. 2023 May 24;9(2):e002945. doi: 10.1136/rmdopen-2022-002945

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.