Translation and Validation of the Hindi Version of Neuropathic Pain Symptom Inventory: A Prospective Cohort Study

INTRODUCTION

Neuropathic pain (NP) is defined as pain that is caused by a lesion or disease of the somatosensory nervous system, affecting 3.3–11.8% of the general population.^[1,2] Post-herpetic neuralgia (PHN) is a commonly encountered NP in clinical practice. NP has been assessed using various questionnaires and tools such as Douleur Neuropathique 4 questionnaire (DN-4),^[3,4] NP symptom inventory (NPSI),^[5] pain detect questionnaire^[6] and the identification pain questionnaire.^[7] These questionnaires have been utilised in pain practice to differentiate NP from non- NP (NNP), and each one of them has its own merits, demerits and limitations.^[5]

NPSI is a patient-reported outcome measure, which is specifically designed to assess the different symptoms of NP. It quantified both the intensity and quality of NP syndromes. It was first validated in the French language in patients with chronic NP with various etiologies.^[5]

The inventory consists of 12 items that assess pain symptoms across five domains: Burning spontaneous pain, pressing spontaneous pain, paroxysmal pain, evoked pain and paraesthesia/dysesthesia. Patients are instructed to rate the intensity and frequency of their symptoms over the past 24 h. Most items are scored using a 0–10 numeric rating scale (NRS), where 0 indicates no symptom and 10 indicates the worst imaginable intensity, while one item uses descriptive categories to capture the temporal pattern of pain.^[5]

The psychometric properties of NPSI help to characterise subgroups of NP patients and to predict the patient’s response to different treatments.^[5] NPSI stands out due to its detailed multidimensional assessment, responsiveness to treatment and applicability across diverse NP syndromes, making it a superior tool for both clinical and research purposes compared to other screening or diagnostic tools such as DN-4, LANSS, or pain DETECT.^[5] It has been reported to have a high test-retest reliability, sensitivity and specificity along with good construct validity.^[5] In addition, NPSI has been translated and validated into several languages.

In our literature search, we observed that it has not been validated in the Hindi language or any other Indian languages. PHN is a leading cause of NP in India, as reported by Mishra.^[8] Hence, the present patient population of PHN was chosen with the aim of validating the Hindi Version of the NPSI (NPSI-H) for the identification and assessment of NP. We translated the English version of the NPSI questionnaire into Hindi first and planned the study with the primary objective to assess the reliability and validity of the NPSI-H. The secondary objectives were to assess the correlation between the NPSI total (NPSI[T]) score, optimal cutoff for NPSI based on NRS-pain and DN-4, with sensitivity and specificity.

MATERIALS AND METHODS

The present prospective cohort study was undertaken after clearance by IEC-Human vide approval number IEC-HR-2023-59-13-R1, dated 30 April 2023, and prospective CTRI registration (CTRI/2023/08/05692) between May 2023 and November 2024. The study was carried out in accordance with the principles of the Declaration of Helsinki 2013 and confirmed the use of patient data for research and educational purposes. Written informed consent was taken from all the participants.

Patients who presented to the pain clinic having a diagnosis of PHN with evident hyperalgesia and allodynia confined to mid-thoracic and lower thoracic dermatomes, also having pain for at least 12 weeks after the healing of rash, with pain intensity ≥4 on a 10 cm visual analogue scale, were included in the study. PHN is a commonly encountered NP found in the Indian population attending pain clinics with symptoms encompassing various dimensions of the NPSI questionnaire, making it a useful multidimensional tool for clinical assessment and research.

Patients were excluded if a history of neurological intervention for PHN was present to avoid any potential modification of pain symptoms due to treatment effects. These interventions included; transcutaneous electrical nerve stimulation and triamcinolone injection, intrathecal methylprednisolone and midazolam injection, stellate ganglion blocks and pulsed radiofrequency ablation therapy, evidence of other sources of pain confounding the diagnosis, known history of taking pregabalin or on any other drug for the treatment of PHN in the past 4 weeks, a past history of myocardial infarction, diabetes mellitus, pancreatitis and vasculitis or recent history of surgery.

The permission for the psychometric validation of NPSI-H was obtained from Bouhassira et al., the authors of the NPSI questionnaire in the French language.^[5] Thereafter, the traditional standard recommendation for cross-cultural adaptation and translation is through four separate steps.^[3] In the first step, the English version of NPSI [Annexure 1] was translated into Hindi using expert translators. In the second step, retranslation of the Hindi version of NPSI was translated back to English again by taking the help of two expert translators. In the third step, the semantic and literal assessment between the translated and retranslated versions was performed. In the last step, practicability and interpretation difficulties of the final Hindi version of the NPSI questionnaire were assessed on a pilot group of 12 patients with NP.

The NPSI(T) and NRS-pain scores were recorded at baseline, that is, on their first visit to the pain clinic, and at the end of the 4^th week of treatment. At each time point, the NPSI-H questionnaire [Annexure 2] was filled twice over an interval of 1 h by two different doctors (labelled as Rater 1 and Rater 2) of similar experience. Although the questionnaire used in the study is a self-reported instrument, responses were documented with the assistance of two independent raters so as to ensure test-retest reliability. Both raters independently recorded and interpreted the participant’s responses as per the standard administration guidelines of the questionnaire. Neither of these doctors was involved in the study, but they were well-versed in the questionnaire. The NRS-pain scores were recorded only twice, once at baseline and then at the 4^th week. However, DN-4 was recorded only once at baseline. Hence, each patient had a total of four filled NPSI-H questionnaires, along with two NRS-pain records and one DN-4 score. Quality of life (QoL) assessment was done using the short form-12 (SF-12) questionnaire. All the filled-out questionnaires (paper-based) provided by 230 patients were properly secured and maintained in a file. A total intensity score NPSI(T) was calculated from the sum of the scores of the 10 descriptors as adapted from the original French version.^[5]

In addition, patients were also requested to fill up the Hindi version of the DN-4 questionnaire^[4] on the 1^st day as baseline. It consists of four broad questions, with sub-parts (a total of 10), out of which two questions are based on interviewing the patient and two on examination findings. The answers are in a yes/no format for each question, which are scored as 1 for a positive response and 0 for a negative response, respectively. The cutoff for NP is taken as a score of ≥4, with a minimum and maximum score ranging from 0 to 10. NRS-pain is an 11 point numerical score ranging from 0 to 10 on a scale, where 0 is no pain and 10 is the worst possible pain. The SF-12 questionnaire measures eight components, represented as physical functioning, role limitations due to physical health problems, general health, vitality, social functioning, role limitations due to emotional problems and mental health in the form of 12 questions in which the participant chooses a single response only.^[9] The four health concepts namely, physical functioning, role physical, role-emotional and mental health, each use two items. The other four concepts namely, bodily pain, general health, energy/fatigue and social functioning each use one item. The physical component summary (PCS) and the mental component summary (MCS) are scored using the norm-based method, using the physical and mental regression weights and a constant for both the measures comes from the general US population. The PCS and MCS scales are transformed to have a mean value of 50 and a standard deviation (SD) of 10.

The sample size was calculated using power analysis and sample size software, and was done on the basis of test-retest agreement using the intra-class correlation coefficient (ICC) between the two values at baseline. The previous study³ validating the Hindi version of a similar NP questionnaire, that is DN-4, showed the test-retest ICC of 0.89, expecting the test-retest ICC as 0.92, in our study, with 80% power and a 5% level of significance, we required 223 patients in the present study. We selected a sample size of 230 patients, accounting for potential attrition during the study period.

Statistical analysis was done using the Statistical Package for the Social Sciences version 20.0. To describe continuous and qualitative variables, mean ± SD and frequency (percentage) were used, respectively, used. Cronbach’s alpha coefficient was calculated for the NPSI(T) score and also after removing each of the items for both raters. A Cronbach’s alpha range from 0.8 to 0.9 indicates good internal consistency (IC). To assess the validity, the Spearman correlation (SC) was used to assess the correlation between the NRS-pain score and NPSI(T) at different time intervals. Furthermore, the ICC and the 95% confidence interval (CI) for the point estimations were reported to assess the agreement between the raters at different follow-up time points.^[10] Then, the sensitivity and specificity of NPSI-H total average scores were calculated using patient global impression of change and clinical global impression of change.^[5] The receiver operative characteristic (ROC) curve was applied to find the discriminant validity of NPSI, considering the NRS-pain <5 and NRS-pain ≥5 and for DN-4 score <4 and DN-4 score ≥4. The optimal cutoff was determined using the Youden index (Sensitivity+specificity - 1) as the maximum. The positive predictive value (PPV) and negative predictive value (NPV), along with sensitivity and specificity, were determined at this optimal cutoff point. SC was performed to find the correlation between the NPSI and QoL.

RESULTS

The Strobe flow chart of patient recruitment is shown in Figure 1. This study involved 230 patients of PHN (107: males and 123: females) with a mean age of 56.83 ± 12.40 years, body weight 59.92 ± 8.56 kg and NRS-pain score of 7.45 ± 1.584. The Cronbach alpha coefficient was >0.8 for NPSI(T) for each item at both baseline and at the 4^th week with both raters [Table 1]. If one item of NPSI was removed, it did not influence the observed IC; thereby, justifying the contribution of each item of NPSI [Table 1].

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Figure 1:

Strobe flow chart of patient recruitment. PHN: Postherpetic neuralgias.

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The NPSI scores at baseline with Rater 1 and Rater 2 are 51.79 ± 16.24 and 46.80 ± 13.79; ICC (95% CI) −0.851 (0.73–0.83), respectively. The NPSI scores at the 4^th week with Rater 1 and Rater 2 are 20.78 ± 9.38 and 20.33 ± 7.70; ICC [95% CI] −0.854 (0.811–0.813), respectively. The ICC value was higher than 0.85, indicating excellent agreement between the two raters at both designated time points.

A significant correlation was observed between the NRS-pain score and NPSI(T) score at both designated time points by both raters, indicating excellent convergent validity [Table 2]. Similarly, a significant correlation was observed between the DN-4 score and NPSI(T), indicating excellent convergent validity [Table 2].

We also applied the ROC curve to assess the discriminative validity of the baseline NPSI(T) and found the optimal cutoff point considering the NRS-pain ≥5 [Figure 2] and DN-4 score ≥4 as a poor score [Figure 3]. The optimal NPSI cutoffs at baseline with NRS-pain were>35.76, and considering the NRS-pain ≥5 as poor, at this point, sensitivity was 83.11%, and specificity was 100% indicating an excellent discriminant power of NPSI-H [Table 3 and Figure 2]. Similarly, the optimal cutoff point of NPSI with DN-4 score ≥4 was 35.7 at baseline; sensitivity and specificity at this point were 76.3% and 100/%, respectively [Table 3 and Figure 3]. The PPV and NPV are shown in Table 3.

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Figure 2:

Receiver operative characteristic (ROC) curve showing the discriminating validity of neuropathic pain symptom inventory-total average score calculated with relevance to baseline numeric rating scale -pain score.

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Figure 3:

Receiver operative characteristic (ROC) curve showing the discriminating validity of neuropathic pain symptom inventory-total average score calculated with relevance to douleur neuropathique 4 questionnaire score at baseline.

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There was a positive-weak correlation between NPSI-T scores with age and body weight at baseline and at the end of the 4^th week of treatment [Table 4].

A moderate negative correlation was observed between the NPSI(T) score and QoL-P at both time points, and a similar moderate negative correlation was observed between the NPSI(T) score and QoL-M at baseline; however, at 4 weeks, no significant correlation was observed [Table 5].

DISCUSSION

The Cronbach’s alpha coefficient of the NPSI-H was >0.8, indicating good IC and ICC was higher than 0.85, indicating excellent agreement between the two raters, both at baseline and 4^th week. The sensitivity and specificity of NPSI-H with NRS ≥5 as the standard were observed to be 83.00% and 100%, respectively, at baseline with an NPSI-H cutoff of >35.76. Similarly, the optimal cutoff point of NPSI-H with DN-4 score ≥4 was 35.7 at baseline; sensitivity and specificity at this point were 76.3% and 100/%, respectively.

NPSI questionnaire, till now, has been cross-culturally adapted and validated in several languages such as Italian,^[11] German,^[12] Persian,^[13] English,^[5] Portuguese,^[14] Spanish^[15] and Japanese.^[16] Most of these versions have been evaluated for reliability and observed to be reliable.

For test-retest reliability, in the present study, we administered the questionnaire over 1 h apart at both time points, that is baseline and at the end of the 4^th week. Two different raters evaluated the test-retest reliability. Like our study, the two-rater format was employed in the Original French^[5] and Persian^[12] validations only. The two-stage administration for checking test-retest reliability is cumbersome and requires huge data management and extensive statistical analysis. There has been no consensus on the length of time that must elapse between the two tests. Different time intervals had been used in the different validation studies pertaining to NPSI are 3 h with French^[5] and Persian,^[13] 3–5 days with Italian,^[11] 24 h with the German,^[12] 23 days with Japanese^[16] and 3–6 weeks apart with Portuguese,^[14] Spanish^[15] validation studies. The original study in French was assessed over an interval of 3 h. In the present study, a 1 h interval seemed appropriate as it was feasible and prevented recalling the answers, along with ruling out the influence of treatment or any spontaneous fluctuations in pain intensity.

The majority of these validation studies included patients with NP of central or peripheral origin.^[5,11,14-16] However, only two validation studies had included patients with both NP and NNP,^[12,13] using the NRS/DN-4 and discriminant analysis, respectively, for assessing validity. In the present study, we included a specific subset of NP, that is, PHN.

To evaluate the discriminant validity, the Spanish validation study^[15] used NPS and the German validation study^[12] used specific discriminant analysis. The former study had included patients with chronic NP, while the latter included patients with both NP and NNP. In the present study, the DN-4 questionnaire, a known validated questionnaire to assess NP, was used to assess the discriminant validity. The cutoff NPSI score reported in the Spanish version^[15] was 38 (sensitivity 85% and specificity 75.2%), which is comparable to the present study result, that is cutoff of 35.75% (sensitivity 76.3% and specificity 100/%).

The NPSI questionnaire consists of various pain items. Out of these, ‘Squeezing’ or ‘Pressure’ pertains to the deep component, while ‘Burning’ pertains to superficial pain sensations.^[17] However, the total NPSI score reflects an overview of pain intensity and cannot differentiate between deep and superficial pain. Considering this fact, in the present study, we used NRS-pain in addition to DN-4 for assessing discriminant validity. The study has a few limitations. First, it is a single-centric study with a limited sample size. Second, based on the hospital statistics, the study was restricted to patients with PHN; however, the inclusion of a larger number of patients with NP of other etiologies would have helped in assessing the validity of the questionnaire over a wider spectrum of patients.

CONCLUSION

We observed that the present study’s results indicate that the NPSI-H questionnaire has excellent essential psychometric properties, including reliability, feasibility and validity. The use of this version should be encouraged for evaluating the NP component in patients with PHN, especially amongst Hindi-speaking populations.