The patterns of associations were much weaker in patients listed for TKR than THR (Table 3). In the minimally adjusted models, there was no evidence of an association of PPTs with total, movement, or rest pain before surgery (P > 0.1). However, following more complete adjustment, the strength of the association increased to borderline significance for total pain severity (P = 0.047). Similarly, a weak association between PPTs and preoperative total pain severity (P = 0.045), but not movement pain or rest pain, was found in the linear mixed model (Table 4).
In the minimally and fully adjusted linear regression models, there was strong evidence of an association between preoperative PPTs and pain severity at 12 months after surgery (P = 0.01 and P = 0.015, respectively; Table 3). These models showed that lower PPTs were associated with more severe pain at 12 months after surgery. When the analyses were repeated with movement pain and rest pain, PPTs were associated with movement pain, but not rest pain, at 12 months after surgery (Table 3).
There was no evidence of an association between preoperative PPTs and pain severity at 12 months after surgery in any of the linear regression models (Table 3). Similarly, further analysis found that PPTs were not associated with rest pain or movement pain at 12 months postoperative (Table 3).
There was no evidence of any association between PPTs and change in pain score from preoperative to 12 months after TKR, using either the prospective analysis adjusted for preoperative PPTs or the linear mixed model approach (Tables 3 and 4). This finding was the same when the analyses were repeated for movement pain and rest pain. Further analyses using PPT tertiles to explore the relationship between preoperative PPTs and change in pain scores showed similar results (Web appendix, available as Supplemental Digital Content, at http://links.lww.com/PAIN/A0).
Additionally, analyses were conducted in both the TKR and THR cohort to explore the interaction of gender with preoperative pain severity, change in pain severity, PPTs and preoperative pain severity, and PPTs and change in pain severity. No strong evidence of an interaction was observed (data not shown).
This study provides novel insight into the impact of preoperative widespread pain sensitivity on chronic pain after THR and TKR. We found a strong association between widespread pressure pain sensitivity and preoperative pain severity in a large sample of patients with advanced hip osteoarthritis (n = 254) and a weaker association in patients with advanced knee osteoarthritis (n = 239). Our longitudinal study design allowed us to find that the association between preoperative PPTs and pain severity still persists at 12 months after THR, but not in TKR. However, despite the association between PPTs and pain severity, we demonstrated that preoperative PPTs did not influence the efficacy of THR or TKR in providing pain relief. This finding suggests that preoperative widespread pressure pain sensitivity does not influence the amount of pain relief that patients gain from joint replacement, independent of preoperative pain severity.
Approximately 10% of patients with THR and 20% of patients with TKR report an unfavorable pain outcome between 3 months and 5 years after surgery. Why some patients develop chronic postsurgical pain is not yet clear because of the complex nature of this condition.8 In addition to the contribution of demographic and socioeconomic factors, research has highlighted the importance of a number of potentially modifiable factors in chronic postsurgical pain, including other chronic pain conditions,55 severity of acute postoperative pain,2 surgical factors,12,51 pain perception abnormalities,31,58 and psychosocial factors, such as depression, anxiety, stress, and pain catastrophizing.12,20,35 Given the multifactorial nature of chronic postsurgical pain, future research into prevention through preoperative screening to identify patients at high risk would need to incorporate a range of potential risk factors. However, as this is an emerging field of research, the individual risk factors need to be explored in detail to determine their potential predictive value and optimal assessment methods.
The findings from our analysis of preoperative data add to the growing literature that demonstrates that higher intensity joint pain is associated with greater widespread pain sensitivity in patients with osteoarthritis.3,4,16,37 However, we are unable to draw conclusions as to the direction of this relationship. The observed association could be interpreted in 2 ways: the severity of joint pain is heightened because of widespread pain sensitization, or widespread pain sensitization is driven by peripheral nociceptive input from the osteoarthritic joint. In support of the first theory, a study of patients with osteoarthritis found that patients with mild structural joint change but high pain had more widespread pain sensitization than patients with severe joint change and high pain, suggesting that some patients with osteoarthritis may have pain that is more driven by changes within the central nervous system than peripheral factors.16 Another study found that there was no association between duration of osteoarthritis symptoms and the extent of widespread pain sensitization, and the authors propose the possibility that pain sensitization is a “trait” rather than a state induced by osteoarthritis pain.37 However, the data to date have been cross-sectional and further longitudinal research is needed before causality can be determined.
There has been increasing interest in the application of QST in a surgical context. Many studies in this field have focused on the potential for preoperative QST to predict the severity of acute postoperative pain.17 Specific to orthopedics, studies have demonstrated that preoperative QST parameters are predictive of acute postoperative pain severity52 and morphine consumption.34 However, with the growing recognition of chronic postsurgical pain,32 the focus has turned toward investigating whether preoperative pain perception abnormalities are predictive of chronic postsurgical pain. This relationship has been explored in a wide range of surgical settings, including hernia repair,1 laparoscopic cholecystectomy,9 shoulder surgery,19 thoracotomy,59 and hysterectomy.11 The findings from these studies are mixed, although some report an association between preoperative QST and chronic postsurgical pain, suggesting that increased preoperative widespread pain sensitivity may be a risk factor for chronic postsurgical pain.19,59 Within the context of orthopedic surgery, a number of studies have demonstrated that preoperative pain perception abnormalities normalize after successful joint replacement surgery.3,18,26,27 Regarding the investigation of the predictive value of preoperative QST parameters, only a limited number of small studies have been conducted and these have demonstrated an association between measures of widespread pain sensitization and chronic pain after joint replacement.31,58 However, our study demonstrates that the observed associations between preoperative QST results and the severity of chronic pain after joint replacement are because of preoperative pain severity and that widespread pain sensitization does not influence the amount of long-term pain relief that patients gain from surgery.
Strengths of this study include the large sample size, long-term postoperative follow-up, use of validated outcome measures to assess pain, and good rates of data collection for the PPTs and questionnaire data. Our longitudinal study design allowed us to prospectively collect data and therefore draw conclusions on causality, an advantage over previous cross-sectional studies.38,47 Demographic and socioeconomic factors known to influence the pain experience, such as age, gender, cohabitation, and educational attainment, were adjusted for in the analyses. The study sample population is representative of the population undergoing THR and TKR as a whole with a similar disease profile, gender mix, and age range as reported by the National Joint Registry of England and Wales,36 and thus we believe the results to be generalizable. However, it is important to acknowledge the limitations of the study when interpreting the results. Pressure pain thresholds were measured as they have been shown to be a reliable and sensitive measure of pain sensitization in patients with osteoarthritis,50,56 and measurements are quick and easy to perform in a clinical setting. However, pain thresholds are a “static” measure and only assess a single point on a continuum of the pain experience.17 Assessing dynamic responses to pain, such as through assessing temporal summation or conditioned pain modulation, may provide further insight into pain modulation processes. In terms of the statistical analysis, many patients reported no pain at 12 months after surgery; it is possible that this ceiling effect observed on the WOMAC pain score may have been masking an effect modification of QST. In addition, the creation of tertiles is somewhat arbitrary; however, there was no evidence of nonlinearity following the inclusion of higher-order quadratic terms. Finally, there are many factors that can influence chronic postoperative pain, and while theoretically, we could have accounted for more of these factors in our analyses, such as psychosocial factors, existence of other chronic pain conditions, previous joint surgery, use of analgesics and acute postoperative pain severity, model convergence becomes difficult. Therefore, we controlled for key confounding variables including demographic and socioeconomic factors.
These findings have both methodological and clinical implications. In terms of methodology, our study highlights that simple analyses investigating the association between preoperative widespread pain sensitivity and postoperative pain severity need to be interpreted with caution, as they fail to fully account for the influence of preoperative pain severity. Using longitudinal multilevel modeling approach allows for analyses to investigate the change in pain severity over time, independent of preoperative pain severity. In terms of clinical implications, our findings provide novel evidence that preoperative widespread pressure pain sensitivity is not associated with the amount of pain relief that patients gain from joint replacement, independent of preoperative pain severity. Previous research has found that preoperative pain-processing abnormalities normalize after joint replacement, suggesting that these abnormalities are maintained by peripheral nociceptive input.3,18,26 Our findings support this hypothesis and provide evidence that preoperative widespread pain sensitivity is not a predictor of response to joint replacement, suggesting that this particular QST parameter would add little value to a preoperative screening protocol to identify patients at high risk of not responding to joint replacement surgery. Further research is needed to confirm these findings and explore whether other measures of altered preoperative pain processing demonstrate similar results.
The authors have no conflicts of interest to declare. This article presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research program (RP-PG-0407-10070). The views expressed in this article are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. The research team acknowledges the support of the NIHR, through the Comprehensive Clinical Research Network.
The authors thank all patients and staff at the Avon Orthopaedic Centre who were involved in the APEX trials. Particular thanks go to the following consultant orthopedic surgeon and anesthetists: Gordon Bannister, John Church, Steve Eastaugh-Waring, Alan Gibson, Williams Harries, Paul Harvie, Katherine Jenkins, Michael Kelly, Nick Koehli, John Leigh, Sanchit Mehendale, Ronelle Mouton, Andrew Porteous, and Jason Webb. The authors also thank the following people who were involved in data collection: Debbie Delgado, Louise Hawkins, Cindy Mann, Leigh Morrison, Dave Rea, Jenny Tyler, and Connie Jamera.
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