Pain neuroscience education in patients with chronic musculoskeletal pain: an umbrella review

Introduction In recent years, pain neuroscience education (PNE) has been the focus of extensive research in the scientific literature in the field of physical therapy, but the results obtained are controversial and its clinical application remains unclear. The main aim of this umbrella review was to assess the effectiveness of PNE in patients with chronic musculoskeletal pain (CMP). Methods We searched systematically in PubMed (Medline), PEDro, EMBASE, CINAHL and PsycINFO. Methodological quality was analyzed using AMSTAR-2 scale and overlapping analysis using GROOVE tool. Results 16 systematic reviews were included. A qualitative synthesis was performed for the following sets of patients with CMP: overall CMP, chronic spinal pain, patients with fibromyalgia and patients with osteoarthritis. In general terms, it seems that the addition of the PNE-based intervention to other treatments, mostly exercise-based interventions although we might refer to it in terms of a multimodal approach, leads to greater clinical improvements than the multimodal approach alone. We have found this especially in the reduction of the influence of psychosocial variables. However, it seems that studies testing the effectiveness of PNE in isolation, systematic reviews with or without meta-analysis did not show statistically significant improvements overall in terms of pain intensity, disability levels or psychosocial variables. Discussion There is a great heterogeneity in the results obtained and the PNE protocols used, a critically low quality in the reviews included and a very high overlap, so there is a need to improve the studies in this field before clinical application. Systematic review registration PROSPERO (CRD42022355634).


Introduction
Chronic Musculoskeletal Pain (CMP) is a major public health concern.Approximately 20% of the adult population suffers from CMP (Goldberg and McGee, 2011), which is one of the leading causes of disability worldwide, according to the Global Burden Disease study (Vos et al., 2012).In addition to reducing the quality of life of those who suffer from this condition (Breivik et al., 2006;Tüzün, 2007), it may also result in a serious socioeconomic burden (Espinoza et al., 2022).CMP is a complex and multifactorial phenomenon (Apkarian and Baliki, 2009).The findings of some studies indicate that these patients develop central sensitization mechanisms that contribute to the chronification of pain (Graven-Nielsen and Arendt-Nielsen, 2010; Adams and Turk, 2018).Furthermore, the perception of pain in patients is influenced by factors such as hypervigilance, catastrophizing, kinesiophobia, and anxiety and depression (Keefe et al., 2004).In this light, treating CMP presents a considerable challenge for health care professionals, who should incorporate biopsychosocial approach that address biological, psychological and social factors into their treatment plan (Turk and Okifuji, 2002;Edwards et al., 2016).
Currently, European guidelines emphasize the importance of patient education as part of the treatment of CMP.Education is a planned experience intended to influence the behavior and knowledge of patients through methods of counseling, teaching, and behavior modification (Engers et al., 2008).Patient education increases patients' knowledge of their condition and promotes positive pain-related beliefs and behaviors (Robinson et al., 2016).Over the past few years, the field of pain neuroscience education (PNE) has attracted a great deal of attention.The aim of this educational strategy is to provide the patient with a thorough understanding of the neurobiological and neurophysiological processes involved in their pain experience (Nijs et al., 2011;Moseley, 2013).It provides patients with an opportunity to improve their understanding of pain and reconceptualize their ideas about it, thereby changing the negative beliefs they have about pain and their incorrect perceptions of it (Moseley and Butler, 2015).Previous research in PNE has suggested that tis intervention could increase knowledge about pain, produce cognitive changes and also have positive effects on pain intensity, disability, kinesiophobia and catastrophizing, as well as on pain-mediating factors such as hypervigilance, anxiety, attitudes and beliefs (Salazar-Méndez et al., 2023;Zimney et al., 2023).
In recent years, PNE has been the focus of extensive research in the scientific literature in the field of physical therapy, and several clinical trials and systematic reviews have been conducted to determine its efficacy.Overall, the results are promising, and show that PNE can be an effective intervention in combination with manual therapy or exercise, although in isolation it may have no effect in patients with CMP (Barbari et al., 2021).However, there are some controversies.A mixed-methods systematic review and meta-analysis found no evidence to indicate that PNE results in clinically important changes over control for pain or disability (Watson et al., 2019).In this regard, it has been suggested that PNE may be effective only for some patients, implying individual differences in response to treatment that may influence outcome variables (Watson et al., 2021).Furthermore, Barbari et al. (2021) highlight that, despite the potential of PNE in CMP patients, the application remains a challenge due to the fact that not all patients can understand PNE concepts in the same way, not all patients are equal despite they are labeled as suffering of chronic MSK pain, and not all clinicians have the training and resources necessaries to apply PNE.
Finally, one challenge in the current scientific literature in this area involves the existence of a large number of systematic reviews, but many of them have overlaps in the studies they include, as well as other methodological shortcomings, which can lead to potentially biased clinical recommendations (Ioannidis, 2016).For this reason, conducting an umbrella review offers a solution, synthesizing the results and conclusions of systematic reviews, and offering insight into possible biases (Lunny et al., 2021).Therefore, the main aim of this umbrella review was to assess and synthetize the previous systematic reviews in the field of PNE for patients with CMP, critically evaluate the published literature in order to elucidate the controversies and determine the effectiveness of PNE in this population.

Methods
This study was conducted in accordance with the Preferred Reporting Items for Overviews of Systematic Reviews including harm checklist (PRIO-harms), which consists of 27 items (56 sub-items), followed by a 5-stage process flow diagram (identification, screening, eligibility, inclusion, and separation of relevant studies) (Bougioukas et al., 2018).The review was previously registered in the international prospective register of systematic reviews PROSPERO (CRD42022355634).

Review inclusion criteria
The inclusion criteria employed in this article were based on methodological and clinical factors such as population, intervention, control, outcomes and study design (PICOS) (Stone, 2002).

Population
The participants selected for the articles were adults with CMP (including chronic low back or neck pain, osteoarthritis, or rheumatoid arthritis, in addition to those who suffer nonspecific or widespread musculoskeletal pain conditions like fibromyalgia).The diagnosis of CMP was consistent with the British Pain Society definition (chronic pain, that lasts beyond the time that tissue healing would normally be expected to have occurred, often taken as ≥3 months) (British Pain Society, 2013).

Intervention and control
We included all systematic reviews assessing the effects of PNE.The intervention should have been composed of planned and structured sessions where patients were educated about the basic neurophysiology of pain, trying to reconceptualize their experience so that it would be considered less threatening (Watson et al., 2019).Interventions based on psychological treatment or cognitive behavioral therapy were excluded.Comparator groups could be non-active interventions, waiting list, minimal interventions (relaxation, breathing or educational advice) or no intervention.If any other treatment (such as medication or manual therapy) was included, it had to be applied in the intervention group as well.

Outcome measures
The measures used to assess the results and effects were variables related to clinical outcomes (pain intensity, disability, depressive symptoms, anxiety, pain catastrophizing, and fear-related movement).

Study design
We selected systematic reviews (with or without a meta-analysis) of randomized controlled clinical trials (RCCTs) or controlled clinical trials (CCTs) and excluded systematic reviews that included RCCTs or CCTs in combination with non-experimental designs.There were no restrictions for any specific language, as recommended by the international criteria (Moher et al., 1998).

Search strategy
We conducted the search for published scientific articles between 1950 and November 14 th , 2022, in the following databases: PubMed (Medline), PEDro, EMBASE, CINAHL, and PsycINFO.The reference sections of the included studies and original studies were screened manually.Supplementary material S1 shows the search strategies, which was adapted for each database.The search was conducted by two independent reviewers (FCM and LSM) using the same methodology.Differences that emerged during this phase were resolved by consensus.The reference sections of the original studies were screened manually, and the authors were contacted for further information if necessary.

Selection criteria and data extraction
Initially, the two independent reviewers conducted a screening (FCM and LSM) assessing the relevance of the systematic reviews (with and without a meta-analysis) regarding the studies' questions and objectives.The first screening was based on each study's title information, abstract, and keywords.The full text was reviewed if there was no consensus or if the abstracts contained insufficient information.In the second phase of the screening, the full text was assessed if the studies met all of the inclusion criteria.Differences between the reviewers were resolved by a discussion and consensus process mediated by a third reviewer (JFFS).The data described in the results section were extracted by means of a structured protocol that ensured that the most relevant information was obtained from each study.

Methodological quality assessment
The two independent reviewers (FCM and LSM) assessed the methodological quality of the systematic reviews (with or without meta-analysis), assessing each of the selected studies based on the Modified Quality Assessment Scale for Systematic Reviews (AMSTAR-2) developed by Barton et al. (2008) a scale shown to be a valid and reliable tool for assessing the methodological quality of systematic reviews.With a total of 16 items (scoring "yes"; "yes in part" and "no"), with a final assessment as a critically low, low, moderate, and high quality.In addition, we calculated the kappa coefficient (κ) and percentage (%) agreement scores to assess reliability prior to any consensus and estimated the inter-rater reliability using κ: (1) κ > 0.7 indicates a high level of agreement between the reviewers; (2) κ of 0.5-0.7 indicates a moderate level of agreement; and (3) κ < 0.5 indicates a low level of agreement (McHugh, 2012).Disagreements on the final quality assessment score were resolved by consensus with a third independent reviewer (JFFS).

Overlapping analysis
To assess the overlap of primary studies among systematics reviews the methodological approach GROOVE (Graphical Representation of Overlap for OVErviews) was employed.This tool is an Excel-based file which automatically calculates the overall covered areas for a whole matrix of evidence, and, at the same time, for each possible pair of SRs included in the overview.The tool summarizes the number of reviews, index publications and primary studies (including double counting) included in the matrix.With this data, it calculates the covered area and provides the interpretation of the overall overlap assessment, being slight if the covered area is <5%, moderate if it is ≥5% and < 10%, high if it is ≥10% and < 15%, and very high if is ≥15%.This tool is intended to be used mainly by authors of overviews of systematic reviews (Pérez-Bracchiglione et al., 2022).

Study selection
The initial search revealed 206 records, and an additional 5 were retrieved manually from the reference list.Through the title and abstract screening and the full-text assessment, 16 systematic reviews were eligible according to our criteria.The study screening strategy is shown in the form of a flow chart (Figure 1).The most analyzed tools for pain intensity were the visual analog pain scale (VAS) and numerical pain rating scale (NPRS).For functionality, the RMDQ, neck disability index (NDI), pain disability index (PDI), fibromyalgia impact questionnaire (FIQ), western Ontario and McMaster Universities Arthritis index (WOMAC) and Quebec back pain disability scale (QBPDS) were used.Finally, for the psychosocial variables were the Tampa Scale of Kinesiophobia (TSK) and the Pain Catastrophizing Scale (PCS).

Characteristics of the included systematic reviews
The control groups in the studies analyzed by the meta-analyses and reviews included in this paper were: manual therapy (MT), exercise, usual treatment, biomedical/anatomical education, dry needling (DN), self-management techniques.

Results of the methodological quality (AMSTAR-2)
Table 2 showed the results of methodological quality.All reviews scored as "critically low" quality.The inter-rater reliability of the methodological quality assessment was high (κ = 0.795).

Qualitative synthesis
A subgroup analysis was performed with the aim of homogenizing the results.Therefore, a qualitative synthesis was performed for the following sets of patients with CMP: reviews that included all kind of patients with CMP (overall CMP), chronic spinal pain, patients with fibromyalgia and patients with osteoarthritis.In addition, results were presented according to the different time points: short term (< 3 months); medium-term (> 3 months but < 12 months) or longterm (≥ 12 months).A common effect size was estimated using the Cochrane recommendations and used for the qualitative synthesis in the figures (Higgins et al., 2023).
Louw et al.Meta-analysis showed statistically significant differences in pain intensity with a moderate clinical effect in seven studies at the postintervention assessment (SMD: −0.76) but it did not show statistically significant differences in fibromyalgia impact, anxiety, and pain catastrophizing.There is low-certainty evidence that in patients with fibromyalgia, PNE can decrease the pain intensity in the postintervention period and the fibromyalgia impact in the follow-up period.However, it appears that PNE showed no effect on anxiety and pain catastrophizing.This review demonstrates that adding PNE to a multimodal treatment including exercise therapy might be an effective approach for improving functional status, pain-related symptoms, anxiety, and depression for patients with FM.CL, Critically Low.AMSTAR 1: Did the research questions and inclusion criteria for the review include the components of PICO?AMSTAR 2: Did the report of the review contain an explicit statement that the review methods were established prior to the conduct of the review and did the report justify any significant deviations from the protocol?AMSTAR 3: Did the review authors explain their selection of the study designs for inclusion in the review?AMSTAR 4: Did the review authors use a comprehensive literature search strategy?AMSTAR 5: Did the review authors perform study selection in duplicate?AMSTAR 6: Did the review authors perform data extraction in duplicate?AMSTAR 7: Did the review authors provide a list of excluded studies and justify the exclusions?AMSTAR 8: Did the review authors describe the included studies in adequate detail?AMSTAR 9: Did the review authors use a satisfactory technique for assessing the risk of bias in individual studies that were included in the review?AMSTAR 10: Did the review authors report on the sources of funding for the studies included in the review?AMSTAR 11: If meta-analysis was performed did the review authors use appropriate methods for statistical combination of results?AMSTAR 12: If meta-analysis was performed, did the review authors assess the potential impact of risk of bias in individual studies on the results of the meta-analysis or other evidence synthesis?AMSTAR 13: Did the review authors account for risk of bias in individual studies when interpreting/ discussing the results of the review?AMSTAR 14: Did the review authors provide a satisfactory explanation for, and discussion of, any heterogeneity observed in the results of the review?AMSTAR 15: If they performed quantitative synthesis did the review authors carry out an adequate investigation of publication bias (small study bias) and discuss its likely impact on the results of the review?AMSTAR 16: Did the review authors report any potential sources of conflict of interest, including any funding they received for conducting the review. 10.3389/fnins.2023.1272068 Frontiers in Neuroscience 09 frontiersin.org The included reviews observe superior effects of the use of PNE with respect to the control groups of conventional physical therapy or usual medical follow-up for the tools used RMDQ, ODI, NDI and PSFS when PNE is combined with TM and/or exercise (Louw et al., 2011(Louw et al., , 2016;;Cuenda-gago and Espejo-antúnez, 2017).However, controversies exist as no superiority could  be demonstrated for the combination of PNE and DN compared to DN alone, as both groups improved on the ODI and NDI scale (Louw et al., 2016).A meta-analysis highlights a possible dependence of the control group compared to NSP on the total outcome effects (Romm et al., 2021).
The included reviews follow the trend of favorable analysis of the use of PNE in the different treatments for TSK, PCS, SOPAR, and FABS scales (Louw et al., 2011(Louw et al., , 2016;;Cuenda-gago and Espejoantúnez, 2017).They also highlight the possible influence of a group and individual treatment and the difference between only receiving one PNE session or several.

Overlap analysis
The overlap analysis performed using the GROOVE tool showed a corrected overlap area of 16.45%, showing a very high level of overlap.The detail of the overlap is shown in Figure 4.
2 meta-analyses analyzed the effects of PNE as sole treatment in low back pain, where a statistically significant result was obtained in the short term [Clarke et al. (2011): MD = 5] although these changes were not clinically significant.In contrast, in the medium term, significant clinical changes favorable to PNE were observed [Clarke et al. (2011): MD = 19].The addition of PNE to treatment appears to improve outcomes in pain intensity, maintained in the short and long term (Barbari et al., 2020).

Overlap analysis
The overlap analysis performed using the GROOVE tool showed a corrected overlap area of 15.45%, showing a very high level of overlap.The detail of the overlap is shown in Figure 7.

Fibromyalgia
Two reviews with meta-analysis (Saracoglu et al., 2022;Suso-Martí et al., 2022) and two reviews analyzed the total effect of PNE in fibromyalgia.The most analyzed tools for pain intensity were the VAS scale and NPRS, and for assessing functionality the FIQ questionnaire and a subscale of the ICF.As for psychosocial variables, they were the HADS scale and the PCS questionnaire.The control groups with which the PNE was compared in the studies analyzed by the meta-analyses and reviews included in this work were: self-management techniques, TM, no intervention, exercise, other educational pathways.
In the medium-and long-term analysis, it could not be affirmed (without significant differences) that PNE decreases pain intensity [Suso-Martí et al. (2022): SMD: −0.42; 95% CI: −0.93 to 0.08], although an overall favorable effect can be observed.PNE improved the efficacy of endogenous pain mechanisms and active coping to persistent pain (García-Ríos et al., 2019).In contrast, a review could not conclude that PNE in isolation treatment has a positive effect on pain intensity in the short and long term (Elizagaray-garcía et al., 2016).
The impact of fibromyalgia was measured by the FIQ questionnaire, where a meta-analysis did not observe a significant difference for PNE in post-intervention [Suso-Martí et al. (2022): SMD: −0.37; 95% CI: −0.85 to 0.11], also observing contradictory evidence on the CIF and SF-36 functionality subscale in the shortmedium term where the combination of exercise and group PNE or other active coping strategies did improve pain intensity for the CIF subscale (Elizagaray-garcía et al., 2016).We did observe a favorable clinical effect on FM severity in the medium and long term in PNE [Suso-Martí et al. (2022): SMD = 0.44; 95% CI: −0.73 to −0.14] coinciding with another meta-analysis showing a large effect of PNE in the intervention groups (SMD = −1.051;95% CI: −1.309 to −0.793) (Saracoglu et al., 2022).

Osteoarthritis
Only one review analyzed the effects of PNE as a treatment in intervention groups (Ordoñez-Mora et al., 2022).Only 4 studies were included in the review and were performed on patients with radiologically proven knee OA (with diagnosis time of over 6 months) and candidates for total knee arthroplasty.Regarding pain intensity, measured by the NRS scale, a positive trend in the use of PNE was observed, but without significant differences when compared to a group without intervention or preoperative biomedical education with manual therapy as a common treatment.However, there were significant changes in favor of PNE combined with exercise compared to exercise alone.There were no significant differences between groups for functionality in the WOMAC scale analysis when PNE was compared to biomedical education.For psychosocial variables, an overall favorable trend was indicated for TSK and PCS without being significant.

Discussion
The main aim of this umbrella review was to assess the effectiveness of PNE in patients with CMP.In general terms, it seems that the addition of the PNE-based intervention to other treatments, mostly exercise-based interventions although we might refer to it in terms of a multimodal approach, leads to greater clinical improvements than the multimodal approach alone.We have found this especially in the reduction of the influence of psychosocial variables.However, it seems that studies testing the effectiveness of PNE in isolation, systematic reviews with or without meta-analysis did not show statistically significant improvements Overlap analysis performed using the GROOVE regarding reviews in patients with chronic spinal pain.overall in terms of pain intensity, disability levels or psychosocial variables.It seems therefore that the main strength of the PNE is the interaction with other interventions to enhance its effectiveness with respect to the outcomes assessed.All the reviews included had scored as "critically low" quality and the overlapping analysis showed a very high level of overlap.These aspects limit the clinical application of the recommendations made to date on PNE in CMP patients, and therefore its clinical efficacy is uncertain and dependent on several factors that need to be further explored.PNE is a clinical intervention that has the communication process as a key point of its application and where the patient feels listened to, cared for and, in addition, allows patients to better understand their clinical condition process (Street et al., 2009).This increased knowledge from a patient perspective, together with an adequate context promoted by empathy, shared understanding between health professional and patient and increasing social support, seems to help improve the influence of psychological variables that are widely present in chronic musculoskeletal pain processes (Lee et al., 2016;Traeger et al., 2019).However, the mechanisms that explain the functioning and benefits of PNE are not entirely clear.It has been suggested that this intervention might be especially relevant for the affective-emotional component of pain (Moseley and Butler, 2015), which could lead to better coping strategies (Nijs et al., 2017).In addition, PNE could modify perceptual error in threat signal assessment in the neural network involved in pain perception, reducing nervous system sensitivity and brain activity (Saracoglu et al., 2022).
Based on the results of the present review, a clinical approach based solely on PNE alone may be insufficient to provide clinically relevant and meaningful results, and it seems that the current state of the art tells us that we should combine it with an active and/or passive intervention (such as exercise-based interventions, manual neuroorthopedic physical therapy, etc.) in order to improve its effectiveness.Positive effects on decreasing pain intensity, disability levels or catastrophic thoughts have been reported when researchers combined PNE together with an exercise-based intervention compared with the exercise-based intervention in isolation in patients with chronic musculoskeletal pain (Siddall et al., 2022) or in patients with chronic non-specific spinal pain (Bonatesta et al., 2021).Given that exercise has already shown positive results in patients with musculoskeletal disorders with pain such as fibromyalgia syndrome (Sosa-Reina et al., 2017;Estévez-López et al., 2021) or chronic non-specific low back pain (Hayden et al., 2005;Searle et al., 2015) in the scientific literature, future studies seem to address whether PNE could improve the efficacy of exercise-based interventions, as is the case for chronic musculoskeletal pain.It seems that our work sheds some light on this issue, although future studies should address some of the limitations and weaknesses found in the present manuscript.Finally, there is great variability in the results found depending on the different variables (content of the sessions, the format, the interventions added to the session, the characteristics of the population or the duration of the intervention).In this regard, recently, a meta-analysis found a linear association between the duration of PNE and the reduction of anxiety symptoms, catastrophizing and kinesiophobia (Salazar-Méndez et al., 2023).Future studies should determine not only whether PNE is effective, but also in which patients it is effective and in what way it is best to apply it.

Limitations
This study presents several limitations.First, part of the included studies presented low methodological quality and a great heterogeneity.Second, there was inconsistency between the systematic reviews in terms of the interventions and control groups, and this limits the strength of the conclusions.Finally, as no statistical aggregation could be performed due to the low number of included studies, the conclusions are somewhat ambiguous as they satisfy a qualitative analysis, and not a quantitative one (which would be more robust).

Conclusion
The addition PNE-based intervention to other treatments leads to greater clinical improvements than alone interventions based on physical therapy or exercise modalities, especially in the reduction of the influence of psychosocial variables.However, the effectiveness of PNE in isolation did not show statistically significant improvements overall in terms of pain intensity, disability levels or psychosocial variables.There is a great heterogeneity in the results obtained and the PNE protocols used, a critically low quality in the reviews included and a very high overlap, so there is a need to improve the studies in this field before clinical application.
to traditional physical therapy interventions was more effective than traditional physical therapy only, wait-list, or medical management control groups.Meta-analysis results show statistically significant changes in both short and long-term pain and disability with a large effect for both short-term pain intensity and long-term disability.Certainty of evidence N/A.Romm et al.Significant effects of PNE were found on all the outcome measures [pain intensity −0.85 (0.30); disability −0.48 (0.30); kinesiophobia −1.71 (0.36); catastrophizing −0.72 (0.20)].Certainty of evidence N/A.effective alone is effective in the short term for the relief of catastrophic pain from catastrophic pain due to erroneous beliefs and attitudes about pain.When PNE is combined with multimodal physiotherapy treatments, it appears that benefits in primary variables (pain and disability) and in some secondary variables (knowledge neurophysiology of pain, catastrophism, pain beliefs and cognitions, kinesiophobia beliefs and cognitions of pain, kinesiophobia, quality of life or life or algometry) are increased.Certainty of evidence N/A.
results showed statistically significant results in favor to PNE compared with control group in pain and kinesiophobia.It was found that PNE alone was more effective when combined with trigger point dry needling and manual therapy.In addition, regardless of therapeutic intensity, a single session alone showed significant improvement, and indirect online education rather than direct education also showed significant improvement.Certainty of evidence N/this systematic review show compelling evidence for PNE affecting passive and active physical movements.Positive effects of PNE on pain perception, disability, and catastrophizing may allow patients to apply this new view of their pain state by reappraising their ability to move.Certainty of evidence N/A.
the use of PNE for in reducing pain ratings, limited knowledge of pain, disability, pain catastrophizing, fearavoidance, unhealthy attitudes, and behaviors regarding pain, limited physical movement and healthcare utilization.Certainty of evidence N/A. to very-low certainty of the evidence suggesting that PNE plus exercise therapy reduces pain, disability, kinesiophobia, and catastrophizing compared to exercise therapy or multimodal physiotherapy at short-and intermediate-term.for short-term pain (n = 428) demonstrated a WMD of 0.73 (95%CI −0.14; 1.61) on a ten-point scale of PNE against no PNE (low certainty evidence).Short-term disability (RMDQ) meta-analysis demonstrated a WMD of 0.42 (moderate certainty evidence); whereas the addition of PNE to physiotherapy interventions demonstrated a WMD of 3.94 (moderate certainty evidence).

Fibromyalgia
promising intervention for the primary outcome measures of pain, physical-function, psychological-function and social-function.in pain, in favor of PNE, were found after treatment, WMD = −1.03and after 3 months, WMD = −1.09.There was moderate evidence supporting the hypothesis that NPE has a small to moderate effect on pain and low evidence of a small to moderate effect on disability immediately after the intervention.PNE has a small to moderate effect on pain and disability at 3 months follow-up in and educational interventions should be carried out within the interventional processes in patients with pain.The findings revealed an improvement in the groups managed with PNE, finding a small effect in favor of the interventions for variables such as kinesiophobia, with no changes observed in the other variables evaluated.Certainty of evidence N/A.educational advice), or no intervention.If any other treatment (such as medication or manual therapy) was included, it had to be applied in the intervention group as well.

FIGURE 2
FIGURE 2Results of mean differences regarding pain intensity in patients with overall chronic musculoskeletal pain.The colors show the certainty of evidence according to GRADE (red = very low certainty evidence; yellow = low certainty evidence; green = moderate certainty evidence, grey = not available).Circles = overall measurement; Triangles = short term measurement; square = long term measurement.SMD, Standardized mean difference; N/A, Not available; CI, Confidence interval.

FIGURE 3
FIGURE 3Results of mean differences regarding disability in patients with overall chronic musculoskeletal pain.The colors show the certainty of evidence according to GRADE (red = very low certainty evidence; yellow = low certainty evidence; green = moderate certainty evidence, grey = not available).Circles = overall measurement; Triangles = short term measurement; square = long term measurement.SMD, Standardized mean difference; N/A, Not available; CI, Confidence interval.

FIGURE 5
FIGURE 5Results of mean differences regarding pain intensity in patients with overall chronic spinal pain.The colors show the certainty of evidence according to GRADE (red = very low certainty evidence; yellow = low certainty evidence; green = moderate certainty evidence, grey = not available).Circles = overall measurement; Triangles = short term measurement; diamond = medium term.SMD, Standardized mean difference; N/A, Not available; CI, Confidence interval.

FIGURE 6
FIGURE 6Results of mean differences regarding disability in patients with overall chronic spinal pain.The colors show the certainty of evidence according to GRADE (red = very low certainty evidence; yellow = low certainty evidence; green = moderate certainty evidence, grey = not available).Circles = overall measurement; Triangles = short term measurement; square = long term measurement; diamond = medium term.SMD, Standardized mean difference; N/A, Not available; CI, Confidence interval.

TABLE 1
Characteristics of the included studies.
(SMD, 21.20; moderate certainty), and pain catastrophizing (WMD, 27.72; very low certainty) that favored the combination of PNE and exercise.These findings suggest that combining PNE and exercise in the management of chronic musculoskeletal pain results in greater shortterm improvements in pain, disability, kinesiophobia, and pain catastrophizing relative to exercise alone.Marris et al.