International Journal of

Environmental Research
and Public Health

Review
Effectiveness of Interventions Based on Pain Neuroscience
Education on Pain and Psychosocial Variables for Osteoarthritis:
A Systematic Review
Leidy Tatiana Ordoñez-Mora 1, * , Marco Antonio Morales-Osorio 2,3,4 and Ilem D. Rosero 1

1 Health and Movement Research Group, Physiotherapy Program, Faculty of Health, Universidad Santiago de
Cali, Santiago de Cali 760033, Colombia; ilemdayana@gmail.com
2 Grupo Internacional de Investigación Neuro-Conductual (GIINCO), Universidad de la Costa,
Barranquilla 080002, Colombia; marco.morales.osorio@gmail.com
3 Facultad de Salud, Carrera de Kinesiología, Universidad Santo Tomás, Arica 1000000, Chile
4 Facultad de Ciencias de la Salud, Carrera de Kinesiología, Universidad Arturo Prat, Iquique 1100000, Chile
* Correspondence: tatiana.ormora@gmail.com; Tel.: +57-5183000

Abstract: Osteoarthritis (OA) is the most common joint condition. It affects more than 300 million
people worldwide, who suffer from pain and physical disability. Objective: To determine the results
of cognitive educational interventions for pain management and psychosocial variables in adults
with OA. Method: A systematic review was conducted based on searches in MEDLINE, OVID,
LILACS, Scopus, PEDro, OTseeker, The Cochrane Library, EBSCO, and Google Scholar. The search



strategy included the main terms neuroscience education and osteoarthritis, without any re-strictions

 with regard to dates or study type (PROSPERO register CRD42021222763). Results: We included
Citation: Ordoñez-Mora, L.T.; four articles that implemented the intervention in 1–6 sessions, addressing concepts related to goal
Morales-Osorio, M.A.; Rosero, I.D. orientation and providing strategies for understanding pain. The results suggest that there is an
Effectiveness of Interventions Based
improvement between the groups (PNE) when compared, but this cannot necessarily be attributed to
on Pain Neuroscience Education on
pain neuroscience education (PNE), as small effect sizes for variables such as pain catastrophizing and
Pain and Psychosocial Variables for
kinesiophobia were observed. The response in the modulation of acute pain following the surgical
Osteoarthritis: A Systematic Review.
procedure may produce a variation in the responses and this may be mediated by medications.
Int. J. Environ. Res. Public Health 2022,
19, 2559. https://doi.org/10.3390/
Conclusion: The study revealed an improvement in favor of the groups managed with PNE, although
ijerph19052559 more studies documenting the topic are warranted.

Academic Editors: Francisco

Keywords: osteoarthritis; chronic pain; physical therapy; neurology; education; catastrophizing
M. Kovacs and José Carmelo
Adsuar Sala

Received: 12 December 2021

Accepted: 13 February 2022 1. Introduction
Published: 23 February 2022 Osteoarthritis (OA) is the most common joint condition. It affects more than 300 million
Publisher’s Note: MDPI stays neutral people worldwide, who suffer from pain and physical disability [1]. Osteoarthritis (OA)
with regard to jurisdictional claims in is the most commonly observed joint condition in the adult population in any region
published maps and institutional affil- of the world. Its prevalence varies according to geographical location, ethnic group,
iations. sex, age, and affected joint [2]. The Global Burden of Disease study in 2017 showed a
prevalence of 3754.2 per 100,000 cases [1–3]. It affects 1 in 8 men and women in the US
(about 27–31 million people) and about 302 million people worldwide [4]. The joints in the
knees, hips, and hands are the most affected [4], and, reportedly, the joint with the greatest
Copyright: © 2022 by the authors. symptomatology is the knee joint. Globally, it is estimated that 250 million people have OA
Licensee MDPI, Basel, Switzerland.
of the knee [5]. OA is a chronic debilitating disease of the mobile joints characterized by
This article is an open access article
the deterioration of the articular cartilage, alteration of the subchondral bone, formation of
distributed under the terms and
osteophyte, narrowing of joint space, and inflammation of the synovial membrane [6].
conditions of the Creative Commons
According to different research studies, adults are more affected by this disease,
Attribution (CC BY) license (https://
which worsens with age. It has been reported that about one-third of all adults globally
creativecommons.org/licenses/by/
4.0/).
present radiological signs of OA and must deal with pain, which leads to a reduction in

Int. J. Environ. Res. Public Health 2022, 19, 2559. https://doi.org/10.3390/ijerph19052559 https://www.mdpi.com/journal/ijerph
Int. J. Environ. Res. Public Health 2022, 19, 2559 2 of 13

mobility that can result in disability and difficulty in maintaining independence [7]. Pain
severity is associated with functional limitations, disability, and health-related quality of
life (HRQoL), which is impaired in patients with this pathology. Functional limitations may
be of particular relevance when OA affects the upper extremities [7]. One study reported
an association between HRQoL, threshold, pain perception, and passive coping strategies
with chronic pain (specifically withdrawing, worrying, and resting) in patients with OA [8].
Pharmacological options for symptom management include the use of oral corticos-
teroids, opioids and, in some cases, intra-articular corticosteroid injections [9,10]. This is in
addition to implementing non-pharmacological approaches, such as education, exercise,
and weight loss, which are the cornerstones of these treatments. Such treatments have
proven to be effective, but they require changes in the patient’s behavior, which are difficult
to obtain. Exercise and weight loss improve functionality and reduce pain [11–13]. Educa-
tion enhances compliance with and adherence to exercise and weight loss programs, which
improves their long-term benefits [14]. Other more traditional treatments, such as orthope-
dic manual therapy, the use of splints, and the physical agent modalities approach provide
short-term benefits in reducing pain, and improving function and physical performance
in patients with OA [15–17]. In turn, there is a tendency to generate an improvement in
multicomponent interventions using adherence-related educational processes [18], conse-
quently resulting in an improvement in pain, among the multiple benefits observed [13].
Modern pain neuroscience has improved the understanding of chronic musculoskeletal
pain, including the role of central sensitization [19]. In the last decade, an educational
model on pain biology and physiology has been recognized as a compelling approach
toward chronic pain management [20–22]. This model refers to a variety of educational
interventions [23] and has been outlined using the following terms: explanation of pain [24],
therapeutic neuroscience education, and pain neuroscience education (PNE) [25].
PNE is increasingly used as part of physiotherapy treatment in patients with chronic
pain. A thorough clinical biopsychosocial assessment is recommended prior to PNE to
allow for an adequate explanation of pain neurophysiology and biopsychosocial interac-
tions, and for this process to be patient-centered [26]. Therefore, new studies are needed
that can evaluate these treatment pathways [27]. No systematic review or meta-analysis
exists, although there are a number of studies investigating the effectiveness of cognitive
educational interventions as an adjuvant therapy in patients with OA. This systematic
review aims to determine the outcomes of cognitive educational interventions on pain and
psychosocial variables in adults with OA.

2. Materials and Methods

This study followed the Cochrane Collaboration specifications for systematic re-
views [28] and the criteria included in the PRISMA checklist [29]. The protocol was
included in the international prospective register of systematic reviews (PROSPERO
CRD42021222763).

2.1. Eligibility Criteria

The following research question (PICO) was established:
Population: Adult patients (18 years of age and older) with OA.
Intervention: Cognitive educational interventions (PNE, pain neurophysiology, pain
therapeutic education, explanation of pain).
Comparison: Conventional therapy or treatment.
Results: Pain intensity, stress level, catastrophizing, kinesiophobia, disability, and
quality of life.
Type of study: Randomized controlled clinical trials, experimental studies, quasi-
experimental studies, and pilot studies that assessed the effects of the interventions and
included outcome measures.
Exclusion criteria: Studies in which the intervention used did not correspond to
neuroscience education or the interventional strategy referred to an area other than physio-
Int. J. Environ. Res. Public Health 2022, 19, 2559 3 of 13

therapy, and studies with cognitive behavioral therapy or education that did not include
the neuroscience component were excluded.

2.2. Information Source and Search Strategy

The study was carried out by resorting to the following databases, digital bibliographic
libraries, or search engines: MEDLINE, OVID, LILACS, Scopus, PEDro, OTseeker, The
Cochrane Library (Cochrane Central Register of Controlled Trials), EBSCO, and Google
Scholar. The search strategy included Neuroscience education and Osteoarthritis as the
main terms. The complete strategy is described in the PROSPERO protocol and Appendix A:
(Pain Education OR pain neurophysiology OR neuroscience education OR pain neuro-
science education AND chronic pain AND osteoarthritis OR osteoarthritides); also see
Appendix A. The search was not restricted to language or date of publication. The searches
were conducted between 22 November 2020 and 31 July 2021.

2.3. Selection of Studies

Study selection began with a calibration process for the selection. Two researchers
(LTO and MMO) blindly and independently initiated the filtering processes after searching
the different databases. Each researcher produced a list of studies after analyzing the
title and abstract of each article. The article was included when there was agreement
between the reviewers and, in the case of discrepancies between them, a third reviewer
(IDR) decided on the inclusion of the article. The reviewer was blinded to the answers
given by each researcher. Eligibility criteria were applied to the full-text analysis in the
final selection. Any disagreement between the authors regarding eligibility, quality, and
data retrieved from the studies was resolved by consensus.

2.4. Information Gathering Process

Data extraction was performed independently using an Excel-generated format (LTO),
which included the first author and year, research design, country, sample size, age, study
type, pathological stage, time elapsed since diagnosis, study objective, presence of phar-
macological treatment, description of the PNE-based intervention, description of the com-
parison intervention or additional interventions, scale used, and outcomes in terms of
pain, stress level, catastrophizing, kinesiophobia, disability, quality of life, adherence,
and adverse events reported, if any. These results were used to present the mean and
standard deviations per reported outcome. MMO and IDR confirmed the accuracy of
the information.

2.5. Quality Rating, Risk of Bias and Certainty of the Included Articles
The quality of the included studies was assessed blindly and independently using
the MINORS scale [30]. This evaluates the presence of a clearly established objective,
the inclusion of consecutive patients, collection of prospective data, analysis adapted to
the design/results presented, reporting of data loss, and equivalence between groups.
Subsequently, a decision was made to include a given study considering a score of 11 as
the minimum criterion. For studies corresponding to clinical trials, the PEDro [31] scale
was used, which evaluates randomization, allocation concealment, similarity of baseline
characteristics, participant masking, therapist masking, assessor masking, outcome data on
at least 85% of participants for at least one primary outcome, intention-to-treat analysis,
and statistical comparisons between groups and their outcomes.
If possible, data analysis was performed using Software Review Manager (Version 5.3,
London, UK). Data were extracted using the weighted mean difference between groups.
Heterogeneity was measured with I2, considering values greater than 40%. Clinical hetero-
geneity was reviewed by analyzing the variability of the participants, the interventions,
and the results. Certainty Analysis to generate this process used the tool Grade [32], which
provides explicit criteria for rating the quality of evidence, including study design, risk of
Int. J. Environ. Res. Public Health 2022, 19, 2559 4 of 13

bias, imprecision, inconsistency, indirectness, and magnitude of effect, with the support of
GRADEpro GDT [33].

3. Results
Considering the systematic searches, a flowchart corresponding to the initial inclusion
of articles and the application of filters was made. Starting with 12,573 titles eligible for
selection, 202 unique records remained after the removal of duplicates. Finally, four articles
were included in the qualitative synthesis of this study, as shown in Figure 1 and Table 1.

Figure 1. Search flowchart. Source: Own source.

Table 1. Characterization of the studies.

Year Population and Intervention Pharmacological

Author Control Scales Used Results
Mean Age Treatment
Rehabilitation (same as the Rehabilitation only No significant effects
control group) + 6 PNE NSAIDs 3 times a day
(weight bearing as NRS, were found in the
IG: 67 (67 years); postoperatively, tapered
Deguchi, N et al. [34] 2019 sessions were carried out by tolerated, 6 times a PCS, comparison items
CG: 52 (63.7 years) a physiotherapist, with each off at 3 weeks PSEQ between groups, except
week in 40- to 60-
postoperatively
session lasting 60 min minute sessions) catastrophizing.
IG: 49 (74.1 ± 9.5) Traditional Opioid treatment NRS,
31 analyzed; CG: preoperative PCS, No differences could be
Louw, A et al. [35] 2019 PNE according to the found between
54 (69.6 ± 10.6) educational Tampa scale,
determined regulation WOMAC the groups.
36 analyzed program
Patients = 12 The second group NRS, There were changes in
Louw, A et al. [36] 2018 [10 women + 2 men] PNE Not specified PCS,
(68.6 ± 8.7 years) was not managed Tampa Scale favor of the PNE group.

IG patients: CSI, Changes were found

27 (72.8 ± 5.6); CG PNE + knee joint Biomedical PCS, regarding kinesiophobia
Lluch et al. [37] 2017 education + Knee Not specified
patients: mobilization Tampa Scale, and catastrophizing
joint mobilization WOMAC
27 (67.7 ± 7.8) for PNE.

Abbreviations: IG (Intervention Group), CG (Control Group), PNE (pain neuroscience education), NSAIDs (non-
steroidal anti-inflammatory drugs), (NRS (Numerical Rating Scale), PCS (Pain Catastrophizing Scale), PSEQ (Pain
Self-Efficacy Questionnaire Score), Tampa (Scale of Kinesiophobia), WOMAC (Western Ontario and McMaster
Universities Osteoarthritis Index), CSI (Central Sensitization Inventory).

3.1. Description of the Intervention

The PNE intervention was performed by a physiotherapist. The duration of the
sessions varied: 40–60 min in one study [34], 30 min in two studies [35,36], and 60 min (first
session) and 30 min (remaining sessions) in one study [37].
Int. J. Environ. Res. Public Health 2022, 19, 2559 5 of 13

Regarding the description of the intervention, the sessions addressed the development
of the following aspects as the interventions were performed: 1. Purpose of neuroscience
education, which included intervention objectives [34]; 2. Explanation of biological models
and pathways [34,37]; 3. Pain and sleep, including pain distraction and inactivity; 4. Pain
and lifestyle; 5. Self-care; 6. Decisions [34], predisposing factors to sensitization, the pain
matrix, pain reconceptualization, surgical experiences, and knowledge transfer [37].
The sessions used prepared images to explain pain, ranging from the definition of
an action potential to pain processing. Metaphorical material was also used, with exam-
ples making reference to the content [34–37], thereby enabling the possibility of creating
PowerPoint presentations or using brochures [35]. Additionally, one of the studies used a
different approach, i.e., book reading, to explain pain [24,37].
The results of the pharmacological treatment did not reveal any changes in the medi-
cation dosages of the groups with which they were compared, nor were any significant dif-
ferences observed in the groups [34,35]. Two studies did not report on medications [34,35].
The adherence levels reported in the studies were 84% [34], 63% at 1-year follow-up,
100% [36], and 81% [37]. None of the studies reported adverse events resulting from the
PNE intervention.
Description of Patients with OA
The studies reported on patients with radiologically proven OA (with diagnosis
time of over 6 months) and candidates for total knee arthroplasty [34,37]. In the other
studies, patients met the Western Ontario and McMaster Universities Osteoarthritis Index
(WOMAC) diagnostic criteria and were candidates for total knee replacement [35,36].

3.2. Assessing the Quality of the Evidence

3.2.1. MINORS Scale
The main reported methodological flaws were found in the prospective evaluation of
the data, the equivalence and management of the groups, and the masked evaluation of the
groups. However, due to the nature of the questionnaires used for pain study processes,
many surveys were self-administered. See Figure 2.

Figure 2. Risk of bias with the Minors scale. Source: Own source with Revman Manager 5.3.

3.2.2. Pedro Scale

With regard to the evaluation of the clinical trials, there were shortcomings in terms of
the masking in the Louw study [35] and in the allocation concealment. See Figure 3.
Int. J. Environ. Res. Public Health 2022, 19, 2559 6 of 13

Figure 3. Risk of bias PEDro scale. Source: Own source with Revman Manager 5.3.

Table 2 shows the main results of the measurements pain, catastrophizing, kinesiopho-
bia, disability, and quality of life found in the review. A meta-analysis of the data was not
possible because of heterogeneity and a lack of unanimity in the interventions presented.

Table 2. Results of the studies for pain, catastrophizing, kinesiophobia, disability, quality of life.

Author Scale Pain Scale Catastrophizing Scale Kinesiophobia Scale Disability Scale Quality of Life

Without significant Significant effects in favor No significant changes

changes in the groups of PNE between the groups
IG: Pain at rest IG: IG:
pre 2.0 (2.6) pre 30.3 (6.5) pre 37.6 (10.6) post
Deguchi, N et al. [34] NRS PCS PSEQ
post 1.1 (1.3) post 16.9 (9.7) 43.4 (10.2)
CG: pain at rest CG: CG:
pre 1.9 (2.3) pre 30.8 (7.7) pre 36.3 (11.1) post
post 0.8 (1.2) post 20.7 (8.4) 38.7 (12.8)

Significant There were no

No significant differences There were no
improvement in both significant differences
between the groups significant differences
groups. There was a between the groups
F (3192) = 0.209, p = 0.819, Tampa Scale of in the groups
Louw, A et al. [35] NRS difference attributable PCS F (3192) = 1.402, WOMAC
power = 0.083. Kinesiophobia F (3195) = 1.501,
to time (p < 0.001) p = 0.245,
(p = 0.075), yes, difference p = 0.222,
with improvements in power = 0.358
in time (p < 0.001) power = 0.355
all patients. (p = 0.247)

There were no
significant differences A difference in favor
between the pre- and There were no significant of the PNE post
post-intervention differences between the intervention.
measures. measures. pre 42.0
pre PNE 5.0 pre 3.3–27.8 (1.0–51.0) Tampa Scale of IQR = 38.5–44.0
Louw, A et al. [36] NRS PCS
IQR = 2.3–6.8 post 7.0 Kinesiophobia Range (31.0–54.0)
Range (0.0–8.0) IQR = 3.3–15.8 post 39.0
post PNE 3.5 Range (0.0–36.0) IQR = 36.0–42.5
IQR = 1.0–5.0 p = 0.081 Range (31.0–46.0)
Range (0.0–7.0) p = 0.036
p = 0.119

There were no There were no

There were no significant Significant changes in
significant differences significant differences
differences between IG favor of the PNE IG
between the groups. between the groups
groups: were reported
IG: IG:
PCS Pre 22.6 ± 11.5 Tampa Scale of pre 34.3 ± 7
Lluch E, et al. [37] CSI pre 37.6 ± 17.2 WOMAC pre 52.4 ± 14.6
post 12.5 ± 10.3 Kinesiophobia post 25.9 ± 5.9
post 30.3 ± 10.2 post 41.4 ± 13.7
CG: CG:
CG: CG:
pre 25.9 ± 13.6 pre 33.7 ± 5.6
pre 38.3 ± 15.6 pre 52.1 ± 18.4
post 24.5 ± 13.6 post 33.6 ± 6.7
post: 38.1 ± 15.7 post 50.1 ± 18.5

Abbreviations: IG (Intervention Group), CG (Control Group), PNE (pain neuroscience education), NRS (Numerical
Rating Scale), PCS (Pain Catastrophizing Scale), PSEQ (Pain Self-Efficacy Questionnaire Score), Tampa (Scale
of Kinesiophobia), WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index), CSI (Central
Sensitization Inventory). Source: Own source
Int. J. Environ. Res. Public Health 2022, 19, 2559 7 of 13

3.3. Pain Results

3.3.1. PNE Compared with Another Intervention
A study added PNE to the conventional rehabilitation process. In this study, significant
results were found with regard to the intensity of pain, both at rest and while walking, in
favor of the group that included PNE when compared with the second group [34].

3.3.2. PNE Compared with Other Educational Processes

A study compared PNE with traditional preoperative management. In this case, the
two groups showed an improvement in pain modulation without significant differences
between their results [35]. Conversely, no significant changes or differences between groups
were found in a study that used PNE in combination with knee joint mobilization [37].

3.3.3. PNE with No Comparison

One study evaluated the effect of PNE on a single group and reported no significant
changes in pain reduction when compared to the baseline [36].

3.4. Catastrophizing Results

3.4.1. PNE Compared with Another Intervention
For catastrophizing, significant results were reported, p = 0.036, in favor of the PNE
group [34].

3.4.2. PNE Compared with Other Educational Processes

No differences were reported in this variable in a comparison between the groups [34].
In another study, post-intervention changes were observed in favor of the PNE group and
at 1 month after treatment when compared with the baseline, but this difference evened
out at the 3-month follow-up [37].

3.4.3. PNE with No Comparison

No significant differences were found in the baseline and post-intervention outcomes
for this measure [36].

3.5. Kinesiophobia Results

3.5.1. PNE Compared with Other Educational Processes
No differences were reported for this measure between the two groups, but a signifi-
cant effect could be observed over time when compared with the baseline in the control
and intervention groups [35].
Significant changes in this measure were reported 3 months postoperatively in favor
of the PNE group compared with the control group [37].

3.5.2. PNE with No Comparison

Significant changes compared with the baseline were reported for kinesiophobia [36].

3.6. Disability Results

PNE Compared with Other Educational Processes
There were no significant differences attributed to either group. There was improve-
ment in this score at 1 month, but the difference leveled off over time [35]. The WOMAC
score was lower for both groups 1 month after treatment when compared with the baseline
(p < 0.01) [37].

3.7. Quality of Life Results

PNE Compared with Another Intervention
A statistically significant difference was found in favor of the PNE group regarding
the quality of life measured using the Pain Self-Efficacy Questionnaire score [34].
Int. J. Environ. Res. Public Health 2022, 19, 2559 8 of 13

3.8. Certainty Analysis

The certainty analysis is presented, each outcome measure evaluated was included
and, due to the differences between the studies, these are addressed separately, and the
degrees of evidence of the working group defined by GRADE were considered.
High certainty: We are very confident that the true effect is close to that of the effect estimate.
Moderate certainty: We are moderately confident in the effect estimate: the true effect is
likely to be close to the effect estimate, but there is a possibility that it is substantially different.
Low certainty: our confidence in the effect estimate is limited: the true effect may be
substantially different from the effect estimate.
Very low certainty: We have very low confidence in the effect estimate: the true effect
is likely to be substantially different from the effect estimate. See Figure 4.

Figure 4. Certainty analysis with GRADE. Conventions: a One of the studies had no concealment
or randomization and blinding of assessment. b Media and DS cannot be accessed, which makes it
impossible to generate the meta-analysis. c There is no blinding of the evaluations, the collection of
the patients is not clear. d The data differ from those reported with this scale in other studies. e there
is no blinding of the evaluations, no second group was generated. f The measurements are generated
in ranges. g The intervals are wide. Source: Own source with GRADEpro GDT.

3.9. Characteristics of the Excluded Studies

The excluded studies were those that did not report data on the specific intervention
of PNE or, when generating the process, another educational concept other than PNE was
mentioned as conventional education without mentioning the neuroscience component.
Similarly, studies that addressed a protocol, but excluded intervention without presentation
of published results, were not considered. See Table 3.
Int. J. Environ. Res. Public Health 2022, 19, 2559 9 of 13

Table 3. Excluded studies.

Autor Year Type of Study Reasons for Exclusion

It is a protocol, mention another
Wang, L et al. [38] 2021 Clinical trial
educational technique
Larsen, J et al. [39] 2020 Clinical trial It is a protocol
Lawford, B et al. [40] 2018 Clinical trial it does not mention the specific technique
Saw MM et al. [41] 2016 Clinical trial mention another educational technique
Bennell Kl et al. [42] 2016 Clinical trial mention another educational technique
Fernandes L et al. [43] 2010 Clinical trial mention another educational technique
Bezalel T et al. [44] 2010 Clinical trial mention another educational technique
Baird CL et al. [45] 2004 Clinical trial mention another educational technique
Ettinger WH et al. [46] 1997 Clinical trial mention another educational technique
Source: Own source.

4. Discussion
Four studies were included that involved the effects of PNE on patients with OA, in
which a reduction in pain was found for the groups whose intervention included PNE,
which may be due to pharmacological modulation without dismissing the effect of the
educational intervention. Significance was found for variables such as kinesiophobia for the
groups with PNE. There is a tendency to improve aspects such as quality of life. However,
it was not a measure included in all the studies. There were no changes in disability level
and the measure of stress level initially considered in the protocol was not addressed in
any of the studies.
The process of neuroscience education aims to transfer knowledge to patients, allowing
them to understand their pain and establish coping strategies, thereby decreasing erroneous
beliefs and challenges associated with pain [47]. The results of this review suggest that
there is an improvement when comparing the treatment groups. However, this cannot be
attributed solely to PNE because small effect sizes were found in most studies for the main
variables, such as pain catastrophizing and kinesiophobia [34,37]. This contrasts with the
results reported by Louw et al. [48], who concluded that, in patients with chronic pain,
there is compelling evidence that an educational strategy addressing the neurophysiology
and neurobiology of pain can have a positive effect on pain, disability, catastrophizing, and
physical performance. In turn, the response in the modulation of acute pain following the
surgical process can produce variations in responses that can be mediated by medications
(ranging from opioids to NSAIDs) and the therapeutic process [49].
Regarding pain intensity, no significant differences were found between the groups.
Another systematic review that included different pathologies with chronic musculoskeletal
pain found that PNE has a small-to-moderate effect on pain intensity with greater long-term
effects for this variable. This could be explained by the fact that 11 of the 18 studies focused
mostly on low back pain, the area most extensively researched with regard to PNE [50].
Regarding the results reported by Louw et al. [36], the intervention used was group-based,
with a duration of 30 min, which may not be sufficient to estimate an actual change in
the patient. However, no differences were found in the level of disability [35,37], which
is consistent with the findings of another study in which the interindividual difference
in the change in disability in response to PNE (7.36/100) did not meet the criterion for
clinical significance (10/100). Therefore, there is insufficient evidence for PNE response
estimation [51].
Among our recommendations, we suggest including preoperative work and reports
regarding medication prescriptions. A previous study on lumbar radiculopathy included
these variables, in addition to the cost estimation [52]. Louw also added this variable
and reported no reduction in expenses or medication consumption with regard to knee
Int. J. Environ. Res. Public Health 2022, 19, 2559 10 of 13

arthroplasty [35]. This may be explained by the differences in the costs of post-surgical
processes between spine and knee.
The fact that Lluch’s study did not include a control group for the comparison of the
two interventions impedes establishing the adequacy of the interventions when compared
with not receiving any education [37]. Limitations were found in all studies regarding the
sample sizes, the adherence reported in the studies, which may result in the introduction
of another type of conclusion in the analysis given by the protocol, and the heterogeneity
in catastrophizing events, which can lead to variability. It is suggested that a report be
fashioned based on the type of pain, which enables subgroup analysis, thereby allowing the
establishment of the profile on which work can be conducted. Regarding the discrepancies
with the originally published protocol of Prospero, the inclusion of only clinical trials
had been considered, in addition to limiting the searches to this type of study; but due to
the lack of literature, it had to be extended to observational studies, which allowed the
inclusion of two more studies within the results.
During the execution of this study, the meta-analysis was a limiting factor, since it
could not be unified or a sum of effects could not be generated. This is due to the fact that
the interventions did not have the same dosing as each other and there were only four
studies. Regarding the implications for practice, the inclusion of educational programs
within the care processes in patients with OA is suggested. Thus, it is recommended that
the authors of intervention studies standardize the evaluation measures in the presentation
of the results and opt for the use of widely disseminated instruments used in other studies
of the same type. This will allow an estimate of the size of the effect to be made.

5. Conclusions
Non-pharmacological 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.
However, this may be due to pharmacological modulation, so further studies are warranted
to make a recommendation regarding this intervention.

Author Contributions: Conceptualization, M.A.M.-O. and L.T.O.-M.; methodology, M.A.M.-O. and

L.T.O.-M.; formal analysis, M.A.M.-O., L.T.O.-M. and I.D.R.; writing—review and editing, M.A.M.-O.,
L.T.O.-M. and I.D.R. All authors have read and agreed to the published version of the manuscript.
Funding: This research was funded by the Directorate General of Research (Dirección General de
Investigaciones) of the Universidad Santiago de Cali (No. 01-2021).
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest. The funders had no role in the design
of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or
in the decision to publish the results.

Appendix A
Search strategies for the different databases
1 Pain Education
2 Pain Neuroscience
3 Pain Neuroscience education
4 Neurophysiology education
5 Therapeutics Neuroscience Education
6 Chronic Pain
7 Osteoarthritis
Int. J. Environ. Res. Public Health 2022, 19, 2559 11 of 13

8 MH Chronic Pain
9 MH Osteoarthritis
10 1 AND 6 AND 7
11 1 AND 6 OR 8 AND 7
12 2 AND 7
13 3 AND 7 OR 9
14 4 AND 7
15 5 AND 7
MH = Medical Topic Headings, TX = Words

References
1. Safiri, S.; Kolahi, A.A.; Smith, E.; Hill, C.; Bettampadi, D.; Mansournia, M.A.; Almasi-Hashiani, A.; Ashrafi-Asgarabad, A.;
Moradi-Lakeh, M.; Qorbani, M.; et al. Global, regional and national burden of osteoarthritis 1990–2017: A systematic analysis of
the Global Burden of Disease Study 2017. Ann. Rheum. Dis. 2020, 79, 819–828. [CrossRef] [PubMed]
2. Organizacioón Mundial de la Salud. Aplicaciones de la Epidemiologiía al Estudio de Los Ancianos. Informe Teécnico. Available
online: http://apps.who.int/iris/handle/10665/39141?locale=e (accessed on 8 November 2021).
3. Michael, J.; Schlüter-Brust, K.; Eysel, P. The epidemiology, etiology, diagnosis, and treatment of osteoarthritis of the knee. Dtsch.
Arztebl. Int. 2010, 107, 152–162. [CrossRef] [PubMed]
4. Kolasinski, S.L.; Kolasinski, S.L.; Neogi, T.; Neogi, T.; Hochberg, M.C.; Hochberg, M.C.; Oatis, C.; Oatis, C.; Guyatt, G.;
Guyatt, G.; et al. Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Care Res. 2020, 72, 149–162.
[CrossRef]
5. O’Neill, T.; McCabe, P.; McBeth, J. Update on the epidemiology, risk factors and disease outcomes of osteoarthritis. Best Pract. Res.
Clin. Rheumatol. 2018, 32, 312–326. [CrossRef]
6. Malemud, C.J. Biologic basis of osteoarthritis: State of the evidence. Curr. Opin. Rheumatol. 2015, 27, 289–294. [CrossRef]
[PubMed]
7. Montero, A.; Mulero, J.; Tornero, C.; Guitart, J.; Serrano, M. Pain, disability and health-related quality of life in osteoarthritis-joint
matters: An observational, multi-specialty trans-national follow-up study. Clin. Rheumatol. 2016, 35, 2293–2305. [CrossRef]
8. Oliveira, P.; Monteiro, P.; Coutinho, M.; Salvador, M.; Costa, M.; Malcata, A. Health-related quality of life and chronic pain
experience in rheumatic diseases. Acta Reumatol. Port. 2009, 34, 511–519. [PubMed]
9. Mandl, L. Osteoarthritis year in review 2018: Clinical. Osteoarthr. Cartil. 2019, 27, 359–364. [CrossRef] [PubMed]
10. Nelson, A. Osteoarthritis year in review 2017 clinical. Osteoarthr. Cartil. 2018, 26, 319–325. [CrossRef]
11. Robson, E.K.; Hodder, R.K.; Kamper, S.J.; O’Brien, K.M.; Williams, A.; Lee, H.; Wolfenden, L.; Yoong, S.; Wiggers, J.;
Barnett, C.; et al. Effectiveness of Weight-Loss Interventions for Reducing Pain and Disability in People with Common
Musculoskeletal Disorders: A Systematic Review with Meta-Analysis. J. Orthop. Sports Phys. Ther. 2020, 50, 319–333. [CrossRef]
[PubMed]
12. Teirlinck, C.H.; Verhagen, A.P.; Reijneveld, E.A.E.; Runhaar, J.; van Middelkoop, M.; van Ravesteyn, L.M.; Hermsen, L.;
de Groot, I.B.; Bierma-Zeinstra, S.M.A. Responders to Exercise Therapy in Patients with Osteoarthritis of the Hip: A Systematic
Review and Meta-Analysis. Int. J. Environ. Res. Public Health 2020, 17, 7380. [CrossRef] [PubMed]
13. Goh, S.-L.; Persson, M.S.M.; Stocks, J.; Hou, Y.; Welton, N.; Lin, J.; Hall, M.C.; Doherty, M.; Zhang, W. Relative Efficacy of Different
Exercises for Pain, Function, Performance and Quality of Life in Knee and Hip Osteoarthritis: Systematic Review and Network
Meta-Analysis. Sports Med. 2019, 49, 743–761. [CrossRef] [PubMed]
14. Gay, C.; Chabaud, A.; Guilley, E.; Coudeyre, E. Educating patients about the benefits of physical activity and exercise for their hip
and knee osteoarthritis. Systematic literature review. Ann. Phys. Rehabil. Med. 2016, 59, 174–183. [CrossRef]
15. Anwer, S.; Alghadir, A.; Zafar, H.; Brismée, J.M. Effects of orthopaedic manual therapy in knee osteoarthritis: A systematic review
and meta-analysis. Physiotherapy 2018, 104, 264–276. [CrossRef]
16. Marotta, N.; Demeco, A.; Marinaro, C.; Moggio, L.; Pino, I.; Barletta, M.; Petraroli, A.; Ammendolia, A. Comparative Effectiveness
of Orthoses for Thumb Osteoarthritis: A Systematic Review and Network Meta-analysis. Arch. Phys. Med. Rehabil. 2021, 102,
502–509. [CrossRef]
17. Letizia Mauro, G.; Scaturro, D.; Gimigliano, F.; Paoletta, M.; Liguori, S.; Toro, G.; Iolascon, G.; Moretti, A. Physical Agent
Modalities in Early Osteoarthritis: A Scoping Review. Medicina 2021, 57, 1165. [CrossRef] [PubMed]
18. Ritschl, V.; A Stamm, T.; Aletaha, D.; Bijlsma, J.W.J.; Böhm, P.; Dragoi, R.; Dures, E.; Estévez-López, F.; Gossec, L.; Iagnocco, A.; et al.
Prevention, screening, assessing and managing of non-adherent behaviour in people with rheumatic and musculoskeletal diseases:
Systematic reviews informing the 2020 EULAR points to consider. RMD Open 2020, 6, e001432. [CrossRef]
19. Nijs, J.; Goubert, D.; Ickmans, K. Recognition and Treatment of Central Sensitization in Chronic Pain Patients: Not Limited to
Specialized Care. J. Orthop. Sports Phys. Ther. 2016, 46, 1024–1028. [CrossRef] [PubMed]
20. Louw, A.; Puentedura, E. Therapeutic Neuroscience Education: Teaching Patients about Pain: A guide for Clinicians; International Spine
and Pain Institute: Story City, IA, USA, 2013.
Int. J. Environ. Res. Public Health 2022, 19, 2559 12 of 13

21. Malfliet, A.; Kregel, J.; Meeus, M.; Cagnie, B.; Roussel, N.; Dolphens, M.; Danneels, L.; Nijs, J. Applying contemporary
neuroscience in exercise interventions for chronic spinal pain: Treatment protocol. Braz. J. Phys. Ther. 2017, 21, 378–387. [CrossRef]
22. Nijs, J.; Malfliet, A.; Ickmans, K.; Baert, I.; Meeus, M. Treatment of central sensitization in patients with “unexplained” chronic
pain: An update. Expert Opin. Pharmacother. 2014, 15, 1671–1683. [CrossRef] [PubMed]
23. Moseley, G.L.; Butler, D.S. Fifteen Years of Explaining Pain: The Past, Present, and Future. J. Pain 2015, 16, 807–813. [CrossRef]
[PubMed]
24. Moseley, G.; Butler, D. Explain Pain Supercharged; NOI Group Publishers: Adelaide City, Australia, 2017.
25. Nijs, J.; Lluch Girbés, E.; Lundberg, M.; Malfliet, A.; Sterling, M. Exercise therapy for chronic musculoskeletal pain: Innovation by
altering pain memories. Man. Ther. 2015, 20, 216–220. [CrossRef] [PubMed]
26. Lluch Girbés, E.; Nijs, J.; Torres-Cueco, R.; López Cubas, C. Pain treatment for patients with osteoarthritis and central sensitization.
Phys. Ther. 2013, 93, 842–851. [CrossRef] [PubMed]
27. Wijma, A.; van Wilgen, C.; Meeus, M.; Nijs, J. Clinical biopsychosocial physiotherapy assessment of patients with chronic pain:
The first step in pain neuroscience education. Physiother. Theory Pract. 2016, 32, 368–384. [CrossRef] [PubMed]
28. Higgins, J.P.; Green, S. Cochrane handbook for systematic reviews. Cochrane Collab. 2008, 5, 74–100.
29. Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.;
Brennan, S.E.; et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 2021, 372, n71.
[CrossRef]
30. Slim, K.; Nini, E.; Forestier, D.; Kwiatkowski, F.; Panis, Y.; Chipponi, J. Methodological index for non-randomized studies
(MINORS): Development and validation of a new instrument. ANZ J. Surg. 2003, 73, 712–716. [CrossRef] [PubMed]
31. Sydney Musculoskeletal Health. PEDro—Physiotherapy Evidence Database—PEDro Scale. 2020. Available online: https:
//pedro.org.au/spanish/resources/pedro-scale/ (accessed on 6 June 2020).
32. Schünemann, H.; Brożek, J.; Guyatt, G.; Oxman, A. (Eds.) GRADE Handbook for Grading Quality of Evidence and Strength of
Recommendations. Updated October 2013. The GRADE Working Group, 2013. Available online: https://gdt.gradepro.org/app/
handbook/handbook.html (accessed on 10 December 2021).
33. GRADEpro GDT: GRADEpro Guideline Development Tool [Software]. McMaster University and Evidence Prime, 2021. Available
online: gradepro.org (accessed on 10 December 2021).
34. Deguchi, N.; Hirakawa, Y.; Izawa, S.; Yokoyama, K.; Muraki, K.; Oshibuti, R.; Higaki, Y. Effects of pain neuroscience education in
hospitalized patients with high tibial osteotomy: A quasi-experimental study using propensity score matching. BMC Musculoskelet.
Disord. 2019, 20, 516. [CrossRef]
35. Louw, A.; Puentedura, E.J.; Reed, J.; Zimney, K.; Grimm, D.; Landers, M.R. A controlled clinical trial of preoperative pain
neuroscience education for patients about to undergo total knee arthroplasty. Clin. Rehabil. 2019, 33, 1722–1731. [CrossRef]
[PubMed]
36. Louw, A.; Zimney, K.; Reed, J.; Landers, M.; Puentedura, E.J. Immediate preoperative outcomes of pain neuroscience education
for patients undergoing total knee arthroplasty: A case series. Physiother. Theory Pract. 2019, 35, 543–553. [CrossRef] [PubMed]
37. Lluch, E.; Dueñas, L.; Falla, D.; Baert, I.; Meeus, M.; Sánchez-Frutos, J.; Nijs, J. Preoperative pain neuroscience education combined
with knee joint mobilization for knee osteoarthritis. Clin. J. Pain 2018, 34, 44–52. [CrossRef] [PubMed]
38. Wang, L.; Xie, S.; Bao, T.; Zhu, S.; Liang, Q.; Wang, X.; Zhang, R.; Xiang, X.; Du, C.; He, C. Exercise and education for community-
dwelling older participants with knee osteoarthritis: A video-linked programme protocol based on a randomised controlled trial.
BMC Musculoskelet. Disord. 2021, 22, 470. [CrossRef]
39. Larsen, J.B.; Skou, S.T.; Arendt-Nielsen, L.; Simonsen, O.; Madeleine, P. Neuromuscular exercise and pain neuroscience education
compared with pain neuroscience education alone in patients with chronic pain after primary total knee arthroplasty: Study
protocol for the NEPNEP randomized controlled trial. Trials 2020, 21, 218. [CrossRef] [PubMed]
40. Lawford, B.J.; Hinman, R.S.; Kasza, J.; Nelligan, R.; Keefe, F.; Rini, C.; Bennell, K.L. Moderators of Effects of Internet-Delivered
Exercise and Pain Coping Skills Training for People with Knee Osteoarthritis: Exploratory Analysis of the IMPACT Randomized
Controlled Trial. J. Med. Internet. Res. 2018, 20, e10021. [CrossRef]
41. Saw, M.M.; Kruger-Jakins, T.; Edries, N.; Parker, R. Significant improvements in pain after a six-week physiotherapist-led exercise
and education intervention, in patients with osteoarthritis awaiting arthroplasty, in South Africa: A randomised controlled trial.
BMC Musculoskelet. Disord. 2016, 17, 236. [CrossRef]
42. Bennell, K.L.; Ahamed, Y.; Jull, G.; Bryant, C.; Hunt, M.A.; Forbes, A.B.; Kasza, J.; Akram, M.; Metcalf, B.; Harris, A.; et al. Physical
Therapist-Delivered Pain Coping Skills Training and Exercise for Knee Osteoarthritis: Randomized Controlled Trial. Arthritis Care
Res. 2016, 68, 590–602. [CrossRef] [PubMed]
43. Fernandes, L.; Storheim, K.; Sandvik, L.; Nordsletten, L.; Risberg, M.A. Efficacy of patient education and supervised exercise vs.
patient education alone in patients with hip osteoarthritis: A single blind randomized clinical trial. Osteoarthr. Cartil. 2010, 18,
1237–1243. [CrossRef] [PubMed]
44. Bezalel, T.; Carmeli, E.; Katz-Leurer, M. The effect of a group education programme on pain and function through knowledge
acquisition and home-based exercise among patients with knee osteoarthritis: A parallel randomised single-blind clinical trial.
Physiotherapy 2010, 96, 137–143. [CrossRef] [PubMed]
45. Baird, C.L.; Sands, L. A pilot study of the effectiveness of guided imagery with progressive muscle relaxation to reduce chronic
pain and mobility difficulties of osteoarthritis. Pain Manag. Nurs. 2004, 5, 97–104. [CrossRef] [PubMed]
Int. J. Environ. Res. Public Health 2022, 19, 2559 13 of 13

46. Ettinger, W.H., Jr.; Burns, R.; Messier, S.P.; Applegate, W.; Rejeski, W.J.; Morgan, T.; Shumaker, S.; Berry, M.J.; O’Toole, M.;
Monu, J.; et al. A randomized trial comparing aerobic exercise and resistance exercise with a health education program in older
adults with knee osteoarthritis: The Fitness Arthritis and Seniors Trial (FAST). JAMA 1997, 277, 25–31. [CrossRef] [PubMed]
47. Nijs, J.; Clark, J.; Malfliet, A.; Ickmans, K.; Voogt, L.; Don, S.; Bandt, H.D.; Goubert, D.; Kregel, J.; Coppieters, I.; et al. In the spine
or in the brain? Recent advances in pain neuroscience applied in the intervention for low back pain. Clin. Exp. Rheumatol. 2017,
107, 108–115.
48. Louw, A.; Diener, I.; Butler, D.S.; Puentedura, E.J. The effect of neuroscience education on pain, disability, anxiety, and stress in
chronic musculoskeletal pain. Arch. Phys. Med. Rehabil. 2011, 92, 2041–2056. [CrossRef] [PubMed]
49. Karlsen, A.; Wetterslev, M.; Hansen, S.; Hansen, M.; Mathiesen, O.; Dahl, J. Postoperative pain treatment after total knee
arthroplasty: A systematic review. PLoS ONE 2017, 12, e0173107. [CrossRef]
50. Bülow, K.; Lindberg, K.; Vaegter, H.B.; Juhl, C.B. Effectiveness of Pain Neurophysiology Education on Musculoskeletal Pain: A
Systematic Review and Meta-Analysis. Pain Med. 2021, 22, 891–904. [CrossRef] [PubMed]
51. Watson, J.A.; Ryan, C.G.; Atkinson, G.; Williamson, P.; Ellington, D.; Whittle, R.; Dixon, J.; Martin, D.J. Inter-Individual Differences
in the Responses to Pain Neuroscience Education in Adults with Chronic Musculoskeletal Pain: A Systematic Review and
Meta-Analysis of Randomized Controlled Trials. J. Pain 2021, 22, 9–20. [CrossRef] [PubMed]
52. Louw, A.; Puentedura, E.; Diener, I. A descriptive study of the utilization of physical therapy for postoperative Rehabilitation in
patients undergoing surgery for lumbar radiculopathy. Eur. Spine J. 2016, 25, 3550–3559. [CrossRef] [PubMed]