Applicability of pain neuroscience education: Where are we now?

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

PNE	Pain neuroscience education
MSK	Musculoskeletal
SRs	Systematic reviews
RCTs	Randomized controlled trials
CLBP	Chronic low back pain
CNP	Chronic neck pain
CFS	Chronic fatigue syndrome
FM	Fibromyalgia
CP	Chronic pain
CSP	Chronic spinal pain
ICF	International Classification of
	Functioning Disability and Health

1. Introduction

Pain neuroscience education (PNE) is winning success and growing interest in scientific literature due to the pain neuroscience evolution over the last two decades in the musculoskeletal (MSK) context [1, 2, 3, 4, 5, 6, 7] and, recently, in paediatrics [8]. The awareness that chronic MSK pain should not only be considered as a temporal extension of acute pain but rather as a self-perpetuating maladaptive response of the nervous system [9, 10, 11, 12, 13, 14, 15, 16, 17], has laid the foundation for this educational model in a purely biopsychosocial vision [7, 18, 19, 20, 21, 22, 23]. Albeit it may be asserted that PNE does not properly belong to the ordinary physiotherapy background, this approach has been introduced in the last two decades as an alternative to the outdate and ineffective educative biomedical models of care [18, 24].

PNE has already been studied in both randomized controlled trials (RCTs) [25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41] and other research designs [42, 43, 44, 45, 46]. Currently, the highest evidence supporting the effectiveness of PNE is based on five systematic reviews (SRs) [3, 47, 48, 49, 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 intervention may not be effective enough in treating adults with chronic MSK pain [51, 52, 53, 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, 59, 60].

Evidence of the neglect of consideration of the external 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, systematic reviews, and guidelines” [58]. According to Rothwell [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 practice;
•
Outcome measures and follow-up;
•
Adverse effects of treatment.

Up to date, no study has yet investigated the applicability of results in the PNE context, therefore a detailed discussion of the most relevant aspects of the aforementioned 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 complicated and relevant issue to analyse. RCTs included in the SRs addressing the effectiveness of PNE [3, 47, 48, 49] have been conducted in different countries all over the world and participants have been recruited from different health facilities. Countries and structures of recruitment are itemised in Table 1.

Table 1
Structure of recruitment in each study

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

Of interest, it must be considered that hospitals, private clinics, university clinical centres and specialized centres offer different structural, organizational and contextual resources and not all healthcare professionals have the same privileged positions and situations. A private clinician can certainly choose to incorporate PNE as a part of the rehabilitation process but, in some cases such as public health structures, the introduction of an educational intervention as proposed in clinical trials may not be contemplated at all. Moreover, RCTs took place in different healthcare systems. Being healthcare systems substantially different from each other as well as funded in various modes in European 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 professionals should ask themselves if the patient would have the same clinical positive outcomes after PNE-sessions compared to the education provided by experts. Therefore, 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 individuals 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 management [33] before the inclusion. However, care-seeking is a common denominator of individuals with chronic pain [62, 63, 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 significant differences in baseline clinical characteristics between groups in some studies. Details are reported in Table 2.

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 $\pm$ 11) than the EP (14.1 $\pm$ 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 $\pm$ 8.24) than the EG (14.43 $\pm$ 7.62)
Van Ittersum et al., 2014	FIQ scores were higher ( $p=$ 0.03) in EP (8.4 $\pm$ 1.6) than the CG (7.5 $\pm$ 2.3)

MD: mean difference; EG: experimental group; CG: control group.

However, readers must be aware that not only statistically significant differences should be considered relevant in RCTs. Indeed, according to de Boer et al., “a relatively small and non-statistically significant difference in a very strong prognostic factor could cause meaningful confounding and vice versa that a large difference in a characteristic unrelated to outcome would cause no confounding at all” [65]. Although randomisation procedures should ensure a fair distribution of baseline characteristics [66, 67], clinicians may critically consider all factors that potentially could underrate 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 (majority 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, 48, 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 3 months [71], 3–6 months [9] or 6 months [72]. Besides, 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 patients 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 central sensitization and psychosocial factors that may affect 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 central sensitization and, according to Nijs and colleagues discussing CLBP, evidence shows that central sensitization may be present in a subgroup of the CLBP population 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, 48, 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, 75, 76, 77], psychosocial factors or personal attitudes [78].

Besides, Gallagher and colleagues [36] enrolled patients with chronic pain “that had been sufficient to disrupt 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 possible 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 current 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 discrepancies upon the differences between participants’ characteristics 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 education and robust literature has identified that patients’ cultural aspects are essential issues in patient education [79, 80, 81]. According to the International Classification of Functioning Disability and Health (ICF) classification system, the cultural background must be considered 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 increase 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 backgrounds. Once again, the ability of clinicians is to establish 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 offered PNE as a single intervention, but other trials included PNE in a multimodal program making challenging the comprehension of its real contribution. Nevertheless, 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 exercise program. Findings of the studies are clearly complementary, but they reveal different results through different combinations of interventions.

With respect to the appropriateness of choices of control groups, it may be asserted that in most of the studies PNE has been compared to robust and consistent treatments, such as manual therapy and exercise. In fact, these treatments are generally recommended in treating 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 clinical practice for patients with CLBP because, as it has just been mentioned, the literature recommends treatments 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 primarily recognized that the education can be offered in three formats: oral individual sessions, group sessions or through delivering booklets and written materials [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 resources in clinical practice; also considering that the one-to-one session in oral format is considered the optimal format of PNE [15, 70] which may allow, with compassion and empathy, the establishment of an effective therapeutic alliance with the patient [51, 52, 53, 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 clinicians without specific training. In fact, in most cases they were questionnaires evaluating self-reported outcomes 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, motor 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].

The latter outcomes measures are considered valid and reliable in literature and they are potentially repeatable 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.

Table 3
Follow-ups in each study

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

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] assessed patients 15 days post-treatment, immediately post-intervention and post-education, respectively. Although the results were clearly positive, it may be argued that the shortness of post-treatment assessments has no granted the long-term assumption of PNE concepts, 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 explicitly 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 disorders [47, 92, 94, 95]. On the contrary, Louw et al. [3] reported in their SR that “no PNE study showed any outcome 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 professional training costs that probably impact on the final costs of PNE.

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 mechanism as well as with aggravating psychosocial factors [69, 70, 96]. However, the methodology of administration 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 applicability [97]. This seems to be the case of the good quality of RCTs investigating the efficacy of PNE [3, 4, 47, 48, 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 effectiveness [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 challenging 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, maladaptive 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 applicability 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, expertise, 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 intervention in a rehabilitative context [99] resulting from the integration of patients’ expectations and pathology, clinical expertise, patients’ and healthcare professionals’ culture, psychosocial factors and available resources.

Authors’ contributions

Analyzed the data: VB, LS, FM. Contributed materials/analysis tools: FM, LS, VB. Wrote the paper: LS, VB, FM, MT. Substantial contributions to conception 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 important 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.

Funding

This research received no external funding.

Footnotes

Acknowledgments

This work was developed within the framework of the DINOGMI Department of Excellence of MIUR 2018–2022 (legge 232 del 2016).

Conflict of interest

The authors declare that they have no competing interests.

References

Jull

Moore

Falla

McCarthy

Sterling

. Grive’s Modern Musculoskeletal Physiotherapy. 4a ed. London: Elsevier. 2016.

Rose

Huerbin

Melick

Marion

Palmer

Schiding

, et al. Regulation of interstitial excitatory amino acid concentrations after cortical contusion injury. Brain Res. 2002 May 10; 935(1–2): 40-6.

Louw

Zimney

Puentedura

Diener

. The efficacy of pain neuroscience education on musculoskeletal pain: a systematic review of the literature. Physiother Theory Pract. 2016 Jul; 32(5): 332-55.

Louw

Diener

Butler

Puentedura

. The effect of neuroscience education on pain, disability, anxiety, and stress in chronic musculoskeletal pain. Arch Phys Med Rehabil. 2011 Dec; 92(12): 2041-56.

Moseley

. Unraveling the barriers to reconceptualization of the problem in chronic pain: the actual and perceived ability of patients and health professionals to understand the neurophysiology. J Pain. 2003 May; 4(4): 184-9.

Moseley

. Reconceptualising pain according to modern pain science. Physical Therapy Reviews. 2007 Sep; 12(3): 169-78.

Moseley

Butler

. Fifteen years of explaining pain: the past, present, and future. J Pain. 2015 Sep; 16(9): 807-13.

Robins

Perron

Heathcote

Simons

. Pain neuroscience education: state of the art and application in pediatrics. Children (Basel). 2016 Dec 21; 3(4): E43.

Roditi

Robinson

. The role of psychological interventions in the management of patients with chronic pain. Psychol Res Behav Manag. 2011; 4: 41-9.

10.

May

. Chronic pain may change the structure of the brain. Pain. 2008 Jul; 137(1): 7-15.

11.

Latremoliere

Woolf

. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009 Sep; 10(9): 895-926.

12.

Woolf

. Central sensitization: uncovering the relation between pain and plasticity. Anesthesiology. 2007 Apr; 106(4): 864-7.

13.

Woolf

. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011 Mar; 152(3 Suppl): S2-15.

14.

Petersen-Felix

Curatolo

. Neuroplasticity – an important factor in acute and chronic pain. Swiss Med Wkly. 2002 Jun 1; 132(21–22): 273-8.

15.

van Wilgen

Keizer

. The sensitization model to explain how chronic pain exists without tissue damage. Pain Manag Nurs. 2012 Mar; 13(1): 60-5.

16.

Seifert

Maihöfner

. Functional and structural imaging of pain-induced neuroplasticity. Curr Opin Anaesthesiol. 2011 Oct; 24(5): 515-23.

17.

Sheng

Kim

. Postsynaptic signaling and plasticity mechanisms. Science. 2002 Oct 25; 298(5594): 776-80.

18.

Louw

Puentedura

Diener

Zimney

Cox

. Pain neuroscience education: which pain neuroscience education metaphor worked best. S Afr J Physiother. 2019; 75(1): 1329.

19.

Gifford

Butler

. The integration of pain sciences into clinical practice. J Hand Ther. 1997 Apr–Jun; 10(2): 86-95.

20.

Louw

Puentedura

Zimney

Schmidt

. Know pain, know gain? A perspective on pain neuroscience education in physical therapy. J Orthop Sports Phys Ther. 2016 Mar; 46(3): 131-4.

21.

Goldberg

. Revisiting the Cartesian model of pain. Med Hypotheses. 2008; 70(5): 1029-33.

22.

Meeus

Nijs

. Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome. Clin Rheumatol. 2007 Apr; 26(4): 465-73.

23.

Kamper

Apeldoorn

Chiarotto

Smeets

Ostelo

Guzman

, et al. Multidisciplinary biopsychosocial rehabilitation for chronic low back pain. Cochrane Database Syst Rev. 2014 Sep 2; (9): CD000963.

24.

Nijs

Roussel

Paul van Wilgen

Köke

Smeets

. Thinking beyond muscles and joints: therapists’ and patients’ attitudes and beliefs regarding chronic musculoskeletal pain are key to applying effective treatment. Man Ther. 2013 Apr; 18(2): 96-102.

25.

Louw

Diener

Landers

Puentedura

. Preoperative pain neuroscience education for lumbar radiculopathy: a multicenter randomized controlled trial with 1-year follow-up. Spine. 2014 Aug 15; 39(18): 1449-57.

26.

Louw

Diener

Landers

Zimney

Puentedura

. Three-year follow-up of a randomized controlled trial comparing preoperative neuroscience education for patients undergoing surgery for lumbar radiculopathy. J Spine Surg. 2016 Dec; 2(4): 289-98.

27.

Malfliet

Kregel

Meeus

Roussel

Danneels

Cagnie

, et al. Blended-learning pain neuroscience education for people with chronic spinal pain: randomized controlled multicenter trial. Phys Ther. 2018 05 1; 98(5): 357-68.

28.

Malfliet

Kregel

Meeus

Danneels

Cagnie

Roussel

, et al. Patients with chronic spinal pain benefit from pain neuroscience education regardless the self-reported signs of central sensitization: secondary analysis of a randomized controlled multicenter trial. PM R. 2018 Dec; 10(12): 1330-1343.e1.

29.

Beltran-Alacreu

López-de-Uralde-Villanueva

Fernández-Carnero

La Touche

. Manual therapy, therapeutic patient education, and therapeutic exercise, an effective multimodal treatment of nonspecific chronic neck pain: a randomized controlled trial. Am J Phys Med Rehabil. 2015 Oct; 94(10 Suppl 1): 887-97.

30.

Gallagher

McAuley

Moseley

. A randomized-controlled trial of using a book of metaphors to reconceptualize pain and decrease catastrophizing in people with chronic pain. Clin J Pain. 2013 Jan; 29(1): 20-5.

31.

Meeus

Nijs

Van Oosterwijck

Van Alsenoy

Truijen

. Pain physiology education improves pain beliefs in patients with chronic fatigue syndrome compared with pacing and self-management education: a double-blind randomized controlled trial. Arch Phys Med Rehabil. 2010 Aug; 91(8): 1153-9.

32.

Moseley

. Joining forces – combining cognition-targeted motor control training with group or individual pain physiology education: a successful treatment for chronic low back pain. Journal of Manual & Manipulative Therapy. 2003 Apr; 11(2): 88-94.

33.

Moseley

Nicholas

Hodges

. A randomized controlled trial of intensive neurophysiology education in chronic low back pain. Clin J Pain. 2004 Sep–Oct; 20(5): 324-30.

34.

Moseley

. Combined physiotherapy and education is efficacious for chronic low back pain. Aust J Physiother. 2002; 48(4): 297-302.

35.

Pires

Cruz

Caeiro

. Aquatic exercise and pain neurophysiology education versus aquatic exercise alone for patients with chronic low back pain: a randomized controlled trial. Clin Rehabil. 2015 Jun; 29(6): 538-47.

36.

Ryan

Gray

Newton

Granat

. Pain biology education and exercise classes compared to pain biology education alone for individuals with chronic low back pain: a pilot randomised controlled trial. Man Ther. 2010 Aug; 15(4): 382-7.

37.

Téllez-García

de-la-Llave-Rincón

Salom-Moreno

Palacios-Ceña

Ortega-Santiago

Fernández-de-Las-Peñas

. Neuroscience education in addition to trigger point dry needling for the management of patients with mechanical chronic low back pain: a preliminary clinical trial. J Bodyw Mov Ther. 2015 Jul; 19(3): 464-72.

38.

van Ittersum

van Wilgen

van der Schans

Lambrecht

Groothoff

Nijs

. Written pain neuroscience education in fibromyalgia: a multicenter randomized controlled trial. Pain Pract. 2014 Nov; 14(8): 689-700.

39.

Van Oosterwijck

Meeus

Paul

De Schryver

Pascal

Lambrecht

, et al. Pain physiology education improves health status and endogenous pain inhibition in fibromyalgia: a double-blind randomized controlled trial. Clin J Pain. 2013 Oct; 29(10): 873-82.

40.

Vibe Fersum

O’Sullivan

Skouen

Smith

Kvåle

. Efficacy of classification-based cognitive functional therapy in patients with non-specific chronic low back pain: a randomized controlled trial. Eur J Pain. 2013 Jul; 17(6): 916-28.

41.

Wälti

Kool

Luomajoki

. Short-term effect on pain and function of neurophysiological education and sensorimotor retraining compared to usual physiotherapy in patients with chronic or recurrent non-specific low back pain, a pilot randomized controlled trial. BMC Musculoskelet Disord. 2015 Apr 10; 16: 83.

42.

Louw

Farrell

Choffin

Foster

Lunde

Snodgrass

, et al. Immediate effect of pain neuroscience education for recent onset low back pain: an exploratory single arm trial. J Man Manip Ther. 2019 Dec; 27(5): 267-76.

43.

Van Oosterwijck

Nijs

Meeus

Truijen

Craps

Van den Keybus

, et al. Pain neurophysiology education improves cognitions, pain thresholds, and movement performance in people with chronic whiplash: a pilot study. J Rehabil Res Dev. 2011; 48(1): 43-58.

44.

Moseley

. Evidence for a direct relationship between cognitive and physical change during an education intervention in people with chronic low back pain. Eur J Pain. 2004 Feb; 8(1): 39-45.

45.

Moseley

. Widespread brain activity during an abdominal task markedly reduced after pain physiology education: fMRI evaluation of a single patient with chronic low back pain. Aust J Physiother. 2005; 51(1): 49-52.

46.

Louw

Puentedura

Diener

Peoples

. Preoperative therapeutic neuroscience education for lumbar radiculopathy: a single-case fMRI report. Physiother Theory Pract. 2015; 31(7): 496-508.

47.

Barbari

Storari

Ciuro

Testa

. Effectiveness of communicative and educative strategies in chronic low back pain patients: A systematic review. Patient Educ Couns. doi: 10.1016/j.pec.2019.11.031.

48.

Tegner

Frederiksen

Esbensen

Juhl

. Neurophysiological pain education for patients with chronic low back pain: a systematic review and meta-analysis. Clin J Pain. 2018 08; 34(8): 778-86.

49.

Clarke

Ryan

Martin

. Pain neurophysiology education for the management of individuals with chronic low back pain: systematic review and meta-analysis. Man Ther. 2011 Dec; 16(6): 544-9.

50.

Diener

Kargela

Louw

. Listening is therapy: Patient interviewing from a pain science perspective. Physiother Theory Pract. 2016 Jul; 32(5): 356-67.

51.

Puentedura

Flynn

. Combining manual therapy with pain neuroscience education in the treatment of chronic low back pain: a narrative review of the literature. Physiother Theory Pract. 2016 Jul; 32(5): 408-14.

52.

Louw

Puentedura

Zimney

. Teaching patients about pain: it works, but what should we call it. Physiother Theory Pract. 2016 Jul; 32(5): 328-31.

53.

Louw

Zimney

O’Hotto

Hilton

. The clinical application of teaching people about pain. Physiother Theory Pract. 2016 Jul; 32(5): 385-95.

54.

Ferguson

. External validity, generalizability, and knowledge utilization. J Nurs Scholarsh. 2004; 36(1): 16-22.

55.

Khorsan

Crawford

. How to assess the external validity and model validity of therapeutic trials: a conceptual approach to systematic review methodology. Evid Based Complement Alternat Med. 2014; 2014: 694804.

56.

Cook

. Handbook of Industrial and Organizational Psychology. 1976.

57.

Rothwell

. External validity of randomised controlled trials: “to whom do the results of this trial apply?”. Lancet. 2005 Jan 1–7; 365(9453): 82-93.

58.

Fernandez-Hermida

Calafat

Becoña

Tsertsvadze

Foxcroft

. Assessment of generalizability, applicability and predictability (GAP) for evaluating external validity in studies of universal family-based prevention of alcohol misuse in young people: systematic methodological review of randomized controlled trials. Addiction. 2012 Sep; 107(9): 1570-9.

59.

Steckler

McLeroy

. The importance of external validity. Am J Public Health. 2008 Jan; 98(1): 9-10.

60.

Healthcare expenditure statistics [homepage on Internet]. Health in the European Union – facts and figures; 2018 [updated 2019 Aug 19]. Available from: https://eceuropa.eu/eurostat/statistics-explained/index.php/Healthcare_expenditure_statistics.

61.

Dueñas

Ojeda

Salazar

Mico

Failde

. A review of chronic pain impact on patients, their social environment and the health care system. J Pain Res. 2016; 9: 457-67.

62.

Carey

Evans

Hadler

Kalsbeek

McLaughlin

Fryer

. Care-seeking among individuals with chronic low back pain. Spine. 1995 Feb 1; 20(3): 312-7.

63.

Carey

Freburger

Holmes

Jackman

Knauer

Wallace

, et al. Race, care seeking, and utilization for chronic back and neck pain: population perspectives. J Pain. 2010 Apr; 11(4): 343-50.

64.

de Boer

Waterlander

Kuijper

Steenhuis

Twisk

. Testing for baseline differences in randomized controlled trials: an unhealthy research behavior that is hard to eradicate. Int J Behav Nutr Phys Act. 2015 Jan 24; 12: 4.

65.

Elkins

. Assessing baseline comparability in randomised trials. J Physiother. 2015 Oct; 61(4): 228-30.

66.

Suresh

. An overview of randomization techniques: an unbiased assessment of outcome in clinical research. J Hum Reprod Sci. 2011 Jan; 4(1): 8-11.

67.

Pain in Europe. A 2003 Report. Available from: https://www.pae-eu.eu/wp-content/uploads/2013/12/Pain-in-Europe-survey-report.pdf.

68.

Nijs

Van Houdenhove

Oostendorp

. Recognition of central sensitization in patients with musculoskeletal pain: application of pain neurophysiology in manual therapy practice. Man Ther. 2010 Apr; 15(2): 135-41.

69.

Nijs

Paul van Wilgen

Van Oosterwijck

van Ittersum

Meeus

. How to explain central sensitization to patients with ‘unexplained’ chronic musculoskeletal pain: practice guidelines. Man Ther. 2011 Oct; 16(5): 413-8.

70.

Treede

Rief

Barke

Aziz

Bennett

Benoliel

, et al. A classification of chronic pain for ICD-11. Pain. 2015 Jun; 156(6): 1003-7.

71.

Williams

Dellon

Rosson

. Management of chronic facial pain. Craniomaxillofac Trauma Reconstr. 2009 May; 2(2): 67-76.

72.

Nijs

Clark

Malfliet

Ickmans

Voogt

Don

, 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 Sep–Oct; 35 Suppl 107(5): 108-15.

73.

Smart

Blake

Staines

Thacker

Doody

. Mechanisms-based classifications of musculoskeletal pain: part 1 of 3: symptoms and signs of central sensitisation in patients with low back (± leg) pain. Man Ther. 2012 Aug; 17(4): 336-44.

74.

Smart

Blake

Staines

Thacker

Doody

. Mechanisms-based classifications of musculoskeletal pain: part 2 of 3: symptoms and signs of peripheral neuropathic pain in patients with low back (± leg) pain. Man Ther. 2012 Aug; 17(4): 345-51.

75.

Smart

Blake

Staines

Thacker

Doody

. Mechanisms-based classifications of musculoskeletal pain: part 3 of 3: symptoms and signs of nociceptive pain in patients with low back (± leg) pain. Man Ther. 2012 Aug; 17(4): 352-7.

76.

Smart

Blake

Staines

Doody

. Clinical indicators of ‘nociceptive’, ‘peripheral neuropathic’ and ‘central’ mechanisms of musculoskeletal pain. A delphi survey of expert clinicians. Man Ther. 2010 Feb; 15(1): 80-7.

77.

Galanti

. An introduction to cultural differences. West J Med. 2000 May; 172(5): 335-6.

78.

Chang

Kelly

. Patient education: addressing cultural diversity and health literacy issues. Urol Nurs. 2007 Oct; 27(5): 411-7; quiz 418.

79.

Bechtel

Davidhizar

. Integrating cultural diversity in patient education. Semin Nurse Manag. 1999 Dec; 7(4): 193-7.

80.

Price

Cordell

. Cultural diversity and patient teaching. J Contin Educ Nurs. 1994 Jul–Aug; 25(4): 163-6.

81.

Leonard

Cano

Johansen

. Chronic pain in a couples context: a review and integration of theoretical models and empirical evidence. J Pain. 2006 Jun; 7(6): 377-90.

82.

Dansie

Turk

. Assessment of patients with chronic pain. Br J Anaesth. 2013 Jul; 111(1): 19-25.

83.

Darlow

Dowell

Baxter

Mathieson

Perry

Dean

. The enduring impact of what clinicians say to people with low back pain. Ann Fam Med. 2013 Nov–Dec; 11(6): 527-34.

84.

Stewart

. Effective physician-patient communication and health outcomes: a review. CMAJ. 1995 May 1; 152(9): 1423-33.

85.

Conti

Gensini

. Doctor-patient communication: a historical overview. Minerva Med. 2008 Aug; 99(4): 411-5.

86.

Neck Pain Guidelines: Revision 2017: Using the Evidence to Guide Physical Therapist Practice. J Orthop Sports Phys Ther. 2017 Jul; 47(7): 511-2.

87.

Bernstein

Malik

Carville

Ward

. Low back pain and sciatica: summary of NICE guidance. BMJ. 2017 Jan 6; 356: i6748.

88.

Brosseau

Wells

Tugwell

Egan

Wilson

Dubouloz

, et al. Ottawa Panel evidence-based clinical practice guidelines for aerobic fitness exercises in the management of fibromyalgia: part 1. Phys Ther. 2008 Jul; 88(7): 857-71.

89.

Fitzcharles

Ste-Marie

Goldenberg

Pereira

Abbey

Choinière

, et al. 2012 canadian guidelines for the diagnosis and management of fibromyalgia syndrome: executive summary. Pain Res Manag. 2013 May–Jun; 18(3): 119-26.

90.

Avellaneda Fernández

Pérez Martín

Izquierdo Martínez

Arruti Bustillo

Barbado Hernández

de la Cruz Labrado

, et al. Chronic fatigue syndrome: aetiology, diagnosis and treatment. BMC Psychiatry. 2009 Oct 23; 9(Suppl 1): S1.

91.

Tegner

Frederiksen

Esbensen

Juhl

. Neurophysiological pain education for patients with chronic low back pain: a systematic review and meta-analysis. Clin J Pain. 2018 08; 34(8): 778-86.

92.

Bodes Pardo

Lluch Girbés

Roussel

Gallego Izquierdo

Jiménez Penick

Pecos Martín

. Pain neurophysiology education and therapeutic exercise for patients with chronic low back pain: a single-blind randomized controlled trial. Arch Phys Med Rehabil. 2018 02; 99(2): 338-47.

93.

Maier-Riehle

Härter

. The effects of back schools – a meta-analysis. Int J Rehabil Res. 2001 Sep; 24(3): 199-206.

94.

Nachemson

. Newest knowledge of low back pain. A critical look. Clin Orthop Relat Res. 1992 Jun; (279): 8-20.

95.

Nijs

Meeus

Van Oosterwijck

Roussel

De Kooning

Ickmans

, et al. Treatment of central sensitization in patients with ’unexplained’ chronic pain: what options do we have. Expert Opin Pharmacother. 2011 May; 12(7): 1087-98.

96.

Merali

Wilson

. Explanatory versus pragmatic trials: an essential concept in study design and interpretation. Clin Spine Surg. 2017 Nov; 30(9): 404-6.

97.

Kim

. Efficacy versus Effectiveness. Korean J Fam Med. 2013 Jul; 34(4): 227.

98.

Wijma

van Wilgen

Meeus

Nijs

. Clinical biopsychosocial physiotherapy assessment of patients with chronic pain: the first step in pain neuroscience education. Physiother Theory Pract. 2016 Jul; 32(5): 368-84.

99.

Testa

Rossettini

. Enhance placebo, avoid nocebo: how contextual factors affect physiotherapy outcomes. Man Ther. 2016 Aug; 24: 65-74.

Applicability of pain neuroscience education: Where are we now?

Abstract

BACKGROUND:

OBJECTIVE:

METHODS:

RESULTS:

Keywords

Abbreviations

1. Introduction

2.1 Setting of the trial

Table 1 Structure of recruitment in each study

Table 2 Baseline clinical characteristics

2.4 Difference between trial protocol and routine practice

2.5 Outcome measures and follow-up

2.5.1 Outcome measures

Table 3 Follow-ups in each study

2.7 Costs

3. Translating PNE from research to clinical practice

4. Conclusions

Authors’ contributions

Funding

Footnotes

Acknowledgments

Conflict of interest

References

Table 1
Structure of recruitment in each study

Table 2
Baseline clinical characteristics

Table 3
Follow-ups in each study