Altered pain processing and sensitisation is evident in adults with patellofemoral pain: a systematic review including meta-analysis and meta-regression

Background and aims: Previous systematic reviews have reported manifestations of pain sensitisation as a feature of painful knee disorders, in particular osteoarthritis, with moderate evidence for pain sensitisation in patellofemoral pain (PFP). However, despite past studies recruiting female mostly adolescent PFP patients, it is unclear if sex or age plays a role. Investigation is required to determine if altered pain processing is a key feature of PFP and if a subgroup of patients is at an increased risk to help provide targeted management. The primary aim of this systematic review was to examine evidence investigating pain processing in PFP. Secondary aims were to evaluate the relationship between pain processing and (1) sex, (2) age and (3) symptom duration. Methods: The protocol was prospectively registered with PROSPERO (CRD42019129851). PubMed, CINAHL, Web of Science and EMBASE were systematically searched from inception to April 2019 for studies investigating pain processing in PFP patients compared to controls using quantitative sensory testing. Each included paper was assessed for methodological quality using a modified version of Downs and Black. Means and standard deviations were extracted to calculate standardised mean differences (SMD) and 95% confidence intervals (95% CI). Where possible meta-analysis and meta-regression were performed using a random effects model. Results: Eleven studies were identified, two medium and nine high quality. Meta-analysis indicates moderate evidence for decreased pressure pain thresholds (SMD-0.68, 95% CI-0.93 to -0.43), increased tactile detection thresholds (SMD 1.35, 95% CI 0.49-2.22) and increased warmth detection thresholds (SMD 0.61, 95% CI 0.30-0.92) in PFP patients compared to controls. Secondary analysis indicates moderate evidence for decreased pressure pain thresholds in female compared to male patients (SMD -0.75, 95% CI-1.34 to -0.16). Meta-regression indicates a moderate correlation between decreasing local and distal pressure pain thresholds and decreasing patient age (local R-2 = 0.556, p = 0.0211; distal R-2 = 0.491, p = 0.0354) but no correlation with symptom duration (p > 0.05). Conclusions: Evidence from this systematic review with meta-analysis and meta-regression appears to suggest the presence of altered pain processing and sensitisation in patients with PFP with increased sensitivity indicated in female patients and younger patients.