapies (e.g., their usual medication or dietary therapy). Collazo-Chao et al. [32] reported a decrease in the analgesic intake, further improving disability, sleep quality and intensity of pain. All the acupuncture techniques assessed demonstrated similar results (e.g., somatic, abdominal and scalp) and agreed with these positive effects. However, there is enough evidence proposed by Webber et al. [39], Ugurlu et al. [44], Zucker et al. [45] and Karatay [46] to state the substantial role of the placebo effect, even if the verum acupuncture showed better results than sham acupuncture [41]. Further studies could compare the changes in serum serotonin and substance P levels both in the application of dry needling and acupuncture to explain analgesic mechanisms differences depending on the application procedures [46]. These conclusions must be interpreted carefully due to the methodological flaws found in these studies since most of them had no comparator groups or the group assignation was not randomized.
None of the studies assessed in the meta-analysis conducted by Deare et al. [18] nor Yang et al. [13] were included in this systematic review due to the publication date or the sample size. However, our conclusions are consistent with all the previous systematic reviews [13,18,21] since they reported low-to-moderate-level evidence that, compared with no treatment and standard therapy, acupuncture improves pain and stiffness in people with FM and moderate-level evidence that the effect of acupuncture does not differ from sham acupuncture for reducing FM symptoms. Thus, the methodological quality flaws that we found in this study are similar to those reported in these prior systematic reviews, this being the main reason for the level of evidence weakness.

Limitations
Finally, there are some limitations of the current systematic review. First, we have only included articles written in the English or Spanish language, so we have discarded some relevant published studies in other languages, such as Chinese, with a high number of potentially relevant acupuncture studies. Furthermore, we did not include those studies which were accepted but unpublished. Secondly, the limited number of studies assessing dry needling in FM populations as well the inclusion of quasi-experimental acupuncture studies with no comparative group in this review are the main reason to advise a careful interpretation of our conclusions. Further research with proper comparators and blinding is needed to reinforce to recommend the use of dry needling or acupuncture in patients with FM.

Conclusions
Due to the lack of studies assessing dry needling and the methodological quality flaws of the studies assessing acupuncture, this systematic review should be interpreted carefully. Overall, there is a low-to-moderate-quality level of evidence that suggests that dry needling is effective for improving pain, disability and quality of life in the short term (up to 6 weeks). The same level of evidence supports acupuncture as an effective complementary treatment to medication and exercise for improving FM severity and symptoms including pain, sleep quality, quality of life, depression, anxiety and fatigue. We did not find any research comparing both techniques in the same study. Further research is needed considering the inclusion of a proper comparator group, larger sample sizes and patient, therapist and/or assessor blinding, if possible, to make more consistent recommendations.