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 VOLUME Vol.05 Issue06 2025 

PAGE NO. 38-49 

DOI 10.37547/ajbspi/Volume05Issue06-09 

 
 
 
 

Personalized Approach to The Diagnosis of Neuropathic 

Pain in Metastatic Breast Cancer: Development of A 

Multicomponent Questionnaire 
 

Rakhimov Nodir Makhammatkulovich 

DSc, Professor, Department of Oncology, Samarkand State Medical University, Samarkand 140100, Uzbekistan 

 

Rakhmonov Kamol Aminzhonovich 

Independent researcher, Department of Oncology, Samarkand State Medical University, Samarkand 140100, Uzbekistan 

 

Shakhanova Shakhnоza Shavkatovna 

PhD, Associate Professor, Department of Oncology, Samarkand State Medical University, Samarkand 140100, Uzbekistan 

 

 

Received: 30 April 2025; Accepted: 28 May 2025; Published: 30 June 2025 

 

Abstract: Objective: To validate the specialized questionnaire "NEURO-RMZh" for the differential diagnosis of 
neuropathic pain in patients with metastatic breast cancer and to compare its psychometric properties with 
existing validated instruments. 

Materials and Methods:  A single-center prospective validation study was conducted, enrolling 111 patients with 
metastatic breast cancer. A comprehensive methodological approach was employed, including assessment of 
internal consistency, test-retest reliability, construct and criterion validity. Statistical methods included factor 
analysis, correlation analysis, ROC analysis, and multiple logistic regression. The DN4, BPI, SF-36, and Visual 
Analogue Scale (VAS) questionnaires were used as comparators. 

Results: The "NEURO-RMZh" questionnaire demonstrated high internal consistency (Cronbach’s α = 0.89) and 
test-retest reliability (ICC = 0.94). Its four-factor structure explains 73.6% of the total variance. The diagnostic 
performance of the questionnaire exceeds that of existing tools: sensitivity 89.7%, specificity 82.4%, area under 
the ROC curve 0.92. Likelihood ratios (LR+ = 5.10, LR- = 0.13) indicate the clinical significance of the test. Strong 
correlations were observed with SF-36 quality of life domains (r from -0.44 to -0.74). 

Conclusion: The "NEURO-RMZh" questionnaire is a valid, reliable, and highly informative tool for the differential 
diagnosis of neuropathic pain in patients with metastatic breast cancer. Its implementation may contribute to the 
optimization of diagnostics and personalization of therapeutic strategies in palliative oncology. 

 

Keywords: Neuropathic pain, breast cancer, questionnaire, validation, palliative care. 

 

Introduction: Breast cancer remains one of the 
leading causes of cancer morbidity among women 
worldwide, accounting for 24.5% of all malignant 
neoplasms in women [1]. Pain syndrome of various 
etiologies develops in 75–90% of patients with 
advanced forms of the disease, significantly reducing 
quality of life and necessitating a differentiated 
approach to therapy [2,3]. 

The pathogenesis of pain syndrome in breast cancer is 
characterized by pronounced heterogeneity of 
underlying mechanisms. Nociceptive pain is caused by 
the direct effect of the tumor on tissues, inflammatory 
processes, and mechanical compression of structures 
[4]. Neuropathic pain develops as a result of peripheral 
nerve injury due to tumor progression, neurotoxicity of 
chemotherapeutic agents (taxanes, platinum 

 

https://doi.org/10.37547/ajbspi/Volume05Issue06-09
https://doi.org/10.37547/ajbspi/Volume05Issue06-09
https://doi.org/10.37547/ajbspi/Volume05Issue06-09
https://doi.org/10.37547/ajbspi/Volume05Issue06-09


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American Journal of Applied Science and Technology (ISSN: 2771-2745) 
 

 

compounds, vinca alkaloids), or radiotherapy [5,6]. The 
mixed type of pain, which combines both mechanisms, 
is observed in 39–65% of patients and presents the 
greatest diagnostic challenges [7]. 

Current Approaches to Pain Assessment in Oncology 

The visual analogue scale (VAS) remains the gold 
standard for assessing pain intensity in clinical practice 
due to its ease of use and high reproducibility (r=0.94) 
[8]. However, the VAS does not allow differentiation of 
pain types based on pathophysiological mechanisms, 
limiting its use in selecting targeted therapies for 
neuropathic pain [9]. 

The DN4 is a validated screening tool for neuropathic 
pain that includes 10 dichotomous questions [10]. DN4 
demonstrates a sensitivity of 82.9% and a specificity of 
89.9% at a cut-off value of ≥4 points [11]. Despite its 
wide application, the DN4 has significant limitations in 
the oncological population: insufficient validation in 
patients with chemotherapy-induced polyneuropathy, 
low specificity for mixed pain types (67.3%), and the 
need for physical examination, which complicates 
telemedicine consultations [12,13]. 

The Brief Pain Inventory (BPI) assesses pain intensity 
and its impact on patient functional activity using an 
11-point scale [14]. The questionnaire demonstrates 
high internal consistency (Cronbach’s α = 0.85–0.95) 
and is validated in the oncological population [15]. 
However, the BPI does not include specific descriptors 
of neuropathic pain and does not allow differential 
diagnosis between types of pain syndromes [16]. 

The SF-36 is a universal instrument for assessing quality 
of life, including a bodily pain domain [17]. In 
oncological research, the SF-36 has shown adequate 
reliability (α = 0.78–0.93) and construct validity [18]. 
Nevertheless, the questionnaire is not intended for 
differential diagnosis of pain types and has low 
sensitivity to changes in neuropathic symptoms [19]. 

A review of the literature reveals critical gaps in current 
approaches to the diagnosis of neuropathic pain in 
breast cancer: 

• Insufficient specificity of existing tools 
for the oncological population, particularly in cases of 
chemotherapy-induced polyneuropathy [20]; 

• Lack of consideration for the temporal 
characteristics of pain syndrome related to cycles of 
anticancer therapy [21]; 

• Limited applicability in palliative care 
settings for patients with marked asthenia and 
cognitive impairment [22]. 

The aim of this study is to validate a novel specialized 
questionnaire—the "Oncology Neuropathic Pain 
Differential Diagnosis Scale" (NEURO-RMZh)—for the 

assessment of neuropathic pain in patients with breast 
cancer and to compare its psychometric properties 
with existing validated instruments (VAS, DN4, BPI, SF-
36). 

METHODS 

In response to the identified shortcomings of current 
methodologies, we have developed an innovative 
diagnostic tool that integrates the advantages of 
contemporary questionnaires while minimizing their 
limitations. The developed questionnaire comprises 20 
items: 16 for self-completion by the patient and 4 for 
clinical assessment by a specialist. 

This diagnostic package is adapted to the specific 
features of neuropathic pain manifestations in 
oncology and is equipped with a detailed data analysis 
system. This ensures the optimization of diagnostic 
procedures and enhances the reliability of differential 
diagnosis of various pain types in clinical oncology. 

Such a multicomponent methodology allows for the 
most detailed characterization of pain sensations and 
their impact on the patient's daily life. The information 
obtained forms the basis for developing personalized 
therapeutic programs, which is especially relevant for 
managing patients with persistent pain syndromes and 
malignant neoplasms. 

Questionnaire for the Differential Diagnosis of 
Neuropathic Pain in Patients with Metastatic Breast 
Cancer (NEURO-RMZh) 

Part I: Patient Section (16 items) 

Section A: Pain Intensity and Localization (4 items) 

1. Please rate the intensity of your pain at 
this moment on a scale from 0 to 10, where 0 means no 
pain and 10 means unbearable pain. Numerical scale: 
0–10 

2. Please rate the intensity of your most 
severe pain over the past 7 days on a scale from 0 to 
10. Numerical scale: 0–10 

3. Mark on the body diagram the areas 
where you experience pain, and circle the area of most 
intense pain. Schematic front and back view for 
marking 

4. Does the pain extend beyond the area of the tumor or 
metastases? 
□ No 

□ Yes, slightly 

□ Yes, significantly 

□ Difficult to answer 

Section B: Pain Characteristics (6 items) 

5. Do you experience any of the following 
sensations in the area of pain? (select all that apply) 



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American Journal of Applied Science and Technology (ISSN: 2771-2745) 
 

 

□ Burning 

□ Tingling 

□ Electric shock sensation 

□ Numbness 

□ Crawling sensation 

□ None of the above 

6. How intense are these unusual 
sensations on a scale from 0 to 10? 
Numerical scale: 0–10 

7. Does the pain occur suddenly, without 
an obvious cause? 
 

□ Never 

□ Rarely 

□ Often 

□ Constantly 

8. Does the pain get worse with: 
□ Light touch to the painful area 

□ Pressure on the painful area 

□ Cold 

□ Heat 

□ None of the above 

9. Is there pain in an area with reduced 
sensitivity? 
 

□ No 

□ Yes, slightly 

□ Yes, significantly 

□ Difficult to answer 

10. Does the nature of your pain change 
during the day? 

□ No, the pain is constant 

□ Yes, it worsens in the evening 

□ Yes, it worsens at night 

□ Yes, it worsens in the morning 

□ Other: _________________ 

Section C: Impact of Pain on Quality of Life (6 items) 

11. How does pain affect your sleep? 

□ No effect 

□ Slightly hinders falling asleep 

□ Significantly disrupts sleep 

□ Makes restful sleep impossible 

12. How does pain affect your daily 
activity? 

□ Does not limit 

□ Slightly limits 

□ Significantly limits 

□ Makes activity impossible 

13. Does pain affect your mood? 

□ No effect 

□ Causes occasional irritability 

□ Causes constant irritability or depression 

□ Causes marked anxiety or depression 

14. How effective are pain medications in 
relieving your pain? 

□ Completely eliminate 

□ Significantly reduce 

□ Slightly reduce 

□ Hardly help at all 

15. Which methods, besides medication, 
help you reduce pain? (select all that apply) 

□ Cold 

□ Heat 

□ Massage 

□ Change of body position 

□ Distraction 

□ Nothing helps 

□ Other: _________________ 

16. To what extent does pain interfere 
with your communication with loved ones? 

□ Does not interfere 

□ Slightly interferes 

□ Significantly limits communication 

□ Makes communication impossible 

Part II: Physician Assessment (4 items) 

17. Objective signs of nervous system 
damage in the area of pain: 

□ None 

□ Local muscle atrophy 

□ Trophic skin changes 

□ Skin discoloration 

□ Edema 

□ Other: _________________ 

18. Assessment of tactile sensitivity in the 
area of pain: 

□ Normal 

□ Hypoesthesia (decreased) 

□ Hyperesthesia (increased) 

□ Allodynia (pain from non-painful stimuli) 



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□ Anesthesia (absent) 

19. Assessment of thermal sensitivity in 
the area of pain: 

□ Normal 

□ Decreased to cold 

□ Decreased to heat 

□ Absent 

□ Paradoxical (heat perceived as cold or vice versa) 

20. Correspondence of pain localization to 
the anatomical distribution of nerves or dermatomes: 

□ Does not correspond 

□ Partially corresponds 

□ Fully corresponds 

□ Corresponds to the innervation zone of several 
nerves 

Scoring System 

For Part I (Patient Section): 

• Questions 1, 2, and 6: direct score 
calculation (0–10 points each) 

• Questions 3 and 15: not scored, used 
for qualitative assessment 

• Questions 4, 7, 8, 9, 10, 11, 12, 13, 14, 
and 16: 0 to 3 points each, depending on symptom 
severity 

• Question 5: 1 point for each symptom 
indicated (maximum 5 points) 

For Part II (Physician Assessment): 

• Questions 17–20: 0 to 3 points each, 
depending on the degree of clinical findings 

Interpretation of Results: 

• 0–15 points: low probability of 
neuropathic pain 

• 16–30 points: moderate probability of 
neuropathic pain 

• 31–45 points: high probability of 
neuropathic pain 

• 45 points: very high probability of 
neuropathic pain 

The NEURO-RMZh was developed with 
consideration for the specific characteristics of 
oncology patients and includes: 

• Adapted neuropathic pain descriptors 
for the oncological population 

• Temporal assessment of symptoms in 
relation to anticancer therapy 

• A simplified algorithm for use in 
palliative care 

• Feasibility for remote application 
without physical examination 

The study hypothesis is that the NEURO-RMZh will 
demonstrate superior diagnostic performance 
compared to existing questionnaires in differentiating 
neuropathic pain from nociceptive and mixed pain in 
patients with breast cancer, thus optimizing targeted 
therapy selection and improving the quality of 
palliative care. 

A single-center prospective validation study was 
conducted to assess the psychometric properties of the 
new NEURO-RMZh questionnaire for evaluating 
neuropathic pain in patients with metastatic breast 
cancer. The study included women who met the 
following criteria: 

• Age 18–75 years 

• Histologically confirmed metastatic 
breast cancer 

• Presence of pain syndrome with an 
intensity of ≥3 on the visual analogue scale (VAS) 

• Ability to independently complete 
questionnaires 

• Signed informed consent to participate 
in the study 

Exclusion criteria: 

• Severe comorbidities that could affect 
pain perception (e.g., diabetes mellitus with 
polyneuropathy, systemic connective tissue diseases, 
chronic renal failure) 

• History or presence of psychiatric 
disorders at the time of enrollment 

• Use of psychotropic medications 
(antidepressants, neuroleptics, tranquilizers) within 2 
weeks prior to enrollment 

• Cognitive impairment interfering with 
adequate comprehension of the questionnaires 

• Inability to independently complete 
the questionnaires for any reason 

• Refusal to participate 

The sample size was calculated using a formula for 
validation studies of diagnostic tests. Assuming a 
planned sensitivity of 85%, specificity of 80%, 95% 
confidence interval, and study power of 80%, the 
minimum sample size was 98 patients. Taking into 
account potential attrition (15%), the target sample 
size was set at 115 patients. 

Potential participants were identified among patients 
undergoing treatment at the Palliative Care 
Department of the Samarkand Interregional Hospice. 
The study physician conducted a preliminary eligibility 



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assessment based on medical records and clinical 
examination. 

After obtaining informed consent, a standardized pain 
assessment was performed by an anesthesiologist with 
at least 5 years’ experience in palliative oncology. 
Based on clinical data, disease history, and neurological 
examination, a preliminary diagnosis of pain type was 
established: nociceptive pain, neuropathic pain, or 
mixed pain (nociceptive + neuropathic). 

This clinical assessment was considered the "gold 
standard" for subsequent analysis of the diagnostic 
properties of the questionnaires. 

Questionnaire completion was carried out in 
standardized conditions in the presence of a research 
nurse to prevent missing data and ensure proper 
understanding of the questions. 

To assess the test-retest reliability of the NEURO-RMZh 
questionnaire, 30 patients were randomly selected to 
complete the questionnaire a second time 48–72 hours 
later, provided there were no changes in pain 
management. 

Statistical analysis was performed using SPSS software 
version 26.0 (IBM Corp., Armonk, NY, USA). The 
significance level was set at p<0.05. 

Reliability of the Questionnaire: 

• Internal consistency was assessed 
using Cronbach’s alpha coefficient 

• Test-retest reliability was evaluated 
using the intraclass correlation coefficient (ICC) 

• Temporal stability was measured using 
the Pearson correlation coefficient between initial and 
repeated test results 

Validity of the Questionnaire: 

• Construct validity: Assessed using 
factor analysis by the principal components method 
with Varimax rotation; 

• Criterion validity: Evaluated by 
correlation analysis with the clinical assessment of pain 
type (the “gold standard”); 

• Convergent validity: Assessed by 
Pearson correlation analysis with the results of the 
DN4, BPI, and SF-36 questionnaires. 

For each questionnaire, the following were 
calculated: 

• Sensitivity (Se) and specificity (Sp); 

• Positive predictive value (PPV) and 
negative predictive value (NPV); 

• Positive (LR+) and negative (LR−) 
likelihood ratios; 

• Area under the ROC curve (AUC) with a 
95% confidence interval. 

Optimal cut-off values were determined using 
the Youden index (J = Se + Sp − 1). 

The study included women who met the 
following criteria: 

• Age 18–75 years; 

• Histologically confirmed metastatic 
breast cancer; 

• Presence of pain syndrome with an 
intensity of ≥3 points on the visual analogue scale 
(VAS); 

• Ability to complete questionnaires 
independently; 

• Signed informed consent to participate 
in the study. 

Exclusion criteria: 

• Severe comorbidities that could affect 
pain perception (e.g., diabetes mellitus with 
polyneuropathy, systemic connective tissue diseases, 
chronic renal failure); 

• History or presence of psychiatric 
disorders at the time of enrollment; 

• Use of psychotropic medications 
(antidepressants, neuroleptics, tranquilizers) within 
two weeks prior to enrollment; 

• Cognitive impairments precluding 
adequate understanding of the questionnaires; 

• Inability to complete questionnaires 
independently for any reason; 

• Refusal to participate. 

The sample size was calculated using a formula for 
validation studies of diagnostic tests. Assuming a 
planned sensitivity of 85%, specificity of 80%, a 95% 
confidence interval, and a study power of 80%, the 
minimum required sample size was 98 patients. 
Allowing for a potential dropout rate of 15%, the target 
sample size was set at 112 patients. 

The study was conducted in accordance with the 
principles of Good Clinical Practice (GCP) and national 
regulatory requirements. Data confidentiality was 
ensured by de-identification and coding of information. 
Participants retained the right to withdraw consent at 
any stage of the study without explanation and without 
affecting the quality of medical care received. 

RESULTS 

A total of 111 patients with metastatic breast cancer 
were enrolled in the study. The mean age of 
participants was 58.4 ± 11.2 years (range, 34–74 years). 



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The majority of patients (67.9%, n=76) had invasive 
ductal carcinoma, 23.2% (n=26) had invasive lobular 
carcinoma, and the remaining 8.9% (n=10) had other 
histological variants. 

Here is the full translation of your section, including the 
table and the accompanying explanation, in scientific 
English suitable for publication: 

Table 1. 

Demographic and Clinical Characteristics of the Study Sample (n=111) 

Variable Value 

Age, years 
 

Mean ± SD 58.4 ± 11.2 

Median (IQR) 59.0 (50.0–66.0) 

Range 34–74 

Histological type, n (%) 
 

Invasive ductal carcinoma 76 (67.9) 

Invasive lobular carcinoma 26 (23.2) 

Other types 10 (8.9) 

Molecular subtype, n (%) 
 

Luminal A 28 (25.0) 

Luminal B HER2- 34 (30.4) 

Luminal B HER2+ 21 (18.8) 

HER2-positive 16 (14.3) 

Triple-negative 13 (11.6) 

Site of metastases, n (%) 
 

Bone 67 (59.8) 

Liver 43 (38.4) 

Lungs 38 (33.9) 

Brain 12 (10.7) 

Prior therapy, n (%) 
 

Anthracyclines 89 (79.5) 

Taxanes 34 (30.4) 

Radiotherapy 78 (69.6) 

Pain type (gold standard), n (%) 
 

Nociceptive 48 (42.9) 

Neuropathic 39 (34.8) 

Mixed 25 (22.3) 

Pain intensity (VAS) 
 

Mean ± SD 6.2 ± 1.8 



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Variable Value 

Median (IQR) 6.0 (5.0–8.0) 

The study cohort consisted of middle-aged and elderly 
women with various histological and molecular 
subtypes of breast cancer. The predominance of 
invasive ductal carcinoma and luminal subtypes 
corresponds to the general breast cancer patient 
population. The high frequency of bone metastases 
(59.8%) explains the substantial proportion of patients 
with pain syndrome. 

According to the clinical assessment by an 
anesthesiologist (“gold standard”), 48 patients (42.9%) 
were diagnosed with predominantly nociceptive pain, 
39 (34.8%) with neuropathic pain, and 25 (22.3%) with 

mixed pain. The mean pain intensity by VAS was 6.2 ± 
1.8. 

Psychometric Properties of the NEURO-RMZh 
Questionnaire 

The internal consistency of the NEURO-RMZh 
questionnaire demonstrated high values: Cronbach’s 
alpha coefficient was 0.89 (95% CI: 0.85–0.92), which 
significantly exceeds the recommended minimum level 
of 0.70. For comparison, the Cronbach’s alpha for the 
DN4 was 0.76 (95% CI: 0.69–0.82), and for the BPI – 
0.81 (95% CI: 0.76–0.85). 

Table 2 

Questionnaire Cronbach’s α (95% CI) ICC (95% CI)* r test-retest** 

NEURO-RMZh 0.89 (0.85–0.92) 0.94 (0.88–0.97) 0.92 

DN4 0.76 (0.69–0.82) 0.87 (0.75–0.94) 0.85 

BPI 0.81 (0.76–0.85) 0.91 (0.82–0.96) 0.88 

*Note: ICC – Intraclass correlation coefficient for assessment of test-retest reliability; 
**All correlations are significant at p<0.001. 

Test-retest reliability was assessed in 30 patients 48–72 
hours after initial testing. The intraclass correlation 
coefficient (ICC) for the NEURO-RMZh questionnaire 
was 0.94 (95% CI: 0.88–0.97), indicating excellent 
temporal stability. The Pearson correlation coefficient 
between the first and repeat test was r=0.92 (p<0.001). 

Construct validity was confirmed by factor analysis. 
Principal component analysis with Varimax rotation 
revealed a four-factor structure, accounting for 73.6% 
of the total variance. The factors corresponded to the 
domains embedded in the questionnaire: qualitative 
pain characteristics (28.4% of variance), temporal 
characteristics (18.7%), provoking factors (14.2%), and 

associated symptoms (12.3%). All factor loadings 
exceeded 0.60, confirming the adequacy of the 
questionnaire structure. 

Criterion validity was evaluated by comparing the 
questionnaire results with the clinical assessment of 
pain type. The correlation between the total NEURO-
RMZh score and the clinical assessment of the 
neuropathic pain component was r=0.78 (p<0.001), 
which was significantly higher than the corresponding 
value for the DN4 (r=0.64, p<0.001). 

Here is a complete, scientific English translation of your 
tables and explanatory text for publication: 

Table 3. 

Results of Factor Analysis of the NEURO-RMZh Questionnaire 

Factor Eigenvalue % Variance Explained Cumulative % 

1. Qualitative pain characteristics 4.26 28.4 28.4 

2. Temporal characteristics 2.81 18.7 47.1 

3. Provoking factors 2.13 14.2 61.3 

4. Associated symptoms 1.85 12.3 73.6 



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The four-factor structure of the questionnaire explains 
73.6% of the total variance, confirming the adequacy of 
the theoretical model. The high KMO value (0.84) 
indicates the suitability of the data for factor analysis. 

Convergent validity was confirmed by significant 
correlations with validated questionnaires: with DN4 
r=0.71 (p<0.001), with the "pain intensity" domain of 
BPI r=0.58 (p<0.001), and with the "physical 
functioning" domain of SF-36 r=–0.52 (p<0.001). 

Table 4. 

Comparative Diagnostic Characteristics of Questionnaires for Identifying Neuropathic Pain 

Parameter 
NEURO-RMZh (≥7 
points) 

DN4 (≥4 points) VAS (≥6 points) p-value* 

Sensitivity, % (95% CI) 89.7 (82.1–94.8) 76.9 (67.2–84.7) 84.6 (76.8–90.5) 0.042 

Specificity, % (95% CI) 82.4 (74.6–88.5) 71.2 (62.1–79.1) 45.2 (36.4–54.3) 0.049 

PPV, % (95% CI) 85.4 (77.9–91.1) 71.4 (62.8–78.9) 58.9 (51.2–66.3) 0.021 

NPV, % (95% CI) 87.7 (80.5–92.8) 76.8 (68.4–83.8) 75.8 (64.7–84.8) 0.038 

LR+ 5.10 (3.42–7.61) 2.67 (1.89–3.77) 1.54 (1.21–1.97) <0.001 

LR– 0.13 (0.07–0.22) 0.32 (0.21–0.48) 0.34 (0.21–0.55) 0.003 

AUC (95% CI) 0.92 (0.87–0.96) 0.79 (0.72–0.86) 0.68 (0.59–0.76) 0.004** 

p-value for comparison of NEURO-RMZh vs DN4 (McNemar’s test for sensitivity/specificity); 
** p-value for AUC comparison (DeLong's Z-test). 
PPV: positive predictive value; NPV: negative predictive value; LR+: positive likelihood ratio; LR–: negative 
likelihood ratio. 

Sensitivity and Specificity: 

• NEURO-RMZh (≥7 points): sensitivity 
89.7% (95% CI: 82.1–94.8%), specificity 82.4% (95% CI: 
74.6–88.5%) 

• DN4 (≥4 points): sensitivity 76.9% (95% 
CI: 67.2–84.7%), specificity 71.2% (95% CI: 62.1–79.1%) 

• VAS (≥6 points): sensitivity 84.6% (95% 
CI: 76.8–90.5%), specificity 45.2% (95% CI: 36.4–54.3%) 

Differences in sensitivity and specificity 
between NEURO-RMZh and DN4 are statistically 
significant (χ²=4.12, p=0.042 for sensitivity; χ²=3.89, 
p=0.049 for specificity). 

Predictive Value: 

• Positive predictive value (PPV): 
NEURO-RMZh – 85.4% (95% CI: 77.9–91.1%), DN4 – 
71.4% (95% CI: 62.8–78.9%) 

• Negative predictive value (NPV): 
NEURO-RMZh – 87.7% (95% CI: 80.5–92.8%), DN4 – 
76.8% (95% CI: 68.4–83.8%) 

Likelihood Ratios: 

• LR+ for NEURO-RMZh: 5.10 (95% CI: 
3.42–7.61) 

• LR+ for DN4: 2.67 (95% CI: 1.89–3.77) 

• LR– for NEURO-RMZh: 0.13 (95% CI: 
0.07–0.22) 

The NEURO-RMZh questionnaire demonstrates 
statistically significantly higher diagnostic performance 
compared to DN4 and VAS. Especially important are the 
high LR+ (5.10) and low LR– (0.13), indicating clinically 
meaningful diagnostic value. 

Table 5. Mean Total Questionnaire Scores by Pain Type 

Pain Type NEURO-RMZh (M±SD) DN4 (M±SD) VAS (M±SD) BPI Intensity (M±SD) 

Nociceptive (n=48) 3.2 ± 1.8ᵃ 1.9 ± 1.2ᵃ 5.8 ± 1.9 5.4 ± 1.7 

Neuropathic (n=39) 9.1 ± 1.6ᵇ 5.8 ± 1.4ᵇ 6.8 ± 1.6 6.9 ± 1.8 

Mixed (n=25) 6.8 ± 2.1ᶜ 4.1 ± 1.7ᶜ 6.2 ± 2.1 6.1 ± 2.0 

F-statistic (p) 142.8 (<0.001) 89.4 (<0.001) 3.2 (0.045) 8.7 (<0.001) 

Different letter indices indicate statistically significant differences between groups (Tukey post hoc test, p<0.05). 



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The NEURO-RMZh questionnaire shows the strongest 
discriminative ability between pain types (F=142.8), 

significantly exceeding DN4 (F=89.4). The clear 
separation of mean values among groups confirms the 
instrument’s ability to differentiate pain syndromes. 

Table 6. 

Results of Multiple Logistic Regression for Predictors of Neuropathic Pain 

Predictor OR 95% CI p-value 

NEURO-RMZh ≥7 points 12.4 4.8–32.1 <0.001 

Taxane chemotherapy 3.2 1.4–7.3 0.006 

Bone metastases 2.1 1.1–4.2 0.031 

Age >60 years 1.8 0.9–3.6 0.089 

Prior radiotherapy 1.4 0.7–2.8 0.342 

A NEURO-RMZh score ≥7 is the strongest independent predictor of neuropathic pain (OR=12.4), confirming its 
high diagnostic value in clinical practice. 

Table 7. 

Correlations of the NEURO-RMZh Total Score with SF-36 Quality of Life Domains 

SF-36 Domain Pearson’s r 95% CI p-value 

Physical functioning –0.68 –0.77 to –0.56 <0.001 

Role-physical functioning –0.61 –0.72 to –0.47 <0.001 

Bodily pain –0.74 –0.82 to –0.64 <0.001 

General health –0.52 –0.65 to –0.36 <0.001 

Vitality –0.58 –0.70 to –0.43 <0.001 

Social functioning –0.55 –0.67 to –0.40 <0.001 

Role-emotional functioning –0.49 –0.63 to –0.33 <0.001 

Mental health –0.44 –0.59 to –0.27 <0.001 

Here is your translated section (Results, Discussion, and 
Conclusion) in scientific, fluent English suitable for 
publication: 

Strong negative correlations were found between the 
severity of neuropathic pain and all quality of life 
domains. The strongest association was observed with 
the "bodily pain" domain (r = –0.74), further supporting 
the construct validity of the questionnaire. 

The presented tables and their interpretation 
demonstrate the comprehensive validation of the 
NEURO-RMZh questionnaire and its superiority over 
existing tools in the diagnosis of neuropathic pain in 
patients with metastatic breast cancer. 

DISCUSSION 

This study presents the first comprehensive validation 
of the specialized NEURO-RMZh questionnaire for the 
diagnosis of neuropathic pain in patients with 

metastatic breast cancer. The obtained results 
demonstrate excellent psychometric properties of the 
new instrument and its significant advantages over 
existing questionnaires in this specific population. 

The internal consistency of the NEURO-RMZh 
questionnaire (Cronbach's α = 0.89) exceeds the 
recommended threshold of 0.70 for clinical 
instruments [1] and is comparable to the best 
indicators of validated pain questionnaires. The 
intraclass correlation coefficient (ICC = 0.94) indicates 
excellent temporal stability, which is critical for 
monitoring pain dynamics. These indicators surpass 
those found for DN4 in our study (α = 0.76, ICC = 0.87) 
and are consistent with results from large international 
validation studies [2,3]. 

The four-factor structure of the questionnaire, 
explaining 73.6% of the total variance, confirms the 
theoretical rationale for the included domains. The 



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American Journal of Applied Science and Technology (ISSN: 2771-2745) 
 

 

identified factors—"qualitative pain characteristics," 
"temporal characteristics," "provoking factors," and 
"associated symptoms"—align with current concepts 
of the multidimensional nature of neuropathic pain [4]. 
The KMO value of 0.84 demonstrates the high 
suitability of the data for factor analysis, confirming 
both the adequacy of the sample size and the quality of 
the data collected. 

The most significant result of the study is the 
demonstration of the superior diagnostic 
characteristics of the NEURO-RMZh compared to the 
widely used DN4. Sensitivity (89.7%) and specificity 
(82.4%) are substantially higher than those of DN4 in 
our sample (76.9% and 71.2%, respectively) and are 
comparable to the best results obtained for DN4 in 
other populations [5,6]. 

Particularly important are the likelihood ratios: LR+ = 
5.10 and LR– = 0.13. According to evidence-based 
medicine criteria, LR+ > 5 and LR– < 0.2 indicate 
clinically significant diagnostic value [7]. These values 
significantly surpass those of DN4 (LR+ = 2.67, LR– = 
0.32), indicating that a positive NEURO-RMZh result 
increases the probability of neuropathic pain fivefold, 
while a negative result reduces this probability by 7.7 
times. 

A fundamental advantage of the NEURO-RMZh is its 
specific adaptation to the features of pain syndrome in 
metastatic breast cancer. Unlike universal tools such as 
DN4, the new questionnaire considers specific 
mechanisms of neuropathic pain in this population, 
including chemotherapy-induced peripheral 
neuropathy, compression syndromes in bone 
metastases, and post-mastectomy pain syndrome 
[10,11]. 

The results of multiple logistic regression confirm the 
clinical relevance of the questionnaire: a score ≥7 is the 
strongest independent predictor of neuropathic pain 
(OR = 12.4), outweighing even established risk factors 
such as prior taxane therapy (OR = 3.2). This suggests 
that the questionnaire captures not only obvious cases 
of neuropathic pain but also more complex clinical 
scenarios. 

It is especially important that the high diagnostic 
performance is maintained across all studied 
subgroups. The stability of the results in patients of 
different ages, metastatic sites, and prior therapies 
demonstrates the questionnaire's universal 
applicability in the heterogeneous population of 
metastatic breast cancer patients. 

Strong correlations between the NEURO-RMZh score 
and SF-36 quality of life domains (r from –0.44 to –0.74) 
further support the construct validity and clinical 
relevance of the tool. The strongest association with 

"bodily pain" (r = –0.74) is expected and confirms that 
the questionnaire accurately measures pain 
perception. Significant correlations with other 
domains, including mental health and social 
functioning, reflect the multidimensional impact of 
neuropathic pain on patients’ lives [12]. 

These results are consistent with data from Gärtner et 
al., who showed that neuropathic pain in breast cancer 
patients is associated with a more pronounced 
reduction in quality of life compared to nociceptive 
pain [13]. The ability of the NEURO-RMZh to identify 
these differences confirms its potential value for 
patient stratification and personalized therapeutic 
approaches. 

Direct comparison with DN4 in our study showed that 
the NEURO-RMZh outperforms DN4 in all key 
parameters. The sensitivity of DN4 in our sample 
(76.9%) was lower than that reported in the original 
study by Bouhassira et al. (82.9%) [15], which may be 
due to the specific features of the oncology population. 
Similar findings were observed by Pérez et al., who 
reported reduced diagnostic accuracy of DN4 in cancer 
patients [16]. 

The use of the visual analogue scale (VAS) alone for 
pain assessment showed unsatisfactory results 
(sensitivity 84.6%, specificity 45.2%), confirming the 
need for specialized tools for the differential diagnosis 
of pain types. These findings align with international 
expert recommendations highlighting the inadequacy 
of assessing only pain intensity for optimal pain 
management [17]. 

This study has several limitations that should be 
considered when interpreting the results. First, it was 
conducted in a single center, which may limit external 
validity. Differences in clinical practice, population 
characteristics, and treatment approaches in other 
centers may affect the diagnostic performance of the 
questionnaire. 

Second, the relatively small sample size (n=111) may 
limit the statistical power for subgroup analyses. 
Although the sample size meets recommendations for 
validation studies of diagnostic instruments [18], larger 
studies are needed to confirm the stability of these 
findings. 

Third, the use of clinical assessment as the "gold 
standard," despite the involvement of two 
independent experts, introduces some subjectivity. 
The absence of objective biomarkers for neuropathic 
pain remains a fundamental challenge in this field [19]. 

Fourth, the cross-sectional design does not allow for 
assessment of the tool's ability to detect changes in 
pain characteristics over time. Longitudinal studies are 
required to assess responsiveness and prognostic 



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American Journal of Applied Science and Technology (ISSN: 2771-2745) 
 

 

value. 

Clinical implications: These findings have important 
clinical implications for palliative oncology. Accurate 
diagnosis of pain type is critical for selecting optimal 
therapeutic strategies, as neuropathic pain requires 
specific treatment approaches [20]. The NEURO-RMZh 
can facilitate earlier detection of neuropathic pain and 
timely administration of appropriate therapy. 

Integration of the questionnaire into routine clinical 
practice may improve the quality of palliative care and 
treatment outcomes. Its simplicity and high diagnostic 
accuracy make it suitable for both specialized centers 
and primary healthcare settings. 

Future research should include multicenter validation 
studies, assessment of responsiveness in longitudinal 
studies, and investigation of the impact of using the 
questionnaire on clinical outcomes and cost-
effectiveness. Promising directions include adaptation 
for other oncological diseases and development of 
digital versions for integration into electronic medical 
records. 

CONCLUSION 

This study presents the first comprehensive validation 
of the specialized NEURO-RMZh questionnaire for the 
diagnosis of neuropathic pain in patients with 
metastatic breast cancer. The results demonstrate 
excellent psychometric characteristics and significant 
advantages over existing diagnostic methods in this 
specific population. 

The NEURO-RMZh questionnaire showed excellent 
internal consistency (Cronbach's α = 0.89) and high 
temporal stability (ICC = 0.94), confirming its reliability 
as a diagnostic tool. The four-factor structure, 
explaining 73.6% of total variance, aligns with modern 
understanding of the multidimensional nature of 
neuropathic pain and provides a solid theoretical basis 
for the included domains. 

The most significant achievements are the sensitivity of 
89.7%, specificity of 82.4%, and area under the ROC 
curve of 0.92. These indicators substantially surpass 
those of the widely used DN4 in the study population 
(sensitivity 76.9%, specificity 71.2%, AUC = 0.79) and 
indicate the high clinical value of the new tool. The 
likelihood ratios (LR+ = 5.10, LR– = 0.13) meet criteria 
for clinically significant diagnostic tests. 

A key advantage of the NEURO-RMZh is its specific 
adaptation to the features of pain syndrome in 
metastatic breast cancer, including chemotherapy-
induced peripheral neuropathy, compression 
syndromes in bone metastases, and post-mastectomy 
pain syndrome. The stability of diagnostic 
characteristics across all subgroups confirms its 

universal applicability in a heterogeneous population. 

The high practical utility of the questionnaire is ensured 
by a short completion time (4.2 ± 1.1 minutes), the 
possibility of self-administration by patients, and high 
acceptability. Strong correlations with SF-36 quality of 
life domains confirm construct validity and the tool’s 
ability to reflect the multidimensional impact of 
neuropathic pain on patients’ functional status. 

The clinical value of the NEURO-RMZh questionnaire 
lies in its ability to enable more accurate and timely 
diagnosis of neuropathic pain, which is critically 
important for optimal therapeutic strategies in 
palliative oncology. Integration of the questionnaire 
into routine clinical practice may improve the quality of 
palliative care, optimize pharmacotherapy for pain, and 
ultimately enhance quality of life for patients with 
metastatic breast cancer. 

Further research should include multicenter validation 
to confirm external validity, longitudinal studies to 
assess responsiveness, and evaluation of the impact of 
the questionnaire on clinical outcomes and cost-
effectiveness. Promising directions include adapting 
the approach for other oncological diseases and 
developing digital versions for integration into 
electronic health systems. 

In summary, the NEURO-RMZh questionnaire is a valid, 
reliable, and practical tool that may become an 
important addition to the diagnostic and monitoring 
toolkit for pain syndrome in palliative oncology, 
contributing to personalized therapeutic approaches 
and improved quality of life for oncology patients. 

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