Journal of Back and Musculoskeletal Rehabilitation 34 (2021) 511–520 511

DOI 10.3233/BMR-200091
IOS Press

Article Commentary

Applicability of pain neuroscience education:

Where are we now?
Valerio Barbari∗ , Lorenzo Storari, Filippo Maselli and Marco Testa
Department of Neurosciences, Rehabilitation, Ophthalmology, Genetic and Maternal Infantile Sciences (DINOGMI),
University of Genova – Campus of Savona, Savona, Italy

Received 3 April 2020

Accepted 29 December 2020

Abstract.
BACKGROUND: Explaining pain to patients through pain neuroscience education (PNE) is currently a widespread treatment
studied in the musculoskeletal context. Presently, there is sufficient evidence supporting the effectiveness of PNE in patients with
chronic musculoskeletal disorders. However, clinicians must pay attention to the actual possibility to transfer research findings in
their specific clinical context.
OBJECTIVE: We analysed the applicability of results of studies focused on PNE, which has not been done previously.
METHODS: A detailed discussion on PNE applicability is provided, starting from published randomized controlled trials that
investigated the effectiveness of PNE.
RESULTS: This paper markedly points out the awareness of clinicians on the need for an accurate contextualization when
choosing PNE as an intervention in clinical practice.

Keywords: Pain neuroscience education, musculoskeletal disorders, applicability, clinical trials

Abbreviations 1. Introduction
PNE Pain neuroscience education Pain neuroscience education (PNE) is winning suc-
MSK Musculoskeletal cess and growing interest in scientific literature due
SRs Systematic reviews to the pain neuroscience evolution over the last two
RCTs Randomized controlled trials decades in the musculoskeletal (MSK) context [1–7]
CLBP Chronic low back pain and, recently, in paediatrics [8]. The awareness that
CNP Chronic neck pain chronic MSK pain should not only be considered as a
CFS Chronic fatigue syndrome temporal extension of acute pain but rather as a self-
FM Fibromyalgia perpetuating maladaptive response of the nervous sys-
CP Chronic pain tem [9–17], has laid the foundation for this educational
CSP Chronic spinal pain model in a purely biopsychosocial vision [7,18–23].
ICF International Classification of Albeit it may be asserted that PNE does not properly
Functioning Disability and Health belong to the ordinary physiotherapy background, this
approach has been introduced in the last two decades as
∗ Corresponding author: Valerio Barbari Department of Neuro-
an alternative to the outdate and ineffective educative
sciences, Rehabilitation, Ophthalmology, Genetic and Maternal In-
biomedical models of care [18,24].
fantile Sciences (DINOGMI), University of Genova – Campus of PNE has already been studied in both randomized
Savona, Savona, Italy. E-mail: ft.valeriobarbari@gmail.com. controlled trials (RCTs) [25–41] and other research de-

ISSN 1053-8127/$35.00 c 2021 – IOS Press. All rights reserved.

512 V. Barbari et al. / Applicability of pain neuroscience education
signs [42–46]. Currently, the highest evidence support-
ing the effectiveness of PNE is based on five systematic
reviews (SRs) [3,47–50]. Overall, the consensus is that
PNE may be a powerful integration in physiotherapy
practice, most notably if combined with manual therapy
and exercise, whereas PNE as a stand-alone interven-
tion may not be effective enough in treating adults with
chronic MSK pain [51–54].
Despite results are highly promising, it is necessary
to clarify its clinical applicability. Applicability, also
called external validity or generalizability, is defined
as “the conceptual as well as the effective link between
knowledge generation and knowledge utilization” [55],
or, according to Cook and Campbell, “the inference
of the causal relationships that can be generalized to
different measures, persons, settings, and times” [56,
57]. The scientific literature has already insisted on the
importance of applicability agreeing that it is extremely
important to pay attention to some features that may
limit the transferability of findings to clinical realities
of each healthcare professionals [58–60].
Evidence of the neglect of consideration of the exter-
nal validity of RCTs, SRs and guidelines has already
been published by Peter M. Rothwell who also sustains
that “lack of consideration of external validity is the
most frequent criticism by clinicians of RCTs, system-
atic reviews, and guidelines” [58]. According to Roth-
well [57], the main issues that potentially affect external
validity are:
– Setting of the trial;
– Selection of patients;
– Characteristics of randomised patients;
– Difference between trial protocol and routine prac-
tice;
– Outcome measures and follow-up;
– Adverse effects of treatment.
Up to date, no study has yet investigated the applica-
bility of results in the PNE context, therefore a detailed
discussion of the most relevant aspects of the afore-
mentioned issues is provided starting from the RCTs
focused on the effectiveness of this intervention.
2. Analysis of applicability
2.1. Setting of the trial
Conceivably, setting of the trials is the most compli-
cated and relevant issue to analyse. RCTs included in
the SRs addressing the effectiveness of PNE [3,47–49]
have been conducted in different countries all over the
world and participants have been recruited from differ-
ent health facilities. Countries and structures of recruit-
ment are itemised in Table 1.
Of interest, it must be considered that hospitals, pri-
vate clinics, university clinical centres and specialized
centres offer different structural, organizational and
contextual resources and not all healthcare profession-
als have the same privileged positions and situations.
A private clinician can certainly choose to incorpo-
rate PNE as a part of the rehabilitation process but, in
some cases such as public health structures, the intro-
duction of an educational intervention as proposed in
clinical trials may not be contemplated at all. More-
over, RCTs took place in different healthcare systems.
Being healthcare systems substantially different from
each other as well as funded in various modes in Eu-
ropean Union [61], clinicians should be aware that the
application of PNE within different countries cannot
certainly be identical. Besides, in most cases clinicians
charged to offer PNE sessions were experts adequately
trained on that skill. Inexperienced healthcare profes-
sionals should ask themselves if the patient would have
the same clinical positive outcomes after PNE-sessions
compared to the education provided by experts. There-
fore, healthcare professionals must accurately choose to
implement PNE depending on their own clinical skills
and political, financial, and organizational constraints.
2.2. Selection of patients
In some RCTs the selection of patients was extremely
strict. In particular, some studies have excluded any in-
dividuals who took drugs or had received conservative
treatments such as physiotherapy within 3 [29,35,36]
or 6 [37] months and participated in a back school or
multidisciplinary cognitive-behavioural pain manage-
ment [33] before the inclusion. However, care-seeking
is a common denominator of individuals with chronic
pain [62–64] and so it may be unconvincing that all
participants did not seek any cure before the inclusion.
Hence, it is likely to suppose that those studies may
have left out some potentially eligible participants and
this issue may limit the applicability of findings to a
narrowed group of individuals in clinical practice. On
the other hand, inclusion criteria were overall similar
within the RCTs. Indeed, patients suffering of chronic
MSK pain aged between 18 and 75 were eligible in all
the PNE-studies making samples enough homogeneous
in these terms. Lastly, there were some statistically sig-
nificant differences in baseline clinical characteristics
between groups in some studies. Details are reported in
Table 2.
 V. Barbari et al. / Applicability of pain neuroscience education 513

Study
Beltran-Alacreu H. et al., 2015 Chronic neck pain
Bodes Pardo G. et al., 2018
Diogo Pires et al., 2015
Gallagher L. et al., 2013
Louw A. et al., 2014
Malfliet A. et al., 2017–2018
Meeus M. et al., 2010
Moseley G.L. et al., 2004
Moseley G.L., 2003
Moseley G.L., 2002
Ryan C.G. et al., 2010
Tèllez-Garcìa M. et al., 2014
Van Ittersum M.W. et al., 2014 Fibromyalgia
Van Oosterwijck J. et al., 2013 Fibromyalgia
Vibe Fersum K. et al., 2013
Wälti P. et al., 2015
Structure of recruitment in each study
Patients
Chronic low back pain
Chronic low back pain
Chronic pain
Chronic low back pain
Chronic low back pain,
chronic neck pain, failed back primary care practices and occupational health services
surgery syndrome, chronic
whiplash associated disorders
Chronic fatigue syndrome
Chronic low back pain
Chronic low back pain
Chronic low back pain
Chronic low back pain
Chronic low back pain
Chronic low back pain
Chronic neck pain
Table 1
Structure of recruitment Country
Referral from University and at an ambulatory primary health Spain
care facility
4 private physiotherapy practices and in Alcala’ University Spain
Waiting list of a Portuguese outpatient clinic Portugal
Waiting list for multidisciplinary pain management and advised Australia
of the project by a telephone call
7 clinical sites United States
Universities and University Hospitals (Ghent and Brussels), Belgium
The medical files available at our university-based chronic Belgium
fatigue clinic
3 private rehabilitation clinics Australia
Physiotherapy clinic from general practitioners, self-referral Australia
and rehabilitation provider
Physiotherapy clinic from general practitioners, self-referral Australia
and rehabilitation provider
Five different physiotherapy departments Scotland
Referred by their physician for physical therapy Spain
Specialized centres for chronic pain and chronic fatigue Belgium
Private practise for internal medicine Belgium
Private physiotherapy outpatient practices, general practitioners Norway
and outpatient spine clinic at Hospital
Telephone contact with referring general practitioners, Switzerland
chiropractors and rheumatologists; in addition, advertisements
in a local news-paper

Table 2
Baseline clinical characteristics
Study Baseline clinical characteristics
Ryan et al., 2010 Duration of pain was longer in the EG than CG.
MD: −6 [−11.8; −0.4] days, (p = 0.04)
Vibe Fersum et al., 2013 FABQ-W (work) scores were higher in CG (19.3 ± 11) than the EP (14.1 ± 9.6); p < 0.05
Walti et al., 2015 Number of women was higher (p < 0.05) in the EG (64.3%) than the CG (42.9%)
PCS scores were higher (p < 0.05) in CG (20.08 ± 8.24) than the EG (14.43 ± 7.62)
Van Ittersum et al., 2014 FIQ scores were higher (p = 0.03) in EP (8.4 ± 1.6) than the CG (7.5 ± 2.3)
MD: mean difference; EG: experimental group; CG: control group.

However, readers must be aware that not only sta-
tistically significant differences should be considered
relevant in RCTs. Indeed, according to de Boer et al.,
“a relatively small and non-statistically significant dif-
ference in a very strong prognostic factor could cause
meaningful confounding and vice versa that a large dif-
ference in a characteristic unrelated to outcome would
cause no confounding at all” [65]. Although randomi-
sation procedures should ensure a fair distribution of
baseline characteristics [66,67], clinicians may criti-
cally consider all factors that potentially could under-
rate or overestimate outcome results and influence the
prognosis.
2.3. Characteristics of randomised patients
All recruited participants were representative of the
clinical reality of each MSK disorder by gender (major-
ity of women) [68], age (almost 50-years-old) [67] and
criteria for taking part in PNE sessions (according to Jo
Nijs and colleagues [69,70]). Therefore, with respect to
those characteristics, clinicians may expect that patients
with chronic MSK pain presenting to their facilities are
similar to those enrolled in research studies.
However, RCTs included in the recent reviews [3,
47–49] recruited patients with different pain durations
and MSK disorders: chronic low back pain (CLBP),
chronic neck pain (CNP), chronic fatigue syndrome
(CFS), fibromyalgia (FM), chronic pain (CP) or chronic
spinal pain (CSP).
Firstly, there is no absolute consensus about the
period beyond which pain must be considered as
“chronic”. Some authors established that threshold at
514 V. Barbari et al. / Applicability of pain neuroscience education
3 months [71], 3–6 months [9] or 6 months [72]. Be-
sides, in 13 RCTs of 16 (81%) patients with pain lasting
for more than 3 months have been enrolled. For what
concern studies with CLBP patients, in six of the pa-
tients who had pain lasting for more than 3 months have
been included, in two RCTs with pain for more than
6 months and in the last one for more than 2 months.
The latter issues related to the heterogeneity of pain
duration must be considered when clinicians decide to
transfer results of clinical trials to other individuals.
In this respect, PNE is recommended in case of cen-
tral sensitization and psychosocial factors that may af-
fect the condition [68,69]. Nevertheless, not all patients
with chronic MSK pain show signs or symptoms of
central sensitization and therefore PNE maybe be not
recommended [73]. Chronic pain does not mean cen-
tral sensitization and, according to Nijs and colleagues
discussing CLBP, evidence shows that central sensiti-
zation may be present in a subgroup of the CLBP pop-
ulation but it does not necessarily constitute a common
characteristic of these patients [73].
The SR by Tegner et al. [47] included only RCTs
recruiting patients with CLBP, but such uniformity of
underlying MSK affection, as mentioned above, was
weak in the other SR by Louw et al. [3]. Indeed, all
the patients enrolled in the included studies by Louw et
al. [3] have been labeled as suffering of chronic MSK
disorders, but is it correct to superimpose patients with
FM and patients with CLBP or CNP? In 2016 the same
authors concluded that perhaps there is a need of a
subgroup testing such as CLBP, as Tegner et al. and
Barbari et al. performed in 2018–2019 [47–49], and this
understandable because many issues may make these
patients systematically different from each-others, such
as for clinical characteristics and pain mechanism [74–
77], psychosocial factors or personal attitudes [78].
Besides, Gallagher and colleagues [36] enrolled pa-
tients with chronic pain “that had been sufficient to dis-
rupt their activities of daily living for more than the
previous 3 months”. However, no diagnostic criteria
have been satisfied and therefore it may be not pos-
sible to overlap findings of that RCT with the others,
or to transfer them into clinical practice. Furthermore,
Malfiet et al. [33,34] recruited patients with chronic
spinal pain (CLBP, CNP, failed back surgery syndrome,
chronic whiplash associated disorders). Findings of the
latter RCT are promising and consistent with the cur-
rent evidence, but it must be considered in line with the
heterogeneity of MSK disorders of participants (e.g.:
whiplash and low back pain). Finally, these discrepan-
cies upon the differences between participants’ char-
acteristics should be adequately considered in order to
select which individual is the one to whom evidence of
PNE should be applied.
Transversely, an important link between setting of
the trial and characteristics of randomised patients
is the cultural background. It may seem trivial but it
must be well-thought-out that PNE is a kind of educa-
tion and robust literature has identified that patients’
cultural aspects are essential issues in patient educa-
tion [79–81]. According to the International Classifica-
tion of Functioning Disability and Health (ICF) classi-
fication system, the cultural background must be con-
sidered as a part of contextual factors and literature has
already argued they are directly involved in chronic
pain states [82], underlying their importance during the
clinical assessment [83]. Besides, since the main format
of PNE is the oral individual education [69], patients’
and clinicians’ cultural backgrounds exponentially in-
crease the influence on outcome results, even because
clinicians are able to influence patients’ attitudes [84].
In this respect, literature reported that communication
is “highly effective” in patient education [85], but at the
same time it is suggested that every single healthcare
provider “must continually refine this capacity during
his/her professional career” [86].
Therefore, communication skills are certainly an
indispensable requirement and should be adapted in
each clinical situation, even according to cultural back-
grounds. Once again, the ability of clinicians is to es-
tablish with common sense the appropriateness of the
intervention based on all factors of the ICF.
2.4. Difference between trial protocol and routine
practice
The study design was not always uniform across the
studies although they were all RCTs. Some authors of-
fered PNE as a single intervention, but other trials in-
cluded PNE in a multimodal program making challeng-
ing the comprehension of its real contribution. Nev-
ertheless, some authors offered PNE to experimental
groups combined with the same intervention offered to
control groups, but, for example in the one by Pires et
al. [35], PNE has been concurrently delivered to both
groups and actually the real discriminating was the ex-
ercise program. Findings of the studies are clearly com-
plementary, but they reveal different results through
different combinations of interventions.
With respect to the appropriateness of choices of con-
trol groups, it may be asserted that in most of the studies
PNE has been compared to robust and consistent treat-
 V. Barbari et al. / Applicability of pain neuroscience education
ments, such as manual therapy and exercise. In fact,
these treatments are generally recommended in treat-
ing most of chronic MSK disorders such as CNP [87],
CLBP [88], FM [89,90] and CFS [91]. However, in the
study by Téllez-Garcìa et al. [37], authors have honestly
acknowledged that actually the combination of PNE and
dry needling may not faithfully reflect the current clini-
cal practice for patients with CLBP because, as it has
just been mentioned, the literature recommends treat-
ments such as manual therapy and, mostly, therapeutic
exercise. On the other hand, the study by Moseley et
al. [34] compared physiotherapy and PNE to the usual
medical management and therefore it might have led to
an initial disadvantage for the control group which is
not a recommended treatment by practice guidelines.
With respect to PNE modalities, it must be pri-
marily recognized that the education can be offered
in three formats: oral individual sessions, group ses-
sions or through delivering booklets and written mate-
rials [3,4,47,49,70,92], but not all studies employed the
same one. Clinicians must be aware of the modalities
of treatments used in clinical trials and consequently
weight findings according to their own available re-
sources in clinical practice; also considering that the
one-to-one session in oral format is considered the opti-
mal format of PNE [15,70] which may allow, with com-
passion and empathy, the establishment of an effective
therapeutic alliance with the patient [51–54].
2.5. Outcome measures and follow-up
2.5.1. Outcome measures
All the RCTs have chosen valid and reliable outcome
measures, reporting exhaustively the relative references.
Overall, they were cheap, easy to give and used by clin-
icians without specific training. In fact, in most cases
they were questionnaires evaluating self-reported out-
comes such as pain, disability and psychosocial factors.
A few studies employed objective outcome measures
related to physical performance:
– Finger-to-floor distance test [93];
– Sit-to-stand test, 50-foot walk test, 5 minutes-walk
test, step count [36];
– Degrees of straight leg raise, forward bending, mo-
tor control with abdominal drawing-in task [33];
– Neck flexor muscle endurance test [29];
– Lumbar range of motion [40];
– Motor control impairment and two-points-discri-
mination tests [41];
– Pressure pain threshold [31,37,39];
– Endogenous pain inhibition [37].
515
The latter outcomes measures are considered valid
and reliable in literature and they are potentially repeat-
able by clinicians in clinical practice in virtue of no
need of particular technical competence or economic
resources.
2.5.2. Follow-up
RCTs investigating the effectiveness of PNE assessed
patients at different follow-ups. All details are reported
in Table 3.
Since the primary objective of rehabilitation is to
make clinical improvements to be maintained over time,
all healthcare professionals should analyse the follow-
up periods in this respect. For example, the studies
by Moseley [33], Meeus [31] and Malfliet [27,28] as-
sessed patients 15 days post-treatment, immediately
post-intervention and post-education, respectively. Al-
though the results were clearly positive, it may be ar-
gued that the shortness of post-treatment assessments
has no granted the long-term assumption of PNE con-
cepts, a key point of educational sessions, limiting the
benefits only in the short-term.
2.6. Adverse effects of treatment
Only 2 studies [35,40] out of 16 (13%) have explic-
itly reported the absence of adverse events and therefore
it may be assumed there is a degree of uncertainty about
the safety of PNE. However, it is likely to suppose that
such security is much more related to the treatments to
which PNE is combined with rather than PNE on its
own. In this respect, robust literature has confirmed that
an educational program focused on the old biomedical
model may be counterproductive, dangerous and may
affect outcomes of patients with chronic MSK disor-
ders [47,92,94,95]. On the contrary, Louw et al. [3] re-
ported in their SR that “no PNE study showed any out-
come to be worse than the control groups”, highlighting
the overall safety of PNE.
2.7. Costs
It is quite difficult to exactly estimate the costs of
PNE sessions being these costs depend on the health
system of the country where the therapy is delivered.
Nevertheless, according to practice guidelines [70] that
recommend only 2 individual sessions prior to starting
active functional treatments, costs do not seem to be
a relevant problem if compared with other treatments
routinely offered in physiotherapy practice. Moreover,
clinicians should consider their PNE-related profes-
sional training costs that probably impact on the final
costs of PNE.
516 V. Barbari et al. / Applicability of pain neuroscience education

Study
Beltran-Alacreu H. et al., 2015
Bodes Pardo G. et al., 2018
Diogo Pires et al., 2015
Gallagher L. et al., 2013
Louw A. et al., 2014
Malfliet A. et al., 2017–2018
Meeus M. et al., 2010
Moseley G.L. et al., 2004
Moseley G.L., 2003
Moseley G.L., 2002
Ryan C.G. et al., 2010
Tèllez-Garcìa M. et al., 2014
Van Ittersum M.W. et al., 2014
Van Oosterwijck J. et al., 2013
Vibe Fersum K. et al., 2013
Wälti P. et al., 2015
Table 3
Follow-ups in each study
Follow-up
Baseline, 4 weeks, 8 weeks, 16 weeks
Baseline, 1 month and 3 months
Baseline, 6 weeks, 3 months
Baseline, 3 weeks, 3 months (for both groups); 15 weeks, 24 weeks (for cross-over group)
Baseline, 1 month, 3 months, 6 months, 12 months
Immediately post-education
Immediately pre and post-treatment
Baseline, 15 days
Baseline, 5 weeks post usual medical management, 1-month post-treatment, 1 year
Baseline, 1 month, 1 year
Baseline, 8 weeks, 3 months (only for self-reported outcomes)
Baseline, 4 weeks
Baseline, 6 weeks, 6 months
Baseline, 2 weeks, 3 months
Baseline, 3 weeks, 1 year
Baseline, 3 months

3. Translating PNE from research to clinical
practice
PNE was firstly proposed as an intervention in 2002
by Lorimer Moseley [40] and it is currently offered in
clinical trials as an educative approach for patients with
chronic pain with a dominance of central pain mech-
anism as well as with aggravating psychosocial fac-
tors [69,70,96]. However, the methodology of adminis-
tration as well as settings and healthcare professionals’
experience in RCTs risk to be not faithfully reproduced
in real clinical circumstances. The high-quality clinical
trials (i.e. explanatory trials) are optimal to demonstrate
the efficacy of interventions in ideal populations and
conditions, but often at the expense of their applicabil-
ity [97]. This seems to be the case of the good quality
of RCTs investigating the efficacy of PNE [3,4,47–49].
Surely, such trials have a critical role, but it is also
clear that pragmatic clinical trials, when compared to
explanatory clinical trials, may highlight results more
generalizable to clinical realities and that testify the
real-world benefit of interventions, also called effec-
tiveness [98]. According to Merali and colleagues, “It
is thus important for health care practitioners to be
able to distinguish between explanatory and pragmatic
features in new clinical trials before incorporating new
interventions into their own clinical practice” [97].
Furthermore, PNE has been proposed throughout
precise modalities [68,69,95]. However, the replication
of rigorous formats of administration seems to be chal-
lenging for clinicians in healthcare settings and, at the
same time, it must be kept in mind that the primary
aim of PNE is to reconceptualize pain according to the
advances in pain neuroscience [6,99]. Therefore, PNE
could be incorporated in all clinical realities dealing
with pain disorders as a new communicative register by
which all characteristics of rehabilitation (therapeutic
alliance, reassurance, positive expectations, maladap-
tive behavior modifications, explanation of chronic pain
or the role of manual therapy and exercise) are all given
and built throughout a new neuroscientific perspective
both in line with pain sciences and with the variability
of clinical features of patients which cannot be standard
and, as a consequence, the treatment as well.
4. Conclusions
Findings related to the efficacy of PNE rising from
clinical trials are affected by several limits of applica-
bility and it is unlikely to generalize findings to entire
population in each clinical setting. This paper markedly
points out the awareness of clinicians on the need for
an accurate contextualization when choosing PNE as
an intervention in clinical practice. Not all patients may
benefit from PNE, not all patients can understand PNE
concepts in the same way, not all patients belief that
an educational session may help the pain state, not all
patients are equal despite they are labelled as suffering
of chronic MSK pain and, lastly but equally relevant,
clinicians have no the same features, attitudes, exper-
tise, training and resources. PNE is surely a powerful
weapon available to clinicians, however, the key of its
success lies in the individual ability to adapt the inter-
vention in a rehabilitative context [99] resulting from
the integration of patients’ expectations and pathol-
ogy, clinical expertise, patients’ and healthcare pro-
fessionals’ culture, psychosocial factors and available
resources.
 V. Barbari et al. / Applicability of pain neuroscience education
Acknowledgments
This work was developed within the framework of
the DINOGMI Department of Excellence of MIUR
2018–2022 (legge 232 del 2016).
Authors’ contributions
Analyzed the data: VB, LS, FM. Contributed ma-
terials/analysis tools: FM, LS, VB. Wrote the paper:
LS, VB, FM, MT. Substantial contributions to concep-
tion and design, acquisition of data: VB, LS, FM, MT.
Analysis and interpretation of data: VB, FM, LS, MT.
Drafting the paper or revising it critically for impor-
tant intellectual content: FM, MT. Final approval of the
version to be published: VB, FM, LS, MT. All authors
have read and approved the final manuscript.
Conflict of interest
The authors declare that they have no competing
interests.
Funding
This research received no external funding.
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