Skip to main content
Download PDF

Impact of central sensitization on pain, disability and psychological distress in patients with knee osteoarthritis and chronic low back pain

BMC Musculoskeletal Disorders volume 24, Article number: 877 (2023) Cite this article

Abstract

Background

Central sensitization (CS) is becoming increasingly recognized as a significant factor in many chronic pain conditions, including knee osteoarthritis (KOA) and chronic low back pain (CLBP). Yet it presently remains unclear how strong is the involvement of CS in KOA and CLBP and which factors are involved in CS in these two chronic disabling diseases.

Methods

This is a cross-sectional study in which included a total of 178 patients with KOA and 118 patients with CLBP. Inclusion criteria for eligible participants for the KOA group were a confirmed diagnosis of KOA according to the American College of Rheumatology criteria, and for the CLBP group a chronic low back pain for more than 3 months. Subjects were excluded if they presented with a diagnosed psychiatric disorder or if they lacked the capacity to provide informed consent, understand study questionnaires or perform physical performance tests. In each group, were assessed; CS-related symptoms using the Central Sentization Inventory (CSI); demographic and clinical characteristics such as disease duration, pain intensity on a visual analog scale, self-reported function using the Lequesne index for KOA patients and the Oswestry Disability index for CLBP patients, and physical performance with the 6 minutes’ walk test; as well as psychosocial risk factors using the Patient Health Questionnaire for depression (PHQ-9), the Generalized Anxiety Disorder (GAD-7) and the Pain Catastrophizing Scale (PCS).

Results

CSI scores significantly correlated with pain intensity and disability in KOA and CLBP patients, and were highly correlated with self-reported symptoms of depression, anxiety and pain catastrophizing. Depression significantly predicted the CSI score in both groups.

Conclusion

These findings provide further evidence for the impact of CS on pain, function and physical performance in KOA and CLBP patients. Psychosocial symptoms such as pain catastrophizing, anxiety and depression should also be considered as they are also associated with CS.

Peer Review reports

Background

Knee osteoarthritis (KOA) and chronic low back pain (CLBP) represent a major cause of pain and disability worldwide, with high costs for the patient, his family, and the society [1, 2]. However, their treatment remains challenging as the underlying pain mechanisms are not fully understood [3]. As there is often a disparity between the chronic pain intensity and the severity of the tissue damage, health care professionals tend to underestimate the pain intensity as compared to what is actually reported by the patients [4]. In KOA, the pain associated with joint disease is different from one patient to another, and shows only a weak association with radiologic imaging features [5, 6]. A complete absence of identifiable pathoanatomical alterations is common in patients with CLBP [7, 8]. Consequently, the degree of spine damage as measured by radiographs, MRI or CT-scans is not correlated with the presence or severity of pain [9].

One reason for this disparity and the unproportionally high pain experience is neuroplastic changes that occur in the peripheral and central nervous system and result in pain sensitization enhancing the nociceptive drive from a damaged structure and hence causing more pain than can be accounted for by the damage [10,11,12,13,14]. In summary, the pathophysiological mechanisms underlying central sensitization (CS) are numerous, including an upregulation of nociception from enhanced synaptic transmission secondary to loss of spinal cord inhibitory inter-neurons, a facilitation of ascending pain mechanisms, an alteration of the descending inhibitory pathways, a facilitation of cognitive-affective mechanisms, and an altered cortical processing of nociceptive inputs [11, 15,16,17,18,19]. These processes result in a heightened and long-lasting response to painful stimuli, and may also lead to non-noxious stimuli being interpreted as painful [11, 15,16,17,18,19].

If direct electrophysiological recordings from central neurons have proved the existence of CS in animal studies, these methods cannot be performed in humans [14]. However, the conclusions drawn from animal studies were used to explain similar pain phenomena in human beings, leading to the introduction of the term ‘human assumed central sensitization’ (HACS) [20]. Several clinical signs and symptoms may indicate HACS, and various methods have been considered for its quantification in human patients. These include questionnaires [21], quantitative sensory testing (QST) [22] including mechanical pressure and injection of hypertonic saline [23, 24], functional Magnetic Response Imaging (fMRI) [25], and brain-derived neurotrophic factor analysis (BDNF) [26, 27].

The Central Sensitization Inventory (CSI) was developed as a screening tool to assess CS-related symptoms in a number of chronic pain conditions [21], including KOA and CLBP. It has been translated into numerous languages [28,29,30,31,32,33] and widely adopted in scientific research and clinical practice. Yet it presently remains unclear how strong is the involvement of CS in KOA and CLBP and which factors are affecting the central pain processing in these two chronic disabling diseases. A better understanding and identification of these factors and their impact on the patient’s condition is therefore important for clinicians in order to work toward a tailored treatment strategy.

The aim of the present study was twofold: (1) to analyze the associations between the CSI score, and pain-related symptoms, self-reported function, physical performance and psychosocial factors in KOA and CLBP patients, (2) to explore potential factors that contribute to CS in these two patients’ groups.

Methods

Study design and setting

This is a cross-sectional study carried out in the department of rheumatology of Tangier’s university hospital in Morocco, between February 2022 and September 2022. Data was prospectively collected from the outpatient department. The study was approved by the ethics committee of Tangier’s university hospital (n 01/2022), and all procedures performed on this study were in accordance with the ethical standards of the 1964 Helsinki declaration. Written informed consent was obtained from all subjects prior to the study.

Participants

Inclusion criteria for eligible participants for the KOA group were a confirmed diagnosis of KOA according to the American College of Rheumatology criteria, and for the CLBP group were a chronic low back pain for more than 3 months. Subjects were excluded if they presented with a diagnosed psychiatric disorder or if they lacked the capacity to provide informed consent, understand study questionnaires or perform physical performance tests.

Data measurement

Sociodemographic data

Personal variables as age, sex, body mass index (BMI) and education level were collected.

Disease characteristics

Duration of disease was measured as the number of years of disease progression. Radiographic evidence of KOA was graded according to the Kellgren-Lawrence scale. The number of co-morbidities was defined. Pain intensity was rated on a visual analog scale (VAS). The Arabic version of the Lequesne index was used to assess function in KOA group [34], while the Arabic version of the Oswestry Disability Index (ODI) [35] was used to assess function in CLBP patients. The six-minute walk test (6MWT) [36] evaluated physical performance in both groups.

Central sensitization

Pain sensitization was assessed using the Arabic version of the Central Sensitization Inventory (CSI). The CSI consists of two parts: A and B [21]. Part A contains 25 items presenting the pain related psychosocial, cognitive and functional items. Each item is rated on a 5-point Likert-type scale (0 = never and 4 = always). Part B (which is not scored) is designed to determine whether one or more specific disorders, including seven separate Central Sensitivity Syndromes (CSS), had been previously diagnosed (restless leg syndrome, chronic fatigue syndrome, fibromyalgia, temporomandibular joint disorder, migraine or tension headaches, irritable bowel syndrome, multiple chemical sensitivities, neck injuries (including whiplash), anxiety or panic attacks, and depression). Part B was not used in the present study. The total CSI score was obtained by summing the scores of the 25 individual items of part A. Higher total CSI scores reflect higher CS self-reported symptomatology (0–29 : sub-clinical, 30–39 : mild, 40–49 : moderate, 50–59 : severe, and 60–100 : extreme) [37]. A 40-points score out of 100 was described as the cut off value, indicative for CS [38]. The Arabic version of the CSI has shown good psychometric properties for test-retest reliability (ICC: 0.699) and internal consistency (Cronbach’s alpha: 0.823).

Psychosocial self-reported measures

Patients completed a number of validated self-reported questionnaires for measuring depression, anxiety, and pain catastrophizing using the Arabic version of the Patient Health Questionnaire-9 (PHQ-9) [39], the Generalized Anxiety Disorder (GAD) score [40] and the Pain Catastrophizing Scale (PCS) respectively. The Arabic version of the PCS has shown good psychometric properties for test-retest reliability (ICC: 0.583) and internal consistency (Cronbach’s alpha: 0.736).

Physical activity

Physical activity was assessed using the Arabic version of the International Physical Activity Questionnaire (IPAQ) [41] and by identifying the daily sedentary time (in minutes).

Sample size calculation

Using an expected correlation coefficient of 0.3 between CSI and the different predictors [42,43,44,45,46], with an 80% power (β = 0.2) and a 5% significance level two-sided test (α = 0.05), a minimum sample size of 85 patients in each group was required for this study [47].

Statistical methods

Descriptive characteristics are expressed using percentages (%) for categorical variables, means ± standard deviation (SD) for normally distributed continuous variables, and median first and third quartile (Q1, Q3) otherwise. To analyze the correlation of pain intensity, self-reported function, physical performance and psychosocial factors with the CSI score, we performed univariate correlation analysis using Pearson correlation coefficients in each group. Simple linear regression was used to identify variables that significantly predicted the CSI. Relationships between candidate variables and the CSI score were tested using multiple linear regression. The results are expressed in terms of unstandardized beta coefficients with 95% confidence intervals (ß, 95% CI) and p values. All analyses were conducted using SPSS V.21. The level of significance was set at p < 0.05.

Results

In this study, 178 patients with KOA and 118 patients with CLBP were included.

Demographic and clinical characteristics of KOA and CLBP patients

The participants’ characteristics are summarized in Table 1.

Table 1 Demographic and clinical characteristics of participants
Full size table

Correlation of pain intensity, self-reported function, physical performance and psychosocial factors with the CSI score in KOA and CLBP

Table 2 shows the correlation coefficients with the CSI score in KOA and CLBP groups. Pain intensity correlated significantly but weakly with the CSI in KOA (r = 0.190, p = 0.012) and CLBP group (r = 0.197, p = 0.033). Self-reported function significantly correlated with the CSI score only in the KOA group (r = 0.361, p < 0.001), while the six-minute walk test for physical performance negatively correlated with the CSI score only in the CLBP group (r=-0.249, p = 0.008). Depression, anxiety and pain catastrophizing scores significantly correlated with the CSI score in both KOA (PHQ-9: r = 0.671, p < 0.001, GAD-7: r = 0.563, p < 0.001, PCS: r = 0.419, p < 0.001) and CLBP (PHQ-9: r = 0.653, p < 0.001, GAD-7: r = 0.482, p < 0.001, PCS: r = 0.411, p < 0.001) groups.

Table 2 Correlation of pain intensity, self-reported function, physical performance and psychosocial factors with the CSI score in KOA and CLBP patients
Full size table

Linear regression analysis of factors affecting the CSI score in KOA and CLBP patients

Using simple linear regression, sex, number of co-morbidities, pain-intensity, depression, anxiety and pain catastrophizing score were found to have a significant regression coefficient in both KOA and CLBP groups (Table 3). Lequesne index and age were also found to have a significant regression coefficient in the KOA and the CLBP group respectively.

For each group, only variables found to have a statistical significance in the univariate analysis were included in the multivariable linear regression, which determined that depression significantly predicted CSI score in both KOA (unstandardized ß= 1.488; CI (0.944, 2.032) p < 0.001), and CLBP patients (unstandardized ß= 1.870; CI (1.062, 2.677) p < 0.001). Number of co-morbidities was also found to significantly predict CSI score in the KOA group (unstandardized ß= 1.775; CI (0.361, 3.190) p: 0,014) (Table 3). The underlying assumptions of the multivariate regression were checked. Analytical and graphical tools confirmed the performance of our model.

Table 3 Regression analysis of factors affecting the CSI score in KOA and CLBP patients
Full size table

Discussion

Our study results suggest that central sensitization, as assessed by CSI, has a significant impact on pain, function and physical performance in KOA and CLBP patients, and that pain catastrophizing, depression and anxiety are strongly correlated with CS in these patients.

Pain intensity significantly correlated with the CSI score in both KOA and CLBP patients. This result is in line with previous studies [44, 45, 48]. CS has been suggested as one of the underlying mechanisms of pain in KOA and CLBP [11, 17, 19, 42]. In fact, repeated nociceptive stimulation from damaged tissues causes nerve endings to change, resulting in a lowered threshold, prolonged and intense response, and increased sensitivity to stimuli that would not normally elicit a response [49]. As a result, spinal cord neurons that would typically only be activated by noxious stimuli can be activated by non-noxious stimuli, leading to allodynia [50]. These neuroplastic changes indicate that pain both induces, and is partly sustained by, central sensitization.

The CSI score significantly correlated with self-reported function in KOA patients and with physical performance in CLBP patients. Several studies previously reported the same associations [13, 42, 46, 51,52,53]. A possible explanation for the correlation of CS with disability in KOA and CLBP might be the “fear avoidance model.” According to this theory, the development of chronic pain and disability is influenced by both neurophysiological processes related to pain sensitization and psychosocial factors such as pain catastrophizing [54, 55]. An enhanced state of sensory sensitivity along with a heightened state of alertness during a pain episode may lead to fear avoidance behavior and result in more disability [56, 57]. Previous studies reported the presence of fear avoidance in patients with KOA [56] and CLBP [58,59,60] and suggested its contribution to pain chronicity and disability. The long-term consequences, such as increased disability or depression, may lower the threshold for pain detection and enhance the intensity of the pain experience [56]. Some studies showed that myofascial release techniques can break this cycle by decreasing pain and trigger-point pain threshold while increasing functional ability [61].

Depression, anxiety and pain catastrophizing strongly correlated with the CSI in both KOA and CLBP patients. This result had been reported in previous studies where the relationship between CS symptoms and psychological factors was emphasized [44, 62,63,64,65,66,67,68,69]. The current finding confirms the validity of the CSI as a tool to assess CS symptomatology within a construct of general distress [21, 67]. Psychosocial and cognitive behavioral factors such as incorrect illness perceptions, pain catastrophizing, anxiety and depression could contribute to and sustain the mechanisms of CS [70]. These associations may be bidirectional. Theoretically, neuroplastic changes originating from nociceptive pathways may spread to some brain areas like the insular, cingulate, prefrontal cortex, and limbic system, leading to pain catastrophizing thoughts, anxiety and depression [70]. These symptoms can increase forebrain activity, leading to the enhancement of central hyperexcitability and sensitization, which results in a vicious cycle leading to chronic pain and disability [19, 62, 70,71,72]. It is important to mention that many of the items on the CSI part A are common elements of anxiety and depressive disorders. Furthermore, we only used part A of the CSI in our study and our patients were maybe more likely to have reported depression or anxiety as a previous CSS diagnosis on CSI part B. It is worth noting that there is a significant overlap of symptoms between these conditions and central sensitization [73], and there is no set of established and scientifically recognized CS-defining criteria [74].

Our regression analysis showed that depression significantly predicted CSI scores in both KOA and CLBP groups. This result is further supported by the findings of Gervais et al. in KOA patients [64] and those of Miki et al. in CLBP patients [44]. Depression may enhance facilitatory pathways in the central nervous system, resulting in sensitization of dorsal horn spinal cord neurons [19, 75]. Anxiety and pain catastrophizing have also been described as one of the modulating factors associated with alterations in supraspinal endogenous pain inhibitory and facilitatory processes, thus maintaining and or aggravating CS pain [76, 77]. Although they were not found to directly predict CSI in our study, anxiety and pain catastrophizing might have an indirect influence on CSI through depression, to which they are highly associated.

Disease duration showed no significant association with CSI in both groups. This is consistent with previous findings in KOA and CLBP patients [43, 48]. Controversially, other studies reported a significant association between clinical pain duration and CS measurements in KOA [5, 78], and CLBP [13]. We might think that the KOA disease or the CLBP must be present for a sufficient period of time and/or have a sufficient degree of tissue injury for central sensitization to occur [13, 78]. Indeed, it has been postulated that persistent activation of peripheral nociceptors may ultimately lead over time to neuroplastic changes within the central nervous system [79, 80]. However, the lack of association of CSI with disease duration in our study, or with the Kellgren-Lawrence radiographic severity grade of KOA suggests that sensitization might be considered as a trait rather than a state, indicating that some individuals may be predisposed to central sensitization irrespective of the duration of their pathological condition.

In our study, the level of physical activity and sedentary behavior were not associated with the CSI in any group. Moriki et al. reported the same finding in a CLBP population [68]. However, previous studies had suggested that physical activity beneficially affected the functioning of the descending pain modulatory systems and facilitatory processes [81], and increased pressure pain tolerance [82]. Further research is needed to establish the relationship between central sensitization and physical activity.

A number of implications arise from the present study’s findings. First, the use of a simple method of sensitization assessment (the CSI) in clinical practice during the initial evaluation, the rehabilitation program, as well as the regular follow-ups may help identify KOA and CLBP patients at risk of a greater pain severity and who may potentially need pain medications targeting the central nervous system (e.g., anticonvulsants; selective serotonin and norepinephrine reuptake inhibitors [71, 83]). Second, psychosocial symptoms such as pain catastrophizing thoughts, anxiety and depression should also be considered as they are highly associated with CS in KOA and CLBP patients. Specific interventions including cognitive behavioral therapies [84] and neuroscience education [85] could be integrated into the treatment plan of these patients, which would more likely lead to better outcomes [86,87,88,89]. Further research would help in providing evidence of the utility of CSI as a treatment-outcome assessment tool after addressing the underlying factors involved in CS in KOA and CLBP patients, and explore whether improvements in CSI scores are associated with reduced pain and improved functioning in these patients.

Several limitations should be considered when interpreting this study’s findings. First, the design was cross-sectional; therefore, it is not possible to draw conclusions regarding causation or predictive validity. Second, the majority of surveys in this study relied on self-reported questionnaires, which raises the possibility of recall bias or overestimation of the indices being measured. Future studies will require more objective and quantitative methods for further verification. Third, the relationships between CSI and the somatosensory function measured by QST are still unknown in this population. In fact, the lack of consensus regarding the correlation between the CSI and QST in the existing literature suggests that the CSI may not reflect a direct measurement of CS [64]. Therefore, further longitudinal studies that include more objective pain sensitivity tests using a mechanism-based approach such as pain tolerance thresholds, spatial and temporal summation, conditioned pain modulation (CPM), spreading sensitization, and offset analgesia [14, 19, 90, 91] and examine their association to the CSI will be required to determine its accuracy in identifying pain processing changes involved in CS in KOA and CLBP patients.

Conclusion

Our study found that central sensitization, as assessed by CSI, has a significant impact on pain, function and physical performance in KOA and CLBP patients. This outcome endorses the relevance of early CS assessment and management in KOA and CLBP patients in order to prevent transition into a chronic pain state. Moreover, the highly significant correlation of depression, anxiety and pain catastrophizing with CSI should be interpreted as a call for better understanding of these psychosocial factors affecting the patients’ pain experience to allow for a more focused and individualized treatment.

Further research would aid in providing evidence of the utility of CSI as a treatment-outcome assessment tool after addressing the underlying factors involved in CS in KOA and CLBP patients, and explore whether improvements in CSI scores are associated with reduced pain and improved functioning in these patients.

Data Availability

The datasets used and/or analyzed during current study are available from the corresponding author on reasonable request.

References

  1. Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 Diseases and injuries 1990–2010: a systematic analysis for the global burden of Disease Study 2010. The Lancet. 2012;380(9859):2163–96.

    Article  Google Scholar 

  2. Becker A, Held H, Redaelli M, Strauch K, Chenot JF, Leonhardt C, et al. Low back pain in primary care: costs of care and prediction of future health care utilization. Spine. 2010;35(18):1714–20.

    Article  PubMed  Google Scholar 

  3. Arendt-Nielsen L, Skou ST, Nielsen TA, Petersen KK. Altered Central Sensitization and Pain Modulation in the CNS in Chronic Joint Pain. Curr Osteoporos Rep. 2015;13(4):225–34.

    Article  PubMed  Google Scholar 

  4. Puntillo K, Neighbor M, O’Neil N, Nixon R. Accuracy of emergency nurses in assessment of patients’ pain. Pain Manag Nurs off J Am Soc Pain Manag Nurses. 2003;4(4):171–5.

    Article  Google Scholar 

  5. Arendt-Nielsen L, Egsgaard LL, Petersen KK, Eskehave TN, Graven- Nielsen T, Hoeck HC, et al. A mechanism-based pain sensitivity index to characterize knee osteoarthritis patients with different Disease stages and pain levels: Pain sensitization in osteoarthritis. Eur J Pain. 2015;19(10):1406–17.

    Article  CAS  PubMed  Google Scholar 

  6. Finan PH, Buenaver LF, Bounds SC, Hussain S, Park RJ, Haque UJ, et al. Discordance between pain and radiographic severity in knee osteoarthritis: findings from quantitative sensory testing of central sensitization. Arthritis Rheum. 2013;65(2):363–72.

    Article  PubMed  Google Scholar 

  7. Ract I, Meadeb JM, Mercy G, Cueff F, Husson JL, Guillin R. A review of the value of MRI signs in low back pain. Diagn Interv Imaging. 2015;96(3):239–49.

    Article  CAS  PubMed  Google Scholar 

  8. Kalichman L, Kim DH, Li L, Guermazi A, Hunter DJ. Computed tomography–evaluated features of spinal degeneration: prevalence, intercorrelation, and association with self-reported low back pain. Spine J. 2010;10(3):200–8.

    Article  PubMed  Google Scholar 

  9. Rubinstein SM, Van Tulder M. A best-evidence review of diagnostic procedures for neck and low-back pain. Best Pract Res Clin Rheumatol. 2008;22(3):471–82.

    Article  PubMed  Google Scholar 

  10. Giesecke T, Gracely RH, Grant MAB, Nachemson A, Petzke F, Williams DA, et al. Evidence of augmented central pain processing in idiopathic chronic low back pain. Arthritis Rheum. 2004;50(2):613–23.

    Article  PubMed  Google Scholar 

  11. Mease PJ, Hanna S, Frakes EP, Altman RD. Pain mechanisms in Osteoarthritis: understanding the role of Central Pain and current approaches to its treatment: Fig. 1. J Rheumatol. 2011;38(8):1546–51.

    Article  CAS  PubMed  Google Scholar 

  12. Hübscher M, Moloney N, Leaver A, Rebbeck T, McAuley JH, Refshauge KM. Relationship between quantitative sensory testing and pain or disability in people with spinal pain—A systematic review and meta-analysis. Pain. 2013;154(9):1497–504.

    Article  PubMed  Google Scholar 

  13. Imamura M, Chen J, Matsubayashi SR, Targino RA, Alfieri FM, Bueno DK, et al. Changes in pressure Pain threshold in patients with chronic nonspecific low back Pain. Spine. 2013;38(24):2098–107.

    Article  PubMed  Google Scholar 

  14. Arendt-Nielsen L, Morlion B, Perrot S, Dahan A, Dickenson A, Kress HG, et al. Assessment and manifestation of central sensitisation across different chronic pain conditions. Eur J Pain. 2018;22(2):216–41.

    Article  CAS  PubMed  Google Scholar 

  15. Sanzarello I, Merlini L, Rosa MA, Perrone M, Frugiuele J, Borghi R, et al. Central sensitization in chronic low back pain: a narrative review. J Back Musculoskelet Rehabil. 2016;29(4):625–33.

    Article  PubMed  Google Scholar 

  16. Malfait AM, Schnitzer TJ. Towards a mechanism-based approach to pain management in osteoarthritis. Nat Rev Rheumatol. 2013;9(11):654–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Staud R. Evidence for Shared Pain mechanisms in Osteoarthritis, Low Back Pain, and Fibromyalgia. Curr Rheumatol Rep. 2011;13(6):513–20.

    Article  PubMed  Google Scholar 

  18. Harte SE, Harris RE, Clauw DJ. The neurobiology of central sensitization. J Appl Biobehav Res. 2018 Jun [cited 2023 Jul 27];23(2). Available from: https://onlinelibrary.wiley.com/doi/https://doi.org/10.1111/jabr.12137.

  19. Roussel NA, Nijs J, Meeus M, Mylius V, Fayt C, Oostendorp R. Central sensitization and altered Central Pain Processing in Chronic Low Back Pain: fact or myth? Clin J Pain. 2013;29(7):625–38.

    Article  PubMed  Google Scholar 

  20. Schuttert I, Timmerman H, Petersen KK, McPhee ME, Arendt-Nielsen L, Reneman MF, et al. The definition, Assessment, and prevalence of (Human Assumed) Central Sensitisation in patients with chronic low back Pain: a systematic review. J Clin Med. 2021;10(24):5931.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Mayer TG, Neblett R, Cohen H, Howard KJ, Choi YH, Williams MJ, et al. The Development and Psychometric Validation of the Central Sensitization Inventory: validation of the Central Sensitization Inventory. Pain Pract. 2012;12(4):276–85.

    Article  PubMed  Google Scholar 

  22. Rolke R, Magerl W, Campbell KA, Schalber C, Caspari S, Birklein F, et al. Quantitative sensory testing: a comprehensive protocol for clinical trials. Eur J Pain. 2006;10(1):77–7.

    Article  CAS  PubMed  Google Scholar 

  23. Bajaj P, Bajaj P, Graven-Nielsen T, Arendt-Nielsen L. Osteoarthritis and its association with muscle hyperalgesia: an experimental controlled study. Pain. 2001;93(2):107–14.

    Article  PubMed  Google Scholar 

  24. O’Neill S, Manniche C, Graven-Nielsen T, Arendt-Nielsen L. Generalized deep-tissue hyperalgesia in patients with chronic low-back pain. Eur J Pain. 2007;11(4):415–20.

    Article  PubMed  Google Scholar 

  25. Wager TD, Atlas LY, Lindquist MA, Roy M, Woo CW, Kross E. An fMRI-Based neurologic signature of Physical Pain. N Engl J Med. 2013;368(15):1388–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Deitos A, Dussán-Sarria JA, de Souza A, Medeiros L, da Graça Tarragô M, Sehn F, et al. Clinical value of serum neuroplasticity mediators in identifying the Central Sensitivity Syndrome in patients with Chronic Pain with and without Structural Pathology. Clin J Pain. 2015;31(11):959–67.

    Article  PubMed  Google Scholar 

  27. Schmelz M, Mantyh P, Malfait AM, Farrar J, Yaksh T, Tive L, et al. Nerve growth factor antibody for the treatment of osteoarthritis pain and chronic low-back pain: mechanism of action in the context of efficacy and safety. Pain. 2019;160(10):2210–20.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kregel J, Vuijk PJ, Descheemaeker F, Keizer D, van der Noord R, Nijs J, et al. The Dutch Central Sensitization Inventory (CSI): factor analysis, discriminative power, and test-retest reliability. Clin J Pain. 2016;32(7):624–30.

    Article  PubMed  Google Scholar 

  29. Pitance L, Piraux E, Lannoy B, Meeus M, Berquin A, Eeckhout C, et al. Cross cultural adaptation, reliability and validity of the French version of the central sensitization inventory. Man Ther. 2016;25:e83–4.

    Article  Google Scholar 

  30. Cuesta-Vargas AI, Roldan-Jimenez C, Neblett R, Gatchel RJ. Cross-cultural adaptation and validity of the Spanish central sensitization inventory. SpringerPlus. 2016;5(1):1837.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Caumo W, Antunes L, Lorenzzi Elkfury J, Herbstrith E, Busanello Sipmann R, Souza A, et al. The Central Sensitization Inventory validated and adapted for a Brazilian population: psychometric properties and its relationship with brain-derived neurotrophic factor. J Pain Res. 2017;10:2109–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Tanaka K, Nishigami T, Mibu A, Manfuku M, Yono S, Shinohara Y et al. Validation of the Japanese version of the Central Sensitization Inventory in patients with musculoskeletal disorders. Fuh JL, editor. PLOS ONE. 2017;12(12):e0188719.

  33. Knezevic A, Neblett R, Jeremic-Knezevic M, Tomasevic-Todorovic S, Boskovic K, Colovic P, et al. Cross-cultural adaptation and psychometric validation of the Serbian version of the Central Sensitization Inventory. Pain Pract. 2018;18(4):463–72.

    Article  PubMed  Google Scholar 

  34. Guermazi M, Mezganni M, Yahia M, Poiraudeau S, Fermanian J, Elleuch MH, et al. [Translation and construct validity of the Lequesne index for arab speaking North African patients with osteoarthritis of the knee]. Ann Readaptation Med Phys Rev Sci Soc Francaise Reeducation Fonct Readaptation Med Phys. 2004;47(5):195–203.

    CAS  Google Scholar 

  35. Guermazi M, Mezghani M, Ghroubi S, Elleuch M, Poiraudeau S, Med AOS. The Oswestry index for low back pain translated into Arabic and validated in a arab population. Ann Readaptation Med Phys Rev Sci Soc Francaise Reeducation Fonct Readaptation Med Phys. 2005;48(1):1–10.

    CAS  Google Scholar 

  36. Ateef M, Kulandaivelan S, Tahseen S. Test–retest reliability and correlates of 6-minute Walk Test in patients with primary osteoarthritis of knees. Indian J Rheumatol. 2016;11(4):192.

    Article  Google Scholar 

  37. Neblett R, Hartzell MM, Mayer TG, Cohen H, Gatchel RJ. Establishing clinically relevant severity levels for the Central Sensitization Inventory. Pain Pract. 2017;17(2):166–75.

    Article  PubMed  Google Scholar 

  38. Neblett R, Cohen H, Choi Y, Hartzell MM, Williams M, Mayer TG, et al. The Central Sensitization Inventory (CSI): establishing clinically significant values for identifying Central Sensitivity syndromes in an Outpatient Chronic Pain Sample. J Pain. 2013;14(5):438–45.

    Article  PubMed  PubMed Central  Google Scholar 

  39. AlHadi AN, AlAteeq DA, Al-Sharif E, Bawazeer HM, Alanazi H, AlShomrani AT, et al. An arabic translation, reliability, and validation of Patient Health Questionnaire in a Saudi sample. Ann Gen Psychiatry. 2017;16(1):32.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Sawaya H, Atoui M, Hamadeh A, Zeinoun P, Nahas Z. Adaptation and initial validation of the Patient Health Questionnaire – 9 (PHQ-9) and the generalized anxiety disorder – 7 questionnaire (GAD-7) in an arabic speaking Lebanese psychiatric outpatient sample. Psychiatry Res. 2016;239:245–52.

    Article  PubMed  Google Scholar 

  41. Helou K, El Helou N, Mahfouz M, Mahfouz Y, Salameh P, Harmouche-Karaki M. Validity and reliability of an adapted arabic version of the long international physical activity questionnaire. BMC Public Health. 2018;18(1):49.

    Article  Google Scholar 

  42. Imamura M, Imamura ST, Kaziyama HHS, Targino RA, Hsing WT, De Souza LPM, et al. Impact of nervous system hyperalgesia on pain, disability, and quality of life in patients with knee osteoarthritis: a controlled analysis. Arthritis Rheum. 2008;59(10):1424–31.

    Article  PubMed  Google Scholar 

  43. Mibu A, Nishigami T, Tanaka K, Manfuku M, Yono S. Difference in the impact of central sensitization on pain-related symptoms between patients with chronic low back pain and knee osteoarthritis. J Pain Res. 2019;12:1757–65.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Miki T, Nishigami T, Takebayashi T, Yamauchi T. Association between central sensitivity syndrome and psychological factors in people with presurgical low back pain: a cross-sectional study. J Orthop Sci. 2021;26(3):337–42.

    Article  PubMed  Google Scholar 

  45. Akeda K, Takegami N, Yamada J, Fujiwara T, Nishimura A, Sudo A. Central Sensitization in Chronic Low Back Pain: a Population-based study of a Japanese Mountain Village. J Pain Res. 2021;14:1271–80.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Ansuategui Echeita J, van der Wurff P, Killen V, Dijkhof MF, Grootenboer FM, Reneman MF. Lifting capacity is associated with central sensitization and non-organic signs in patients with chronic back pain. Disabil Rehabil. 2021;43(26):3772–6.

    Article  PubMed  Google Scholar 

  47. Hulley SB, editor. Designing clinical research. 4th ed. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins; 2013.

    Google Scholar 

  48. Neogi T, Frey-Law L, Scholz J, Niu J, Arendt-Nielsen L, Woolf C, et al. Sensitivity and sensitisation in relation to pain severity in knee osteoarthritis: trait or state? Ann Rheum Dis. 2015;74(4):682–8.

    Article  PubMed  Google Scholar 

  49. Treede RD, Meyer RA, Raja SN, Campbell JN. Peripheral and central mechanisms of cutaneous hyperalgesia. Prog Neurobiol. 1992;38(4):397–421.

    Article  CAS  PubMed  Google Scholar 

  50. Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain. 2009;10(9):895–926.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Guérard O, Dufort S, Forget Besnard L, Gougeon A, Carlesso L. Comparing the association of widespread pain, multi-joint pain and low back pain with measures of pain sensitization and function in people with knee osteoarthritis. Clin Rheumatol. 2020;39(3):873–9.

    Article  PubMed  Google Scholar 

  52. White DK, Felson DT, Niu J, Nevitt MC, Lewis CE, Torner JC, et al. Reasons for functional decline despite reductions in knee Pain: the Multicenter Osteoarthritis Study. Phys Ther. 2011;91(12):1849–56.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Ansuategui Echeita J, Schiphorst Preuper HR, Dekker R, Reneman MF. Central sensitization and functioning in patients with chronic low back pain: a cross-sectional and longitudinal study. J Back Musculoskelet Rehabil. 2022;35(6):1179–90.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Uddin Z, Woznowski-Vu A, Flegg D, Aternali A, Wickens R, Wideman TH. Evaluating the novel added value of neurophysiological pain sensitivity within the fear‐avoidance model of pain. Eur J Pain. 2019;23(5):957–72.

    Article  PubMed  Google Scholar 

  55. Vlaeyen JWS, Linton SJ. Fear-avoidance and its consequences in chronic musculoskeletal pain: a state of the art. Pain. 2000;85(3):317–32.

    Article  PubMed  Google Scholar 

  56. Herbert MS, Goodin BR, Pero ST, Schmidt JK, Sotolongo A, Bulls HW, et al. Pain Hypervigilance is Associated with Greater Clinical Pain Severity and enhanced experimental Pain sensitivity among adults with symptomatic knee osteoarthritis. Ann Behav Med. 2014;48(1):50–60.

    Article  PubMed  Google Scholar 

  57. Rollman GB. Perspectives on hypervigilance. Pain. 2009;141(3):183–4.

    Article  PubMed  Google Scholar 

  58. Meyer K, Tschopp A, Sprott H, Mannion A. Association between catastrophizing and self-rated pain and disability in patients with chronic low back pain. J Rehabil Med. 2009;41(8):620–5.

    Article  PubMed  Google Scholar 

  59. Nagarajan M, Nair MR. Importance of fear-avoidance behavior in chronic non-specific low back pain. J Back Musculoskelet Rehabil. 2010;23(2):87–95.

    Article  CAS  PubMed  Google Scholar 

  60. Owens MA, Bulls HW, Trost Z, Terry SC, Gossett EW, Wesson-Sides KM, et al. An examination of Pain Catastrophizing and Endogenous Pain modulatory processes in adults with chronic low back Pain. Pain Med. 2016;17(8):1452–64.

    Article  PubMed  Google Scholar 

  61. Mahbobeh S, Alireza M, Soheila Y, Leila A. Effects of Myofascial Release technique on Pain and disability in patients with chronic lumbar disc herniation: a Randomized Trial. Phys Med Rehabil Kurortmed. 2017;27(04):218–25.

    Google Scholar 

  62. Aoyagi K, He J, Nicol AL, Clauw DJ, Kluding PM, Jernigan S, et al. A subgroup of chronic low back Pain patients with Central Sensitization. Clin J Pain. 2019;35(11):869–79.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Campbell CM, Buenaver LF, Finan P, Bounds SC, Redding M, McCauley L, et al. Sleep, Pain Catastrophizing, and central sensitization in knee osteoarthritis patients with and without Insomnia: Insomnia and Pain in OA patients. Arthritis Care Res. 2015;67(10):1387–96.

    Article  Google Scholar 

  64. Gervais-Hupé J, Pollice J, Sadi J, Carlesso LC. Validity of the central sensitization inventory with measures of sensitization in people with knee osteoarthritis. Clin Rheumatol. 2018;37(11):3125–32.

    Article  PubMed  Google Scholar 

  65. Huysmans E, Ickmans K, Van Dyck D, Nijs J, Gidron Y, Roussel N, et al. Association between Symptoms of Central Sensitization and cognitive behavioral factors in people with chronic nonspecific low back Pain: a cross-sectional study. J Manipulative Physiol Ther. 2018;41(2):92–101.

    Article  PubMed  Google Scholar 

  66. Kosińska B, Tarnacka B, Turczyn P, Gromadzka G, Malec-Milewska M, Janikowska-Hołowenko D, et al. Psychometric validation of the Polish version of the Central Sensitization Inventory in subjects with chronic spinal pain. BMC Neurol. 2021;21(1):483.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Kregel J, Schumacher C, Dolphens M, Malfliet A, Goubert D, Lenoir D, et al. Convergent validity of the Dutch Central Sensitization Inventory: associations with Psychophysical Pain measures, Quality of Life, disability, and Pain cognitions in patients with chronic spinal Pain. Pain Pract. 2018;18(6):777–87.

    Article  PubMed  Google Scholar 

  68. Moriki K, Tushima E, Ogihara H, Endo R, Sato T, Ikemoto Y. Combined effects of lifestyle and psychosocial factors on central sensitization in patients with chronic low back pain: a cross-sectional study. J Orthop Sci. 2022;27(6):1185–9.

    Article  PubMed  Google Scholar 

  69. Neblett R, Hartzell MM, Williams M, Bevers KR, Mayer TG, Gatchel RJ. Use of the Central Sensitization Inventory (CSI) as a treatment outcome measure for patients with chronic spinal pain disorder in a functional restoration program. Spine J. 2017;17(12):1819–29.

    Article  PubMed  Google Scholar 

  70. Bushnell MC, Čeko M, Low LA. Cognitive and emotional control of pain and its disruption in chronic pain. Nat Rev Neurosci. 2013;14(7):502–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Clauw DJ. Diagnosing and treating chronic musculoskeletal pain based on the underlying mechanism(s). Best Pract Res Clin Rheumatol. 2015;29(1):6–19.

    Article  PubMed  Google Scholar 

  72. Kulkarni B, Bentley DE, Elliott R, Julyan PJ, Boger E, Watson A, et al. Arthritic pain is processed in brain areas concerned with emotions and fear. Arthritis Rheum. 2007;56(4):1345–54.

    Article  CAS  PubMed  Google Scholar 

  73. López-Ruiz M, Losilla JM, Monfort J, Portell M, Gutiérrez T, Poca V et al. Central sensitization in knee osteoarthritis and fibromyalgia: Beyond depression and anxiety. Doering S, editor. PLOS ONE. 2019;14(12):e0225836.

  74. Scerbo T, Colasurdo J, Dunn S, Unger J, Nijs J, Cook C. Measurement Properties of the Central Sensitization Inventory: a systematic review. Pain Pract. 2018;18(4):544–54.

    Article  PubMed  Google Scholar 

  75. Brosschot JF. Cognitive-emotional sensitization and somatic health complaints. Scand J Psychol. 2002;43(2):113–21.

    Article  PubMed  Google Scholar 

  76. Clark JR, Nijs J, Yeowell G, Holmes P, Goodwin PC. Trait sensitivity, anxiety, and personality are Predictive of Central sensitization symptoms in patients with chronic low back Pain. Pain Pract. 2019;19(8):800–10.

    Article  PubMed  Google Scholar 

  77. Quartana PJ, Campbell CM, Edwards RR. Pain catastrophizing: a critical review. Expert Rev Neurother. 2009;9(5):745–58.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Foucher KC, Chmell SJ, Courtney CA. Duration of symptoms is associated with conditioned pain modulation and somatosensory measures in knee osteoarthritis. J Orthop Res. 2019;37(1):136–42.

    Article  PubMed  Google Scholar 

  79. Brisby H. Pathology and possible mechanisms of nervous system response to Disc Degeneration. J Bone Jt Surg. 2006;88(suppl2):68–71.

    Google Scholar 

  80. Flor H. Cortical reorganisation and chronic pain: implications for rehabilitation. J Rehabil Med. 2003;35(0):66–72.

    Article  Google Scholar 

  81. Naugle KM, Riley JL. Self-reported physical activity predicts Pain inhibitory and facilitatory function. Med Sci Sports Exerc. 2014;46(3):622–9.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Anshel MH, Russell KG. Effect of aerobic and strength training on pain tolerance, pain appraisal and mood of unfit males as a function of pain location. J Sports Sci. 1994;12(6):535–47.

    Article  CAS  PubMed  Google Scholar 

  83. Skljarevski V, Desaiah D, Liu-Seifert H, Zhang Q, Chappell AS, Detke MJ, et al. Efficacy and safety of Duloxetine in patients with chronic low back Pain. Spine. 2010;35(13):E578–85.

    Article  PubMed  Google Scholar 

  84. Nijs J, Malfliet A, Ickmans K, Baert I, Meeus M. Treatment of central sensitization in patients with ‘unexplained’ chronic pain: an update. Expert Opin Pharmacother. 2014;15(12):1671–83.

    Article  CAS  PubMed  Google Scholar 

  85. Nijs J, Leysen L, Vanlauwe J, Logghe T, Ickmans K, Polli A, et al. Treatment of central sensitization in patients with chronic pain: time for change? Expert Opin Pharmacother. 2019;20(16):1961–70.

    Article  PubMed  Google Scholar 

  86. Louw A, Diener I, Butler DS, Puentedura EJ. The Effect of Neuroscience Education on Pain, disability, anxiety, and stress in Chronic Musculoskeletal Pain. Arch Phys Med Rehabil. 2011;92(12):2041–56.

    Article  PubMed  Google Scholar 

  87. Malfliet A, Kregel J, Coppieters I, De Pauw R, Meeus M, Roussel N, et al. Effect of Pain Neuroscience Education Combined with cognition-targeted Motor Control Training on chronic spinal Pain: a Randomized Clinical Trial. JAMA Neurol. 2018;75(7):808–17.

    Article  PubMed  PubMed Central  Google Scholar 

  88. de Lange FP, Koers A, Kalkman JS, Bleijenberg G, Hagoort P, van der Meer JWM, et al. Increase in prefrontal cortical volume following cognitive behavioural therapy in patients with Chronic Fatigue Syndrome. Brain J Neurol. 2008;131(Pt 8):2172–80.

    Article  Google Scholar 

  89. Ang DC, Chakr R, Mazzuca S, France CR, Steiner J, Stump T. Cognitive-behavioral therapy attenuates nociceptive responding in patients with fibromyalgia: a pilot study. Arthritis Care Res. 2010;62(5):618–23.

    Article  Google Scholar 

  90. Arendt-Nielsen L. Pain sensitisation in osteoarthritis. Clin Exp Rheumatol. 2017.

  91. Arendt-Nielsen L, Nie H, Laursen MB, Laursen BS, Madeleine P, Simonsen OH, et al. Sensitization in patients with painful knee osteoarthritis. Pain. 2010;149(3):573–81.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to all the patients whose participation made this study possible.

Funding

Not applicable.

Author information

Authors and Affiliations

  1. Rheumatology Department, Faculty of Medicine and Pharmacy, Mohammed VI University Hospital, Abdelmalek Essaadi University, Tangier, Morocco

    Doha Dahmani, Fatima Zahrae Taik, Imane Berrichi & Fatima Ezzahra Abourazzak

  2. Laboratory of Life and Health Sciences, Faculty of Medicine and Pharmacy of Tangier, Abdelmalek Essaadi University, Tangier, Morocco

    Fatima Zahrae Taik, Maryam Fourtassi & Fatima Ezzahra Abourazzak

Authors
  1. Doha Dahmani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fatima Zahrae Taik
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Imane Berrichi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maryam Fourtassi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fatima Ezzahra Abourazzak
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

D.D. participated in the study design and statistical analysis, and drafted the manuscript. F.Z.T. participated in the study design and statistical analysis, and revised the draft manuscript. I.B. contributed in the study design and data collection. M.F. participated in the study design and revised the manuscript. F.E.A. elaborated the idea of the study, participated in the study design and revised the draft manuscript. All authors read and approved the final manuscript. All authors take full responsibility for the integrity and accuracy of all aspects of the work.

Corresponding author

Correspondence to Doha Dahmani.

Ethics declarations

Ethics approval and consent to participate

The study was approved by the ethics committee of Tangier’s university hospital (n 01/2022). All procedures performed on this study were in accordance with the ethical standards of the 1964 Helsinki declaration. Written informed consent was obtained from all subjects prior to the study.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dahmani, D., Taik, F.Z., Berrichi, I. et al. Impact of central sensitization on pain, disability and psychological distress in patients with knee osteoarthritis and chronic low back pain. BMC Musculoskelet Disord 24, 877 (2023). https://doi.org/10.1186/s12891-023-07019-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12891-023-07019-z

Keywords

BMC Musculoskeletal Disorders

ISSN: 1471-2474

Contact us