Table 5

Level of conclusion for associations between inflammatory signs and altered pain perception (pain sensitivity and neuropathic-like pain)

Associations	Level of evidence					Level of conclusion
Inflammatory signs—pain sensitivity	A1	A2	B	C	D	Level of conclusion
Effusion/synovitis		Neogi et al50[+]	Petersen et al49[+]	Sofat et al47[ns]		2
BMLs		Neogi et al50[ns]		Sofat et al47[ns]		2
Pro-inflammatory cytokines						4
IL-1β				Lee et al44[ns]
IL-6				Imamura et al43[ns]
IL-6				Lee et al44[+]
TNF-α				Imamura et al43[ns]
TNF-α				Lee et al44[+]
CRP			Arendt-Nielsen et al42[+]	Lee et al44[+]		3
Inflammatory signs—neuropathic-like pain
Effusion/synovitis				Radojčić et al46[+]		4
Pro-inflammatory cytokines						4
IL-1β				Li et al45[ns]
IL-1β				Tchetina et al48[+]
IL-6				Li et al45[ns]
IL-6				Radojčić et al46[ns]
TNF-α				Li et al45[ns]
TNF-α				Tchetina et al48[+]

Level of evidence: A1=systematic reviews and meta-analyses, based on minimally two independent A2 studies; A2=prospective cohort studies with sufficient sample size and follow-up; adequately controlled for confounding factors and precluding selective loss to follow-up; B=prospective cohort studies, but lacking the quality criteria of A2; retrospective cohort studies and case–control studies; C=non-comparative studies; D=expert opinion. [+] Significant positive association. [ns] Not significant association. [-] Significant negative association.
Level of conclusion: 1=one A1 or at least two independent A2 studies that support each other’s conclusions and do not show conflicting evidence; 2=one A2 or at least two independent B studies that support each other’s conclusions and do not show conflicting evidence; 3=one B or at least two C studies that support each other’s conclusions and do not show conflicting evidence; 4=research at level C or two or more independent studies at higher level that do not support each other’s conclusions and hence, show conflicting evidence; consensus=there is no evidence, but consensus (level D); no conclusions=there is no evidence and no consensus.
BMLs, bone marrow lesions; CRP, C reactive protein; IL, interleukin; TNF-α, tumour necrosis factor-α.