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Comparison of DN4 and DN4 Interview Tests in the Identification of Neuropathic Pain after Fracture Surgery

Abstract

Objective:

This study aimed to compare results obtained with the DN4 (in-person interview) and DN4i (telephone interview) questionnaires in identifying neuropathic pain after fracture surgery.

Methods:

This study was methodological, using questionnaires administered in person (DN4) or via telephone (DN4i). The participants were at least 18 years old, underwent fracture surgery at a university hospital between January 2017 and July 2020, signed the Informed Consent Form (ICF), and could go to the Orthopedics and Traumatology Hospital. Pearson’s correlation coefficient determined the agreement between the total score obtained during in-person and telephone interviews. The kappa coefficient evaluated the agreement between individual questionnaire items.

Results:

Of the 53 participants, 50 presented the same result for neuropathic pain screening in DN4 and DN4i, including 41 with a positive score for neuropathic pain and 12 with a negative score. The Pearson’s correlation coefficient and kappa coefficient were r = 0.84.

Conclusion:

DN4 and DN4i presented a strong agreement between individual items of the questionnaires and the total scores obtained.

Keywords
complex regional pain syndromes; fracture fixation; interview, telephone; pain; surveys and questionnaires

Resumo

Objetivo:

Comparar os resultados obtidos através do questionário DN4 com os do DN4i com aplicação via telefônica na identificação de dor neuropática após cirurgia de fraturas.

Métodos:

Este foi um estudo metodológico com questionário aplicado presencialmente (DN4) e por telefone (DN4i). Foram elegíveis os participantes maiores de 18 anos de idade submetidos à cirurgia de fraturas em um hospital universitário no período de janeiro de 2017 a julho de 2020, que assinaram o Termo de Consentimento Livre e Esclarecido (TCLE) e puderam comparecer ao departamento de Ortopedia e Traumatologia do hospital. A concordância entre a pontuação total obtida na aplicação presencial e por telefone foi avaliada por meio do coeficiente de correlação de Pearson. O coeficiente de Kappa foi utilizado para avaliar a concordância entre os itens individuais dos questionários.

Resultados:

Dos 53 participantes, 50 apresentaram resultado igual para rastreio de dor neuropática em relação ao DN4 com o DN4i, sendo 41 com escore positivo para dor neuropática e 12 com escore negativo. O coeficiente de correlação de Pearson e o coeficiente Kappa apresentaram r = 0.84.

Conclusão:

O uso telefônico do DN4i comparado à aplicação presencial do DN4 apresenta forte concordância tanto entre os itens individuais dos questionários quanto entre a pontuação total obtida.

Palavras-chave
dor; entrevistas por telefone; fixação de fratura; inquéritos e questionários; síndrome da dor regional complexa

Introduction

Neuropathic pain is “a pain arising as a direct result of an injury or disease affecting the somatosensory system.”11 Jensen TS, Baron R, Haanpää M, et al. A new definition of neuropathic pain. Pain 2011;152(10):2204–2205 Neuropathic pain-associated factors include the female gender and advanced age.22 Torrance N, Smith BH, Bennett MI, Lee AJ. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. J Pain 2006;7(04):281–289 Recent studies also reported that fracture and surgery are a common etiology for neuropathic pain.33 Dey S, Guthmiller KB, Varacallo M. Complex Regional Pain Syndrome. In: StatPearls. Treasure Island (FL): StatPearls Publishing September 4, 2022,44 DeGeorge BR Jr, Van Houten HK, Mwangi R, Sangaralingham LR, Larson AN, Kakar S. Outcomes and Complications in the management of distal radial fractures in the Elderly. J Bone Joint Surg Am 2020;102(01):37–44

Although epidemiological data on neuropathic pain remains not detailed in the literature, it has evolved in recent years.55 Bouhassira D. Neuropathic pain: Definition, assessment and epidemiology. Rev Neurol (Paris) 2019;175(1-2):16–25 In Brazil, its estimated prevalence in patients with chronic pain and neuropathic characteristics is 14.5%.66 Udall M, Kudel I, Cappelleri JC, et al. Epidemiology of physiciandiagnosed neuropathic pain in Brazil. J Pain Res 2019;12:243–253

Among the tools for neuropathic pain screening, the Douleur Neuropathique 4 (DN4) questionnaire is more practical than others as it has fewer items and a high capacity to discriminate neuropathic pain from nociceptive pain.77 Santos JG, Brito JO, de Andrade DC, et al. Translation to Portuguese and validation of the Douleur Neuropathique 4 questionnaire. J Pain 2010;11(05):484–490,88 Morgan KJ, Anghelescu DL. A Review of adult and pediatric neuropathic pain assessment tools. Clin J Pain 2017;33(09):844–852 DN4, developed by the French neuropathic pain group, contains ten items answered as yes or no; a score equal to or higher than four indicates the presence of neuropathic pain.99 Bouhassira D, Attal N, Alchaar H, et al. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 2005;114(1-2):29–36 In addition, the DN4 interview (DN4i) has the initial seven items alone, and a positive score is equal to or higher than 3.99 Bouhassira D, Attal N, Alchaar H, et al. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 2005;114(1-2):29–36 Santos et al.77 Santos JG, Brito JO, de Andrade DC, et al. Translation to Portuguese and validation of the Douleur Neuropathique 4 questionnaire. J Pain 2010;11(05):484–490 validated and translated the DN4 into Brazilian Portuguese.

Fast, highly sensitive tools for detecting neuropathic pain, whether used in person or not, allow a detailed determination of epidemiology and etiology, appropriate choice of therapeutic interventions, and prognostic definition. Therefore, this study aimed to compare the results obtained through the in-person application of the DN4 questionnaire and the DN4i administered via telephone to identify neuropathic pain after fracture surgery.

Materials and Methods

This study is methodological and based on medical records of patients undergoing fracture surgery in our hospital from January 2017 to July 2020. The Research Ethics Committee approved this study under number (CAAE: 28504919.5.0000.5134).

This study used a convenience sample and recruited all patients meeting the eligibility criteria, i.e., aged 18 or over undergoing fracture surgery in our hospital and who signed the Informed Consent Form (ICF) and could attend the hospital’s Orthopedics and Traumatology department. Patients who refused to participate in the study, did not answer the phone call, or died were excluded.

A previously trained group of orthopedists from our clinical staff applied the validated DN4 translated into Brazilian Portuguese to patients in person. After 4 to 6 months, two researchers unaware of the results obtained by orthopedists administered the DN4i questionnaire by telephone to their respective patients. All collected data was organized in an Excel spreadsheet for later analysis.

The DN4 questionnaire has two parts. The first part is an interview with seven items, while the second is a sensory examination with three items. DN4i contains only the interview, allowing self-application by the patient or telephone use. The seven-item part encompasses two domains: the first evaluates the characteristics of the pain (burning, painful cold sensation, and electric shock), and the second assesses symptoms associated with abnormal sensations in the same area (tingling, pins and needles, numbness, and itching). The second part of DN4, the sensory examination, addresses hypoesthesia to touch, hypoesthesia to needle prick, and pain caused or increased by brushing. Each item in both questionnaires is answered as “yes” (equivalent to 1) or “no” (equivalent to 0). The sum of the scores can range from 0 to 10 for DN4, and from 0 to 7 for DN4i. A score positive for neuropathic pain corresponds to a sum ≥ 4 for DN4 and ≥ 3 for DN4i.99 Bouhassira D, Attal N, Alchaar H, et al. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 2005;114(1-2):29–36

An independent investigator performed the analysis. Descriptive statistics characterized the sample considering all variables collected. These data were presented as measures of central tendency (mean/median) and dispersion (standard deviation) for quantitative variables and frequency and percentage for categorical variables.

The Pearson’s correlation coefficient investigated the agreement between the total questionnaire score obtained in person (DN4) and by telephone (DN4i). Considering the statistically significant data, the interpretation of the magnitude of the correlation coefficient occurred as follows: strong (r ≥ 0.6), moderate (r ≤ 0.59), and weak (r ≤ 0.29).1010 Cohen J. Set Correlation and Contingency Tables. Appl Psychol Meas 1988;12(04):425–434

The weighted kappa statistic determined the agreement between individual questionnaire items. The interpretation of kappa occurred as follows: excellent (> 0.80), substantial (> 0.60), moderate (0.40-0.60), and fair to poor (< 0.40).1111 Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977;33(01):159–174 The SPSS 17.0 statistical software for Windows performed all analyses using a 5% significance level.

Results

In total, 71 participants were eligible for the study. The final sample had 53 participants with analyzable data, of which 50 (94.3%) presented the same results in DN4 and DN4i for neuropathic pain screening. ►Fig. 1 shows the sample layout.

Fig. 1
Sample recruitment according to eligibility criteria.

Table 1 shows the sociodemographic and clinical characteristics of the participants with analyzable data. Considering the Numerical Verbal Pain Scale, ranging from 0 to 10, 26.4% of the participants reported values between 2 and 8, of which half (13.2%) had a positive score on DN4i.

Table 1
Sociodemographic and clinical characteristics of the sample (n = 53)

The orthopedists administering DN4 in person obtained 13 positive (sum ≥ 4) and 40 negative scores, while the two researchers who made the telephone calls got 12 positive (sum ≥ 3) and 41 negative results. ►Table 2 compares the percentages of positive scores for DN4 and DN4i items.

Table 2
Comparison of positive response frequencies at DN4 and DN4i items (n = 53)

Pearson’s correlation coefficient for agreement between the total questionnaire score was r = 0.84 (p < 0.001), deemed strong considering its magnitude. Regarding the agreement between the individual items of the questionnaires, the kappa coefficient was r = 0.84 (p < 0.001), which is excellent.

Discussion

Seven of the 12 positive DN4i scores were from females, including four subjects with diabetes mellitus. This finding reinforces the factors associated with the development of neuropathic pain, such as female gender and diabetes mellitus as an associated comorbidity.22 Torrance N, Smith BH, Bennett MI, Lee AJ. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. J Pain 2006;7(04):281–289,1212 Smith BH, Torrance N. Epidemiology of neuropathic pain and its impact on quality of life. Curr Pain Headache Rep 2012;16(03): 191–198,1313 Edgley C, Hogg M, De Silva A, Braat S, Bucknill A, Leslie K. Severe acute pain and persistent post-surgical pain in orthopaedic trauma patients: a cohort study. Br J Anaesth 2019;123(03): 350–359

The most predominant fracture site was the ankle (n = 23), and 17.4% of the affected subjects had a positive score on DN4i. Rbia et al.1414 Rbia N, van der Vlies CH, Cleffken BI, Selles RW, Hovius SER, Nijhuis THJ. High Prevalence of Chronic Pain With Neuropathic Characteristics After Open Reduction and Internal Fixation of Ankle Fractures. Foot Ankle Int 2017;38(09):987–996 reinforce this finding, identifying the prevalence of neuropathic pain after ankle fracture surgery in 23% of 271 patients, impacting their quality of life.

Attal et al.1515 Attal N, Bouhassira D, Baron R. Diagnosis and assessment of neuropathic pain through questionnaires. Lancet Neurol 2018; 17(05):456–466 suggested doctors and healthcare professionals should use DN4i for fast neuropathic pain screening. A previous study from Bouhassira et al.99 Bouhassira D, Attal N, Alchaar H, et al. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 2005;114(1-2):29–36 suggested the potential DN4i use in telephone surveys due to the significant discriminating properties of the seven items. This observation was based on the fact that DN4i’s sensitivity (78%) and specificity (81.2%) are slightly lower than DN4 (82.9% and 89.9%, respectively).99 Bouhassira D, Attal N, Alchaar H, et al. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 2005;114(1-2):29–36,1616 Toth C, Lander J, Wiebe S. The prevalence and impact of chronic pain with neuropathic pain symptoms in the general population. Pain Med 2009;10(05):918–929 However, VanDenKerkhof et al.1717 VanDenKerkhof EG, Stitt L, Clark AJ, et al. Sensitivity of the DN4 in Screening for Neuropathic Pain Syndromes. Clin J Pain 2018;34 (01):30–36 point out that test sensitivity may vary according to the clinical condition. These authors cited, for instance, a 92.5% sensitivity for central pain, while Aho et al.1818 Aho T, Mustonen L, Kalso E, Harno H. Douleur Neuropathique 4 (DN4) stratifies possible and definite neuropathic pain after surgical peripheral nerve lesion. Eur J Pain 2020;24(02): 413–422 reported a 66.2% sensitivity for peripheral nerve injury after a surgical procedure.

Despite the suggestion of telephone use of DN4i by Bouhassira et al.,99 Bouhassira D, Attal N, Alchaar H, et al. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 2005;114(1-2):29–36 few studies in the literature have analyzed it. One of them1616 Toth C, Lander J, Wiebe S. The prevalence and impact of chronic pain with neuropathic pain symptoms in the general population. Pain Med 2009;10(05):918–929 validated the method during a complementary telephone survey, which had no reference, to determine the prevalence of chronic pain with neuropathic pain symptoms in a random populational sample from Alberta, Canada. Research participants received the call a week after the inperson application of DN4, which favors memory bias, as the patients could remember their answers and repeat them. Furthermore, the call was from the same doctor who applied DN4, compromising the internal and external validity of the study. In our study, different staff members performed the in-person application of the DN4 and the telephone interview using DN4i; however, these professionals had the same training, and the longer interval (4 to6months) could control the memory bias.

Keene et al.1919 Keene DJ, Knight R, Bruce J, et al. Chronic pain with neuropathic characteristics after surgery for major trauma to the lower limb: prevalence, predictors, and association with pain severity, disability, and quality of life in the UKWHiST trial. Bone Joint J 2021; 103-B(06):1047–1054 corroborated that the use of the DN4i questionnaire via telephone months after DN4 application did not reduce the sensitivity for neuropathic pain screening in their multicenter study to identify the prevalence of neuropathic pain after lower limb fracture surgery through the application of DN4 in the third and sixth months. As a result, they observed that 10% of patients without neuropathic pain 3 months after surgery had pain at 6 months, which differs from the expectation that the intensity and character of pain improve with the time after the injury.1919 Keene DJ, Knight R, Bruce J, et al. Chronic pain with neuropathic characteristics after surgery for major trauma to the lower limb: prevalence, predictors, and association with pain severity, disability, and quality of life in the UKWHiST trial. Bone Joint J 2021; 103-B(06):1047–1054

This study has some limitations, such as the difficulty in contacting patients who underwent surgery longer ago, which limited the number of participants. As it includes femur fractures, mortality bias in post-osteosynthesis surgical treatment must be considered since the mortality rate after 1 year of treatment is significant. Another critical point is the cognitive bias in older patients, as we did not apply specific instruments for cognitive screening over the telephone.

Our study also has strengths, as the practicality of the connection avoids unnecessary contact and facilitates the recruitment of the general population for epidemiological studies with no impact of social distancing situations such as the COVID-19 pandemic. The telephone use of DN4i also allows studies comparing clinical outcomes in different regions.

Future studies are potentially required to investigate whether telephone DN4i predicts treatment response since subjects with higher scores may be more responsive. It is also relevant to develop epidemiological studies to better detail these data in the literature, considering the greater practicality of telephone interviews. Research in hospitals analyzing the number of operated patients who developed neuropathic pain is also plausible for adjustments in given therapeutic approaches and management.

Conclusion

The application of the DN4i questionnaire by telephone compared to the in-person application of the DN4 questionnaire shows strong agreement between individual items of the tools and the total score obtained.

  • Financial Support
    The Scientific Initiation Scholarship Program from Faculdade de Ciências Médicas de Minas Gerais (PROBIC/FCMMG), linked to the Stricto Sensu Postgraduate Program, supported this study.
  • Work developed at the Hospital Universitário Ciências Médicas de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

Acknowledgments

We would like to thank Isabel Gomes, PhD, for her assistance in the statistical analysis, and Neylor Pace Lasmar, PhD, and Rodrigo Barreiros Vieira for providing the data.

References

  • 1
    Jensen TS, Baron R, Haanpää M, et al. A new definition of neuropathic pain. Pain 2011;152(10):2204–2205
  • 2
    Torrance N, Smith BH, Bennett MI, Lee AJ. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. J Pain 2006;7(04):281–289
  • 3
    Dey S, Guthmiller KB, Varacallo M. Complex Regional Pain Syndrome. In: StatPearls. Treasure Island (FL): StatPearls Publishing September 4, 2022
  • 4
    DeGeorge BR Jr, Van Houten HK, Mwangi R, Sangaralingham LR, Larson AN, Kakar S. Outcomes and Complications in the management of distal radial fractures in the Elderly. J Bone Joint Surg Am 2020;102(01):37–44
  • 5
    Bouhassira D. Neuropathic pain: Definition, assessment and epidemiology. Rev Neurol (Paris) 2019;175(1-2):16–25
  • 6
    Udall M, Kudel I, Cappelleri JC, et al. Epidemiology of physiciandiagnosed neuropathic pain in Brazil. J Pain Res 2019;12:243–253
  • 7
    Santos JG, Brito JO, de Andrade DC, et al. Translation to Portuguese and validation of the Douleur Neuropathique 4 questionnaire. J Pain 2010;11(05):484–490
  • 8
    Morgan KJ, Anghelescu DL. A Review of adult and pediatric neuropathic pain assessment tools. Clin J Pain 2017;33(09):844–852
  • 9
    Bouhassira D, Attal N, Alchaar H, et al. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 2005;114(1-2):29–36
  • 10
    Cohen J. Set Correlation and Contingency Tables. Appl Psychol Meas 1988;12(04):425–434
  • 11
    Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977;33(01):159–174
  • 12
    Smith BH, Torrance N. Epidemiology of neuropathic pain and its impact on quality of life. Curr Pain Headache Rep 2012;16(03): 191–198
  • 13
    Edgley C, Hogg M, De Silva A, Braat S, Bucknill A, Leslie K. Severe acute pain and persistent post-surgical pain in orthopaedic trauma patients: a cohort study. Br J Anaesth 2019;123(03): 350–359
  • 14
    Rbia N, van der Vlies CH, Cleffken BI, Selles RW, Hovius SER, Nijhuis THJ. High Prevalence of Chronic Pain With Neuropathic Characteristics After Open Reduction and Internal Fixation of Ankle Fractures. Foot Ankle Int 2017;38(09):987–996
  • 15
    Attal N, Bouhassira D, Baron R. Diagnosis and assessment of neuropathic pain through questionnaires. Lancet Neurol 2018; 17(05):456–466
  • 16
    Toth C, Lander J, Wiebe S. The prevalence and impact of chronic pain with neuropathic pain symptoms in the general population. Pain Med 2009;10(05):918–929
  • 17
    VanDenKerkhof EG, Stitt L, Clark AJ, et al. Sensitivity of the DN4 in Screening for Neuropathic Pain Syndromes. Clin J Pain 2018;34 (01):30–36
  • 18
    Aho T, Mustonen L, Kalso E, Harno H. Douleur Neuropathique 4 (DN4) stratifies possible and definite neuropathic pain after surgical peripheral nerve lesion. Eur J Pain 2020;24(02): 413–422
  • 19
    Keene DJ, Knight R, Bruce J, et al. Chronic pain with neuropathic characteristics after surgery for major trauma to the lower limb: prevalence, predictors, and association with pain severity, disability, and quality of life in the UKWHiST trial. Bone Joint J 2021; 103-B(06):1047–1054

Publication Dates

  • Publication in this collection
    20 May 2024
  • Date of issue
    Jan-Feb 2024

History

  • Received
    18 Feb 2023
  • Accepted
    21 July 2023
Sociedade Brasileira de Ortopedia e Traumatologia Al. Lorena, 427 14º andar, 01424-000 São Paulo - SP - Brasil, Tel.: 55 11 2137-5400 - São Paulo - SP - Brazil
E-mail: rbo@sbot.org.br