Abstract
Background
Patients with lower extremity wounds often experience neuropathic pain; however, there is no validated assessment tool to specifically measure wound‐related neuropathic pain. The study aimed to assess the prevalence of neuropathic pain in lower extremity wounds using different assessment tools and to identify factors associated with neuropathic pain.
Methods
A cross‐sectional study of 130 patients with lower extremity wounds of different etiologies assessed neuropathic pain through clinical examinations, the Short Form McGill Pain Questionnaire‐2 (SF‐MPQ‐2), and the Douleur Neuropathique 4 Questions (DN4). Pain intensity was measured using the Visual Analog Scale (VAS).
Results
In total, 38 (29%) experienced neuropathic pain (DN4 score ≥ 4), and 75% (n = 97) described pain using one or more neuropathic pain descriptors on the SF‐MPQ‐2. The frequently reported descriptors on the neuropathic sub‐scale were “pain caused by light touch” (59%) and “tingling or pins and needles” (49%). There was a positive correlation between DN4 and the neuropathic sub‐scale of SF‐MPQ‐2, and the major difference between the tools is the design and time consumption. Univariate analysis revealed that younger age, arterial wound type, infection, and morphine consumption were associated with neuropathic pain (DN4 score ≥ 4). In multivariate analysis, arterial wound type increased the risk of neuropathic pain five‐fold. Younger age and morphine consumption were also significantly associated with neuropathic pain, whereas infection was not.
Conclusion
Neuropathic wound pain is frequent, and the prevalence relies on the applied assessment tool. Arterial wound type, younger age, and morphine consumption are associated with neuropathic wound pain.
Keywords: lower extremity wound, neuropathic wound pain, pain assessment tool
Key message.
This cross‐sectional study explores the prevalence of neuropathic pain in lower extremity wounds with different etiologies and factors associated with pain. Study results confirm that neuropathic pain is common, and the prevalence depends on the assessment tool. Arterial wounds, younger age, and morphine consumption are associated with neuropathic wound pain.
INTRODUCTION
Lower extremity wounds are a rising condition among adults. 1 A chronic lower extremity wound is estimated to affect approximately 1.5 percent of the general population worldwide. 2 Many patients consider pain as the most significant concern associated with their wounds rather than healing. 3 The presence of pain in wound healing and wound care is frequently encountered yet often overlooked. 4 Healthcare professionals tend to focus on the assessment of the wound rather than the pain experienced by the patient. 5 A possible explanation for this behavior is uncertainty about assessing pain and strategies used for effective pain management. 6 Undertreatment of wound pain affects the patient's physical function, impairs psychological well‐being, and interferes with social interactions. 7 Furthermore, wound pain can have a negative impact on wound healing. 6 , 8
Wound‐related pain is complex, including acute and chronic pain. Wound pain can be nociceptive due to tissue damage/inflammation, or neuropathic due to lesions or diseases of the nervous system itself. 9 Neuropathic pain arises from abnormal processing of nerve pain signals, and the pain is often described as shooting, burning, or tingling. 10 Patients with neuropathic wound pain are at risk of developing central sensitization due to the prolonged pain signals from the wound site. 11 The continuous input of pain signals can result in an abnormal response of the nerves, resulting in hyperalgesia (increased sensitivity to pain) and allodynia (non‐painful stimuli are interpreted as painful). 12
Pain experience is characterized by individual variability known to be multidimensional and experienced uniquely by individuals. 13 Therefore, various measurements and questionnaires are used to evaluate pain as objectively as possible. 14 Over the past decades, focus on wound pain management has increased; however, there are challenges in assessing wound pain since different pain assessment tools are recommended, and these tools have been designed and tested on other pain conditions than wound pain. 14
This study aimed to assess the prevalence of neuropathic pain in lower extremity wounds using different pain assessment tools and to evaluate the applicability of these questionnaires among patients with lower extremity wounds. A further aim was to identify factors associated with neuropathic pain.
METHODS
Study design and population
The study is a cross‐sectional single‐center study conducted at the Wound Healing Center outpatient clinic at Bispebjerg Hospital, Copenhagen, Denmark, between May 2020 and July 2022. The clinic is a tertiary referral center for approximately 2.5 million people in the Capital Region of Denmark. Inclusion criteria were as follows: new open wound located on the thigh, leg, or foot, and age 18 years or older. Exclusion criteria were cognitive impairment and inability to understand and read Danish.
The patient population has been described in detail elsewhere. 15 To explore neuropathic pain, we used an additional questionnaire and performed additional clinical tests. The data presented in the current manuscript have not been published previously.
Data collection and clinical assessment
Routine clinical examination and wound assessment were performed by a physician (wound specialist) where the wound diagnosis was made (arterial, venous, diabetic, traumatic, immunological, unspecified wound). The first author (LS) conducted all clinical wound examinations (infection signs, necrosis, and visible structure in the wound) and collected data on wound characteristics and completed the questionnaires with the participants during the visit. Wound size was measured with a ruler as length and width. Peripheral neuropathy was examined with Bailey Duraban monofilament (U.K) 10 g. The monofilament was applied on the first, third, and fifth metatarsal heads and plantar surface of the distal hallux. Loss of sensation on one site indicates a sign of peripheral neuropathy. 16
To explore the prevalence of central sensitization, we examined for allodynia by lightly brushing a piece of cotton wool over the skin 1 cm from the wound edge and asked the patients if it caused pain. Hyperalgesia was assessed with Bailey Duraban monofilament (U.K) 75 g at 1 cm from the wound edge, and the patients were asked if they experienced pain. Temporal summation was evaluated at 1 cm from the wound edge with Bailey Duraban monofilament (U.K) 75 g, which was repeatedly applied to the skin (10 times at 1‐s intervals), and patients were asked if it caused increased pain. Afterward, we tested for aftersensation, which is a sensation that persists (for 1–5 s) after the stimulus has ended.
Pain questionnaires
Patients with more than one wound were asked to select the wound with the worst pain when answering questions regarding pain and were specifically asked to keep in mind their wound‐related pain.
Douleur Neuropathique 4 Questions (DN4)
To estimate the prevalence of neuropathic pain, we used a validated, translated Danish version of the Douleur Neuropathique 4 Questions (DN4). The DN4 questionnaire has a high sensitivity for detecting neuropathic pain, ranging from 82% to 95%, and a high specificity, ranging from 78% to 97%. 17 The DN4 consists of a seven‐item interview and a three‐item physical examination, with a score range of 0–10. The interview includes questions about pain characteristics (burning, painful cold, electric shocks, tingling, pins and needles sensation, numbness, and itchiness), while the physical examination tests sensitivity to touch, pin‐prick, and brush in an area of 1 cm around the wound. Total scores ≥4/10 indicate neuropathic pain, while the seven‐item interview format (DN4‐interview) indicates neuropathic pain with scores ≥3/7. 18
Short Form McGill Pain Questionnaire‐2 (SF‐MPQ‐2)
The Danish version of the Short Form McGill Pain Questionnaire‐2 (SF‐MPQ‐2) was used to assess the type of wound pain, particularly the frequency of neuropathic pain. The SF‐MPQ‐2 demonstrates high reliability and validity in measuring both neuropathic and non‐neuropathic pain. 19 The questionnaire consists of 22 pain descriptors and four sub‐scales. It includes six continuous pain descriptors, six intermittent pain descriptors, six neuropathic pain descriptors, and four affective descriptors. Each item is rated based on a 0–10 scale where 0 is no pain and 10 is the worst imaginable pain during the past week. The four sub‐scale scores are calculated by summing the numerical values of each item, and the total score (220) represents the sum of values for all 22 items. Higher sub‐scale scores or total scores suggest greater pain symptoms. 19
Visual analog scale (VAS)
The overall pain intensity was measured on a 100 mm visual analog scale (VAS). The left end of the line is labeled “No pain” (0 mm), and the right end is labeled “Worst imaginable pain” (100 mm). The patients were asked to score their average pain for 1 week preceding the study, at rest and during ambulation, by drawing a vertical line. The Visual Analog Scale (VAS) is widely used in both epidemiological and clinical research as a measure of pain intensity, demonstrating high reliability and consistency. 20
Statistical analysis
All descriptive and statistical analyses were performed using SPSS Statistics (version 29.0.1.0 IBM, USA). The figures were created in GraphPad Prism software (Version 9.4.1, San Diego, CA). Continuous data were presented as the median with quartiles, and categorical data as numbers with percentages. Kruskal–Wallis and Mann–Whitney tests were used for comparisons of the prevalence of neuropathic pain in different wound types and VAS between patients with higher/lower DN4 scores. Spearman's correlation coefficient (r) was used to analyze the correlation between the neuropathic sub‐scale of the SF‐MPQ‐2 questionnaire, the DN4 questionnaire, and VAS. To identify factors associated with DN4 scores ≥4, logistic regression analyses were performed. Variables considered for inclusion in the model were factors that had an association with neuropathic pain in previous studies. Univariable and multivariable regression analyses were performed, and the results were presented as odds ratios (ORs) with 95% confidence intervals (CIs) and p‐values. Due to the limited sample size (38 patients with DN4 scores ≥4), we included no more than seven factors in the model. The included variables were sex (male versus female), age (per year), wound diagnosis (arterial, venous, and immunological, respectively, versus all others), neuropathy, infection, hyperalgesia, and morphine consumption. Non‐parametric tests were chosen as data were shown not to be normally distributed. All tests were considered statistically significant at a p < 0.05.
Ethical considerations
Informed consent was obtained from all participants before inclusion. Observational studies require no scientific ethics approval in Denmark. The study was approved by the Capital Region Knowledge Center for Data reviews (number: P‐2020‐161).
RESULTS
Patient characteristics
A total of 130 patients were included in this study. The sample consisted of almost equal parts of men and women. The mean age was 70 years (SD ± 11.4). Hypertension was the most frequent comorbidity, followed by cardiovascular disease, dyslipidemia, and diabetes (Table 1).
TABLE 1.
Demographic and clinical data (N = 130).
| N (%) | |
|---|---|
| Age | |
| <49 | 8 (6) |
| 50–59 | 16 (12) |
| 60–69 | 33 (25) |
| 70–79 | 50 (39) |
| 80–89 | 21 (16) |
| >90 | 2 (2) |
| Sex | |
| Male | 70 (54) |
| Female | 60 (46) |
| Comorbidity | |
| Hypertension | 81 (62) |
| Cardiovascular disease | 53 (41) |
| Dyslipidemia | 50 (39) |
| Diabetes | 44 (34) |
| Autoimmune disease | 33 (25) |
| Chronic obstructive pulmonary disease | 22 (17) |
| Depression | 4 (3) |
| Peripheral neuropathy | 62 (48) |
| Allodynia | 27 (21) |
| Hyperalgesia | 49 (38) |
| Temporal summation | 38 (29) |
| Aftersensation | 23 (18) |
| Wound duration | |
| <4 weeks | 20 (15) |
| >4 weeks | 110 (85) |
| Wound diagnosis | |
| Venous | 34 (26) |
| Arterial | 23 (18) |
| Diabetic | 11 (9) |
| Pressure | 21 (16) |
| Immunological | 7 (5) |
| Traumatic | 20 (15) |
| Unspecified | 14 (11) |
Note: Autoimmune disease: Rheumatoid arthritis, psoriasis, vasculitis, scleroderma, and thyroid disease.
Wound characteristics
Wound types were venous (26%), arterial (18%), pressure (16%), traumatic (15%), diabetic foot ulcer (9%), immunological (5%), and 11% were of mixed/unknown etiology (Table 1). Half (54%) of the patients were suffering from wounds in the lower legs, 45% on the feet, and only 1% had a wound on the thigh. Most of the patients (110) had wounds for more than 4 weeks (85%) at the point of the initial clinic visit. We performed a sensitivity analysis excluding the 20 patients with an ulcer duration <4 weeks and found that demographic and clinical characteristics such as age, sex, pain, and comorbidities were similar between patients with ulcer durations <4 weeks and >4 weeks, respectively. We therefore chose to include the entire sample of 130 patients in all further analyses.
Prevalence of neuropathic pain
Of the 130 patients, 38 (29%) had a DN4 score ≥4/10 and 33 (25%) had a DN4 score ≥3/7 (interview items), indicating the presence of neuropathic pain. On the neuropathic sub‐scale of SF‐MPQ‐2, 97 of the patients (75%) described their pain by choosing one or more of the neuropathic pain descriptors (Figure 1, Tables S1 and S2). As shown in Figure 2, patients with arterial wounds had a statistically significantly (p < 0.05) higher neuropathic pain score on the DN4 questionnaire compared with other wounds, except immunological wounds (p = 0.195). The neuropathic sub‐scale of SF‐MPQ‐2 was significantly higher for patients diagnosed with arterial, immunological, traumatic, venous, and pressure wounds compared to patients with diabetic wounds (p < 0.05). There was a positive correlation between the neuropathic sub‐scale of SF‐MPQ‐2 and DN4 (r = 0.68; p < 0.001, 95% CI 0.57 to 0.76).
FIGURE 1.
Prevalence of neuropathic pain and pain management in different wound etiologies (N = 130).
FIGURE 2.
Comparison of neuropathic pain scores in different pain scales (N = 130, median (IQR)).
Pain intensity
The median pain score on VAS was 50 mm (IQR 17.5–70.3 mm) at rest and 57 mm (IQR 27.5–83.5 mm) during ambulation in patients with a DN4 score >4. The median total score of SF‐MPQ‐2 was 28 (IQR 3–65) and 8 (IQR 0–18) on the neuropathic sub‐scale of SF‐MPQ‐2. As shown in Figure 3, patients with a DN4 score ≥4 had a significantly higher VAS score at rest and during ambulation compared to patients with DN4 scores <4 (p < 0.001).
FIGURE 3.
Comparison of pain intensity (VAS) between patients using DN4 score (N = 130, median (IQR)).
There was a positive correlation between the neuropathic sub‐scale of SF‐MPQ‐2 and VAS at rest (r = 0.64; p < 0.001, 95% CI 0.52 to 0.74) and during ambulation (r = 0.59; p < 0.001, 95% CI 0.47–0.70). DN4 score was also positively correlated with VAS at rest (r = 0.42; p < 0.001, 95% CI 0.27 to 0.56) and VAS during ambulation (r = 0.50; p < 0.001, 95% CI 0.36–0.62).
The VAS results for each wound type have been published previously. 21
Neuropathy and central sensitization
Forty‐eight percent of the patients had signs of peripheral neuropathy, 21% had allodynia, and 38% had hyperalgesia. Approximately one‐third of the patients (29%) had signs of temporal summation, and 18% experienced aftersensation. There was a negative correlation between peripheral neuropathy and allodynia (r = −0.03) and hyperalgesia (r = −0.25), but this correlation was statistically significant only between peripheral neuropathy and hyperalgesia (p = 0.004, 95% CI −0.41 to −0.08).
Analgesic medication
In total, 38% of the patients were in treatment with opioids (eg, morphine, oxycodone), 16% with anticonvulsants (eg, gabapentin, pregabalin), 71% with paracetamol, and 19% with nonsteroidal anti‐inflammatory drugs (eg, ibuprofen). It was not specified whether analgesic medication was prescribed for wound‐related pain.
Out of the patients with DN4 ≥ 4 (38), 16% were in treatment with anticonvulsants, whereas 53% were in treatment with opioids.
As shown in Figure 1, a higher percentage of patients with pressure wounds were treated with anticonvulsants compared with other wound types. The difference was significant when compared to arterial, venous, and traumatic wounds, respectively (p < 0.05).
Factors associated with DN4 score ≥4
In univariate analyses, age, wound type, infection, and morphine consumption were significantly associated with the presence of neuropathic pain (DN4 score ≥ 4), as shown in Table 2. However, in multivariable analyses, infection was not significantly associated with neuropathic pain, but younger age (OR per year 0.96, 95% CI 0.92–0.99), as well as morphine consumption (OR 2.96, 95% CI 1.20–6.61). Patients with arterial wounds were five times more likely to have neuropathic wound pain compared with other wound diagnoses (OR 5.2, 95% CI 1.68–19.8) (Table 2).
TABLE 2.
Logistic regression models of factors associated with DN4 ≥ 4 (N = 130).
| Univariate analysis | Multivariate analysis | ||||
|---|---|---|---|---|---|
| Factors | No. (%) | OR (95% CI) | p‐Value | OR (95% CI) | p‐Value |
| Female sex a | 60 (64) | 1.07 (0.50–2.29) | 0.858 | 0.97 (0.41–2.39) | 0.974 |
| Age (year) | 0.96 (0.93–0.99) | 0.027 | 0.96 (0.92–0.99) | 0.027 | |
| Wound type b | |||||
| Arterial | 23 (18) | 4.1 (1.49–11.0) | 0.006 | 5.2 (1.68–16.4) | 0.004 |
| Venous | 34 (26) | 0.81 (0.25–1.98) | 0.681 | 1.23 (0.41–3.72) | 0.712 |
| Immunological | 7 (5) | 1.25 (0.22–7.01) | 0.801 | 0.73 (0.10–5.22) | 0.755 |
| Neuropathy | 62 (48) | 0.98 (0.46–2.10) | 0.962 | 1.21 (0.48–3.08) | 0.683 |
| Infection | 13 (10) | 3.24 (1.01–10.4) | 0.048 | 3.59 (0.91–14.2) | 0.069 |
| Hyperalgesia | 49 (38) | 1.86 (0.86–4.0) | 0.115 | 2.30 (0.91–5.81) | 0.077 |
| Morphine | 49 (38) | 2.41 (1.11–5.2) | 0.026 | 2.69 (1.10–6.61) | 0.030 |
Male sex served as the reference group.
All other wound types combined (other and unspecified) served as the reference group.
DISCUSSION
This study showed that neuropathic pain is frequently present in various wound types, and the estimated prevalence depends on the used assessment tool.
In the present study, one‐third of patients had a positive neuropathic pain score on the DN4 questionnaire (DN4 score ≥ 4), and approximately three‐quarters of the patients chose one or more of the neuropathic pain descriptors on the neuropathic sub‐scale of SF‐MPQ‐2. However, only 16% of patients with a DN4 score ≥ 4 were in treatment with anticonvulsants, whereas 53% were treated with opioids. A possible explanation can be uncertainty or lack of knowledge about the treatment of neuropathic pain among healthcare professionals. The study population was often referred from primary care, where the knowledge and experience in treating neuropathic pain with anticonvulsants, which is the first‐line treatment, can be inadequate. 22 Other reasons can be a lack of effect, which may lead to a lack of compliance or fear of side effects and addiction. Our results revealed that patients with lower extremity wounds can develop central sensitization, which is associated with neuropathic pain symptoms. 23 It is essential to manage central sensitization symptoms, but the goal is to prevent central sensitization by early pain management.
The study confirmed previous findings that ischemic wounds are painful, and a high percentage of the patients experience neuropathic pain. 24 Furthermore, our results showed that patients suffering from venous and immunological wounds often experience neuropathic pain as well. Therefore, it is important for healthcare professionals to remember that neuropathic wound pain is frequent regardless of the wound etiology.
Undertreatment of wound pain is still an important issue that needs to be addressed. The first step in wound pain management is to acknowledge that all types of wounds can be painful. It is important for healthcare professionals to distinguish between neuropathic and nociceptive pain when evaluating and managing the patient's symptoms. Therefore, there is a need for a brief and easy pain assessment tool that can differentiate between the types of pain, allowing for more targeted and effective pain management strategies. The assessment of neuropathic pain is mostly based on questionnaires. 25 Several specific questionnaires have been developed for the assessment of neuropathic pain in general, but there is no validated neuropathic pain assessment tool for patients with lower extremity wounds. 14 Studies have already revealed that neuropathic pain is common in leg wounds; however, neuropathic pain goes unrecognized by healthcare professionals, with the consequent delay in appropriate treatments. 24 , 26
In this study, we used two validated neuropathic pain questionnaires to assess their ability and usability in diagnosing neuropathic wound pain. There was a substantial positive correlation between the neuropathic sub‐scale of SF‐MPQ‐2 and DN4, but it is difficult to compare the two questionnaires. Both questionnaires have high sensitivity and specificity in diagnosing neuropathic pain. 25 , 27 SF‐MPQ‐2 assesses both neuropathic and non‐neuropathic pain and the intensity of pain solely by interviewing the patient, whereas DN4 diagnoses the presence of neuropathic pain through patient interview as well as clinical examination. Both questionnaires are useful tools for screening for neuropathic wound pain; however, DN4 is brief with defined a cut‐off score which makes it more useful in a busy clinical setting. The SF‐MPQ‐2 is time‐consuming but is beneficial in specifying the type and intensity of wound pain.
A novel aspect of the present study is the comparison of pain intensity between patients with high and low neuropathic pain scores and exploration of factors associated with a high neuropathic pain score. Our results showed that patients with neuropathic pain (DN4 score ≥ 4) have a significantly higher VAS score than patients with DN4 score < 4. Factors associated with neuropathic pain were younger age, arterial wounds, opioid consumption, and infection. These findings highlight the importance of characterizing the type of wound pain specifically in patients with high VAS scores and/or when pain requires treatment with potent analgesics.
Previous studies have shown that older people experience wound pain more frequently than younger people; however, they manage pain better than younger people due to a higher pain threshold and lower pain sensitivity. 28 , 29 Our results support these findings as multivariate analysis showed that younger age was significantly associated with neuropathic pain (DN4 score ≥ 4). Another possible explanation is that younger people are better at expressing and describing their pain than older people. By contrast, we did not find an association between neuropathic pain and patient sex.
To our knowledge, this is the first study that investigates the prevalence of neuropathic pain in lower extremity wounds of different etiologies by using different assessment tools that combine pain intensity, quality, and clinical assessment. Findings from the study are therefore clinically relevant for clinicians treating a variety of lower extremity wounds. However, our sample is probably not very representative of the general population with lower extremity wounds since we only recruited hospital outpatients, who often have complicated wounds. We included participants with a variety of wound diagnoses, and due to the small sample size in some of the subgroups, it is difficult to conclude for all wounds; however, the included patients represent the population attending specialized outpatient wound clinics.
In conclusion, neuropathic wound pain is frequent and undertreated due to diagnostic complexity and a lack of recommended assessment tools. Factors associated with neuropathic wound pain are ischemic wounds, young age, wound infection, and morphine consumption. Both DN4 and SF‐MPQ‐2 are useful tools for screening for neuropathic pain, but there is a need for a brief and validated assessment tool for neuropathic wound pain. Clinicians must understand the etiology of wound pain and ensure appropriate management of wound pain.
AUTHOR CONTRIBUTIONS
LS study design and data collection, analyzed the data, interpreted the data, and drafted the manuscript for intellectual content. FBM study design, analyzed the data, and revised the manuscript for intellectual content. CJM revised the manuscript for intellectual content. SFT statistical analysis, interpreted the data, and revised the manuscript for intellectual content. All authors approved the final manuscript.
FUNDING INFORMATION
This research received no external funding.
CONFLICT OF INTEREST STATEMENT
The authors have no conflicts of interest to declare that are relevant to the content of this article.
Supporting information
Data S1.
ACKNOWLEDGMENTS
We thank our colleague Dr. Ewa Anna Burian for input and advice.
Sabah L, Moltke FB, Moffatt CJ, Thomsen SF. Evaluation of neuropathic pain in lower extremity wounds using different assessment tools: A cross‐sectional study. Pain Pract. 2025;25:e70029. 10.1111/papr.70029
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available upon a reasonable request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data S1.
Data Availability Statement
The data that support the findings of this study are available upon a reasonable request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.