Gli instrumenti di screening devono essere applicati nella diagnosi del DN ? Si Nadine ATTAL INSERM U-987 Centre d’Evaluation et de Traitement de la Douleur Hôpital Ambroise Paré, Boulogne-Billancourt FRANCE Incontro Nazionale Neurofisiologia : Nuove Strategi Controverise sulla diagnosi e terapia del dolore neuropatico Palermo 29-30 novembre 2012

Gli instrumenti di screening Presentation of the main instruments Research applications Diagnostic workup of neuropathic pain and clinical relevance of the screening tools

Neuropathic Pain Questionnaires Screening/ Diagnosis Evaluation/ Measurement BASED ON SYMPTOM DESCRIPTION IMPORTANCE OF THE LANGUAGE OF PAIN

Diagnostic value of pain descriptors Multidimensional Assessment of Chronic Pain THE McGILL PAIN QUESTIONNAIRE R. Melzack Diagnostic value of pain descriptors (e.g. Dubuisson and Melzack, 1976, Mason et al., 1989)

Non neuropathic pain (n = 97) Burning 54 29 Electric shock 53 21 Beating 9 23 Cold 22 10 tingling 48 25 Itching 33 Dull 18 46 Tiring 35 57

Neuropathic pain screening tools Questionnaire (NPQ) Krause & Backonja, Clin J Pain, 2003 ID Pain Portenoy, Curr Med Res Op, 2006 Pain Detect Freynhagen et al, Curr Med Res Op, 2006 LANSS Pain Scale Bennett, Pain, 2001 DN4 Bouhassira et al, Pain, 2005 Neuropathic pain screening tools any neuropathic pain SteP Scholz et al, PLoS Med 2009 Low back pain

Validation studies Similarities Selection of potentially discriminant items Comparison of patients with or without NP Identification of the most discriminant combinations of items Similarities

Differences in the clinical expression of NP Neuropathic Pain (%) Non-neuropathic Pain (%) Burning  68 *** 30 Squeezing 49 38 Cold pain 26 * 10 Shooting 65 *** 17 Lancinating 76 65 Tingling 60 *** 16 Pins and needles 66 *** 17 Itching 29 *** 6 Numbness 66 *** 30 *** P<0.001 P= 0.015 Bouhassira et al. Pain 2005;114(1-2):29-36.

Validations studies Similarities Differences Selection of potentially discriminant items Comparison of patients with or without NP Identification of the most discriminant combinations of items Similarities Differences Inclusion and diagnostic criteria: - only peripheral neuropathic pain (LANSS, NPQ, PainDetect, IDpain) - both peripheral and central neuropathic pain (DN4) Design of the questionnaire: - inclusion of items related to the examination (LANSS, DN4) - self-questionnaires (NPQ, PainDetect, IDpain) Self-administered LANSS (S-LANSS) and DN4 (DN4-Interview) have also been validated

Validation in mixed neuropathic pain LBP with typical radicular pain LBP without radiations Sensitivity: 80% Specificity: 92% Administration of the DN4 at both sites Attal et al. J Pain 2011

Differences in the presentation of the screening tools

"core" neuropathic pain symptoms + LANSS NPQ DN4 PainDetect IDpain Burning + Electric shocks Tingling, pins and needles, pricking Pain evoked by touching Numbness Painful cold Tactile hypoesthesia Adapted from Bennett et al., Pain, 2007

Discriminative value of the screening tools Sensitivity Specificity Predictive accuracy LANSS 85% 80% NPQ 74% 76% Not reported DN4 83% 90% 86% Pain Detect Several comparative studies of DN4 vs others (Unal-Cevik et al., J Pain 2010; Hallstrom and Norrbrink Pain 2011 ; Padua et al Neurol Sci 2012) Haanpaa et al., Pain 2011

Is the language of pain universal? Several screening tools have been translated into many other languages than the original one (>30). The discriminant properties of some questionnaires have been confirmed into several languages. LANSS Spanish (Perez et al., 2006); Turkish (Koc et al., 2010) DN4 Spanish (Perez et al., 2007); Turkish (Unal-Cevik et al., 2010); Portugese (Santos et al., 2010) Arabic, (Harifi et al., 2010) ; Dutch (Van Seventer et al 2012) Is the language of pain universal? Pain qualites are probably related to mechanisms

Applications of NeP screening tools Education/communication Research applications - Epidemiology Other research applications 3) Clinical practice

Education/information

Epidemiology 8.2% 6.9% British Study (Torrance et al., J Pain 2006) French Study (STOPNEP) (Bouhassira et al., Pain 2008) Participants 6,000 30,000 Screening tool S-LANSS DN4-Interview Response Rate 52.4% 81.2% Prevalence of Chronic Pain 48% 31.7% Prevalence of Chronic Pain with neuropathic characteristics 8.2% 6.9% These results should be interpreted with caution since the screening tools have not been formally validated for use in the general population

Epidemiology Quality of life Anxiety/depression Attal et al Pain 2011 Pain with NC (n = 805) Anxiety/depression Pain without NC (n = 786) Score (SF12) No pain (n = 1237) HAD score 60 % 50 70 ** ** 60 40 50 30 40 ** 30 20 20 ** 10 ** 10 Mental health Physical health Abnormal score Abnormal anxiety score Abnormal depression score ** p < 0.01 Attal et al Pain 2011

Proportion of patients with neuropathic pain Neuropathic pain in diabetic patients (DN4) (VanAcker et al., 2009) Post-surgical pain (PainDetect, DN4) (eg, Steegers et al 2008; Von Sperling et al., 2010) Cancer (LANSS) (Mercadante et al., 2009 ) Multiple sclerosis (DN4) (Padua et al Pain 2012)

Other research applications Predictive factors for the development of neuropathic pain: Post-surgical pain (LANSS, DN4) (Martinez et al Pain 2012) PHN: The DN4 score during the acute phase is predictive of PHN ( Bouhassira et al Pain 2011) Pathophysiological studies Arthritis pain (PainDetect) (Gwylim et al Arthritis Rheum 2009) CMT painful neuropathy (DN4) (Pazzaglia et al Pain 2010) Therapeutic studies Inclusion of patients in clinical trials (Yuan et al Neurology 2009; Vranken et al Pain 2010) Other research applications

Are screening tools really helpful for the clinical diagnosis of NP ? Comparison with the proposed NeuPsig diagnostic algorithm Conditions of use and limitations

Grading system Treede et al Neurology 2008 Neither No One Both Yes Pain Pain distribution neuroanatomically plausible and History suggest relevant lesion or disease Working hypothesis: Possible neuropathic pain Unlikely to be neuropathic pain Unconfirmed as neuropathic pain Probable neuropathic pain Definite neuropathic pain Confirmatory tests: a: Negative or positive sensory signs, confined to innervation territory of the lesioned nervous structure b: Diagnostic test confirming lesion or disease explaining neuropathic pain Leading complaint History Examination Neither No One Both Yes Treede et al Neurology 2008

Clinical case 38 years old female patient Cervico-dorsal syringomyelia Bilateral shoulder pain Hypoesthesia to cold and tactile stimuli only on the left side Is this neuropathic pain ?

Clinical case Pain improved with physical therapy and aggravated by effort, no neuropathic characteristics DN4 : 2/10 Subsequently attributed to capsulitis Non neuropathic pain in a lesioned area

Symptoms ? Grading system Treede et al Neurology 2008 Neither No One Pain Pain distribution neuroanatomically plausible and History suggest relevant lesion or disease Working hypothesis: Possible neuropathic pain Unlikely to be neuropathic pain Unconfirmed as neuropathic pain Probable neuropathic pain Definite neuropathic pain Confirmatory tests: a: Negative or positive sensory signs, confined to innervation territory of the lesioned nervous structure b: Diagnostic test confirming lesion or disease explaining neuropathic pain Leading complaint History Examination Grading system Neither No One Both Yes Treede et al Neurology 2008 Symptoms ?

Pain due to cortical stroke Michel et al, Revue Neurol 1990

Screening tools are correlated to the degree of certainty of the nervous lesion Bennett et al, Pain, 2006 Also found by Guastella et al Pain 2011

Conditions of use and limitations of the screening tools Screening tools were validated in patients with only one pain location or pain predominantly in one location. In patients with multiple pain locations, screening tools should be administered successively to the different locations.

Screening tools should not be used in patients with diffuse pain (e.g. fibromyalgia) tingling burning numbness electric shocks pins and needles Perrot et al., Pain 2010

Conditions of use and limitations of the screening tools Screening tools fail to identify 10-20% of patients with clinician diagnosed neuropathic pain. Screening tools do not replace the clinical judgement Screening tools do not give information about the cause of pain. Screening tools are not adapted to assess the effects of treatment. Bouhassira and Attal Pain 2011

Conditions of use and limitations of the screening tools Lack sensitivity if pain is mild (Perez et al, 2007)

The ideal diagnostic workup 1/Screening : is the pain neuropathic ? Screening tools 2/ Diagnosis Clinical context Painful area Clinical examination Complementary tests as needed Bouhassira and Attal Pain 2010

Gli instrumenti di screening devono essere applicati nella diagnosi del DN ? Si : devono applicati nella screening Screening tools have contributed to « demystify » neuropathic pain. Provided they are used properly, screening tools can be used as a first step in the diagnostic workup, but should be combined with a general assessment of the patients and do not replace clinical judgment

M. Lanteri-Minet (Nice) B. Laurent (Saint-Etienne) G. Mick (Voiron) UNIVERSITÉ VERSAILLES SAINT-QUENTIN H. Alchaar (Nice) F. Boureau (Paris) B. Brochet (Bordeaux) J. Bruxelle (Paris) G. Cunin (Paris) M. Lanteri-Minet (Nice) B. Laurent (Saint-Etienne) G. Mick (Voiron) A. Serrie (Paris) D. Valade (Paris) DN4 validation