Prognostics for pain in osteoarthritis: Do clinical measures predict pain after total joint replacement?

Abstract

A significant proportion of osteoarthritis (OA) patients continue to experience moderate to severe pain after total joint replacement (TJR). Preoperative factors related to pain persistence are mainly studied using individual predictor variables and distinct pain outcomes, thus leading to a lack of consensus regarding the influence of preoperative parameters on post-TJR pain. In this prospective observational study, we evaluated knee and hip OA patients before, 3 and 6 months post-TJR searching for clinical predictors of pain persistence. We assessed multiple measures of quality, mood, affect, health and quality of life, together with radiographic evaluation and performance-based tasks, modeling four distinct pain outcomes. Multivariate regression models and network analysis were applied to pain related biopsychosocial measures and their changes with surgery. A total of 106 patients completed the study. Pre-surgical pain levels were not related to post-surgical residual pain. Although distinct pain scales were associated with different aspects of post-surgical pain, multi-factorial models did not reliably predict post-surgical pain in knee OA (across four distinct pain scales) and did not generalize to hip OA. However, network analysis showed significant changes in biopsychosocial-defined OA personality post-surgery, in both groups. Our results show that although tested clinical and biopsychosocial variables reorganize after TJR in OA, their presurgical values are not predictive of post-surgery pain. Derivation of prognostic markers for pain persistence after TJR will require more comprehensive understanding of underlying mechanisms.

Fig 1. Experimental design, timeline and data collected.

Knee and hip osteoarthritis patients entered a 4 visit (V1-V4), pre- and post-total joint replacement surgery, longitudinal, observational study. V1 and V2 occurred before surgery. V3 and V4 took place at 3 and 6 months after surgery. At each visit, participants underwent a series of assessments. *Brain MRI session. mo, months; MRI, magnetic resonance imaging; T1WI, T1-weighted imaging; rsfMRI, resting state functional magnetic resonance imaging; DTI, diffusion tensor imaging.

Fig 2. Recruitment and retention for KOA and HOA, and healthy control participants.

The full battery of assessments was performed in osteoarthritis patients. Healthy individuals were recruited to act as controls in brain imaging analyses (not reported here). All patients were recruited from the same tertiary care hospital. Healthy participants were recruited from the general population in the Porto area. IC, Inclusion criteria; MRI, magnetic resonance imaging; KOA, knee osteoarthritis; HOA, hip osteoarthritis; THR, total hip replacement; TKR, total knee replacement.

Fig 3. Influence of baseline pain levels on post-surgical residual pain.

The scatterplots depict patients’ percentage residual pain after surgery (% residual pain, where 100% = no change from pre-surgical levels, 0% = full recovery) (a), and post-surgery absolute pain intensity (b) relative to pre-surgical levels, as a function of pre-surgical levels, for all four pain outcome measures for KOA and HOA, at 3 (blue) and 6 (red) months post-surgery. Symbols represent subjects. Shaded areas indicate 95% confidence intervals. Results in bold represent statistical significance at p<0.05. BPI Severity, Brief Pain Inventory Pain: severity subscale; HOOS Pain, Hip Injury and Osteoarthritis Outcome Score: pain subscale; NRS, Numeric Rating Scale; SF36 Pain, Short-form (36) Health Survey: pain subscale.

Fig 4. Principal component analysis identified five factors characterizing baseline KOA.

Pain- and affect-related questionnaires, their subscales, and performance measures (prior to surgery) were examined together to identify dominant underlying factors. a. Correlation matrix ordered based on principal component analysis results (Pearson’s r represented by color bar). The five identified components were labeled according to membership properties. b. Factor loadings are shown for the five components. To highlight dominant factors threshold of factor loading was set on 0.5/-0.5, after Promax oblique rotation. 6MWT, six minute walking test; DN4, The Neuropathic Pain 4 questions; HADS(A), The Hospital Anxiety and Depression Scale, Anxiety; HADS(D), The Hospital Anxiety and Depression Scale, Depression; KOOS, Knee Injury and Osteoarthritis Outcome Score, (ADL–Function in daily living), (S -Knee Symptoms), (SR–Function in sport and recreation), (QOL–knee related quality of life); MPQ, McGill Pain Questionnaire, (A–Affective score) (S–Sensory score); PCS, Pain Catastrophizing Scale, (R–Rumination subscale), (M–Magnification subscale), (H–Helplessness subscale); SF36, Short-form (36) Health Survey, (PF–Physical Functioning), (PH–physical role functioning), (EP–emotional role functioning), (EF–energy/fatigue), (E–emotional well-being), (SF–social functioning), (GH–general health); TUG, (Timed -up and go test).

Fig 5. Network representation of OA pain characteristics.

a) Network graphs depict interrelations between clinical and pain-related questionnaire subscale measures at baseline, and at 6 months post-surgery, for KOA and HOA patients. Network communities were derived from the PCA analysis. Links represent the top 25% correlations of each network. b) The bar graph displays mean change of global correlation coefficients (Pearson’s Δr) for KOA and HOA, at 3- and 6-months post-surgery. Both groups had significant change in the overall interrelations between clinical and pain-related characteristics (KOA mean Δr 3months: 0.14, t = 13.37, mean Δr 6months: 0.16 t = 14.93, HOA mean Δr 3months:0.28, t = 8.72, mean Δr 6months:0.26 t = 9.23, p<0.001). The extent of change remained stable from 3 to 6 months post-surgery and was substantially higher in the HOA group at 3 months (t = 4.62, p<0.001) and 6 months (t = 3.44, p<0.001). c) Graph theory-based modularity and mean clustering coefficients for correlation networks at baseline, 3 and 6 months. The HOA networks shows significant topological reorganization 3 months (mcc: t = -8.19, modularity: t = -9.22, p<0.001) and 6 months after surgery (mcc, t = -10.62, modularity, t = -9.02, p<0.001), while KOA remains stable. BL, baseline; 3m, 3 months; 6m, 6 months; Statistical risk probability was computed under 10.000 times repeated random resampling. **p<0.001, *p<0.05.