Is There a Possible Neuropathic Pain Component in Knee Osteoarthritis?
Cemile Sevgi POLAT, Asuman DOĞAN, Didem SEZGİN ÖZCAN, Belma Füsun KÖSEOĞLU, Sinem KOÇER AKSELİM
Department of Physical Medicine and Rehabilitation, Ankara Physical Medicine and Rehabilitation Training and Research Hospital, Ankara, Turkey
Keywords: Knee osteoarthritis; neuropathic pain; physical function; risk factors
Objectives: This study aims to investigate the neuropathic pain (NP) component in patients with osteoarthritis (OA) of the knee and its association with physical function, risk factors, and stages of OA.
Patients and methods: One hundred and nine patients (16 males, 93 females; mean age 62.5±8.5 years; range 44 to 81 years) diagnosed with knee OA according to the American College of Rheumatology criteria were enrolled in this study between July 2014 and June 2015. Patients were evaluated with visual analog scale for pain severity, PainDETECT questionnaire for presence and severity of neuropathic pain, Western Ontario and McMaster Universities osteoarthritis index for physical function, and the Kellgren-Lawrence system for severity of OA. Presence of the associated risk factors were also questioned.
Results: A total of 12 patients (11%) were classified as having likely NP and 23 patients (21.1%) were classified as having possible NP. PainDETECT scores were significantly correlated with the visual analog scale scores and Western Ontario and McMaster Universities osteoarthritis index pain, physical function and total scores. Patients with neuropathic pain had significantly longer symptom duration than the patients without NP. However, we found no relationship between the other risk factors and NP.
Conclusion: This study demonstrated that some of the knee OA patients had a NP component as the underlying cause of knee pain. Patients with NP had longer symptom duration, increased severity of pain, and disability. Therefore, the presence of NP component in these patients should be considered. Once it is determined, appropriate intervention strategies for NP should be incorporated in the routine treatment modalities of knee OA.
Osteoarthritis (OA) is a common progressive joint disease characterized by loss of articular cartilage and periarticular bone remodeling. It causes joint pain and pain is the most common disabling symptom for patients with OA.(1-3) The pain of knee OA is generally classified as nociceptive, due to cartilage damage. However, since cartilage is both an avascular and aneural tissue, the mechanism of pain is likely to be complex and the synovium, bone and soft tissue probably contribute to pain generation.(4,5) In addition, subchondral bone pathology may cause neuropathy after destruction of the chondral structure, because the subchondral bone is densely innervated.(4) Rat models of knee OA have shown that sensory nerve fibers innervating the knee are significantly damaged with destruction of subchondral bone junction and induce neuropathic pain (NP).(6) Like other chronic pain conditions, central sensitization may contribute to OA pain arising from chronic nociceptor stimulation and subsequent modification of central pain transmitting neurons.(7-9) Central sensitization in OA may present with several clinical features which are characteristic for NP conditions.(10) The characteristic verbal complaints include burning, prickling, itching, electric shock feeling, pins and needles, numbness, tingling, and sensitivity to heat, cold, touch or pressure.(11) Due to the characteristic complaints of NP reported by our patients, we consider that there is a NP component in the pain of knee OA. Although the risk factors for symptomatic knee OA have been identified,(12) to our best knowledge, a limited number of studies have evaluated the relationship between risk factors and NP in knee OA.(10) Therefore, in this study, we aimed to investigate the NP component in patients with OA of the knee and its association with physical function, risk factors, and stages of OA.
Patients and Methods
A total of 109 knee OA patients (16 males, 93 females; mean age 62.5±8.5 years; range 44 to 81 years) who applied to Ankara Physical Medicine and Rehabilitation Training and Research Hospital between July 2014 and June 2015 were enrolled. Knee OA was diagnosed according to the American College of Rheumatology classification criteria.(13) Ankara Physical Medicine and Rehabilitation Training and Research Hospital Ethics Committee approved the study protocol. A written informed consent was obtained from each patient. The study was conducted in accordance with the principles of the Declaration of Helsinki.
All patients had knee pain for more than three months. Patients with any previous history of knee surgery, infection, rheumatoid arthritis and other pain/neurological conditions such as radiculopathies, diabetes mellitus, vitamin B12 deficiency, coxarthrosis, stroke, traumatic brain injury, and patients who were already receiving medical treatment for NP were excluded. Patients were questioned about the affected knee, pain duration, and sociodemographic factors including age, sex, job, education, and body mass index (BMI).
All patients completed the visual analog scale (VAS) for pain at rest and at movement, Western Ontario and McMaster Universities osteoarthritis index (WOMAC) scale and the painDETECT questionnaire (PDQ). WOMAC scale was used to assess the functional status. It consists of subsections for pain (five questions), stiffness (two questions), and physical functionality (17 questions). In 5-point Likert form, 0 is none while 4 is extreme pain, with 0 as the best and 96 as the worst. The Turkish reliability and validity studies were conducted.(14) The Leeds Assessment of Neuropathic Symptoms and Signs pain scale, the neuropathic pain questionnaire, the Douleur Neuropathique (Neuropathic Pain) with four questions, and the PDQ have been developed for the measurement of NP.(15-18) Among existing measures, the PDQ appears to be the most appropriate assessment tool for use in OA.(19)
PainDETECT questionnaire was used to assess the features of pain experienced by participants in the preceding four weeks. It contains a body drawing for patients to indicate the sites of pain and any radiation present, assessment of pain quality with a marker of severity from hardly noticed to very strongly, pattern of pain and measures of current, worst and average pain severity. The painDETECT score ranged from 0 to 38. Patients were divided into three groups: likely NP (score ≥19), possible NP (score ≥13 to ≤18), and unlikely NP (score ≤12).(18) The Turkish version of the PDQ was developed and validity and reliability studies were conducted.(20)
Each patient’s knee X-rays were taken while the patient was standing, knee extended in anteroposterior position. We used the Kellgren- Lawrence grading system.(21)
Data were analyzed by using SPSS version 11.5 (SPSS Inc., Chicago, IL, USA). Distribution of continuous variables was assessed by Shapiro- Wilk test. Descriptive statistics were expressed as mean ± standard deviation for continuous variables and as median (minimum-maximum) for discrete variables. Correlation analysis between the painDETECT scores and age, BMI, disease duration, VAS, and WOMAC scores were performed with Spearman correlation test. Comparisons between patients with likely, possible and unlikely NP groups in terms of sociodemographic and clinical characteristics were measured by Kruskal-Wallis test for continuous variables and Chi-square test (or Fisher’s exact test) for categorical variables. Post-hoc analysis was performed to detect which pairs of groups differ significantly. P<0.05 was considered statistically significant.
shows the socio-demographic characteristics of patients, while clinical variables were shown in Table 2.
In this study, 12 patients (11%) were classified as likely NP, 23 patients (21.1%) were classified as possible NP, and 74 patients (67.9%) were classified as unlikely NP.
PainDETECT score was weakly and positively correlated with the VAS at rest and at movement (r=0.272, p=0.044, and r=0.333, p<0.001), WOMAC pain score (r=0.358, p<0.001), WOMAC physical function score (r=0.220, p=0.022) and WOMAC total score (r=0.280, p=0.003).
Table 3 shows the demographic and clinical characteristics of patients based on PainDETECT scores. There were differences in symptom duration (p=0.001), pain VAS at rest (p=0.034), pain VAS at movement (p=0.041), WOMAC pain (p=0.004), WOMAC physical function (p=0.030), and WOMAC total score (p=0.008) between likely NP and unlikely NP groups.
In this study, we have demonstrated that knee OA patients with longer symptom duration have NP component in their knee pain and that patients with NP component have severe pain and disability than patients without NP component. Also, we have found no relationship between NP and risk factors and stages of OA.
Historically, the pain of OA knee has been considered to be nociceptive pain; however, cumulative data suggest that both nociceptive and neuropathic mechanisms can play role in the pain of OA.(8,22) Hochman et al.(10) evaluated 80 knee OA patients and found that 34% of patients reported NP descriptors including burning, tingling, numbness, and pins and needles. Similarly, Oteo-Álvaro et al.(23) found high prevalence of NP features in patients with knee OA. Our study is in accordance with these studies in terms of NP component in the pain of OA knee.
We investigated the association between NP component and physical function in the knees of OA patients. Ohtori et al.(4) found that painDETECT scores were correlated with WOMAC pain score, but there was no correlation with WOMAC physical function score. On the other hand, we found that painDETECT scores were correlated with WOMAC pain score and WOMAC physical function score. Therefore, we consider that patients with NP component in their knee pain may have severe pain and disability. The investigators have reported that NP occurs in association with damage to nerves innervating subchondral bone in late stage.(4,6) Because of this data, we hypothesize that the increased symptom duration may influence development of NP component in knee OA. Likewise, Hochman et al.(10) suggested that longer term nociceptive input may lead to more alterations in central
pain processing and increase the possibility of developing NP. They determined that patients who used NP descriptors had a longer OA duration compared with patients who did not use NP descriptors in their study. In our study, there was a significant difference in symptom duration between unlikely NP and likely NP groups. Therefore, in late stage, patients with longer symptom duration may have a NP component in their knee OA pain. Thus longer symptom duration may be considered as a risk factor of NP.
Risk factors for symptomatic knee OA have been reviewed(12) but only one study has examined the relationship between risk factors and NP in knee OA.(10) Female sex, age, and BMI are well-known risk factors for OA, as shown in previous studies.(24-28) Also, in the literature, a low level of education was found to be a significant factor associated with OA.(29,30) Hochman et al.(10) compared age, sex, and educational level in knee OA patients between those who used NP descriptors and who did not use NP descriptors. They found that the patients who used NP descriptors were younger and were more likely to be females, although only the age difference reached statistical significance and there was no significant difference in level of education between the groups. In our study, there was no difference in sex, age, and educational level between unlikely NP and likely NP groups and there was also no correlation between painDETECT scores and BMI. We consider that this may be a result of most of our patients being housewives and having a low level of education. According to these findings, we believe that level of education, age, sex, and BMI are not risk factors for NP in knee OA.
In this study, we investigated the association between radiographic severity and NP component in knee OA. The association between radiographic severity in OA and pain remains indeterminate. There are many patients who have radiographic evidence of OA in the absence of pain and those who have little radiographic evidence of OA with moderate to severe pain.(31) Finan et al.(32) suggested that central sensitization in knee OA is apparent among patients with high levels of pain in the absence of moderate-to-severe radiographic evidence of knee OA. In our study, there was significant correlation between painDETECT scores and the VAS score, but we found no correlation between painDETECT scores and the Kellgren-Lawrence grades. Based on our observations, findings on radiographic evaluation appear to correlate with the patient’s age rather than the patient’s symptoms. The relationship between radiographic severity in OA and pain requires further examination.
There are several limitations of our study. First, although psychological factors may contribute to central sensitization and NP in knee OA,(8,33) they were not evaluated in this study. Hochman et al.(19) showed the association between depression and NP presence. Second, the reliability of PDQ for NP in knee OA has not been conducted. Although PDQ was developed and validated in adults with chronic low back pain, we used it to evaluate NP component in knee OA like the other studies.(4,34) PDQ was modified for use in knee OA by Hochman et al.(19) and they claim that the modified PDQ may facilitate the identification of a neuropathic component in knee OA.
Despite limitations, to our knowledge, this is one of the rare studies that examined the association between risk factors and NP in knee OA. We detected that some patients have a NP component in their knee OA pain and patients with NP have longer symptom duration. Therefore, the presence of NP component in these patients should be considered. Once it is determined, appropriate intervention strategies for NP should be incorporated in the routine treatment modalities of the knee OA.
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article
The authors received no financial support for the research and/or authorship of this article.
- Alshami AM. Knee osteoarthritis related pain: a narrative review of diagnosis and treatment. Int J Health Sci (Qassim) 2014;8:85-104.
- Mahajan A, Verma S, Tandon V. Osteoarthritis. J Assoc Physicians India 2005;53:634-41.
- Felson DT. The sources of pain in knee osteoarthritis. Curr Opin Rheumatol 2005;17:624-8.
- Ohtori S, Orita S, Yamashita M, Ishikawa T, Ito T, Shigemura T, et al. Existence of a neuropathic pain component in patients with osteoarthritis of the knee. Yonsei Med J 2012;53:801-5.
- Sofat N, Ejindu V, Kiely P. What makes osteoarthritis painful? The evidence for local and central pain processing. Rheumatology (Oxford) 2011;50:2157-65.
- Ohtori S, Inoue G, Orita S, Takaso M, Eguchi Y, Ochiai N, et al. Efficacy of combination of meloxicam and pregabalin for pain in knee osteoarthritis. Yonsei Med J 2013;54:1253-8.
- Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science 2000;288:1765-9.
- Kidd BL, Langford RM, Wodehouse T. Arthritis and pain. Current approaches in the treatment of arthritic pain. Arthritis Res Ther 2007;9:214.
- Im HJ, Kim JS, Li X, Kotwal N, Sumner DR, van Wijnen AJ, et al. Alteration of sensory neurons and spinal response to an experimental osteoarthritis pain model. Arthritis Rheum 2010;62:2995-3005.
- Hochman JR, French MR, Bermingham SL, Hawker GA. The nerve of osteoarthritis pain. Arthritis Care Res (Hoboken) 2010;62:1019-23.
- BennettMI,AttalN,BackonjaMM,BaronR,Bouhassira D, Freynhagen R, et al. Using screening tools to identify neuropathic pain. Pain 2007;127:199-203.
- Zhang Y, Jordan JM. Epidemiology of osteoarthritis. Rheum Dis Clin North Am 2008;34:515-29.
- Altman RD. Criteria for classification of clinical osteoarthritis. J Rheumatol Suppl 1991;27:10-2.
- Tüzün EH, Eker L, Aytar A, Daşkapan A, Bayramoğlu M. Acceptability, reliability, validity and responsiveness of the Turkish version of WOMAC osteoarthritis index. Osteoarthritis Cartilage 2005;13:28-33.
- Bennett M. The LANSS Pain Scale: the Leeds assessment of neuropathic symptoms and signs. Pain 2001;92:147-57.
- Krause SJ, Backonja MM. Development of a neuropathic pain questionnaire. Clin J Pain 2003;19:306-14.
- Bouhassira D, Attal N, Alchaar H, Boureau F, Brochet B, Bruxelle J, et al. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 2005;114:29-36.
- Freynhagen R, Baron R, Gockel U, Tölle TR. Pain DETECT: a new screening questionnaire to identify neuropathic components in patients with back pain. Curr Med Res Opin 2006;22:1911-20.
- Hochman JR, Gagliese L, Davis AM, Hawker GA. Neuropathic pain symptoms in a community knee OA cohort. Osteoarthritis Cartilage 2011;19:647-54.
- Alkan H, Ardic F, Erdogan C, Sahin F, Sarsan A, Findikoglu G. Turkish version of the painDETECT questionnaire in the assessment of neuropathic pain: a validity and reliability study. Pain Med 2013;14:1933-43.
- Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis 1957;16:494-502.
- Kosek E, Ordeberg G. Abnormalities of somatosensory perception in patients with painful osteoarthritis normalize following successful treatment. Eur J Pain 2000;4:229-38.
- Oteo-Álvaro Á, Ruiz-Ibán MA, Miguens X, Stern A, Villoria J, Sánchez-Magro I. High Prevalence of Neuropathic Pain Features in Patients with Knee Osteoarthritis: A Cross-Sectional Study. Pain Pract 2015;15:618-26.
- Nishimura A, Hasegawa M, Kato K, Yamada T, Uchida A, Sudo A. Risk factors for the incidence and progression of radiographic osteoarthritis of the knee among Japanese. Int Orthop 2011;35:839-43.
- Eaton CB. Obesity as a risk factor for osteoarthritis: mechanical versus metabolic. Med Health R I 2004;87:201-4.
- Cooper C, Snow S, McAlindon TE, Kellingray S, Stuart B, Coggon D, et al. Risk factors for the incidence and progression of radiographic knee osteoarthritis. Arthritis Rheum 2000;43:995-1000.
- Hart DJ, Doyle DV, Spector TD. Incidence and risk factors for radiographic knee osteoarthritis in middle- aged women: the Chingford Study. Arthritis Rheum 1999;42:17-24.
- Lohmander LS, Gerhardsson de Verdier M, Rollof J, Nilsson PM, Engström G. Incidence of severe knee and hip osteoarthritis in relation to different measures of body mass: a population-based prospective cohort study. Ann Rheum Dis 2009;68:490-6.
- Lee KM, Chung CY, Sung KH, Lee SY, Won SH, Kim TG, et al. Risk factors for osteoarthritis and contributing factors to current arthritic pain in South Korean older adults. Yonsei Med J 2015;56:124-31.
- Thumboo J, Chew LH, Lewin-Koh SC. Socioeconomic and psychosocial factors influence pain or physical function in Asian patients with knee or hip osteoarthritis. Ann Rheum Dis 2002;61:1017-20.
- Hannan MT, Felson DT, Pincus T. Analysis of the discordance between radiographic changes and knee pain in osteoarthritis of the knee. J Rheumatol 2000;27:1513-7.
- 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;65:363-72.
- Bradley LA, McKendree-Smith NL. Central nervous system mechanisms of pain in fibromyalgia and other musculoskeletal disorders: behavioral and psychologic treatment approaches. Curr Opin Rheumatol 2002;14:45-51.
- Moreton BJ, Tew V, das Nair R, Wheeler M, Walsh DA, Lincoln NB. Pain phenotype in patients with knee osteoarthritis: classification and measurement properties of painDETECT and self-report Leeds assessment of neuropathic symptoms and signs scale in a cross-sectional study. Arthritis Care Res (Hoboken) 2015;67:519-28.