The Journal of Pain, Vol 12, No 10 (October), 2011: pp 1080-1087 Available online at www.sciencedirect.

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The Neuropathic Components of Chronic Low Back Pain: A Prospective Multicenter Study Using the DN4 Questionnaire
Nadine Attal,*,** Serge Perrot,*,y Jacques Fermanian,z and Didier Bouhassira*,**
^  * INSERM U 987, Centre dEvaluation et de Traitement de la Douleur, Hopital Ambroise Pare, APHP, Boulogne-Billancourt, France. y  ^ Service de medecine interne, CHU Hotel Dieu, Paris, France. z Service de biostatistiques, CHU Necker, APHP, Paris, France.  ** Universite Versailles Saint-Quentin, Versailles, France.

Abstract: The present study investigated the neuropathic components of chronic low back pain (LBP) in patients with and without lower limb pain using the DN4 questionnaire and conrmed its psychometric properties. Patients (n = 132) from 11 French multidisciplinary pain or rheumatology centers were classied by a rst investigator into 4 groups derived from the Quebec Task Force Classication of Spinal Disorders (QTFSD): group 1 (pain restricted to the lumbar area); group 2 (pain radiating proximally); group 3 (pain radiating below the knee without neurologic signs); and group 4 (pain radiating towards the foot in a dermatomal distribution, with neurological signs, corresponding to typical radiculopathy). A second investigator applied the DN4 questionnaire to the lower limb (groups 2 to 4) and lower back. A comparison of groups 1 and 4 conrmed the psychometric properties of DN4 (sensitivity 80%; specicity 92%, for a cutoff of 4/10, similar to other neuropathic conditions). In the lower limb, the proportion of patients with neuropathic pain (NP) was related to the distality of pain radiation (15, 39, and 80% in groups 2, 3 and 4, respectively; P < .0001). In the lower back, the proportion of patients with NP was higher for patients with typical radicular pain compared with the other groups (P = .006). Thus, typical radiculopathy has similar characteristics as other neuropathic conditions and is conrmed as the commonest neuropathic syndrome in LBP patients. The observation that neuropathic and nociceptive components of LBP vary in the back and lower limb probably accounts for the discrepancies of reported prevalence rates of NP in LBP. As this study was essentially based on a questionnaire, future studies combining standard clinical sensory testing, specic questionnaires, and more objective assessment of the sensory lesion are now required to further investigate the neuropathic component of chronic LBP. Perspective: This study conrms the psychometric properties of the DN4 questionnaire to assess neuropathic pain in patients with low back pain. Neuropathic mechanisms largely contribute to pain in the lower limb as compared to the back, but neuropathic pain is not restricted to typical radiculopathy. This may have signicant implications for the choice of treatment strategy in these patients.
2011 by the American Pain Society Key words: Low back pain, radiculopathy, DN4, neuropathic pain.

ow back pain (LBP) with or without lower limb pain is one of the most challenging chronic pain disorders to treat,16 due in part to its heterogeneity, probably reecting multiple underlying mechanisms. This heteroge-

Received January 12, 2011; Revised March 23, 2011; Accepted May 12, 2011. This study was supported by Pzer France. ^ Address reprint requests to Nadine Attal, INSERM U 987, Hopital  Ambroise Pare, APHP, 9 avenue Charles de Gaulle, 92100 BoulogneBillancourt, France. E-mail: nadine.attal@apr.aphp.fr 1526-5900/$36.00 2011 by the American Pain Society doi:10.1016/j.jpain.2011.05.006

neity may account for the poorer results obtained in clinical trials of treatments for chronic lumbar radiculopathy than for other neuropathic pain (NP) conditions.3,4,12 Both neuropathic and nociceptive mechanisms are thought to contribute to the pain experienced by many patients with low back and leg pain, but neuropathic mechanisms are widely believed to play a more important role in leg pain, whereas nociceptive mechanisms seem to play a greater role in back pain.17-19 However, the current denition of neuropathic LBP remains vague, with no consensus concerning its best clinical determinants.6,17,25 Is neuropathic LBP restricted

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Attal et al to LBP with typical radiculopathy, as suggested by many experts?30 Does this term also apply to patients with LBP and less typical leg pain radiation?20 Could it even apply to patients with pure LBP?6,23,25 It is difcult to resolve these issues through complementary investigations, because nerve lesions are often difcult to ascertain in these patients and neuroimaging is generally uninformative and lacks specicity.1,13,30 It is therefore essential to improve the clinical identication and characterization of neuropathic components of LBP in patients with and without leg pain. This has recently been attempted through the use of questionnaires,18,23,30 physical examination,19,28,30 and quantitative sensory testing.20,27 However, in previous studies, patients were screened for neuropathic symptoms with respect to their pain in general, rather than in particular painful areas, such as the lower limb or the back.18,23,30 It is therefore impossible to determine whether the estimated prevalence rates of NP in LBP patients, ranging from 37%18 to 55%,23 apply to the lower limb, the back, or both, in these studies. Furthermore, in the absence of a gold standard, the distinction between NP and nonneuropathic pain (NNP) in these studies was based on the opinion of the physicians.18,30 In this multicenter study, we investigated the neuropathic component of LBP in patients with and without leg pain, using the DN4 questionnaire.10 Our approach was original in 2 ways: 1) we applied the DN4 to different painful areas (the back and, if applicable, the most distal area of pain radiation in the leg); and 2) the identication of NP and NNP was not based on the physicians opinion. Instead, patients were classied into 4 groups on the basis of pain radiation to the leg and neurological decits. These 4 groups were derived from the Quebec Task Force Classication for Spinal Disorders (QTFSD).2,29 As the DN4 was initially validated in patients with welldened neurological lesions excluding radiculopathies,10 we initially conrmed its discriminant validity by comparing 2 well-characterized groups of patients from the QTFSD: group 4 (typical radiculopathy fullling the recently proposed criteria for probable or denite NP);32 and group 1 (pain restricted to the low back area and considered to be nociceptive).10,18 We also aimed to determine whether radiculopathies had particular features differentiating them from other NP conditions, as suggested in a recent study.30 Finally, we investigated whether prior back surgery had an impact on the likelihood of NP, the proportion of patients having undergone such surgery not being specied in previous studies.18,30

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criteria were: age $18 years, pain in the low back and, when applicable, in the leg of at least moderate severity ($40 on a 100-mm Visual Analog Scale), pain duration of at least 3 months for both leg and back pain, and ability to give written informed consent. Patients were excluded if they had cauda equina syndrome, vertebral fracture, developmental deformities of the spine, spine infection or tumor or inammatory spondylopathy. Patients with other pain more severe than chronic low back pain, bilateral lower limb pain, severe comorbid conditions, diffuse widespread pain (eg, bromyalgia), chronic alcoholism or substance abuse, or who were felt unlikely to understand the questionnaire correctly for whatever reason, were also excluded. The etiological diagnosis of low back pain was based on standardized clinical assessment (see further) and spinal imaging (CT scan or MRI) in all patients.

Study Design
This study was carried out at 11 French multidisciplinary pain or rheumatology centers. At every center, each patient was seen by 2 investigators, with an interval of no more than 2 days between examinations. No treatment was initiated between the 2 visits. All the investigators were physicians experienced in pain medicine and trained in neurology or rheumatology. The rst investigator recorded low back and lower limb pain intensity with numerical scales (010), carried out a physical examination of the patient, and classied the patient according to the revised version of the Quebec Task Force Classication of Spinal Disorders (QTFSD; see below). The physical examination included a search for neurological decits in the most distal area of radiating pain in the lower limb, by comparison with the contralateral lower limb. This examination was standardized and included the use of a Q-tip to assess ne tactile deficits, a Somedic brush to assess gross tactile decits or to detect brush-evoked allodynia, a standard safety pin to assess the response to pinprick, and a cold and hot tube to assess the response to thermal stimuli. Vibration decits were assessed by applying a standard tuning fork to the painful area of the leg, when feasible, and the ankle. Patients who did not detect the stimuli or who had a weaker response on the painful rather than on the normal side were considered to have sensory decits. Fingeroor distance was also evaluated and a modied Schober test was carried out to assess the range of motion for lumbar exion.24 The patient was then referred to a second investigator blind to the results of the rst visit, for the detection of a neuropathic component of pain with the DN4 questionnaire (Douleur Neuropathique en 4 questions).10 This questionnaire contains 7 items relating to symptoms (eg, sensations of burning, electric shock, painful cold, tingling, pins and needles, numbness, itching) and 3 items relating to physical examination (hypoesthesia to brushing, assessed with a Somedic brush, hypoethesia to ne tactile stimuli, assessed with a weak Von Frey monolament (5.1 g), and brush allodynia), with each element scored as present (1) or absent (0). In our initial validation study, we found that

Methods
This study was approved by the institutional review board and all patients gave written informed consent for participation.

Patients
Consecutive patients (both men and women) with chronic low back pain, with or without radiating unilateral or bilateral lower limb pain, were recruited for this study following referral by their physicians. The inclusion

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Neuropathic Component of Low Back Pain groups for analysis of the discriminant qualities of the DN4 questionnaire, to demonstrate its validity for the assessment of neuropathic components in less typical groups or pain areas. Sensitivity, specicity, and Youden index (sensitivity 1 specicity 1),31 were calculated by comparing groups 1 and 4. The corresponding ROC (receiver operating characteristics) curves were plotted and the area under the curve (AUC) was calculated by the trapezoid method.

a score of at least 4/10 in this questionnaire was indicative of neuropathic pain, with excellent sensitivity and specicity (82.9 and 89.9%, respectively). Here, we used the DN4 to investigate both the back and the most distal area of radiating pain in the lower limb (for patients with lower limb pain). The sensory examinations for the DN4 involved comparisons between the painful and the contralateral lower limb and between the painful area and an adjacent nonpainful area for the back. After the second visit, treatment was provided to the patients, in accordance with the usual practices of the center concerned.

Results
In total, 132 patients (52 men, 80 women, mean age: 54.7 6 14.3, range 2285 years, mean low back pain intensity: 6.4 6 1.77, range 410) were included in the study. The expert diagnoses proposed for these patients included herniated disc (n = 40), spinal stenosis due to facet joint arthropathy (n = 24), degenerative disc disease (n = 17), degenerative lumbar spine (n = 56), and lumbar scoliosis (n = 2), based on clinical history and MRI or CT scan. Two suspected etiologies were given for 17 patients. A subgroup of patients (n = 30, 23%) had previously undergone surgery for their back or lower limb pain. The procedures carried out included lumbar discectomy (n = 18), chemonucleolysis (n = 2), laminectomy (n = 7), and lumbar arthrodesis (n = 3). Patients were classied into 4 groups according to the QTFSD (Table 1). There were no signicant demographic differences between the groups in terms of age, duration of pain, sex ratio, or analgesic treatment except for the proportion of patients receiving antiepileptics, which was higher in group 4 compared to group 1 (P = .02) (Table 1). The intensity of pain in the back area (in all 4 groups) and in the lower limbs (in the 3 groups of patients with radiating pain in the lower limb) was similar in all groups. Clinical examination of the back area showed that nger-oor distance was signicantly lower in group 1 than in groups 2, 3, and 4 (Table 1). As expected, neurologic examination showed a higher frequency of neurologic decits in group 4 (Table 1). In this group, pain most commonly involved L5 (n = 18) or S1 (n = 7), but rarely L4 (n = 2). The proportion of patients who had previously undergone spinal surgery on the back was also signicantly higher in the patients of group 4 (Table 1).

The Quebec Task Force Classication of Spinal Disorders (QTFSD)

The QTFSD is an original classication of spinal disorders into 11 groups on the basis of clinical examination, pain localization, the results of paraclinical investigations and response to treatment, developed to reect the clinical entities encountered in clinical practice.2,29 Our classication was derived from the rst 4 groups of QTFSD patients, based on clinical criteria alone. Patients were assigned to group 1 if they reported pain in the lumbar area without radiation below the gluteal fold. Patients were assigned to group 2 if they had pain in the lumbar area with proximal radiation (ie, to the lower limb, but not beyond the knee). Patients were assigned to group 3 if they had pain in the lumbar area radiating below the knee and no neurologic signs (ie, normal reexes and an absence of motor impairment or sensory decits). Patients were assigned to group 4 if they had pain radiating to the lower limb and extending towards the foot in a dermatomal distribution, associated with sensory decits or other neurologic signs (focal muscular weakness, absent or reduced femoris or triceps surae reexes).

Statistical Analysis and Assessment of the Psychometric Properties of DN4 for LBP
For all statistical analyses, we set the type 1 error at 5%. Quantitative variables were described by the mean, standard deviation (SD), and range; qualitative variables were described by frequency and percentages. We compared the 4 QTFSD groups, for both the lower back and the lower limb, through Chi2 tests or Fishers exact tests, as appropriate, for qualitative variables, and analysis of variance with t-tests for pairwise comparisons of the means of quantitative variables. Analyses of variance were also performed to assess the possible impact of surgery, duration of pain, etiology of pain, and rheumatologic indices (Schober modied sign $ or <19) on the neuropathic characteristics of pain in the 4 groups of patients. Based on recently proposed criteria for neuropathic pain,32 all the patients in QTFSD group 4 (radiculopathy) were considered to have probable or denite neuropathic pain. By contrast, none of the patients in group 1 (low back pain without radiating pain) fullled the criteria for possible or probable neuropathic pain. These categories were used as control

Discriminant Validity of the DN4 Questionnaire

Comparison of the diagnostic properties of DN4 in groups 1 and 4 of the QTFSD showed that a cutoff score of 4/10 resulted in the highest sensitivity (80%) and specicity (92%) of the full questionnaire (Table 2). The ROC curve plotted for the total score is presented in Fig 1.

Results of the DN4 Questionnaire for the 4 Groups

For the lower back area, the proportion of patients with DN4 score $4/10 was signicantly higher in group 4 compared to the other groups (Fig 2, Table 3). Mean DN4 score for the lower back area was

Attal et al Table 1.

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Demographic Data and Clinical Characteristics for the 4 Groups of LBP Patients
GROUP 1 N = 40 GROUP 2 N = 27 56.4 6 14.7 48/52 11 (40.7) 7 (25.9) 8 (29.6) 2 (7.4) 0 0 6.3 6 1.9 5.7 6 2.0 4 (14.8) 4 (14.8) 9 (33.3) 10 (37) 5 (18.5) 19.7 6 3.0 27.7 6 14.4 6 (22.2) 1 (3.7) 0 0 0 13 (48.1) 11 (44) 3 (11.1) 4 (14.8) 8 (32) 3 (12) 2 (7.4) GROUP 3 N = 38 55.4 6 15 .7 34/66 14 (36.8) 12 (31.6) 8 (21.1) 5 (13.2) 1 (2.6) 0 6.7 6 1.7 7.1 6 1.9 8 (21.1) 9 (23.7) 5 (13.2) 16 (42.1) 5 (13) 19.7 6 2.6 26.7 6 12.5 0 4 (1.5) 0 0 0 12 (36.4) 19 (57.6) 3 (7.8) 6 (15.7) 9 (27.3) 5 (15.2) 4 (10.5) GROUP 4 N = 27 49.9 6 12.49 44/56 7 (25.9) 15 (55.6) 5 (18.5) 2 (7.4) 0 0 5.7 6 2.1 5.7 6 1.9 5 (18.5) 5 (18.5) 5 (18.5) 12 (44.4) 16 (59) 19.2 6 2.8 32.9 6 16.5 20 (74.1) 6 (22.2) 12 (44.4) 8 (29.6) 3 (11.1) 14 (51.8) 13 (52) 3 (11.1) 5 (18.5) 9 (33.3) 5 (18.5) 2 (7.4)

Age 55.8 6 13.7 Sex (male/female) 35/65 Etiology of pain (n, %) Spine degeneration 24 (60) Disc herniation* 6 (15) Spinal stenosis 3 (7.5) Discopathy 8 (20) Scoliosis 1 (2.5) Myofascial 1 (2.5) Pain intensity (NRS) back 6.7 6 1.4 Pain intensity (NRS) leg Pain duration (n, %) 36 months 2 (5) 712 months 5 (12.5) 13 months3 years 9 (22.5) >3 years 24 (60) Past surgery (back) (n, %)y 4 (10) Schober sign 20.3 6 2.5 Fingeroor distancez 18.1 6 15.7 Neurological examination of the painful area of the leg Sensory decits (n, %)x Allodynia/hyperalgesia (n,%)x Motor decits (n, %) Reex abnormalities (n, %) Amyotrophy (n, %) Analgesic treatment (n, %) Step I analgesics/NSAIDs 15 (37.5) Step II analgesics 18 (51.4) Opioids 3 (7.5) Antidepressants 5 (14.3) Antiepileptics 5 (14.3) Muscle relaxants 5 (12.5) None 4 (10)

NOTE. Data are means 6 SD unless otherwise specied. Clinical examinations were carried out on the most distal area or radiating pain in the leg for groups 2 to 4. *P = .0012 between groups. yP = .003 between group 4 and groups 1, 2 and 3. zF = 4.5; P = .005 between groups. xSensory decits include tactile, pinprick or thermal decits in the painful area. Allodynia/ hyperalgesia refer to any type of evoked pain in response to brushing, pressure, cold or heat stimuli.

signicantly different between the 4 groups (F = 3.7, P = .01) with higher scores obtained in group 4 than in group 1 (P = .002) or group 3 (P = .004), and an almost signicant difference between groups 4 and 2 (P = .06) (Table 3). For the distal area of radiating pain in the lower limb, the proportion of patients with DN4 score $4/10 was signicantly higher in group 4 compared to the other groups (Fig 3, Table 3). Mean DN4 score differed signicantly between the 3 groups with pain radiation (F = 18.7; P < .001) and was higher in group 4 than in groups 2 and 3 (P < .001), but similar between groups 2 and 3 (P = .3) (Table 3). The proportion of patients with a positive DN4 score for the lower limb (indicating neuropathic pain) and a negative DN4 score for the backie, with mixed neuropathic and nociceptive painwas 7.4% in group 2, 23.7% in group 3, and 51.8% in group 4 (P = .04). The duration, etiology of pain and rheumatologic indices (ie, Schober sign, nger oor distance; see Table 1) had no effect on the presence of neuropathic pain in either

the back or the lower limb. However, the proportion of patients with neuropathic pain in the lower back area was signicantly higher in the patients of group 4 who had undergone prior back surgery than in those who had not undergone surgery (P = .04) (Table 3). Mean DN4 score was also higher in these patients (P = .007) (Table 3). By contrast, the proportion of patients with neuropathic lower limb pain was similar for patients with and without prior back surgery in this group (P = .3). No signicant difference was observed as regards DN4 results in the other 3 groups of patients with or without past back sugery, probably because few of these patients had undergone prior back surgery (Table 3).

Discussion
In this multicenter study, we used a standardized clinical approach combined with the DN4 questionnaire to identify the neuropathic components of low back pain (LBP). We found that the relative contributions of

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Neuropathic Component of Low Back Pain

Table 2.

Specicity, Sensitivity and Youden Index Corresponding to the Total Score (ie, the Sum of Items) of the DN4 Questionnaire
SENSITIVITY 100 96.3 81.5 81.5 80 62.9 59.3 37.0 11.1 0 0 SPECIFICITY 0 26.3 65.7 81.6 92 94.7 97.4 100 100 100 100 YOUDEN INDEX 0 .23 .47 .63 .72 .57 .56 .37 .11 0 0

TOTAL SCORE 0 1 2 3 4 5 6 7 8 9 10

neuropathic and nonneuropathic mechanisms to LBP differed between the lower back and the lower limb. It is therefore necessary to assess both the back and lower limb areas carefully when searching for neuropathic components of LBP. Typical radiculopathy was conrmed as the commonest NP syndrome in LBP patients, but the DN4 questionnaire appeared suitable to identify neuropathic components of LBP in less typical cases, which may signicantly affect the choice of treatment strategy for these patients.

Figure 1. ROC curves for the distinction between group 4 of the QTFSD (typical radiculopathy) and group 1 (low back pain without radiating pain) based on the DN4 questionnaire. The area under curve was .92 (6.09). et al30) and the application of the questionnaire (no specication of the painful area considered in the study by Scholz et al,30 whereas we assessed the back and leg areas separately). Another possible reason may relate to differences in the rate of prior back surgery for low back pain in their study as compared to ours.

Neuropathic Leg Pain Psychometric Properties of the DN4 Questionnaire and Characteristics of Radiculopathy
The comparison of DN4 questionnaire results between QTFSD group 4, corresponding to typical radiculopathy and fullling the recently proposed criteria for probable or denite neuropathic pain,32 and group 1, corresponding to low back pain without radiating lower limb pain, generally considered nociceptive pain, conrmed the excellent discriminant validity of the DN4 questionnaire in LBP patients (80% sensitivity and 92% specicity). These results are very similar to those obtained in our initial validation study for other neuropathic pain conditions.10 They conrm the relevance of the DN4 questionnaire for identifying neuropathic components in LBP patients. They also indicate that the data obtained for other neuropathic conditions can be extrapolated to radiculopathy. In this respect, radiculopathy does not seem to have any specic characteristics differentiating it from other neuropathic pain states, consistent with the ndings of other studies using specic NP assessment questionnaires or screening tools.5,8,18,23 By contrast, a recent study by Scholz et al,30 based on a comparison of symptoms and signs between radicular pain and axial low back pain, suggested that the neuropathic symptoms of radiculopathy were atypical.15 Furthermore, the sensitivity and specicity of DN4, which was used as a control instrument by these authors, was much lower than in our study.30 Based on our ndings, we believe that these discrepancies result principally from differences in the methods used to classify patients (classication based on physicians opinions in the study by Scholz The established psychometric properties of the DN4 questionnaire in typical patient groups conrmed the relevance of DN4 for the assessment of neuropathic characteristics of pain in more atypical cases. We found that neuropathiclower limb pain affected nearly 40 % of patients with a distal extension of pain below the knee (group 3 of the QTFSD) but was uncommon in patients with proximal limb pain radiation (group 2). These data conrm previous observations suggesting that neuropathic pain in LBP patients, although more frequent in typical radiculopathy, is not restricted to this group.18,23 They also suggest that the degree of neuropathic pain in the lower limb is related to the distal nature of pain radiation. Sensory decits have recently been identied

Figure 2. Proportion of patients with a score $4/10 for the DN4 questionnaire applied to the lower back, in the 4 groups of LBP patients based on the Quebec Task Force Classication of Spinal Disorders (QTFSD). The proportion of patients with a DN4 score $4/10 for the low back was signicantly higher in group 4 than in the other groups (P = .006).

Attal et al Table 3.

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Results of the DN4 Questionnaire at the Back and Lower Limb Areas in the 4 Groups of Patients With or Without Past Back Surgery
GROUP 1 GROUP 2 N = 27 6 (22) 21 (78) 2.2 6 1.6 N=5 2 (40) 3 (60) 3.1 6 1.4 N = 22 4 (18) 18 (82) 1.9 6 1.6 N = 27 4 (15) 23 (85) 2.3 6 1.5y GROUP 3 N = 38 5 (13) 33 (87) 1.8 6 1.5* N=5 1 (17) 4 (80) 2.0 6 1.3 N = 33 4 (12) 29 (88) 2.0 6 1.7 N = 38 15 (39) 23 (61) 2.8 6 1.9y GROUP 4 N = 27 10 (37) 17 (63) 3.0 6 1.8 N = 16 8 (50) 8 (50) 3.8 6 1.8 N = 11 2 (18) 9 (82) 1.9 6 1.9 N = 27 22 (80) 5 (19) 5.3 6 2.1 N = 40 3 (8) 37 (93) 1.79 6 1.8* N=4 1 (25) 3 (75) 1.2 6 1.1 N = 36 2 (5) 34 (85) 1.8 6 1.4 N = 40

Lower back (all patients) DN4 score $4/10 (n, %) DN4 score <4/10 (n, %) Mean DN4 score 6 SD Lower back (patients with prior back surgery) DN4 score $4/10 (n, %) DN4 score <4/10 (n, %) Mean DN4 score 6 SD Lower back (patients with no prior back surgery) DN4 score $4/10 (n, %) DN4 score <4/10 (n, %) Mean DN4 score 6 SD Lower limb (all patients) DN4 score $4/10 (n, %) DN4 score <4/10 (n, %) Mean DN4 score 6 SD

*P < .01. yP < .001 for paired comparison between groups 1, 2 or 3 and group 4.

by quantitative sensory testing in patients with proximal pain radiation to the lower limb or pseudoradicular pain, suggesting a possible continuum between pseudoradicular pain and typical radiculopathy.20 However, as sensory decits were tested in the foot (which was not painful in cases of pseudoradicular pain), the authors were unable to draw rm conclusions concerning the role of neuropathic mechanisms in the pain itself. Our data suggest that, in patients with proximal pain radiation to the lower limb, pain results mostly from local proximal disorders not involving the nerves or roots, consistent with classical hypotheses.19 By contrast, a substantial proportion of patients with distal pain radiation to the leg up to the ankle, even without sensory decits or dermatomal pain extension, probably have radiculopathy. The proportion of such patients was similar among those with and without a history of back surgery. Our data are consistent with previous observations showing that pain does not necessarily follow a typical dermatomal pattern in patients with conrmed lumbar radicular compression.26 Furthermore, even in patients with typical radiculopathy, sensory decits are detected in only 50 to 60% of cases at standard examination.9,20,22 Thus, the DN4 questionnaire appears more sensitive to detect neuropathic pain in these atypical cases compared to the recently proposed classication for neuropathic pain;32 indeed, according to this classication which does not take into account pain descriptors, these patients would not be considered as neuropathic mainly because pain does not follow a typical dermatomal pattern.32 These ndings have implications for treatment, because patients without typical radiculopathy are generally considered by most clinicians to have nonneuropathic pain and are therefore unlikely to receive appropriate drug treatments or to be considered for clinical trials of antineuropathic drugs.

Neuropathic Pain in the Lower Back

Neuropathic pain occurred less frequently in the lower back than in the lower limb, consistent with traditional views. However, the proportion of patients with NP in the back area differed between the 4 groups. The proportion of patients with a neuropathic components to back pain was highest for patients with typical radicular pain (group 4 of the QTFSD; 37%), particularly for those who had previously undergone back surgery. It has been suggested that local NP in the back area may be caused by lesions of nociceptive sprouts within the degenerative disk.11,17,25 Our results suggest that, at least in patients with a history of back surgery, other mechanisms, such as postsurgical scars or local nerve root lesions, may also contribute specically to neuropathic back pain. Previous studies evaluating

Figure 3. Proportion of patients with a score $4/10 for the DN4 questionnaire applied to the lower limb, in the 3 groups of LBP patients with pain radiating to the lower limb, based on the QTFCSD. The proportion of patients with a DN4 score $4/10 for the lower limb was signicantly higher in group 4 than in the other 2 groups (P < .0001).

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Neuropathic Component of Low Back Pain that patients with neuropathic components of pain in both the back and lower limb areas, as identied by DN4, are the most suitable candidates for inclusion in clinical trials of antineuropathic drugs. These data highlight the importance of assessing different painful areas when searching for neuropathic components of LBP, with a potentially signicant impact on treatment strategy.

the neuropathic component of LBP did not indicate the proportion of patients with a history of back surgery.18,30 Differences in these proportions might account for the differences in estimated prevalence rates for NP in LBP patients reported by these studies.

The Concept of Mixed Neuropathic Low Back Pain

The term mixed pain has been proposed for pain conditions that may have both a nociceptive and a neuropathic component.18 However, the proportion of mixed pain in LBP patients was not clearly established in previous studies. Furthermore, the use of this concept may itself be misleading. For example, in a recent study using the PainDetect questionnaire as a screening tool for the identication of neuropathic LBP, the term mixed pain was applied to patients who had intermediate scores, eg, between the low range suggestive of nociceptive pain and the high range indicative of NP.18,20 In our study, 52% of our patients with radiculopathy had NP in the lower limb and NNP in the back, whereas the proportion of patients with this particular pattern of pain was much lower in the other groups. These patients may probably be considered as having mixed mechanisms to account for their lower back and lower limb pain. However, mixed neuropathic and nociceptive mechanisms may probably also account for pain in the same body area. Thus it is likely that mixed mechanisms account for low back pain in patients with neuropathic components of pain at the lower back, particularly those with typical radiculopathy in the leg (NP being observed in 37% of these patients at the lower back). Differences in the degrees of neuropathic and nociceptive mechanisms operating in most LBP patients with radiculopathy may account for the lack of therapeutic response to antineuropathic agents, such as pregabalin or tricyclic antidepressants, the gold standard for other NP conditions, in recent clinical trials of chronic lumbosacral radiculopathy.3,4,7 Conversely, it seems likely

Methodological Considerations
In this study we assessed the patients on the basis of a simple neurological examination. We did not use quantied methods such as quantitative sensory testing or laser-evoked potentials, despite their high sensitivity for the detection of small ber function,14,21 because we wished to use a standard and inexpensive bedside assessment method easily applicable at all centers. Future studies combining standard clinical sensory testing, specic questionnaires, and more objective assessment of the nerve lesion, such as quantitative sensory testing or laser-evoked potentials, are now required to further investigate the neuropathic component of chronic LBP.

Disclosures
Nadine Attal, Serge Perrot, and Didier Bouhassira have received honoraria from Pzer France.

Acknowledgments
The authors wish to thank Mapi for data management and statistical analysis and Drs. Bera Louville, Bernardin,  Bernouville, Cunin, Dupuich, Estebe, Ginies, Le Corveiller,  Lietar, Lorenzi, Lussiez, Mick, Monnier, Navez, Nayve,  Pouyol, Puech, Ramee, Revnic, Rians, Ribiere, Rioult, Rozenberg and Vaserman for their participation in this study.

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