Psychological therapies for the management of chronic neuropathic pain in adults

  • Protocol
  • Intervention



This is the protocol for a review and there is no abstract. The objectives are as follows:

  1. To assess the efficacy of psychological treatments on outcomes in the domains of pain experience, disability, mood, and health care use, in adults with chronic neuropathic pain.

  2. To assess any harm from psychological treatments in adults with chronic neuropathic pain.


Neuropathic pain is an increasing problem for which existing therapies have limited effectiveness. It is appropriate to offer psychologically based treatment, which aims to rehabilitate patients despite continuing pain, to reduce pain and its effects on everyday life, or both. This protocol draws on a template for reviews of drugs used to relieve neuropathic pain. The aim is for all reviews of neuropathic pain conditions to use the same methods, based on new criteria for what constitutes reliable evidence in chronic pain (Moore 2010). Material has been added from a recent review of psychological treatments for all chronic pain in adults (Williams 2012) from which this review emerges.

Description of the condition

The 2011 International Association for the Study of Pain definition of neuropathic pain is "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system" (Haanpää 2011; see also Jensen 2011). Neuropathic pain may be caused by nerve damage, but is often followed by changes in the central nervous system (CNS) (Moisset 2007). Pain can be severe and complex (Apkarian 2011; Tracey 2011). Many people with neuropathic pain conditions are significantly disabled, with moderate or severe pain for many years (Doth 2010; Smith 2012; Williams 2011).

In primary care in the UK the incidences, per 100,000 person-years observation, have been reported as 28 (95% CI 27 to 30) for postherpetic neuralgia, 27 (95% CI 26 to 29) for trigeminal neuralgia, 0.8 (95% CI 0.6 to 1.1) for phantom limb pain and 21 (95% CI 20 to 22) for painful diabetic neuropathy (Hall 2008). Estimates vary between studies, often because of small numbers of cases. A systematic review of chronic pain demonstrated that some neuropathic pain conditions, such as painful diabetic neuropathy, can have prevalence rates up to 400 per 100,000 person-years (McQuay 2007); the prevalence of neuropathic pain was reported as about 7% in a systematic review of studies published since 2000 (Moore 2013), and Haanpää 2011 reported prevalence ranging from 3.3% to 8.2%.

Neuropathic pain is known to be difficult to treat effectively, with only a minority of individuals experiencing a clinically relevant benefit from any one intervention (Kalso 2014; Moore 2013a). A multidisciplinary approach is now advocated, with pharmacological interventions being combined with physical or cognitive interventions, or both. Pharmacological treatments are varied and often given in combination; a recent overview shows that efficacy varies with condition (Kalso 2014), with pain relief of at least 50% reduction in pain intensity (Moore 2013a) for a minority, and with numbers needed to treat to benefit (NNT) usually between 4 and 10 (Moore 2013a).

In earlier reviews on all chronic pain except headache (Eccleston 2009; Williams 2012), we searched for all published randomised controlled trials (RCTs) of interventions described as psychological in nature, and recovered trials principally of behaviour therapy (BT) or cognitive behavioural therapy (CBT). RCTs of interventions for headache were excluded for several reasons: for consistency with the previous reviews (Eccleston 2009; Williams 2012); and because CBT for headache aims primarily to reduce the frequency, duration, and intensity of headache pain rather than to rehabilitate despite ongoing pain. Readers are referred to other reviews (Nestoriuc 2007; Nestoriuc 2008); Cochrane systematic reviews are in progress. Internet trials were also excluded because they are the subject of an existing review (Eccleston 2014). The Williams 2012 review found 42 trials, of which 35 provided data (N = 4788) for meta-analysis. CBT showed small positive effects on disability and catastrophising, but not on pain or mood, when compared with active controls. CBT showed small to moderate effects on pain, disability, mood, and catastrophising when compared with treatment as usual or waiting list. Only a small effect on mood persisted at follow-up. The only positive effect of BT was on catastrophising immediately after treatment, but there were relatively few behaviour therapy studies. The quality of trials and trial reporting is improving (Morley 2006; Williams 2012), although the quality of treatment remains variable (Williams 2012).

Description of the intervention

A broad family of treatments is included in the general term 'psychological'. In essence, treatments have been developed that are specifically designed to alter psychological processes thought to underlie or significantly contribute to pain, distress, and/or disability (Eccleston 2011; Eccleston 2013; Morley 1999; Morley 2013). The design of psychological treatments is normally informed by specific theories of the aetiology of human behaviour, or treatments have developed pragmatically through observation and study of response to intervention (Eccleston 2013). In practice, there is variety in the types of interventions used, and not all have been evaluated for their effectiveness (Morley 2006; Morley 2013). The evidence base for psychological therapies is dominated by studies of programmatic and protocolised treatments from a behavioural or cognitive behavioural tradition of clinical psychology (Eccleston 2013). Psychological therapies are commonly presented as being offered after orthodox treatments have failed, when the treatment goal shifts from one of removing or alleviating pain to one of managing pain and its myriad adverse consequences on quality of life (Lumley 2011; Morley 2006).

How the intervention might work

Most, but not all, psychological treatments consist of cognitive or behavioural therapies, or both. A typical treatment protocol for cognitive behavioural therapy (CBT) uses methods aimed directly at assessing the thoughts and biases in thinking associated with pain, and the extent of avoidance of unpleasant thoughts (Morley 1999). Behavioural methods focus on the identification of behaviour that is contingent upon pain, or upon events that provide pain relief or comfort; it aims to reduce behavioural avoidance or persistence with painful experiences where such avoidance or persistence impedes progress towards valued goals (Van Damme in press). Most therapies involve education, and many are incorporated within larger treatment programmes involving physical and occupational or vocational therapy (Morley 2006). Non-CBT interventions will be included to the extent that they are based on defined psychological theories and treatment methods for which there is some evidence of efficacy in the broader field of clinical psychology (Eccleston 2013).

Why it is important to do this review

Chronic painful conditions comprised five of the 11 top-ranking conditions for years lived with disability in 2010 (Vos 2012), and are responsible for considerable loss of quality of life, employment, and increased health costs (Moore 2013). Neuropathic pain has been under-recognised (see Description of the condition, and Smith 2012) and some forms of neuropathic pain, such as diabetic neuropathy and postsurgical chronic pain (often neuropathic in origin), are increasing in prevalence (Hall 2008). Neuropathic pain has a particularly severe impact on quality of life (Smith 2007), and its origins and persistence are difficult for people with neuropathic pain to understand. In psychologically based pain management, it is not usual to distinguish between diagnoses and the predominant model of musculoskeletal pain may serve those with neuropathic pain rather poorly. It is time to disaggregate the compound review of psychologically based pain management for all chronic pain except headache (Williams 2012), which concluded that there was no need for more general RCTs or reviews of mixed chronic pain, and that reviews of specific types of chronic pain were needed, consistent with those of medical interventions. There is an increased need to evaluate psychological treatments in this field. The only existing review is outside Cochrane and of poor quality (Wetering 2010) (see Eccleston 2010).


  1. To assess the efficacy of psychological treatments on outcomes in the domains of pain experience, disability, mood, and health care use, in adults with chronic neuropathic pain.

  2. To assess any harm from psychological treatments in adults with chronic neuropathic pain.


Criteria for considering studies for this review

Types of studies

We will include studies if they are randomised controlled trials (RCTs) comparing a credible psychological treatment, or a compound treatment with primary psychological content, with placebo, other active treatment, treatment as usual, or waiting list control. We will judge a psychological treatment credible if it was based on an extant psychological model or framework, and its delivery was from, or was supervised by, a healthcare professional qualified in psychology.

Studies will be included if they:

  • were available as a full publication or report of a RCT;

  • had a design that placed a psychological treatment as an active treatment;

  • were published (or electronically pre-published) in a peer-reviewed science journal;

  • had 20 or more participants in each treatment arm at the end of the treatment or follow-up assessment.

Types of participants

Studies should include adult participants (18 years and above) with neuropathic pain of at least three months' duration. There is a wide range of chronic neuropathic pain conditions including:

  • painful diabetic neuropathy (PDN);

  • postherpetic neuralgia;

  • trigeminal neuralgia;

  • phantom limb pain;

  • postoperative or traumatic neuropathic pain;

  • complex regional pain syndrome (CRPS), Type I and Type II;

  • cancer-related neuropathy;

  • human immunodeficiency virus (HIV) neuropathy;

  • spinal cord injury.

We will include studies of participants with more than one type of neuropathic pain; in such cases we will analyse results according to the primary condition.

Types of interventions

We will include studies if at least one trial arm consisted of a psychology intervention, with at least one comparator arm of a placebo condition, other active treatment, treatment as usual, or waiting list control. A psychology intervention is defined as one which defines its psychotherapeutic content in terms of methods specifically designed to alter psychological processes thought to underlie or significantly contribute to pain, distress, and/or disability (Eccleston 2013; Morley 1999; Morley 2013). Such methods are informed by specific theories of the aetiology of human behaviour for which there is some evidence of efficacy in the broader field of clinical psychology (Eccleston 2013).

Types of outcome measures

We aim to use outcomes in the domains of pain experience, disability, negative mood, and health care use, as well as adverse events. We anticipate that studies will use a variety of outcome measures, with the majority of studies using standard subjective scales (numerical rating scale (NRS) or visual analogue scale (VAS) for pain intensity or pain affect, or both. We are particularly interested in the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) definitions for moderate and substantial benefit in chronic pain studies (Dworkin 2008). These are defined as at least 30% pain relief over baseline (moderate) and at least 50% pain relief over baseline (substantial); for pain interference as measured by the Brief Pain Inventory (BPI 1994), at least half a standard deviation or one point on a 0 to 10 mean of the seven interference items; and for depression as measured by the Beck Depression Inventory (BDI 1961 but see Morley 2002), at least half a standard deviation or a change of at least five points.

Primary outcomes
  1. Pain experience, e.g. self-rating of pain intensity or pain distress on a visual analogue scale, numerical rating scale or similar

  2. Mood, e.g. standard anxiety scale such as Spielberger State/Trait Anxiety Inventory, standard depression scale such as Beck Depression Inventory BDI 1961), standard distress scale such as the Hospital Anxiety and Depression Scale

  3. Disability or quality of life, e.g. Brief Pain Inventory (BPI 1994), Medical Outcomes Study SF-36 or SF-12

  4. Adverse events and dropouts

Secondary outcomes
  1. Health care use, e.g. medication use, healthcare visits, healthcare procedures, hospital stays

Search methods for identification of studies

We will search electronic databases, journal pre-publication websites, and reference lists.

Electronic searches

We will search the following databases from their inception to the present:

  • Cochrane Central Register of Controlled Trials (CENTRAL);

  • MEDLINE (via Ovid);

  • EMBASE (via Ovid);

  • PsycINFO(via Ovid).

The search strategy for MEDLINE is in Appendix 1.

We will apply no language restrictions.

At least two review authors will review all abstracts, consulting the third review author when necessary to decide on inclusion or exclusion.

Searching other resources

We will review the bibliographies of any randomised trials identified and of review articles, and search clinical trial databases (for example, and WHO ICTRP ( to identify additional published or unpublished data. We will not contact investigators or study sponsors.

Data collection and analysis

If possible, we will perform separate analyses according to particular neuropathic pain conditions.

We will compile a Summary of Findings table.

Selection of studies

We will determine eligibility by reading the abstract of each study identified by the search. We will eliminate studies that clearly do not satisfy the inclusion criteria, and we will obtain full copies of the remaining studies; two review authors will make decisions. Two review authors (LH, AW) will read these studies independently and reach agreement by discussion. We will not anonymise the studies before assessment. We will create a PRISMA flow chart.

Data extraction and management

Two review authors (LH, AW) will independently extract data, using a standard form, and check for agreement before entry into RevMan (RevMan 2012). We will include information about the pain condition and number of participants treated, type of intervention, study design (type of control), study duration and follow-up, outcome measures used, data for primary measure in each domain, attrition, and adverse events.

Assessment of risk of bias in included studies

We will assess risk of bias using the recommended Cochrane guidance (Higgins 2011). Of the five suggested 'Risk of bias' categories, we will include random sequence generation (selection bias), allocation concealment (selection bias), blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), and selective reporting (reporting bias). Although we will include the risk 'blinding participants and personnel', because neither therapists nor patients can be blinded to whether they deliver or receive treatment, we will follow the procedure used in our previous review (Williams 2012): two authors (AW, CE) will apply a quality rating scale specifically designed for psychological interventions in pain (Yates 2005). The scale includes items on treatment manualisation, therapist training, and equality of participants' treatment expectations across conditions, since these items in part address issues of patient and therapist non-blinding.

Measures of treatment effect

Where an outcome domain is measured by different instruments in different trials, we will analyse data by effect size as continuous outcomes for which we will calculate the standard mean difference (SMD) with 95% confidence interval (CI). Where appropriate, we will apply categories of improvement as defined by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) group (Dworkin 2008) and analyse dichotomously. For dichotomous outcomes we will calculate the odds ratio (OR) with 95% CI.

Unit of analysis issues

If there is more than one treatment arm, we will combine them where they represent sufficiently similar treatment.

Dealing with missing data

Since for continuous variables we cannot assign participants who were excluded from analysis, we use the data provided by authors; the distinction between intention-to-treat (ITT) and per protocol (PP) analyses is made in the quality scores.

Assessment of heterogeneity

We will deal with clinical heterogeneity by combining studies that examine similar conditions. We will assess statistical heterogeneity with the use of the I² statistic, and where I² is greater than 50%, we will consider possible reasons.

Assessment of reporting biases

Reporting biases are included in the quality scale (Yates 2005).

Data synthesis

We will use a random-effects model for meta-analysis, assuming significant clinical heterogeneity.

Subgroup analysis and investigation of heterogeneity

Ideally, we plan subgroup analysis by type of neuropathic pain (specifically painful diabetic neuropathy; postherpetic neuralgia; trigeminal neuralgia; phantom limb pain; postoperative or traumatic neuropathic pain; complex regional pain syndrome; cancer-related neuropathy; human immunodeficiency virus (HIV) neuropathy; spinal cord injury), but we anticipate too few data for this on the basis of previous reviews of chronic pain. No other subgroup analyses are planned.

Sensitivity analysis

We plan no sensitivity analysis because the evidence base is known to be too small to allow reliable analysis. We will examine details of dose escalation schedules in the unlikely situation that this could provide some basis for a sensitivity analysis.


CRG Funding Acknowledgement: The National Institute for Health Research (NIHR) is the largest single funder of the Cochrane PaPaS Group. Disclaimer: The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NIHR, NHS or the Department of Health.


Appendix 1. Search strategy for MEDLINE

1 exp Psychotherapy/
2 behavior therapy/ or cognitive therapy/
3 exp Biofeedback, Psychology/
4 behavio#r therap*.tw.
5 cognitive therap*.tw.
6 (relax* adj3 technique*).tw.
7 (relax* adj3 (technique* or therap*)).tw.
8 meditat*.tw.
9 psychotherap*.tw.
10 (psychological adj2 (treatment* or therap*)).tw.
11 "group therapy".tw.
12 "self-regulation training".tw.
13 "coping skill*".tw.
14 "pain-related thought*".tw.
15 (behavio#r* adj3 rehabilitat*).tw.
16 (psychoeducation adj2 group*).tw.
17 (psycho-education adj2 group*).tw.
18 ("mind and body relaxation technique*" or "mind-body relaxation technique*").tw.
19 exp mind-body therapies/ or relaxation therapy/
20 or/1-19
21 exp Neuralgia/
22 Chronic Pain/
23 (neuralgia* or neurodynia).tw.
24 ((neuropathic or nerve*) adj3 pain*).tw
25 or/21-24
26 20 and 25
27 randomized controlled
28 controlled clinical
29 randomized.ab.
30 placebo.ab.
31 drug therapy.fs.
32 randomly.ab.
33 trial.ab.
34 or/27-33
35 exp animals/ not
36 34 not 35
37 26 and 36

Contributions of authors

CE directed the project.
CE, LH, and AW all contributed to the conceptualising and authoring of the review.

Declarations of interest

Christopher Eccleston: none known. CE is funded by the UK National Institute for Health Research for work on a series of reviews informing the unmet need of chronic pain and providing the evidence for treatments of pain. This title is part of this research programme.

Leslie Hearn: none known.

Amanda Williams: none known.

Sources of support

Internal sources

  • None, Other.

External sources

  • The National Institute for Health Research (NIHR), UK.

    NIHR Cochrane Programme Grant: 13/89/29 - Addressing the unmet need of chronic pain: providing the evidence for treatments of pain.