Study | Associations | Results | Confounders | Level of evidence |
Effusion/synovitis and pain sensitivity | ||||
Petersen et al49 | A significant BLOKS group effect in the ANOVA of the PPTs | Site 1 (ANOVA: F2=3.14, p<0.03) Site 2 (ANOVA: F2=6.59, p<0.001) Site 3 (ANOVA: F2=4.04, p<0.01) Site 4 (ANOVA: F2=3.43, p<0.02) Site 5 (ANOVA: F2=2.40, p<0.07) Site 6 (ANOVA: F2=4.49, p<0.006) Site 7 (ANOVA: F2=1.24, p<0.3) | BMI, sex and age | B |
Neogi et al50 | Hoffa-synovitis (baseline)—PPT patella (baseline) | β=−0.42 (95% CI: −0.67 to −0.18) | Age, sex, BMI, race, study site, KL, presence of patellofemoral OA, depressive symptoms, catastrophising, widespread pain, use of analgesics | A2 |
Hoffa-synovitis (baseline)—PPT patella change (follow-up 24 months) | β=−0.30 (95% CI: −0.52 to −0.08) | |||
Hoffa-synovitis (baseline)—PPT wrist (baseline) | β=−0.19 (95% CI: −0.35 to −0.03) | |||
Hoffa-synovitis (baseline)—PPT wrist change (follow-up 24 months) | β=−0.10 (95% CI: −0.26 to 0.06) | |||
Effusion (baseline)—PPT patella (baseline) | β=0.23 (95% CI: −0.03 to 0.49) | |||
Effusion (baseline)—change PPT patella (follow-up 24 months) | β=−0.04 (95% CI: −0.28 to 0.19) | |||
Effusion (baseline)—PPT wrist (baseline) | β=−0.24 (95% CI: −0.40 to −0.07) | |||
Effusion (baseline)—PPT wrist change (follow-up 24 months) | β=−0.24 (95% CI: −0.41 to −0.08) | |||
Hoffa-synovitis (baseline)—TS patella (baseline) (n=1111) | OR=0.83 (95% CI: 0.63 to 1.08) | |||
Hoffa-synovitis (baseline)—TS patella incident (n=716) | OR=1.12 (95% CI: 0.75 to 1.66) | |||
Hoffa-synovitis (baseline)—TS wrist (baseline) (n=1111) | OR=0.84 (95% CI: 0.75 to 1.66) | |||
Hoffa-synovitis (baseline)—TS wrist incident (n=716) | OR=1.22 (95% CI: 0.85 to 1.75) | |||
Effusion (baseline)—TS patella (baseline) (n=1111) | OR=0.89 (95% CI: 0.67 to 1.18) | |||
Effusion (baseline)—TS patella incident (n=716) | OR=1.54 (95% CI: 1.01 to 2.36) | |||
Effusion (baseline)—TS wrist (baseline) (n=1111) | OR=1.13 (95% CI: 0.85 to 1.51) | |||
Effusion (baseline)—TS wrist incident (n=716) | OR=0.94 (95% CI: 0.66 to 1.35) | |||
Sofat et al47 | Synovitis—PPT | r=−0.02, N.S. | N.A. | C |
BMLs and pain sensitivity | ||||
Neogi et al50 | BMLs—PPT patella (baseline) | β=0.14 (95% CI: −0.16 to 0.08) | Age, sex, BMI, race, study site, KL, presence of patellofemoral OA, depressive symptoms, catastrophising, widespread pain, use of analgesics | A2 |
BMLs—change PPT patella (follow-up 24 months) | β=0.03 (95% CI: −0.25 to 0.31) | |||
BMLs—PPT wrist (baseline) | β=0.05 (95% CI: −0.14 to 0.25) | |||
BMLs—PPT wrist change (follow-up 24 months) | β=−0.10 (95% CI: 0.29 to 0.10) | |||
BMLs sum—PPT patella (baseline) | β=0.03 (95% CI: −0.01 to 0.08) | |||
BMLs sum—change PPT patella (follow-up 24 months) | β=−0.01 (95% CI: −0.05 to 0.04) | |||
BMLs sum—PPT wrist (baseline) | β=0.00 (95% CI: −0.03 to 0.03) | |||
BMLs sum—PPT wrist change (follow-up 24 months) | β=0.00 (95% CI: −0.03 to 0.03) | |||
BMLs—TS patella (baseline) (n=1111) | OR=0.95 (95% CI: 0.68 to 1.32) | |||
BMLs—TS patella incident (n=716) | OR=0.92 (95% CI: 0.56 to 1.49) | |||
BMLs—TS wrist (baseline) (n=1111) | OR=1.04 (95% CI: 0.74 to 1.45) | |||
BMLs—TS wrist incident (n=716) | OR=1.05 (95% CI: 0.68 to 1.62) | |||
BMLs sum—TS patella (baseline) (n=1111) | OR=0.98 (95% CI: 0.93 to 1.03) | |||
BMLs sum—TS patella incident (n=716) | OR=1.00 (95% CI: 0.92 to 1.07) | |||
BMLs sum—TS wrist (baseline) (n=1111) | OR=0.98 (95% CI: 0.93 to 1.04) | |||
BMLs sum—TS wrist incident (n=716) | OR=1.00 (95% CI: 0.94 to 1.07) | |||
Sofat et al47 | BML_load—PPT | r=−0.069, N.S. | N.A. | C |
nBML—PPT | r=−0.114, N.S. | |||
Inflammatory cytokines and pain sensitivity | ||||
Imamura et al43 | IL-6—PPT | N.S. | / | C |
IL-10—PPT | N.S. | |||
TNF-α—PPT | Significantly associated with the majority of PPT measures of the muscular, ligamentous or subcutaneous sources (p<0.05) | |||
Lee et al44 | Log IL-6—PPT quadriceps | F=0.98, p=N .S. | BMI | C |
Log IL-6—(PPT quadriceps)² | N.S. | |||
Log IL-6—PPT thumb | F=0.02, N.S. | |||
Log IL-6—(PPT thumb)² | N.S. | |||
Log IL-6—PPT trapezius | F=0.97, N.S. | |||
Log IL-6—(PPT trapezius)² | N.S. | |||
Log IL-6—HPT | F=0.27, N.S. | |||
Log IL-6—HPR at 49°C | F=4.51, p=0.04 | |||
Log IL-6—(HPR at 49°C)² | F=4.27, p=0.05 | |||
Log IL-6—HPR at 51°C | F=5.79, p=0.02 | |||
Log IL-6—(HPR at 51°C)² | F=5.26, p=0.03 | |||
Log IL-6—CPR | F=0.03, p=N .S. | |||
Log IL-6—CPR² | N.S. | |||
Log IL-6—CPT | F=5.96, p=0.02 | |||
Log IL-6—CPT² | F=6.57, p=0.02 | |||
IL-1β—pain measures | N.S., data N.R. | |||
TNF-α—pain measures | N.S., data N.R. | |||
C reactive protein and pain sensitivity | ||||
Arendt-Nielsen et al42 | hsCRP—local/spreading sensitisation/TS | Association sign, data N.R. | Unadjusted | B |
Lee et al44 | Log CRP—PPT quadriceps | F=8.13, p=0.009 | Unadjusted | C |
Log CRP—(PPT quadriceps)² | F=6.58, p=0.02 | |||
Log CRP—PPT thumb | F=7.44, p=0.01 | |||
Log CRP—(PPT thumb)² | N.S. | |||
Log CRP—PPT trapezius | F=9.99, p=0.004 | |||
Log CRP—(PPT trapezius)² | F=9.36, p=0.006 | |||
Log CRP—HPT | F=0.55, p=N .S. | |||
Log CRP—HPR at 49°C | F=1.17, N.S. | |||
Log CRP—(HPR at 49°C)² | N.S. | |||
Log CRP—HPR at 51°C | F=1.96, N.S. | |||
Log CRP—(HPR at 51°C)² | N.S. | |||
Log CRP—CPR | F=5.20, p=0.03 | |||
Log CRP—CPR² | F=5.11, p=0.03 | |||
Log CRP—CPT | F=0.74, N.S. | |||
Log CRP—CPT² | N.S. | |||
Effusion/synovitis and neuropathic-like pain | ||||
Radojčić et al46 | 11-point synovitis—NPQ | r=0.25, p=0.011 | BMI, sex and age | C |
Inflammatory cytokines and neuropathic-like pain | ||||
Li et al45 | IL-1β—painDETECT | r=−0.019, N.S. | N.A. | C |
IL-6—painDETECT | r=−0.034, N.S. | |||
TNF-α—painDETECT | r=−0.115, N.S. | |||
Radojčić et al46 | Plasma IL-6—NPQ | β=4.029 (95% CI: −0.032 to 0.838) | BMI, sex and age | C |
Synovial fluid IL-6—NPQ | β=0.043 (95% CI: 0.005 to 0.082) | |||
Tchetina et al48 | TNF-α—DN4 | r=0.330, p=0.02 | N.A. | C |
IL-1β—DN4 | r=0.496, p<0.01 | |||
IL-1β—painDETECT | r=0.313, p=0.04 |
ANOVA, analysis of variance; BLOKS, Boston-Leeds Osteoarthritis Knee Score; BMI, body mass index; BMLs, bone marrow lesions; CPR, cold pain rating; CPT, cold pain tolerance; DN4, Douleur Neuropathique-4 Questions; HPR, heat pain rating; HPT, heat pain threshold; (hs)CRP, (high-sensitivity) C reactive protein; IL, interleukin; KL, Kellgren-Lawrence score; N.A., not applicable; NPQ, Neuropathic Pain Questionnaire; N.S., not significant; OA, osteoarthritis; PPT, pressure pain threshold; TNF-α, tumour necrosis factor-α; TS, temporal summation.