Neural Mobilization: A Systematic Review of Randomized Controlled Trials with an Analysis of Therapeutic Efficacy

Richard F. Ellis, B. Phty, Post Grad Dip and Wayne A. Hing, PT, PhD

Abstract

Neural mobilization is a treatment modality used in relation to pathologies of the nervous system. It has been suggested that neural mobilization is an effective treatment modality, although support of this suggestion is primarily anecdotal. The purpose of this paper was to provide a systematic review of the literature pertaining to the therapeutic efficacy of neural mobilization. A search to identify randomized controlled trials investigating neural mobilization was conducted using the key words neural mobilisation/mobilization, nerve mobilisation/mobilization, neural manipulative physical therapy, physical therapy, neural/nerve glide, nerve glide exercises, nerve/neural treatment, nerve/neural stretching, neurodynamics, and nerve/neural physiotherapy. The titles and abstracts of the papers identified were reviewed to select papers specifically detailing neural mobilization as a treatment modality. The PEDro scale, a systematic tool used to critique RCTs and grade methodological quality, was used to assess these trials. Methodological assessment allowed an analysis of research investigating therapeutic efficacy of neural mobilization. Ten randomized clinical trials (discussed in 11 retrieved articles) were identified that discussed the therapeutic effect of neural mobilization. This review highlights the lack in quantity and quality of the available research. Qualitative analysis of these studies revealed that there is only limited evidence to support the use of neural mobilization. Future research needs to re-examine the application of neural mobilization with use of more homogeneous study designs and pathologies; in addition, it should standardize the neural mobilization interventions used in the study.

Keywords: Neural Mobilization, Neurodynamics, Randomized Controlled Trial, Systematic Review, Therapeutic Efficacy

In the past, neural tension was used to describe dysfunction of the peripheral nervous system. More recently, there has been a shift away from a purely mechanical rationale to include physiological concepts such as structure and function of the nervous system. Neurodynamics is now a more accepted term referring to the integrated biomechanical, physiological, and morphological functions of the nervous system1–4. Regardless of the underlying construct, it is vital that the nervous system is able to adapt to mechanical loads, and it must undergo distinct mechanical events such as elongation, sliding, cross-sectional change, angulation, and compression. If these dynamic protective mechanisms fail, the nervous system is vulnerable to neural edema, ischaemia, fibrosis, and hypoxia, which may cause altered neurodynamics1,2.

When neural mobilization is used for treatment of adverse neurodynamics, the primary theoretical objective is to attempt to restore the dynamic balance between the relative movement of neural tissues and surrounding mechanical interfaces, thereby allowing reduced intrinsic pressures on the neural tissue and thus promoting optimum physiologic function1,2,4–7. The hypothesized benefits from such techniques include facilitation of nerve gliding, reduction of nerve adherence, dispersion of noxious fluids, increased neural vascularity, and improvement of axoplasmic flow1,2,4–10. However, these etiological mechanisms for the clinically observed effects of neural mobilization still require robust validation. At present, the positive clinically observed effect of neural mobilization is mainly based on anecdotal evidence. Therefore, the purpose of this paper was to systematically review and assess the therapeutic efficacy of neural mobilization for treatment of altered neurodynamics through evaluation of appropriate randomized controlled trials (RCTs). It was hypothesized that the findings might guide evidence-based practice in the clinical application of neural mobilization.

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Methods

Literature Search Strategy

A search to identify RCTs examining neural mobilization was conducted in March 2007. The following electronic databases were searched: MEDLINE via PubMed (from 1966 onwards), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (from 1982 onwards), the Cochrane Controlled Trials Register in the Cochrane Library (latest edition), SPORT-Discus (from 1830 onwards), Allied and Complementary Medicine Database (AMED) (from 1985 onwards), Physiotherapy Evidence Database (PEDro) (from 1953 onwards), ProQuest 5000 International, ProQuest Health and Medical Complete, EBSCO MegaFile Premier, Science Direct (from 1995 onwards) and Web of Science (from 1945 onwards).

The search strategy of these databases included terms and keywords related to the intervention: neural mobilisation/mobilization, nerve mobilisation/mobilization, neural manipulative physical therapy, physical therapy, neural/nerve glide, nerve glide exercises, nerve/neural treatment, nerve/neural stretching, neurodynamics and nerve/neural physiotherapy. Randomized controlled trial or RCT was the key term used in relation to the methodology of the studies. The titles and/or abstracts of these citations were reviewed to identify papers specifically detailing neural mobilization used as a treatment modality. The search was limited to studies written in or translated to English and those utilizing human subjects. There was no limitation regarding the date the studies were published, other than the date limitations of each selected database. In addition, the reference lists of each paper were searched to identify other relevant papers.

Study Selection

The method for selection of relevant studies was consistent with suggested guidelines for conducting systematic reviews11. The following inclusion criteria were used to select relevant papers for the review:

• Type of participant: participants older than 18, of either gender, and with a clinical diagnosis consistent with neurodynamic dysfunction (musculoskeletal conditions with symptoms of pain and/or paresthesia indicative of compromise of the peripheral nervous system).
• Type of study design: randomized controlled trials.
• Type of intervention: use of a manual or exercise technique designed to have a direct effect on neural tissue with the purpose of dynamically influencing (e.g., sliding, stretching, moving, mobilizing etc.) the neural tissue.
• Outcome measurements: at least one of the following outcome measurements used to assess the status of the nervous system: pain rating (e.g., Visual Analogue Scale [VAS], function-specific pain VAS (i.e., work- or sport-related pain), pain and or range of movement (ROM) during neural tissue provocation tests (NTPT), functional disability scores (e.g., Short-form McGill Pain Questionnaire, Northwick Park Questionnaire, and Oswestry Disability Index).

Methodological Quality Assessment

Three reviewers independently assessed the methodological quality of each RCT. The PEDro Scale (Table ​(Table1),1), developed by The Centre of Evidence-Based Physiotherapy (CEBP), was utilized to assess each paper12. The PEDro Scale, an 11-item scale, is a validated, reliable, and versatile tool used to rate RCTs for the PEDro Database13–15. The PEDro scale has been used as a measure of methodological quality in many systematic literature reviews16–20.

TABLE 1

PEDRO Scale (modiffed from Maher et al13).

An overall score of methodological quality, or quality score (QS), was determined for each paper by each of the three reviewers as a total of positive scores for 10 of the 11 items (i.e., N/10). Unlike the other items, Criterion One of the PEDro scale relates to external validity and was not used in the final total PEDro score13,15. A consensus method was used to discuss and resolve discrepancies between the markings of each paper between the reviewers. The agreed QS for each paper is included in Table ​Table22.

TABLE 2

Randomized controlled trials of neural mobilization as a treatment modality in order of PEDRO score.

The various items of the PEDro Score deal with different aspects of RCT analysis including internal validity, external validity, and statistics. In order to allow quantitative analysis of the methodological quality of a systematic review, van Tulder et al11 recommended the analysis of the internal validity criteria of any rating tool. For the PEDro Scale, seven items relating to internal validity were identified. These seven items include items 2, 3, and 5 through 9 (Table ​(Table1).1). An internal validity score (IVS) has also been used in other systematic reviews21 to allow calculation of the number of internal validity criteria met for that particular rating system and to thereby give an assessment of methodological quality. It was decided to calculate an IVS for this review based on the relevant internal validity criteria of the PEDro Scale. The positive scores of each of these seven items were added together to calculate the IVS (Table ​(Table22).

To stratify methodological quality, the summated score of the 7-item IVS, calculated from the initial PEDro score (QS), was divided into three categories. A study of high methodological quality obtained IVS values of 6–7, a moderate quality obtained IVS values between 4–5, and a limited quality was scored between 0–3. This decision was made based on even cut-off points between 0 and 7.

Analysis of Therapeutic Efficacy

When RCTs are heterogeneous, there is no available method to quantitatively assess the relative benefit (or lack thereof) of one intervention versus another because the studies compare dissimilar patient populations or interventions. In situations where the heterogeneity of primary studies prevents use of a quantitative meta-analysis to summarize the results, recommendations are typically made based on a qualitative assessment of the strength of the evidence21. The RCTs reviewed for this paper were considered heterogeneous because they explored a variety of pathologies and different types of neural mobilization techniques. Consequently, a quantitative meta-analysis was not appropriate and results were analyzed in a qualitative fashion. The qualitative assessment involved the following categories scored specifically for each type of intervention:

• Level 1: Strong evidence: provided by generally consistent findings in multiple RCTs of high quality.
• Level 2: Moderate evidence: provided by generally consistent findings in one RCT of high quality and one or more of lower quality.
• Level 3: Limited evidence: provided by generally consistent findings in one RCT of moderate quality and one or more low-quality RCTs.
• Level 4: Insufficient evidence: provided by generally consistent findings of one or more RCTs of limited quality, or when no RCTs were available, or when studies provided conflicting results.

Clinical Benefit

Lastly, to determine whether a clinical benefit for neural mobilization could be concluded, a ranking system similar to that used by Linton and van Tulder11 was used. A positive effect was concluded if the intervention (i.e., neural mobilization) was statistically significantly more beneficial compared to the control for at least one key outcome variable, a negative effect if the intervention was less effective than the control, and a neutral effect was concluded where the intervention and control did not statistically differ significantly for any of the outcome variables23.

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Results

Selection of Studies

Ten RCTs, represented by 11 published articles8,10,24–32, satisfied the inclusion criteria following the electronic and manual reference list searches. The articles published by Coppieters et al8,28 are from the same subject group and were thus classified as one RCT.

Methodological Quality

The methodological quality for each paper, represented by the IVS, is detailed in Table ​Table2.2. Nine of 11 studies8,10,25–28,30–32 reviewed were given an IVS of 4 or 5 and were of moderate methodological quality. Two of the studies24,29 were given an IVS of 3, suggesting limited methodological quality. Table ​Table33 presents statistics relating to the percentage of each item that was satisfied for an IVS score.

TABLE 3

Number and percentage of the studies meeting each PEDRO criteria.

All of the 11 studies satisfied the items relating to random allocation of subjects, measures of one key outcome taken from greater than 85% of the population, use of intention-to-treat analysis (where this was required due to a drop-out group), and results of statistical analysis reported (items 2, 8, 9, and 10). All 11 studies did not satisfy items 5 and 6, which relate to subject and therapist blinding. Two studies24,29 did not satisfy item 7, which relates to rater blinding. This suggests that these two studies lacked all three forms of blinding (subject, therapist, and rater). The other 9 studies were single-blinded (rater-blinded) studies. There was no clear trend established for item 4, which relates to concealed allocation of subjects.

Study Characteristics

All ten RCTs used different methods of application of neural mobilization (e.g., cervical lateral glide, slump sliders, peripheral nerve sliders, etc.), and some studies chose to combine these techniques with home-based neural mobilization exercises. There were also differing neurodynamic dysfunctions examined, including lateral epicondylalgia, carpal tunnel syndrome, post-operative spinal surgery, non-radicular low back pain, and neurogenic cervico-brachial pain syndrome. Therefore, all ten RCTs were clinically and therapeutically heterogeneous, necessitating a qualitative analysis for summarizing the results. Table ​Table44 contains details of study characteristics.

TABLE 4

Randomized controlled trials of neural mobilization as a treatment modality.

Therapeutic Efficacy

Of the 11 studies identified, 6 different categories or types of treatment were identified (Table ​(Table5).5). Using the qualitative rating system, as mentioned earlier, it appears there is limited evidence (Level 3) to support the use of neural mobilization that involves active nerve and flexor tendon gliding exercises of the forearm24,26,30, cervical contralateral glides8,28,32, and Upper Limb Tension Test 2b (ULTT2b) mobilization29,31 in the treatment of altered neurodynamics or neurodynamic dysfunction. There was inconclusive evidence (Level 4) to support the use of neural mobilization involving slump stretches27 and combinations of neural mobilization techniques10,25 in the treatment of altered neurodynamics or neurodynamic dysfunction.

TABLE 5

Level of evidence for therapeutic ef cacy per intervention type.

Clinical Benefit

Table ​Table44 lists the study details of the 11 studies. More studies found a positive effect8,24–28,30,32 than a neutral effect10,29,31 .

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Discussion

A search to identify RCTs investigating neural mobilization yielded 11 studies that met the inclusion criteria for this review. Analyses of these studies, using the criteria of Linton and van Tulder11, indicated that 8 of the 11 studies8,24–28,30,32 concluded a positive benefit from using neural mobilization in the treatment of altered neurodynamics or neurodynamic dysfunction. Three of the 11 studies10,29,31 concluded a neutral benefit, which suggests that neural mobilization was no more beneficial than standard treatment or no treatment. Nine of the 11 studies8,10,25–28,30–32 reviewed demonstrated moderate methodological quality; the two remaining studies24,29 yielded limited methodological quality. Studies exhibited weaknesses in random allocation, intention to treat, concealed allocation, and blinding; consequently, our ability to review and assess the therapeutic efficacy of neural mobilization for treatment of altered neurodynamics through evaluation of appropriate randomized controlled trials was substantially limited.

Methodological weaknesses can lead to over- or underestimations of actual outcomes. For example, blinding can significantly eliminate bias and confounding, and is essential in maintaining the robustness of an RCT. Blinding is difficult for use in studies involving manual therapy33,34, although in this review only 9 of the 11 studies blinded the raters. Some have argued that blinding for use in manual therapy studies is useful34, although it is arguable that non-masked raters could bias outcome findings.

The outcome measures used by the RCTs in this review also lacked homogeneity. A battery of different scales was used, and findings are not transferable across populations. One method used to standardize measures of success is the use of a minimal clinically important different score (MCID). MCID relates to the smallest change in a clinical outcome measure, which correlates to a person feeling “slightly better” than the initially recorded state33. Findings can be dichotomized into success or failure. In research that analyzes the therapeutic benefit of an intervention, the MCID is an important statistic, as it represents a level of therapeutic benefit significant enough to change clinical practice34. MCIDs are population- and pathology-specific, and they require analysis to determine a properly computed value. To our knowledge, all or a majority of the outcome scales used have not been evaluated for an MCID for the population examined in our study.

Due to the heterogeneity in respect to the neural mobilization interventions used in these RCTs, it is difficult to make general conclusions regarding neural mobilization as a general therapeutic tool. Over all, six different categories or types of neural mobilization treatments were identified (Table ​(Table5).5). Of these, there was limited evidence to support the use of active nerve and flexor tendon gliding exercises of the forearm24,26,30, cervical contralateral glides8,28,32, and Upper Limb Tension Test 2b (ULTT2b) mobilization29,31 in the treatment of altered neurodynamics or neurodynamic dysfunction. There was inconclusive evidence to support the use of slump stretches27 and combinations of neural mobilization techniques10,25 in the treatment of altered neurodynamics or neurodynamic dysfunction.

Future studies are needed and a larger, more comprehensive body of work is required before conclusive evidence is available. We found only 10 RCTs met the inclusion criteria for this systematic review. Unfortunately, all studies were clinically heterogeneous in that each looked at a number of different pathologies and different types of neural mobilization. This made quantitative analysis of therapeutic efficacy impossible. As Reid and Rivett21 have stated, direct quantitative comparison, within the realms of systematic review, is very difficult when pathologies, interventions, and outcome measures are heterogeneous. For example, even for this review there were a number of studies that looked at neural mobilization in treatment for lateral epicondylalgia29,32, carpal tunnel syndrome24,26,30,31, and cervicobrachial pain8,25,28. The specific neural mobilization intervention differed between studies, making, in these cases, the treatments too heterogeneous for statistical pooling.

With respect to the clinical implications of these findings, it is interesting to note that generally all the RCTs that looked at neural mobilization for upper quadrant (i.e., cervical spine, shoulder girdle, and upper limb) problems, with the exception of one study 25, concluded that there was limited evidence for therapeutic efficacy. This is in direct contrast to studies that examined neural mobilization for lower quadrant (i.e., lumbar spine, pelvic girdle, and lower limb) problems10,25,27 in that all provided inconclusive evidence for therapeutic efficacy. From a more specific pathological perspective, for neural mobilization of cervical nerve roots, three papers supported the use of cervical contralateral glide mobilization. For neural mobilization of the median nerve in people with carpal tunnel syndrome, three papers supported the use of active nerve and flexor tendon gliding exercises of the forearm24,26,30.

Future Research

Considering the results of the extensive literature search carried out for this review, there is an obvious paucity of research concerning the therapeutic use of neural mobilization. Not only is there a lack in quantity of such research, upon dissection of the scarce research that is available, there is also a lack of quality. Future research should look not only at similar pathologies but also at similar neural mobilization techniques.

Another key feature of these studies is that only clinical outcome measures were used. In the introduction, we discussed the biomechanical, physiological, and morphological theories underlying neural mobilization. One of the key theories for using neural mobilization is to exploit the mechanical effect that this form of mobilization has on the neural tissue and its mechanical interface. It is possible to use objective in-vivomeasurements of neural movement (i.e., glide, slide, stretch, etc.) via real-time diagnostic ultrasound. It will be important to eventually substantiate clinical improvements with objective measurement of neural movement. For example, recent unpublished data have demonstrated that it is possible to visualize and quantify, with reasonable reliability, sciatic nerve movement during neural mobilization35. As it has been postulated that an improvement in nerve mobility may explain any perceived benefits of neural mobilization, it would be relevant to make a comparison of clinical measures with objective measures (e.g., ROM and neural mobility) in an in-vivo situation in studies that examine neural mobilization. Such a comparison may give clues as to whether neural mobilization is more likely to impose a mechanical effect or a neurophysiological effect on the nervous system.

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Conclusion

Neural mobilization is advocated for treatment of neurodynamic dysfunction. To date, the primary justification for using neural mobilization has been based on a few clinical trials and primarily anecdotal evidence. Following a systematic review of the literature examining the therapeutic efficacy of neural mobilisation, 10 RCTs discussed in 11 studies were retrieved. A majority of these studies concluded a positive therapeutic benefit from using neural mobilization. However, in consideration of their methodological quality, qualitative analysis of these studies revealed that there is only limited evidence to support the use of neural mobilization. Future research needs to examine more homogeneous studies (with regard to design, pathology, and intervention), and we suggest that they combine clinical outcome measures with in-vivo objective assessment of neural movement.

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