Influence of pain neuroscience education and exercises for the management of neck pain: A meta-analysis of randomized controlled trials
Chronic musculoskeletal pain affects approximately 40% of adolescents,  leading to increased school absenteeism, reduced social and recreational engagement, diminished educational attainment, impaired vocational functioning, and social difficulties.  Neck pain, particularly prevalent among adolescents aged 16 to 18 years with rates up to 29.5%,  emerges as 1 of the most common manifestations. This condition induces both biological and psychosocial impairments, including reduced pressure pain thresholds, decreased neck and scapular muscle endurance, sleep disturbances, heightened pain catastrophizing, kinesiophobia, diminished self-efficacy, and central sensitization symptoms.  Multimodal interventions are developed to control neck pain, such as self-management and active movement-based strategies.  However, they only focus on psychological and pharmacological interventions.  Pain neuroscience education is an educational approach that explains pain as a neural output emerging from complex biological, psychological, and social interactions. This intervention aims to facilitate patients’ understanding of pain mechanisms and promote the reconceptualization of maladaptive pain beliefs. In clinical settings, pain neuroscience education helps patients comprehend the underlying biological and physiological processes that shape their pain experience. Pain neuroscience education emphasizes that pain is not merely a response to tissue damage but also a complex interaction of the nervous system, psychological factors, and social influences.  It’s commonly used for patients with chronic pain conditions like low back pain, fibromyalgia, or complex regional pain syndrome, where pain perception can be heightened due to nervous system sensitivity rather than direct injury.  Its combination with exercise holds some potential in the relief of neck pain.  Recently, several studies have explored the efficacy of pain neuroscience education plus exercises for neck pain, but their routine use is not well established.  Therefore, we perform this meta-analysis to study the effects of pain neuroscience education plus exercises in patients with neck pain. 

This meta-analysis were performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses).  Since this was a meta-analysis of previously published studies, and thus ethical approval and patient consent were not required. 2.1. Search strategy and study selection We have searched the databases including PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases from inception to August 2023 by using the keywords: “pain neuroscience education” AND “exercise” OR “physical training” AND “neck pain.” The inclusive selection criteria were as follows: study design was RCT; patients were diagnosed with neck pain; intervention treatments were pain neuroscience education plus exercises versus exercises. Pain neuroscience education was delivered to the exercise, and included the discussion of acute pain, the transition from acute to chronic pain, central sensitization, brain plasticity, pain modulation and the importance of exercise, and the role of cognitions, emotions and sleep in pain.  2.2. Data extraction and outcome measures The following information were collected: author, number of women, age, body mass index, pain scores and detail methods between 2 groups. Data were extracted independently by 2 investigators, and discrepancies were resolved by consensus. The primary outcomes were VAS after treatment and VAS after 3 months. Secondary outcomes included functional disability index and pain catastrophizing scale. 2.3. Quality assessment in individual studies We evaluated the methodological quality of the included studies by using the modified Jadad scale,  in which 3 items were included: randomization (0–2 points), blinding (0–2 points), dropouts and withdrawals (0–1 points). The score of Jadad scale varied from 0 to 5 points, and Jadad score ≤ 2 suggested low quality, while Jadad score ≥ 3 indicated high quality.  2.4. Statistical analysis We calculated mean difference (MD) with 95% confidence interval (CI) for continuous outcomes. I 2 statistic was applied to assess heterogeneity, and I 2 > 50% indicated significant heterogeneity.  Random-effect model was used for significant heterogeneity, and otherwise fixed-effect model was applied. We detected the potential heterogeneity via omitting 1 study in turn for the meta-analysis or performing subgroup analysis. Publication bias was not evaluated because of the limited number (<10) of included studies. All statistical analyses were performed using Review Manager Version 5.3 (The Cochrane Collaboration, Software Update, Oxford, UK). 

We have searched the databases including PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases from inception to August 2023 by using the keywords: “pain neuroscience education” AND “exercise” OR “physical training” AND “neck pain.” The inclusive selection criteria were as follows: study design was RCT; patients were diagnosed with neck pain; intervention treatments were pain neuroscience education plus exercises versus exercises. Pain neuroscience education was delivered to the exercise, and included the discussion of acute pain, the transition from acute to chronic pain, central sensitization, brain plasticity, pain modulation and the importance of exercise, and the role of cognitions, emotions and sleep in pain.  

The following information were collected: author, number of women, age, body mass index, pain scores and detail methods between 2 groups. Data were extracted independently by 2 investigators, and discrepancies were resolved by consensus. The primary outcomes were VAS after treatment and VAS after 3 months. Secondary outcomes included functional disability index and pain catastrophizing scale. 

We evaluated the methodological quality of the included studies by using the modified Jadad scale,  in which 3 items were included: randomization (0–2 points), blinding (0–2 points), dropouts and withdrawals (0–1 points). The score of Jadad scale varied from 0 to 5 points, and Jadad score ≤ 2 suggested low quality, while Jadad score ≥ 3 indicated high quality.  

We calculated mean difference (MD) with 95% confidence interval (CI) for continuous outcomes. I 2 statistic was applied to assess heterogeneity, and I 2 > 50% indicated significant heterogeneity.  Random-effect model was used for significant heterogeneity, and otherwise fixed-effect model was applied. We detected the potential heterogeneity via omitting 1 study in turn for the meta-analysis or performing subgroup analysis. Publication bias was not evaluated because of the limited number (<10) of included studies. All statistical analyses were performed using Review Manager Version 5.3 (The Cochrane Collaboration, Software Update, Oxford, UK). 

3.1. Literature search, study characteristics, and quality assessment Figure demonstrates the flowchart of the search and selection results. Initially, 184 relevant articles were found, and finally 4 eligible randomized controlled trials (RCTs) were included in the meta-analysis.  Table shows the baseline characteristics of the eligible RCTs in the meta-analysis. They were published between 2021 and 2022, and total sample size was 246. The treatment duration varied from 6 weeks to 6 months. Among the 4 studies included here, 2 studies reported VAS after treatment and VAS after 3 months,  3 studies reported functional disability index  and 2 studies reported pain catastrophizing scale.  All included studies were regarded to have high quality because their Jadad scores varied from 3 to 4. 3.2. Primary outcomes: VAS after treatment and VAS after 3 months Compared with exercise intervention for neck pain, pain neuroscience education plus exercise was associated with significantly reduced VAS after treatment (MD = −1.12; 95% CI = −1.51 to −0.73; P < .00001) with no heterogeneity remained among the studies ( I 2 = 0%, heterogeneity P = .83, Fig. ) and VAS after 3 months (MD = −1.24; 95% CI = −2.26 to −0.22; P = .02) with significant heterogeneity remained among the studies ( I 2 = 62%, heterogeneity P = .11, Fig. ). 3.3. Sensitivity analysis Significant heterogeneity remained among the included studies for VAS after 3 months. However, we did not perform the sensitivity analysis by omitting 1 study in turn due to only 2 RCTs included for its meta-analysis. 3.4. Secondary outcomes Compared to exercise intervention for neck pain, pain neuroscience education plus exercise was able to substantially reduce functional disability index (MD = −1.22; 95% CI = −1.46 to −0.97; P < .00001; Fig. ) and pain catastrophizing scale (MD = −4.25; 95% CI = −5.50 to −3.00; P < .00001; Fig. ). 

Figure demonstrates the flowchart of the search and selection results. Initially, 184 relevant articles were found, and finally 4 eligible randomized controlled trials (RCTs) were included in the meta-analysis.  Table shows the baseline characteristics of the eligible RCTs in the meta-analysis. They were published between 2021 and 2022, and total sample size was 246. The treatment duration varied from 6 weeks to 6 months. Among the 4 studies included here, 2 studies reported VAS after treatment and VAS after 3 months,  3 studies reported functional disability index  and 2 studies reported pain catastrophizing scale.  All included studies were regarded to have high quality because their Jadad scores varied from 3 to 4. 

Compared with exercise intervention for neck pain, pain neuroscience education plus exercise was associated with significantly reduced VAS after treatment (MD = −1.12; 95% CI = −1.51 to −0.73; P < .00001) with no heterogeneity remained among the studies ( I 2 = 0%, heterogeneity P = .83, Fig. ) and VAS after 3 months (MD = −1.24; 95% CI = −2.26 to −0.22; P = .02) with significant heterogeneity remained among the studies ( I 2 = 62%, heterogeneity P = .11, Fig. ). 

Significant heterogeneity remained among the included studies for VAS after 3 months. However, we did not perform the sensitivity analysis by omitting 1 study in turn due to only 2 RCTs included for its meta-analysis. 

Compared to exercise intervention for neck pain, pain neuroscience education plus exercise was able to substantially reduce functional disability index (MD = −1.22; 95% CI = −1.46 to −0.97; P < .00001; Fig. ) and pain catastrophizing scale (MD = −4.25; 95% CI = −5.50 to −3.00; P < .00001; Fig. ). 

In order to study the influence of pain neuroscience education plus exercise on the management of neck pain, our meta-analysis included 4 RCTs and 246 patients with neck pain. The results found that pain neuroscience education plus exercise was able to significantly reduce VAS after treatment, VAS after 3 months, functional disability index and pain catastrophizing scale. These suggested the efficacy of pain neuroscience education plus exercise to improve pain relief and functional recovery for patients with neck pain. Regarding the sensitivity analysis, significant heterogeneity was seen for the VAS after 3 months. Several factors may account for the heterogeneity. Firstly, the severity and duration of neck pain was different, which affected the efficacy assessment. Secondly, the treatment duration of pain neuroscience education plus exercise varied from 6 weeks to 6 months. Thirdly, the various levels of education background affected the understanding and recognition of pain neuroscience education. In patients with neck pain, pain neuroscience education and exercise benefited to control catastrophizing, and anxiety and increase muscle endurance.  The adolescents who received their combination intervention found pain neuroscience education to be a facilitator of pain reconceptualization and a positive attitude as well as performance towards exercise.  Blended learning of pain neuroscience education aims to combine face-to-face and online educational sessions using electronic devices or platforms, which benefits to improve the implementation and efficacy.  We also should consider several potential limitations. Firstly, our analysis is based on only 4 RCTs and more RCTs are needed to confirm our findings. Secondly, significant heterogeneity was observed in this meta-analysis, which may be caused by different procedures and duration of pain neuroscience education plus exercise. Thirdly, different education backgrounds affected the understanding and recognition of pain neuroscience education. 

This meta-analysis suggested that pain neuroscience education and exercise was able to improve the relief and functional recovery of neck pain. 

Data curation: Chao Yang. Formal analysis: Chao Yang. Funding acquisition: Chao Yang. Resources: Yue Zhang. Software: Yue Zhang. Supervision: Yue Zhang. 

