Table 2

Characteristics of included studies (n=9)

Study 1st author, year, country, designParticipants’ characteristicsMarker(s) of inflammationExperimental pain assessmentStatistical analysisQuality
Arendt-Nielsen,42 2014, Denmark, CSPatients grouped according to experimental pain
CPM, knee
Most sensitised: n=42 (52% female); mean age 64.57±7.63 years; BMI=28.98±5.64 kg/m2; KL=1.95±0.94
Medium sensitised: n=193 (30% female); mean age 67.71±3.66 years; BMI=27.46±3.93 kg/m2; KL=1.54±0.69
Least sensitised: n=46 (30% female); mean age 63.40±7.32 years; BMI=27.68±4.03 kg/m2; KL=1.82±0.85
TS, knee
Most sensitised: n=46 (49% female); mean age 65.37±5.87 years; BMI=26.82±3.75 kg/m2; KL=1.77±0.72
Medium sensitised: n=187 (55% female); mean age 65.80±7.28 years; BMI=28.20±4.64 kg/m2; KL=1.74±0.83
Least sensitised: n=48 (37% female); mean age 63.37±7.95 years; BMI=30.14±4.78 kg/m2; KL=2.04±0.77
OA definition: ACR
Symptoms duration: N.R.
OA duration: N.R.
Blood samples
Serological markers: hsCRP
PPT (8 knee locations, muscle tibialis anterior, muscle extensor carpi radialis)
TS (pressure pain)
Repeated measures ANOVA and post-hoc test (t-test with Bonferroni correction)Good
Imamura,43 2015, Brazil, CSOA group: n=53 (100% female); mean age 71.23±7.62 years; BMI=28.33±5.95 kg/m2
OA definition: ACR, KL grade 2–4 and VAS >4 (averaged daily pain for the past month and lasting ≥3 months)
Symptoms duration: at least 24 months; median 96 months (range 36–150)
OA duration: N.R.
Blood samples
Proinflammatory cytokines: IL-6, IL-8, TNF-α
Anti-inflammatory cytokine: IL-10
PPT over vastus medialis, adductor longus, rectus femoris, vastus lateralis, tibialis anterior, peroneus longus, iliacus, sartorius, gracilis, quadratus lumborum and popliteus
PPT over supraspinous ligaments (L1–L2, L2–L3, L3–L4, L4–L5, L5–S1, S1–S2)
Hyperalgesia: pinch and roll manoeuvre at the L1, L2, L3, L4, L5, S1 and S2 dermatomes
Spearman correlation
Mann-Whitney U
Lee,44 2011, USA, CSOA group: n=26 (76.9% female); mean age 59±7.5 years; BMI=27.5 (IQR: 24.8–32.6) kg/m2
OA definition: clinically diagnosed knee OA, documented by a physician
Symptoms duration: N.R.
OA duration: N.R.
Controls: n=33 (69.7% female); mean age 57.7±10.3 years; BMI=27.9 (IQR: 24.3–30.0) kg/m2
Blood samples
CRP, IL-6, IL-1β, TNF-α
PPT at the trapezius, 1st metacarpophalangeal joint and quadriceps
Heat pain threshold+suprathreshold heat pain ratings on ventral forearm
Cold pressor task
General linear mixed modelsFair
Li,45 2020, China, CSn=83 (74.7% female); mean age 63.4±10.4 years; BMI=N.R.
OA definition: ACR
KL grade
1: 20
2: 48
3: 12
4: 3
Symptoms duration: N.R.
OA duration: N.R.
SF samples
Inflammatory cytokines:
IL-1β, IL-6, TNF-α
painDETECTSpearman correlationFair
Neogi,50 2016, USA, cohortn=1111 with knee OA or at risk (62% female), mean age 66.9±7.5 years; BMI=29.7±4.8 kg/m2; 38% with radiographic knee OA
Subjects free of TS at baseline
n=716 (61% female); mean age 66.3±7.4 years; BMI=29.7±4.8; 37% with radiographic knee OA
OA definition: sample from MOST Study
KL grade 0–3 and frequent knee pain in the past 30 days or no frequent pain, but with at least one risk factor (history of knee injury/operation, overweight/obese)
Symptoms duration: N.R.
OA duration: N.R.
Hoffa-synovitis (0–3) (WORMS)
Effusion (0–3) (WORMS)
BMLs (0–3) (WORMS)
PPT knee (peripheral sensitisation)
PPT wrist (central sensitisation)
TS mechanical (central sensitisation)
Linear regression
Logistic regression
Conditional logistic regression
Petersen,49 2016, Denmark, CCPatients with KOA
n=16 (75% female), mean age 67.9±5.75 years; BMI=30.5±3.0 kg/m2; KL grade: 3.9 (95% CI: 3.7 to 4.0)
OA duration: 11.5 years (95% CI: 4.2 to 18.8)
Symptoms duration: N.R.
n=24 (46% female), mean age 67.5±4.9 years; BMI=30.7±2.65 kg/m2; KL grade: 4 (95% CI: 4.0 to 4.0)
OA duration: 13.5 years (95% CI: 8.8 to 18.1)
Symptoms duration: N.R.
BLOKS 2 and 3
n=21 (57% female), mean age 69.1±4.1 years; BMI=29.1±2.7 kg/m2; KL grade: 3.9 (95% CI: 3.7 to 4.0)
OA duration: 15.3 years (95% CI: 10.0 to 20.6)
Symptoms duration: N.R.
OA definition: patients with KOA scheduled for TKA
VAS <10 mm, KL <2, no long-lasting pain problems in the past year
n=33 (55% female), mean age 66.3±1.8 years; BMI=27.0±1.4 k g/m2
Degrees of synovitis: no (BLOKS 0), low (BLOKS 1), moderate (BLOKS 2) or severe (BLOKS 3)
PPT (7 sites in the peripatellar region)ANOVAFair
Radojčić,46 2017, Denmark, CSn=104 (62% female); mean age 66.78±7.24 years; BMI=30.4±5.21 kg/m2
OA definition: ACR (clinical and radiological); patients scheduled for TKA
Symptoms duration: ≥6 months before enrolment
OA duration: N.R.
Synovitis (MOAKS)
Effusion/synovitis (MOAKS)
Synovitis (11-point score on CE images)
Blood and SF
Plasma IL-6
NPQSpearman correlation
Linear regression
Logistic regression
Sofat,47 2019, UK, CSPatients with OA (n=120)
Advanced OA
n=78 (64% female); mean age 68.9±7.7 years; BMI=32.3±5.6 kg/m2
Mild OA
n=42 (71% female); mean age 64.1±9.6; BMI=29.2±4.7 kg/m2
OA definition: ACR; KL grade ≥2
Symptoms duration: N.R.
OA duration: N.R.
Synovitis (MOAKS)
BML load (MOAKS)
  • 5 areas on the knee

  • 5 areas on contralateral knee

  • Lateral malleolus

  • Right and left radius

Pearson correlationGood
Tchetina,48 2020, Russia, CSn=50 (74% female); mean age 67.6±7.5 years; BMI=30.5±9.05 kg/m2
3: 37
4: 13
OA definition: ACR, KL
Symptoms duration: permanent pain during the last 3 months before enrolment
OA duration: 9.9 years (range 3–30)
Blood samples
TNF-α, IL-1β gene expression
Spearman correlationFair
  • ACR, American College of Rheumatology; ANOVA, analysis of variance; BLOKS, Boston-Leeds Osteoarthritis Knee Score; BMI, body mass index; BML, bone marrow lesion; CC, case–control; CE-MRI, contrast-enhanced MRI; CPM, conditioned pain modulation; CS, cross-sectional; DN4, Douleur Neuropathique-4 Questions; hsCRP, high-sensitivity C reactive protein; IL, interleukin; KL, Kellgren-Lawrence score; KOA, knee osteoarthritis; MOAKS, MRI Osteoarthritis Knee Score; NPQ, Neuropathic Pain Questionnaire; N.R., not reported; OA, osteoarthritis; PPT, pressure pain threshold; SF, synovial fluid; TKA, total knee arthroplasty; TNF-α, tumour necrosis factor-α; TS, temporal summation; VAS, Visual Analogue Scale; WORMS, Whole Organ MRI Score.