Our study suggests that there are differing prevalence rates of NP in the various treatment stages of KOA, including the outpatient stage and the preoperative and postoperative TKA stages. To our knowledge, this is the first report to compare the prevalence of NP in different treatment stages of KOA. This may lead to personalized treatment strategies for different treatment stages of KOA. Our findings also add evidence to a growing body of literature that NP contributes to a portion of KOA pain.
The prevalence of NP in KOA patients in the outpatient department or community has been reported in several studies. The lowest prevalence (5.4%) was reported by Ohtori, while the highest prevalence (33.3%) was reported in Oteo-Alvaro’s research (10, 21). A meta-analysis showed that 23% of KOA patients had symptoms of NP (12). The large range of prevalence shows the great heterogeneity encountered in KOA patients. Compared with this previous research, our research had the lowest prevalence of NP in outpatient KOA patients. Potential explanations for the different prevalence rates of NP between our research and other studies include the following: 1. differential recruitment practices (depending on the people investigated, outpatient or community setting (10, 11)); 2. differential inclusion and exclusion criteria (inclusion criteria such as knee pain patients or patients diagnosed as KOA; exclusion criteria such as whether to exclude patients with possibly related diseases, such as lumbar disease); and 3. ethnic and cultural differences between regions and countries (for example, the lowest prevalence of NP in previous reports occurred in an East Asian country (10)). In this context with varied prevalence rates of NP, we suggest that cross-domain and multinational research using unified standards should be conducted in the future. However, based on our results, we suggest that it is not necessary to use neuropathic tools to regularly screen patients with KOA in the outpatient department.
There are a limited number of studies focused on the prevalence of NP in patients during the preoperative-TKA period, and the reported prevalence has shown a wide range of differences. In one study, after investigating 96 patients during the preoperative TKA period, Phillips reported that only one in ninety-six patients had a PainDETECT score greater than 19 (14). In contrast, Kurien found that NP existed in 30% of patients before TKA (22). In our study, 2.5% of patients likely had NP, while 17.5% of patients possibly had NP in the pre-TKA group. This result is in the range of previous research (1.0%-30%) and showed a relatively low prevalence of NP. However, compared with the prevalence in the outpatient department patients, the prevalence of NP in patients during the pre-TKA period was dramatically higher. Because the waiting time for TKA varies from months to years across different hospitals, we suggest that screening for NP in patients waiting for TKA and providing anti-NP medication may be useful to relieve their pain during the waiting period.
This study confirms that although TKA is effective in relieving pain, a certain proportion of patients still endure persistent pain, and NP contributes to persistent pain after TKA. However, the prevalence of NP after TKA varied from 0-15% in different reports depending on the follow-up time and population investigated. For example, Albayrak reported that 15.3% of patients likely have NP, the prevalence increased up to 22.9% in the severe pain patients (NRS>3) (15), while Masahiro Hasegawa reported 9% of patients after TKA endure unclear pain, although no patients met the criteria for likely NP according to the PainDETECT questionnaire in Japan (16). A review estimated that the prevalence of NP ranges from 5.2% to 13% in the 6-month postoperative period (23). Compared with these results, our study demonstrated a relatively low prevalence of NP after TKA and similar rate as Masahiro Hasegawa’s research. Despite the fact that medications for anti-NP have been demonstrated to be useful for the treatment of persistent pain after TKA in several reports (24, 25), due to the low prevalence of NP after TKA, we suggest that it is not necessary to regularly screen for NP in these patients.
Numerous risk factors of NP have been identified in KOA patients. Hochman found the pain intensity, presence of referred back/hip pain, number of painful joints and one or more self-reported neurological conditions were risk factors of NP in KOA patients (11). Albayrak reported that being widowed, having a low education level, being a housewife, having employment that required physical effort, having presurgical pain at rest and having presurgical restricted walking distance were risk factors for NP after TKA (15). Moreover, pain intensity and PainDETECT scores have been strong correlated in several studies (10, 14, 26-28). In line with their results, we also found that the NRS and WOMAC pain scores had high correlations with NP, and the patients with high NRS and WOMAC pain scores had a higher risk of NP. Therefore, due to the strong correlation between pain intensity and NP, we suggest evaluating NP in patients with high NRS and WOMAC pain scores. In the future, more risk factors should be investigated to help clinicians identify these patients.
This study has some limitations. First, we did not investigate the length of time with knee pain, which limited further analyses with correlations of NP and time because central sensitization may depend on the duration of persistent pain. Therefore, the time issue should be considered in future research. Second, the changes in NP before and after TKA in the same patients were not recorded in this study. Whether NP existing before TKA affects the development of NP after TKA remains unclear. This should be clarified in future research.
Our study has implications for both clinical practice and future research. Compared with medications treating nociceptive pain, the treatment strategy for NP is different and includes antidepressant, antiepileptic, topical anesthetic, and opioid agents (29). However, because the prevalence of NP is different depending on the treatment stages of KOA, clinicians should consider NP features in different treatment stages and develop a personalized pain treatment strategy, especially in patients waiting for TKA with higher NRS and WOMAC pain scores. In addition, the mechanisms of NP should be further elucidated, which may help to treat NP in these patients.