# Neuropathic Component Characteristics in Chronic Secondary Musculoskeletal Pain After Postmenopausal Osteoporotic Fractures: A Pilot Cross-Sectional Study

Marie-Eva Pickering, Serge Perrot, Dualé Christian, Véronique Morel, Nicolas Macian, Bruno Pereira

<figure><img src="image_1.png" /></figure>

## ► To cite this version:

Marie-Eva Pickering, Serge Perrot, Dualé Christian, Véronique Morel, Nicolas Macian, et al.. Neuro-pathic Component Characteristics in Chronic Secondary Musculoskeletal Pain After Postmenopausal Osteoporotic Fractures: A Pilot Cross-Sectional Study. Pain Research and Management, 2024, 2024, 10.1155/prm/9766698. [hal-05445246]

HAL Id: hal-05445246

https://hal.science/hal-05445246v1

Submitted on 6 Jan 2026

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

<figure><img src="image_2.png" /></figure>

Distributed under a Creative Commons CC BY 4.0 - Attribution - International License
Research Article

# Neuropathic Component Characteristics in Chronic Secondary Musculoskeletal Pain After Postmenopausal Osteoporotic Fractures: A Pilot Cross-Sectional Study

Marie-Eva Pickering<sup>1</sup>,<sup>1</sup> Serge Perrot,<sup>2</sup> Dualé Christian,<sup>3</sup> Véronique Morel,<sup>3</sup> Nicolas Macian,<sup>3</sup> and Bruno Pereira<sup>4</sup>

Correspondence should be addressed to Marie-Eva Pickering; mepickering@chu-clermontferrand.fr

Received 31 July 2024; Accepted 14 December 2024

Academic Editor: Massimiliano Valeriani

Copyright © 2024 Marie-Eva Pickering et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**Background:** The neuropathic characteristics of pain occurring after an osteoporosis (OP)-related fracture are often unrecognized. The aim of this pilot study is to identify, in patients suffering from pain localized on the site of a previous osteoporotic fracture, the presence of neuropathic characteristics, their medical management, and their impact on quality of life.

**Methods:** This pilot cross-sectional study on consecutive patients in University Hospital, Rheumatology Department, Clermont-Ferrand, France, was approved by the Ethics Committee (IRB number 2023-CF34). Pain was evaluated with the Numeric Pain Rating Scale (NPRS), Neuropathic Component of Chronic pain (NCCP) was screened with the DN4 questionnaire, and sleep was assessed with the Pittsburg questionnaire. Depression, anxiety, quality of life, and concomitant treatment were also evaluated. Results were expressed using effect sizes (ESs) and 95% confidence intervals.

**Results:** Fifty new patients with a history of at least one fully documented fragility vertebral fracture (VF) or nonvertebral fracture (NVF) due to osteoporosis, in the last 2 years minus the previous 6 months, were included. Findings show that 21% patients with VF and 28% patients with NVF reported NCCP (DN ≥ 4). NCCP patients had more intense pain (NPRS = 5.1 ± 2.9 vs. 2.9 ± 2.7, ES = 0.82 [0.18; 1.44], *p* = 0.019) and impaired sleep compared to patients without NCCP (ES = 0.71 [0.08; 1.33], *p* = 0.043). A remarkable point was that patients had no specific oral or topical treatment for NCCP and were only taking on demand paracetamol and nonsteroidal anti-inflammatory drugs.

**Conclusions:** Future research should focus on the neuropathic characteristics of pain patients with OP, in order to better manage OP-related pain.

**Keywords:** fracture; neuropathic pain; osteoporosis; treatment

## 1. Introduction

Osteoporosis (OP) affects up to 30% of postmenopausal women and is characterized by loss of bone mineral density, deterioration in bone microarchitecture, increased risk of fragility fracture, and morbidity [1, 2] When a fracture damages the neat fiber meshing of bone architecture, it also

disrupts the sensory nerve fibers at different levels of the bone structure, leading to pH changes and local acidosis, reinforced by the overactivity of osteoclasts and the release of algogenic products [3, 4]. A fracture usually healing over several weeks, but acute pain may become chronic with peripheral and central sensitization, involving an array of neurotransmitters, receptors (i.e., N-methyl-D-aspartate

<footnote n="1"><sup>1</sup>Rheumatology Department, CHU Gabriel Montpied, Clermont-Ferrand 63000, France</footnote>

<footnote n="2"><sup>2</sup>Pain Center, Cochin Hospital, INSERM U987, Paris Cité University, Paris, France</footnote>

<footnote n="3"><sup>3</sup>Clinical Investigation Center, PIC/CIC, University Hospital, CHU, Clermont-Ferrand, France</footnote>

<footnote n="4"><sup>4</sup>Biostatistics Unit DRCI, University Hospital, Clermont-Ferrand, France</footnote>
receptors (NMDARs)) [5], and cells (glial cells) and the
modulation of descending pain pathways [6]. Chronic pain
after osteoporotic vertebral fracture (OVF) is often re-
ported by the patient as “back pain” or “low back pain” that
may be invalidating, all the more since OP affects older
persons who also suffer from other comorbidities [7]. Low
back pain, with an estimated lifetime prevalence of 84% [8],
is a major cause of disability [9]. An under-recognized
neuropathic component in back pain in the general pop-
ulation has been underlined in the literature [10], and this
also applies to vertebral OP since axial low back pain is
traditionally presented as nociceptive [8, 11]. OP is often
considered to be a silent pathology until a fracture occurs,
but studies suggest that OP with and without fracture may
be a painful pathology. Using the Pain-Detect Question-
naire (PD-Q) and looking for pain symptoms, a study
revealed that without any vertebral fracture (VF), the
percentage of osteoporotic patients with nociceptive back
pain and neuropathic pain (NP) or mixed pain was 85% and
15%, respectively [12]. The presence of NP after an OVF
[13] is not well defined, and data on NP management in
osteoporotic fractures are still scarce. A recent Italian study
[14] showed in patients with OVFs a prevalence of neu-
ropathic components of chronic back pain ranging from
5.5% to 23.6%, according to the used tool, PD-Q and
LANSS, respectively. According to the ICD 11 definition
[15], the type of pain occurring with OP and osteoporotic
fractures refers to chronic secondary musculoskeletal pain,
and a neuropathic component may be present. The genesis
of the neuropathic component of chronic secondary
musculoskeletal pain (NCCP) is not clear yet. It may occur
with nociceptive and nociplastic pain following damage to
the bone, to nervous structures, and/or secondary to central
or peripheral sensitization phenomena.

Characterization of the NP component in OP is im-
portant to consider, as it is associated with a deleterious
impact on the quality of life and function. The aim of this
pilot study is therefore to identify in patients suffering from
pain localized on the site of osteoporotic fractures, vertebral
but also nonvertebral, the occurrence of a neuropathic
component, its medical management, and its impact on
quality of life.

## 2. Methods

2.1. *Participants.* We conducted a pilot cross-sectional study, according to the STROBE checklist criteria [16]. The study was approved on March 6, 2023, by the Ethics Committee (IRB00013412, “CHU de Clermont-Ferrand IRB 1,” IRB number 2023-CF34) with compliance to the French policy of individual data protection. New patients referred to the Rheumatology Department by their General Practitioner were consecutively recruited for the management of their OP. They were informed about the study and provided informed consent to the processing of personal data. Inclusion criteria were a history of at least one vertebral or nonvertebral osteoporotic fracture confirmed by imaging over the last 2 years, but at least 6 months before inclusion. Exclusion criteria were acute pathology, acute back pain, and

any other cause of back pain including chronic widespread
pain or fibromyalgia.

2.2. *Tests and Questionnaires.* VFs were identified by con-
ventional radiographs, morphometry analysis, and dual-
energy X-ray absorptiometry (DXA). All patients had OP
and attended the clinic for specific management of OP.

Pain was evaluated with the Numeric Pain Rating Scale (NPRS). This scale is an 11-point scale for patient self-reporting of pain. Patients verbally rated the intensity of their average and worst pain over the last week on a scale from “0” (no pain) to “10” (worst pain possible). Severe pain was > 6/10 on the NPRS. NP was screened with the “neuropathic pain in 4 questions questionnaire (DN4)” [17], a clinical tool for the diagnosis of NP. This questionnaire includes a series of four questions consisting of both sensory descriptors and signs related to bedside sensory examination. Two questions are based on the interview of the patient, and two are based on a standardized clinical examination. A score of 1 is given to each positive item and 0 to each negative item. The total score is the sum of the 10 items, and the cutoff value for the diagnosis of NP is a total score of 4/10.

Anxiety and depression were evaluated with the Hospital
Anxiety and Depression Scale (HADS) [18]. This fourteen-
item scale is used to identify possible and probable anxiety
and depression disorders. Seven of the items relate to anxiety
and seven relate to depression (high scores indicate more
severe disease).

Sleep quality was evaluated with the Pittsburgh Sleep
Quality Index (PSQI) [19]. This questionnaire with 19 items
consists of 7 domains: subjective sleep quality, sleep latency,
duration, disturbances, habitual sleep efficiency, use of sleep
medication, and daytime dysfunction (high scores indicate
poorer sleep quality).

Quality of life was evaluated with Short-form Health
Survey SF-36. This questionnaire [20] is a measure of health
status and quality of life of the patient. It includes eight
health concepts divided into two categories, physical health
and mental health. The physical health category includes
general health perception, physical functioning, role limi-
tations due to physical health problems, and bodily pain. The
mental health category includes role limitations due to
emotional problems, social functioning, mental health, and
vitality. It also includes a single item that provides an in-
dication of perceived change in health (higher scores in-
dicate better health quality).

Body mass index (BMI) was calculated as the ratio of an
individual's weight in kilograms divided by the height in
meters squared (BMI = kg/m²).

2.3. *Statistics.* The sample size estimation was determined to guarantee a satisfactory statistical power for the analysis of neuropathic component effect on the quality of life of patients suffering from pain localized on the site of osteoporotic fractures. Sample size was calculated according to CONSORT Statement extension for randomized pilot and feasibility trials and Cohen's recommendations [21],
defining effect size (ES) limits as small (ES: 0.2), medium (ES: 0.5), and large (ES: 0.8, "grossly perceptible and therefore large"). According to data reported in the literature and considering this study as a pilot, it seems suitable to include 50 patients in order to be able to highlight ES at least one standard deviation, with a type I error of 5% and statistical power greater than 80%.

Continuous data were expressed according to their statistical distribution with mean and standard deviation. The assumption of normality was analyzed using the Shapiro-Wilk test. The comparisons between groups (such as fracture with or without NP) were performed using Student's t-test or Mann-Whitney test if the assumptions of t-test were not met. The equality of variances was analyzed using the Fisher-Snedecor test. Concerning categorical data, the comparisons were conducted using chi-squared or Fisher's exact test. Statistical analyses were performed using Stata software (Version 15, StataCorp, College Station, USA). All statistical tests were carried out for a two-sided type I error at 5%. The results were expressed using ESs and 95% confidence intervals and were interpreted according to aforementioned Cohen's recommendations.

## 3. Results

Fifty women with postmenopausal OP were included (Table 1). The mean age of the participants was 69.1 ± 7.7 years. Patients had OVFs (n = 29, 58%) or osteoporotic fractures on other locations (ONVF) (hip and wrist) (n = 21, 42%). OVFs were multiple (n = 18, 36%) or single (n = 11, 22%). The most common site of OVFs was lumbar spine, with single (n = 8, 16%) or multiple fractures (n = 7, 14%) (Figure 1).

Pain intensity in the total population was NPRS: 3.5 ± 2.7, and 14 patients had DN ≥ 4 (28%). Twelve patients (24%) displayed neuropathic characteristics with at least one point on the DN4 questionnaire. Concerning the 14 patients with DN ≥ 4, 6/50 patients had VFs and 8/50 had fractures in other locations: 12% had NP in OVF (6% lumbar and 6% thoracic). Out of 29 patients with an OVF, 6 patients had NP (21%). Patients with a neuropathic component had not received any of the recommended treatments for NP and had not been evaluated for suspicion or presence of NP previously.

Patients with NCCP had more pain (5.1 ± 2.9 vs. 2.9 ± 2.7, ES = 0.82 [0.18; 1.44], *p* = 0.019), more severe pain (> 6) (64% vs. 33%, *p* = 0.046), and impaired sleep (10.1 ± 4.7 vs. 7.2 ± 3.5, ES = 0.71 [0.08; 1.33], *p* = 0.043). However, SF-36 physical (ES = -0.11 [-0.72; 0.50]) and mental dimensions (ES = -0.29 [-0.90; 0.32]), anxiety (ES = 0.30 [-0.31; 0.91]), and depression (ES = 0.26 [-0.36, 0.86]) were not significantly different according to fracture with NP component/characteristics.

There were no significant differences between OVF and ONVF groups for age, BMI, pain, quality of life scores, anxiety, depression, and sleep and no significant differences between patients with or without NP for BMI, quality of life, and depression.

Patients were taking over-the-counter analgesics as needed: paracetamol (30%) and nonsteroidal anti-inflammatory drugs (25%). Only one patient was on

<table><caption>TABLE 1: Characteristics of patients and the presence of neuropathic pain (NP).</caption><thead><tr><th></th><th>Fracture with no NP</th><th>Fracture with NP</th><th>p value</th></tr></thead><tbody><tr><td>n</td><td>21</td><td>29</td><td></td></tr><tr><td>Age</td><td>70.6 (7.4)</td><td>65.2 (6.9)</td><td>0.04</td></tr><tr><td>BMI</td><td>25.1 (9.4)</td><td>22.5 (5.0)</td><td>0.09</td></tr><tr><td>PSQI</td><td>7.2 (3.5)</td><td>10.1 (4.7)</td><td>0.04</td></tr><tr><td>SF-36 physical</td><td>42.9 (11.8)</td><td>41.6 (9.2)</td><td>0.70</td></tr><tr><td>SF-36 mental</td><td>46.9 (10.1)</td><td>43.7 (12.1)</td><td>0.50</td></tr><tr><td>HADS depression</td><td>5.0 (3.5)</td><td>5.9 (3.0)</td><td>0.48</td></tr><tr><td>HADS anxiety</td><td>7.5 (2.8)</td><td>10.3 (6.6)</td><td>0.29</td></tr></tbody></table>

Note: Values are expressed as mean (standard deviation).

<figure><img src="image_3.png" /><figcaption>FIGURE 1: Sites of fragility osteoporotic fractures.</figcaption></figure>

antidepressant (venlafaxine) for anxiety symptoms. None was on anticonvulsants, antidepressants, or topical patches (lidocaine 5% and capsaicin 8%) for NP, as recommended in guidelines.

## 4. Discussion

This pilot study in postmenopausal women with fractures shows that 28% patients exhibit NCCP at nonvertebral site and 21% patients at vertebral site. These findings confirm results from a recent study [14] that showed a prevalence of up to 23.6% NP using LANSs questionnaire, one of the three commonly used tools with PD-Q and DN4 to detect the presence of NP components [22]. In our study, we used the DN4 questionnaire in French, the language in which it was first validated, and its psychometric properties to assess NP were confirmed in patients with low back pain [23]. This is important as many tools have been translated and not revalidated in another language or clinical setting and might bias NP assessment [8]. However, the DN4 is not specific to NP of bone fracture origin and the use of this metric may be confounded by NP that is present from other origins, although we were careful to check this was not the case. DN4 only defines the presence or absence of neuropathic characteristics, not evaluating mixed pain unlike other tools such as the PD-Q. In the future, it could be interesting to explore the relationship between these tools further. The study also
shows that patients with the NP component had more pain, more severe pain, and impaired sleep compared to patients with no NP. Concerning the localization of the VF, the sample of our pilot study was not large enough to identify differences between dorsal and lumbar locations as regards the severity and quality of pain and other measured parameters. This aspect should be considered in a future study in order to identify the impact of the localization of the fracture on a patient's clinical condition, mobility, and quality of life.

Fragility fractures in OP, often revealed by acute pain, have a large impact on the quality of life of patients as they may lead to chronic pain of variable intensity, duration, and characteristics, including NP. Complaints on back pain are however rarely attributed to OP itself [24], and OP fracture as an etiology of back pain is often overlooked. Interestingly, the presence of a NP component in our patients was new to them, as they had never been assessed for NCCP previously nor treated with recommended NP treatments before their outpatient specialist visit. This observation calls for additional recommendations to present guidelines especially on back and low back pain, as these often do not specify OP consequences as a possible cause of NP development that is still under-recognized in OP patients.

This pilot study was well powered in order to highlight large ESs that have been verified for the relationships between pain, impaired sleep, and NP. Parameters of quality of life including depression and anxiety, although often described in NP patients, do not show, in this work, significant magnitude of difference with small to mild ESs less than 0.3. Parameters of quality of life including depression and anxiety, although often described in NP patients, do not reach significance probably because of the small sample size of the study, and larger samples should be included in future trials in order to obtain larger subgroups. The study however shows that sleep is significantly affected by the presence of NP. Pain is known to disrupt sleep, lack of sleep increases pain perception [25], and sleep disturbances are particularly troublesome in patients with painful rheumatic disease [26]. Sleep efficiency (NREM sleep) [27, 28] and quality of life are reduced in NP [29]. Although the mechanism of this bidirectional association between sleep disturbances and NP remains unclear, the opioidergic, dopaminergic, immune systems as well as orexins, adenosine, and the hypothalamic-pituitary-adrenal axis are known to be involved.

In conclusion, this pilot cross-sectional study showed that NCCP is present in some patients after OP fragility fracture and impairs their sleep. Diagnosis and treatment of NCCP occurring in the context of OP need to be implemented earlier in the care journey. Future research on studies with larger samples also needs to focus on the characteristics and prognosis of NCCP in patients with OP in order to better understand and manage it and assist patients for pain alleviation and better sleep and everyday life quality.

## Data Availability Statement

The data used to support the findings of this study are available from the corresponding author upon reasonable request.

## Ethics Statement

Ethical approval was obtained.

## Consent

Patient consent was obtained.

## Conflicts of Interest

The authors declare no conflicts of interest.

## Author Contributions

Marie-Eva Pickering was the leader of the project. Bruno Pereira performed the statistics. All authors contributed equally in writing the article.

## Funding

The authors received no funding for this manuscript.

## Acknowledgments

The authors thank the patients for their collaboration.

## References

[1] J. E. Compston, M. R. McClung, and W. D. Leslie, "Osteoporosis," *The Lancet* 393, no. 10169 (2019): 364–376, https://doi.org/10.1016/S0140-6736(18)32112-3.

[2] K. Briot, C. Roux, T. Thomas, et al., "2018 Update of French Recommendations on the Management of Postmenopausal Osteoporosis," *Joint Bone Spine* 85, no. 5 (2018): 519–530, https://doi.org/10.1016/j.jbspin.2018.02.009.

[3] C. Mattia, F. Coluzzi, L. Celidonio, and R. Vellucci, "Bone Pain Mechanism in Osteoporosis: A Narrative Review," *Clinical Cases in Mineral and Bone Metabolism: The Official Journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases* 13, no. 2 (2016): 97–100, https://doi.org/10.11138/ccmbm/2016.13.2.097.

[4] P. W. Mantyh, "Mechanisms That Drive Bone Pain across the Lifespan," *British Journal of Clinical Pharmacology* 85, no. 6 (2019): 1103–1113, https://doi.org/10.1111/bcp.13801.

[5] G. Pickering, B. Pereira, V. Morel, et al., "Rationale and Design of a Multicenter Randomized Clinical Trial With Memantine and Dextromethorphan in Ketamine-Responder Patients," *Contemporary Clinical Trials* 38, no. 2 (2014): 314–320, https://doi.org/10.1016/j.cct.2014.06.004.

[6] M. E. Pickering, R. M. Javier, S. Malochet, G. Pickering, and J. Desmeules, "Osteoporosis Treatment and Pain Relief: A Scoping Review," *European Journal of Pain* 28, no. 1 (2023): 3–20, https://doi.org/10.1002/ejp.2156.

[7] M. E. Pickering and R. Chapurlat, "Where Two Common Conditions of Aging Meet: Osteoarthritis and Sarcopenia," *Calcified Tissue International* 107, no. 3 (2020): 203–211, https://doi.org/10.1007/s00223-020-00703-5.

[8] G. Baranidharan, B. Bretherton, C. Comer, R. Duarte, and K. Cromie, "Neuropathic Pain Questionnaires for Back Pain, What Do We Know?" *Musculoskeletal Science and Practice* 63 (2023): 102714, https://doi.org/10.1016/j.msksp.2022.102714.

[9] S. A. Harrisson, R. Ogollah, K. M. Dunn, N. E. Foster, and K. Konstantinou, "Prognosis of Patients With Neuropathic
Low Back-Related Leg Pain: An Exploratory Study Using
Prospective Data From UK Primary Care," *The Journal of Pain*
25, no. 2 (2024): 533-544, https://doi.org/10.1016/
j.jpain.2023.09.016.

[10] R. Baron, A. Binder, N. Attal, R. Casale, A. H. Dickenson, and R. D. Treede, "Neuropathic Low Back Pain in Clinical Practice," *European Journal of Pain* 20, no. 6 (2016): 861-873, https://doi.org/10.1002/ejp.838.

[11] R. Freynhagen, R. Baron, U. Gockel, and T. R. Tölle, "PainDETECT: A Newscreening Questionnaire to Identify Neuropathic Components in Patients With Back Pain," *Current Medical Research and Opinion* 22, no. 10 (2006): 1911-1920, https://doi.org/10.1185/030079906X132488.

[12] K. Fujimoto, K. Inage, S. Orita, et al., "The Nature of Osteoporotic Low Back Pain without Acute Vertebral Fracture: A Prospective Multicenter Study on the Analgesic Effect of Monthly Minodronic Acid Hydrate," *Journal of Orthopaedic Science* 22, no. 4 (2017): 613-617, https://doi.org/10.1016/j.jos.2017.01.022.

[13] M. Suzuki, S. Orita, M. Miyagi, et al., "Vertebral Compression Exacerbates Osteoporotic Pain in an Ovariectomy-Induced Osteoporosisrat Model," *Spine* 38, no. 24 (2013): 2085-2091, https://doi.org/10.1097/brs.000000000000001BRS.0000000000000001.

[14] A. Moretti, S. Liguori, M. Paoletta, et al., "Characterization of Neuropathic Component of Back Pain in Patients With Osteoporotic Vertebral Fractures," *NeuroRehabilitation* 51, no. 2 (2022): 325-331, https://doi.org/10.3233/NRE-220040.

[15] S. Perrot, M. Cohen, A. Barke, et al., "The IASP Classification of Chronic Pain for ICD-11: Chronic Secondary Musculoskeletal Pain," *Pain* 160, no. 1 (2019): 77-82, https://doi.org/10.1097/j.pain.00000000000001389.

[16] "Strobe," https://www.strobe-statement.org/checklists/.

[17] D. Bouhassira, N. Attal, H. Alchaar, et al., "Comparison of Pain Syndromes Associated With Nervous or Somatic Lesions and Development of a New Neuropathic Pain Diagnostic Questionnaire (DN4)," *Pain* 114, no. 1 (2005): 29-36, https://doi.org/10.1016/j.pain.2004.12.010.

[18] A. S. Zigmond and R. P. Snaith, "The Hospital Anxiety and Depression Scale," *Acta Psychiatrica Scandinavica* 67, no. 6 (1983): 361-370, https://doi.org/10.1111/j.1600-0447.1983.tb09716.x.

[19] D. J. Buysse, C. F. Reynolds, T. H. Monk, S. R. Berman, and D. J. Kupfer, "The Pittsburgh Sleep Quality Index: A New Instrument for Psychiatric Practice and Research," *Psychiatry Research* 28, no. 2 (1989): 193-213, https://doi.org/10.1016/0165-1781(89)90047-4.

[20] J. E. Ware, Jr and C. D. Sherbourne, "The MOS 36-Item Short-Form Health Survey (SF-36): I. Conceptual Framework and Item Selection," *Medical Care* 30, no. 6 (1992): 473-483, https://doi.org/10.1097/00005650-199206000-00002.

[21] J. Cohen, *Statistical Power Analysis for the Behavioral Sciences*, 2nd ed edition (Hillsdale, NJ: Lawrence Erlbaum Associates, Publishers, 1988).

[22] M. Ríos-León, J. Taylor, A. Segura-Fragoso, and A. Barriga-Martín, "Usefulness of the DN4, S-LANSS and PainDETECT Screening Questionnaires to Detect the Neuropathic Pain Components in People With Acute Whiplash-Associated Disorders: A Cross-Sectional Study," *Pain Medicine* 25, no. 5 (2023): 344-351, https://doi.org/10.1093/pnm/pnad165.

[23] N. Attal, S. Perrot, J. Fermanian, and D. Bouhassira, "The Neuropathic Components of Chronic Low Back Pain: A Prospective Multicenter Study Using the DN4

Questionnaire," *The Journal of Pain* 12, no. 10 (2011): 1080-1087, https://doi.org/10.1016/j.jpain.2011.05.006.

[24] J. Nijs, A. Apeldoorn, H. Hallegraeff, et al., "Low Back Pain: Guidelines for the Clinical Classification of Predominant Neuropathic, Nociceptive, or Central Sensitization Pain," *Pain Physician* 18, no. 3 (2015): E333-E346.

[25] M. Zhu and H. Huang, "The Underlying Mechanisms of Sleep Deprivation Exacerbating Neuropathic Pain," *Nature and Science of Sleep* 15 (2023): 579-591, https://doi.org/10.2147/NSS.S414174.

[26] M. E. Pickering, R. Chapurlat, L. Kocher, and L. Peter-Derex, "Sleep Disturbances and Osteoarthritis," *Pain Practice* 16, no. 2 (2016): 237-244, https://doi.org/10.1111/papr.12271.

[27] L. J. Leys, K. L. Chu, J. Xu, et al., "Disturbances in Slow-Wave Sleep Are Induced by Models of Bilateral Inflammation, Neuropathic, and Postoperative Pain, but Not Osteoarthritic Pain in Rats," *Pain* 154, no. 7 (2013): 1092-1102, https://doi.org/10.1016/j.pain.2013.03.019.

[28] R. Cardis, S. Lecci, L. M. Fernandez, et al., "Cortico-Autonomic Local Arousals and Heightened Somatosensory Arousability During NREMS of Mice in Neuropathic Pain," *Elife* 10 (2021): e65835, https://doi.org/10.7554/elife.65835.

[29] E. F. Afolalu, F. Ramlee, and N. K. Y. Tang, "Effects of Sleep Changes on Pain-Related Health Outcomes in the General Population: A Systematic Review of Longitudinal Studies With Exploratory Meta-Analysis," *Sleep Medicine Reviews* 39 (2018): 82-97, https://doi.org/10.1016/j.smrv.2017.08.001.