AGREEMENT AND CORRELATION BETWEEN THE SELF-REPORT

LEEDS ASSESSMENT OF NEUROPATHIC SYMPTOMS AND

SIGNS AND DOULEUR NEUROPATHIQUE 4 QUESTIONS

NEUROPATHIC PAIN SCREENING TOOLS IN SUBJECTS WITH

LOW BACK–RELATED LEG PAIN

Jeremy Walsh, M Manip Th, a Martin I. Rabey, M Manip Th,b and Toby M. Hall, PhDc

a Honorary ReCollege of Surge

b Physiotherapc Adjunct Sen

Western AustraliThis work s

Physiotherapy, TSubmit reque

Honorary ResearIreland (e-mail: J

Paper submittaccepted Novemb

0161-4754/$3Copyright ©doi:10.1016/j.

196

ABSTRACT

Objective: The self-report Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) and DouleurNeuropathique 4 Questions (DN4) neuropathic pain screening tools have been shown to be reliable, valid, and able todifferentiate neuropathic pain from inflammatory or mixed pain syndromes. However, no studies have compared thesetools to determine whether their outcomes are similar. This study evaluated agreement and correlation between theS-LANSS and DN4 in the identification of neuropathic pain in subjects with low back–related leg pain.Methods: This observational study compared S-LANSS and DN4 scores in 45 patients with low back–related legpain. The S-LANSS and DN4 cutoff scores of 12 and 4, respectively, were used to classify subjects as positive ornegative for the presence of neuropathic pain for each screening tool. The κ statistic was used to determine whetherthere was agreement in classification of neuropathic pain between the 2 screening tools. Pearson correlation coefficientwas used to determine correlation between scores of the 2 screening tools.Results: Neuropathic pain was identified in 15 subjects (33%) using the S-LANSS and in 19 subjects (42%) using theDN4. Agreement on neuropathic pain classification was fair, with a κ value of 0.34. There was moderate to goodcorrelation (r = 0.62; P b .001) between scores obtained from the 2 tools.Conclusions: The finding of fair agreement suggests that despite the moderate to good correlation between scores,the cutoff points for the classification of neuropathic pain of the 2 tools may not be congruent. (J Manipulative PhysiolTher 2012;35:196-202)

Key Indexing Terms: Neuropathic Pain; Leg; Pain; Sciatica; Diagnosis

Neuropathic pain arises from a lesion to neuralstructures, and lesions to neural structures in thelumbar region may give rise to leg pain.1

However nonneural lumbar structures such as disk,2

facet joint,3 and muscle4 may also give rise to leg pain,which may be inflammatory or nociceptive in nature as

search Fellow, School of Physiotherapy, Royaons, Dublin, Ireland.ist, Queens Road Medical Practice, Guernsey.ior Teaching Fellow, Curtin University, Pertha.hould be attributed to the Department ofrinity College Dublin, Ireland.sts for reprints to: Jeremy Walsh, M Manip Thch Fellow, 2 The Meadows, Belgooly, Dublineremywalsh2010@gmail.com).ed April 11, 2011; in revised formMay 13, 2011er 16, 2011.6.002012 by National University of Health Sciencesjmpt.2012.02.001

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opposed to neuropathic. As these lumbar structures maygive rise to leg pain via different pain mechanisms, it isimportant to identify the pain mechanism in patients withleg pain to have a better understanding of the disorder andperhaps inform management strategies. Consensus amongnational and international guidelines for the managementof low back pain (LBP) recommends that diagnostictriage should be performed.5 Patients with LBP should beclassified into 1 of 3 diagnostic groups—nonspecific LBP,serious pathology (eg, tumor, infection, fracture), orradicular syndrome.5 Radicular syndrome (ie, sciatica,radiculopathy, or nerve root pain) is characterized byradiating leg pain and paresthesia as well as clinical signsof neurologic impairment and in approximately 90% ofcases is caused by a herniated disk with nerve rootcompression.6 As this diagnostic group involves lesions toor impairment of nervous tissue, neuropathic pain is apossible consequence.

Neuropathic pain involves the combination of positiveand negative symptoms in patients in whom pain is due to

197Walsh et alJournal of Manipulative and Physiological TherapeuticsNeuropathic Pain Screening ToolsVolume 35, Number 3

pathologic changes of neural tissue.7 Positive symptomsinclude pain, paresthesia, and spasm. In contrast, anesthesiaand weakness are negative sensory and motor symptoms.This combination of positive and negative symptomsmay broadly differentiate neuropathic pain from nonneu-ropathic; however, this may not always be the case, andso sometimes, it can be difficult to distinguish neuro-pathic from nonneuropathic pain. Furthermore, somedisorders may consist of “mixed” pain, whereby neuro-pathic and inflammatory pain mechanisms coexist. In thesecases, determining the more dominant pain mechanismmay be desirable.

As neuropathic pain differs mechanistically from non-neuropathic pain, management of each type may differ.Therefore, identification of the underlying or dominant painmechanism in patients presenting with pain is important.Screening tools have been developed to aid identification ofneuropathic pain including the Leeds Assessment ofNeuropathic Symptoms and Signs (LANSS),8 self-reportLANSS (S-LANSS),9 Douleur Neuropathique 4 Questions(DN4),10 Pain DETECT,11 Neuropathic Pain Question-naire,12 ID Pain,13 and Standardized Evaluation of Pain(StEP).14 Each tool characterizes neuropathic pain by thepresence of positive and negative symptoms and signsincluding spontaneous pain, paresthesias, dysesthesias,allodynia, and motor and sensory loss.15,16 Consideringthe importance of identifying the presence of neuropathicpain to inform management, reliability, validity, anddiagnostic accuracy of such screening tools are imperative.Furthermore, whether they are comparable and may be usedinterchangeably should be determined.

Identification of neuropathic pain may be difficult inconditions such as radiculopathy where neuropathic painand inflammatory pain may occur concurrently.17 However,differentiation between neuropathic pain and inflammatorypain is important because each requires a different treatmentapproach and has a different prognosis.18 The authors ofPain DETECT reported that radiculopathies, consideredmixed pain syndromes (inflammatory and neuropathiccomponents), have clinical characteristics similar to definiteneuropathic pain.11 Perez et al19 came to similar conclu-sions using the DN4 where a score of 4 or more indicatesneuropathic pain. The DN4 has been shown to have goodface validity and interrater reliability.10 Validity of thisscreening tool remained unchanged whether patients had“pure” neuropathic pain or mixed pain syndromes.

The ability of the LANSS screening tool to identifyneuropathic pain in mixed pain states was not tested in theoriginal validation study.8 Kaki et al20 attempted todetermine whether a subgroup of back pain sufferers withneuropathic pain could be identified using the LANSS;however, there was no expert clinical diagnosis or any othercriterion standard used. The S-LANSS is a short form ofthe LANSS screening tool and is a valid and reliableself-report instrument.9 A score of 12 is suggested to

indicate neuropathic pain.9 However, in a study that usedclinician assessments to identify 3 pain groups (inflamma-tory, mixed, and neuropathic pain), median S-LANSSscores were 6 for inflammatory pain, 14 for mixed pain,and 18 for neuropathic pain, suggesting sensitivity toneuropathic pain within the mixed pain group.9

As the S-LANSS and DN4 have both been shown to bereliable, valid, and able to differentiate neuropathic painfrom inflammatory or mixed pain syndromes, it might beexpected that there would be agreement and correlationbetween these screening tools in a single group of subjects.However, no studies have compared these tools todetermine whether their outcomes are similar. The aim ofthis study was to determine agreement and correlationbetween the S-LANSS and DN4 in the identification ofneuropathic pain in subjects with low back–related leg pain,a group which might be expected to contain subjects withinflammatory pain, mixed pain, and neuropathic pain.Secondary aims were to determine whether disability orpsychosocial variables (anxiety, depression, and fear-avoidance beliefs) differed between subjects classifiedwith or without neuropathic pain and whether any ofthese variables would predict the classification of neuro-pathic pain according to either screening tool. The rationalefor these secondary aims was the strong evidence thatsome forms of neuropathic pain are associated withimpairments in physical and social functioning, anxietyand depression,21,22 and psychosocial comorbidities23

and that baseline disability, anxiety, and fear-avoidancebeliefs among other factors predicted pain and disabilityat 1 year in patients with low back pain with andwithout radiculopathy.24

METHODS

Ethical approval was granted by the St James's Hospital/Adelaide and Meath hospitals incorporating the NationalChildrens Hospital Joint Research Ethics Committee(Dublin, Ireland). Subjects were able to withdraw fromthe study at any time and gave written informed consentbefore the study commencement.

Subjects were recruited from consecutive patientsattending the Back Pain Screening Clinic (BPSC) at theAdelaide and Meath hospitals incorporating the NationalChildren's Hospital (AMNCH), Dublin, in June/July 2007.General practitioners in the hospitals catchment areasreferred patients to the BPSC, AMNCH accident andemergency department, or AMNCH hospital consultants.25

The purpose of the clinic was to screen patients with lowback pain to fast track them to appropriate management. Allpatients underwent screening examination by 1 of 2 BPSCphysiotherapists as routine. Recruitment was based onpresenting symptoms as determined during this examina-tion. Consecutive patients who satisfied the inclusion

Table 1. Participant characteristics

Characteristic Value

SexMale 22Female 23

AgeMean (SD) 46 (11) yRange 26-70 y

Mean (SD) duration of symptoms 5.6 (5.7) moMean (SD) pain intensity 6.1 (2.6)/10

Table 2. The frequency of positive/negative findings ofneuropathic pain determined by the S-LANSS and the DN4

S-LANSS

DN4

TotalPositive Negative

Positive 10 5 15Negative 9 21 30Total 19 26 45

198 Journal of Manipulative and Physiological TherapeuticsWalsh et alMarch/April 2012Neuropathic Pain Screening Tools

criteria (presence of low back–related leg pain, able tounderstand English, age 18-70 years) and were notdisqualified by the exclusion criteria (absence of leg pain,signs of serious pathology, history of spinal surgery, orneurologic disease) were invited to participate in the study.

Of 134 consecutive new patients attending the BPSC,54 were excluded from the study for the followingreasons: absence of leg pain (47), unable to understandEnglish (3), history of spinal surgery (1), and suspectedserious pathology (3). Therefore, 80 patients were invitedto take part, of which 35 declined, and so 45 subjectsparticipated. Characteristics of the 45 study patients aredetailed in Table 1.

After examination by the BPSC physiotherapist, subjectscompleted the S-LANSS questionnaire and the self-complete section of the DN4. An independent examinerblinded to the findings of the screening examinationconducted the patient examination section of the DN4.

Subjects completed the Oswestry Disability Index(ODI), the Hospital Anxiety and Depression Scale(HADS), and the Fear-Avoidance Beliefs Questionnaire(FABQ). The ODI is a self-administered questionnaire,which yields a percentage score. Zero percent to 20% iscategorized as minimal disability, 20% to 40% as moderate,40% to 60% as severe, 60% to 80% as crippled, and greaterthan 80% as bedbound or exaggerating.26 This question-naire has been shown to be a reliable and valid measure ofdisability.27,28 The HADS is also a self-administeredquestionnaire, consisting of 7 statements in relation toanxiety and 7 in relation to depression. Each question isscored, and a total score is calculated for each variable. Ascore of 0 to 7 is considered “normal”; 8 to 10, “borderlineabnormal”; and 11 to 21, “abnormal” for each variable.29

This has been shown to be a robust measurement tool foranxiety and depression.30 The FABQ measures how muchfear and avoidance about work and physical activity areaffecting a person with low back pain. This questionnairecontains several statements in relation to how muchphysical activity or work affects pain. The fear-avoidancebeliefs about work (FABQ-W) scale has a total score of42 (7 items), whereas the fear-avoidance beliefs aboutphysical activity (FABQ-PA) scale has a maximum score of24 (4 items). For both scales, the higher the score, the

greater the fear and avoidance beliefs shown by the patientfor physical activity or work.31 A 10-cm visual analogscale was used so that the patient could rate their averagepain intensity, on the day of testing, according to this scale.

An independent examiner scored the S-LANSS andDN4 questionnaires and determined whether that scorerepresented a positive or negative finding for the presenceof neuropathic pain according to the originally describedcutoff scores of 12 and 4, respectively.9,10

To determine whether there was agreement in classifi-cation of neuropathic pain between the 2 screening tools,the κ statistic was used. The 95% confidence intervalsaround the observed κ values were determined by thegeneral method described by Fleiss32 and implemented inan online Web calculator (www.statpages.org).33

To determine whether any correlation existed betweenscores of the 2 questionnaires, Pearson correlation coeffi-cient was calculated.

Independent t tests were used to determine if subjectsclassified as having neuropathic pain differed to those notclassified with neuropathic pain as determined by eachscreening tool in terms of disability, anxiety, depression, orfear-avoidance beliefs. Logistic regression analyses wereperformed to determine if these variables predicted classifica-tion of neuropathic pain for either screening tool. All data wereanalyzed using SPSS version 15.0 (SPSS Inc., Chicago, IL).

RESULTS

For the S-LANSS, 15 (33%) of 45 subjects scoredgreater than or equal to 12 and so were classified withneuropathic pain according to this screening tool. Using theDN4, 19 (42%) of 45 subjects scored greater than or equalto 4 and so were classified with neuropathic pain accordingto this screening tool. Table 2 illustrates the frequencies forpositive/negative findings for each screening tool.

A κ value (95% confidence interval [CI]) of 0.34(0.06-0.57) was calculated, representing a fair level ofagreement between the 2 screening tools in terms ofclassification of neuropathic pain.34

Mean (SD) score on the S-LANSS was 9.5 (5.5),whereas that of the DN4 was 3.1 (2.0). Pearson correlationcoefficient was determined as r = 0.62 (P b .001)demonstrating a moderate to good correlation betweenscores from the 2 screening tools.35

Table 3. Comparison of disability and psychosocial variables between subjects classified with neuropathic pain or nonneuropathic painfor each of the screening tools

S-LANSS, mean (SD) t test DN4, mean (SD) t test

NP Non-NP P NP Non-NP P

ODI 36 (15) 39 (16) .65 37 (16) 37 (16) .93HADS-A 9 (4) 8 (3) .48 8 (4) 8 (3) .99HADS-D 7 (4) 6 (4) .70 7 (4) 6 (4) .59FABQ-W 22 (11) 21 (12) .91 18 (10) 24 (12) .13FABQ-PA 16 (3) 18 (5) .29 17 (4) 17 (4) .86

HADS-A, HADS anxiety score; HADS-D, HADS depression score.

Table 4. Logistic regression analyses of disability and psychosocial variables for each screening tool with classification of neuropathicpain as the dependent variable

S-LANSS DN4

Wald Sig. Exp(B) (95% CI) Wald Sig. Exp(B) (95% CI)

Disability 0.30 0.58 0.98 (0.92-1.05) 0.15 0.70 0.99 (0.93-1.05)Anxiety 1.71 0.19 1.17 (0.92-1.50) 0.18 0.67 0.95 (0.75-1.21)Depression 0.09 0.76 1.04 (0.79-1.38) 0.81 0.34 1.13 (0.86-1.49)FABQ-W 0.04 0.84 1.01 (0.95-1.07) 2.59 0.11 0.95 (0.90-1.01)FABQ-PA 1.60 0.21 0.89 (0.75-1.07) 0.04 0.85 1.02 (0.86-1.20)

Sig., significance; Exp(B), odds ratio.

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Table 3 details mean scores for disability, anxiety,depression, and fear-avoidance beliefs for those who wereclassified as having neuropathic pain and those who werenot classified as having neuropathic pain according to eachscreening tool. Mean disability scores were in the“moderate” category (20-40) for neuropathic pain andnonneuropathic pain groups for both screening tools. Meananxiety scores were in the borderline abnormal category(8-10) for both neuropathic pain and nonneuropathic paingroups, for both screening tools. However, there were nodifferences in any of the variables studied between subjectsclassified with or without neuropathic pain according toeither the S-LANSS or the DN4 (P N .05).

Logistic regression analyses revealed that none of thevariables tested predicted the classification of neuropathicpain by either screening tool (Table 4). Pseudo-R2 values(Cox and Snell, Nagelkerke) indicated that between 7.5%and 10.4% of variance in S-LANSS, NP classification wasexplained by these variables, whereas that of DN4 wasbetween 7.5% and 10.1%.

DISCUSSION

The results of this study showed that there was fairagreement (κ = 0.34) and moderate to good correlationbetween the S-LANSS and the DN4 in a group of patientswith low back–related leg pain. The finding of moderateto good correlation between scores shows that the 2questionnaires may indeed be broadly consistent. However,

the finding of fair agreement perhaps indicates that despitethe moderate to good correlation between scores, the cutoffpoints of the 2 tools may not be wholly congruent.Therefore, although a high score on either tool may indicatea high score on the other, a classification of neuropathicpain according to 1 tool may not imply the same classi-fication on the other. In light of this, perhaps the 2 toolsshould not be used interchangeably, at least in terms of theclassification of neuropathic pain.

The criterion standard for the diagnosis of neuropathicpain is clinical assessment. In general, screening tools forneuropathic pain fail to identify up to 20% of patients withclinician-diagnosed neuropathic pain.36 This led to thesuggestion that these tools offer guidance for clinicians butshould not replace clinical judgment.36 However, as there isno consensus regarding the diagnosis of neuropathic pain36

and the different tools were validated in different countries,the fair agreement between the 2 tools in this study mayreflect differences in the criterion standard clinicalexaminations used in the initial validation studies.

Differing levels of sensitivity and specificity have beennoted9,37 for the LANSS when studies have been conductedin differing settings to those of the original author.8

Furthermore, a significant relationship exists between anexpert clinicians increasing certainty of a diagnosis ofneuropathic pain and increasing S-LANSS scores.38 Theconcept that pain may be more or less neuropathic appearsto have construct validity, but there has been a suggestionthat any further subgrouping needs further validation.38,39

Differing criterion standards in the initial validation studies

200 Journal of Manipulative and Physiological TherapeuticsWalsh et alMarch/April 2012Neuropathic Pain Screening Tools

may have led to the formation of cutoff points along apresenting continuum from unlikely neuropathic pain todefinite neuropathic pain, which were not analogous acrossthe 2 screening tools. Hence, although the similar contentmay yield good to moderate correlation between scores, itis possible that not wholly congruous cutoff points resultedin fair rather than more substantial agreement betweenthe S-LANSS and the DN4 in terms of classification ofneuropathic pain.

The S-LANSS is a self-administered questionnairetaking a few minutes to complete, which correctly identifiesup to 80% of patients with neuropathic pain.9 The DN4takes slightly longer to complete due to the inclusion of abrief clinical examination component. It has 83% sensitivityand 90% specificity.10 In this study, the S-LANSSidentified 33% of patients with low back–related leg painas having neuropathic pain, compared with that of 42% bythe DN4. It may be that the inclusion of the clinicalexamination component in the DN4 is slightly morediscriminatory than the wholly self-completed S-LANSS.It may, therefore, be pertinent to compare the DN4 to theLANSS, as both these tools have a clinical examinationcomponent. Recently, the StEP, which composes of 6interview questions regarding pain characteristics andabnormal sensations, 9 sensory threshold tests, and thestraight leg raise test, has shown 92% sensitivity and 97%specificity for distinguishing between radicular and axialback pain when expert clinical examination was used as thecriterion standard.14 The StEP was compared with the DN4in the same group of patients, and the sensitivity andspecificity of the DN4 were reported as 61% and 73%,respectively.14 Without the physical examination compo-nent of the DN4 being included in the data analysis, thesefigures were 68% and 56%, respectively. It is, therefore,possible that the inclusion of a more thorough physicalexamination increases diagnostic accuracy. Abnormalresponse to pinprick was the best indicator of whethersymptoms were of NP rather than inflammatory pain.Abnormal responses to cold or warm stimuli and bluntpressure further assisted this differentiation. The StEP wasable to differentiate numerous subgroups of subjects withlow back–related leg pain including neuropathic pain, forwhich physical tests were the most discriminatory factors.14

There were no significant differences in disability,anxiety, depression, or fear-avoidance behaviors betweensubjects classified with or without neuropathic pain,regardless of which screening tool was used. Similarly,none of those variables were able to predict the classifica-tion of neuropathic pain by either the S-LANSS or theDN4. As neuropathic pain is typically associated withimpairments in such quality of life and psychosocialvariables21,22,23 and considering that baseline disability,anxiety, and fear-avoidance beliefs among other factorspredicted pain and disability at 1 year in patients with lowback pain with and without radiculopathy,24 it might be

expected that a neuropathic pain subgroup of patients withlow back–related leg pain would differ from those withoutneuropathic pain and that these variables might predict thepresence of neuropathic pain. However, our findings werein contradiction to this. This may be because the study wasnot powered to detect any differences present or that thecutoff points of the S-LANSS and the DN4 are not sensitiveenough to allow determination of such differences. It wasobserved that mean scores for disability and anxiety forgroups of subjects classified with or without neuropathicpain were in the moderate and borderline abnormalcategories, respectively, regardless of which screeningtool was used. This may show that subjects with a legpain component to their low back pain are moderatelydisabled and borderline abnormal in terms of anxiety,regardless of whether the leg pain is neuropathic in nature.

LimitationsIn this study, the S-LANSS and DN4 neuropathic pain

screening tools were compared in subjects with low back–related leg pain. However, no criterion standard forneuropathic pain was used. To compare both tools againsta single criterion standard may have informed our findingsand discussion of the cutoff points. However, as there is noconsensus regarding a criterion standard diagnosis ofneuropathic pain, direct comparison between the 2 toolswas used in this study. Another limitation of this study isthat although the DN4 has a clinical examinationcomponent, the S-LANSS does not. It may, therefore, bepertinent to compare the DN4 to the LANSS, as both thesetools have a clinical examination component. Although nosignificant differences in disability or psychosocial vari-ables were identified between subjects classified with orwithout neuropathic pain by either screening tool, this mayhave been because the sample size was too small to detectany differences present. Studies of similar nature shouldconsider using larger groups of patients in the future.

CONCLUSION

Several screening tools for neuropathic pain have beendeveloped. Our findings showed that 2 of these toolsshowed moderate to good correlation but only fairagreement, which suggests that they may not necessarilybe used interchangeably and that classification according to1 tool may not imply the same classification on the other. Inthe present study, neither the S-LANSS nor the DN4 wasable to differentiate between subjects with neuropathic painand those without neuropathic pain in terms of disability orsome psychosocial variables. Considering these findingsand the number of screening tools available, perhapsconsensus-based attempts at formulating a universalscreening tool from an amalgamation of the available

201Walsh et alJournal of Manipulative and Physiological TherapeuticsNeuropathic Pain Screening ToolsVolume 35, Number 3

tools might improve consistency and diagnostic accuracy inthe examination of neuropathic pain.

Practical Applications• There is fair agreement between the S-LANSS andDN4 in subjects with low back–related leg pain.

• There is moderate to good correlation between theS-LANSS and DN4 in subjects with low back–related leg pain.

• Cutoff points for the S-LANSS and DN4 may notbe congruent.

FUNDING SOURCES AND POTENTIAL CONFLICTS OF INTEREST

No funding sources or conflicts of interest were reportedfor this study.

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