Table 4

Associations between inflammatory signs and measures of altered pain perception mechanisms

StudyAssociationsResultsConfoundersLevel of evidence
Effusion/synovitis and pain sensitivity
Petersen et al49A significant BLOKS group effect in the ANOVA of the PPTsSite 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 ageB
Neogi et al50Hoffa-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 analgesicsA2
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 al47Synovitis—PPTr=−0.02, N.S.N.A.C
BMLs and pain sensitivity
Neogi et al50BMLs—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 analgesicsA2
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 al47BML_load—PPTr=−0.069, N.S.N.A.C
nBML—PPTr=−0.114, N.S.
Inflammatory cytokines and pain sensitivity
Imamura et al43IL-6—PPTN.S./C
TNF-α—PPTSignificantly associated with the majority of PPT measures of the muscular, ligamentous or subcutaneous sources (p<0.05)
Lee et al44Log IL-6—PPT quadricepsF=0.98, p=N .S.BMIC
Log IL-6—(PPT quadriceps)²N.S.
Log IL-6—PPT thumbF=0.02, N.S.
Log IL-6—(PPT thumb)²N.S.
Log IL-6—PPT trapeziusF=0.97, N.S.
Log IL-6—(PPT trapezius)²N.S.
Log IL-6—HPTF=0.27, N.S.
Log IL-6—HPR at 49°CF=4.51, p=0.04
Log IL-6—(HPR at 49°C)²F=4.27, p=0.05
Log IL-6—HPR at 51°CF=5.79, p=0.02
Log IL-6—(HPR at 51°C)²F=5.26, p=0.03
Log IL-6—CPRF=0.03, p=N .S.
Log IL-6—CPR²N.S.
Log IL-6—CPTF=5.96, p=0.02
Log IL-6—CPT²F=6.57, p=0.02
IL-1β—pain measuresN.S., data N.R.
TNF-α—pain measuresN.S., data N.R.
C reactive protein and pain sensitivity
Arendt-Nielsen et al42hsCRP—local/spreading sensitisation/TSAssociation sign, data N.R.UnadjustedB
Lee et al44Log CRP—PPT quadricepsF=8.13, p=0.009UnadjustedC
Log CRP—(PPT quadriceps)²F=6.58, p=0.02
Log CRP—PPT thumbF=7.44, p=0.01
Log CRP—(PPT thumb)²N.S.
Log CRP—PPT trapeziusF=9.99, p=0.004
Log CRP—(PPT trapezius)²F=9.36, p=0.006
Log CRP—HPTF=0.55, p=N .S.
Log CRP—HPR at 49°CF=1.17, N.S.
Log CRP—(HPR at 49°C)²N.S.
Log CRP—HPR at 51°CF=1.96, N.S.
Log CRP—(HPR at 51°C)²N.S.
Log CRP—CPRF=5.20, p=0.03
Log CRP—CPR²F=5.11, p=0.03
Log CRP—CPTF=0.74, N.S.
Effusion/synovitis and neuropathic-like pain
Radojčić et al4611-point synovitis—NPQr=0.25, p=0.011BMI, sex and ageC
Inflammatory cytokines and neuropathic-like pain
Li et al45IL-1β—painDETECTr=−0.019, N.S.N.A.C
IL-6—painDETECTr=−0.034, N.S.
TNF-α—painDETECTr=−0.115, N.S.
Radojčić et al46Plasma IL-6—NPQβ=4.029 (95% CI: −0.032 to 0.838)BMI, sex and ageC
Synovial fluid IL-6—NPQβ=0.043 (95% CI: 0.005 to 0.082)
Tchetina et al48TNF-α—DN4r=0.330, p=0.02N.A.C
IL-1β—DN4r=0.496, p<0.01
IL-1β—painDETECTr=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.