Table 1. Study characteristics.

Study/Year	Journal	Country	Study design	KOA diagnostic criteria	Sample characteristics	Evaluation tool	Main findings	p-value
Alshuft et al. (2016)	PLoS One	United kingdom	Case-control	Radiological	KOA group (n = 40, 52.5% female), age = 66.09 ± 8.47 years; control group (n = 30, 56.7% female), age = 62.72 ± 7.44 years	MRI	In KOA compared to control group, a thinner cortex in the right anterior insula and left precuneus cortex (long pain duration) was observed.	both p < 0.001
Baliki et al. (2011)	PLoS One	United State of America	Case-control	Medical	KOA group (n = 20, 20% female), age = 53.50 ± 7.4; control group (n = 46, 56.5% female) age = 38.77 ± 12.5 years	MRI	In KOA compared to control group, decreased GM density in the insula, middle ACC, hippocampus, paracentral lobule, visual cortex, and regions of the inferior temporal cortex was observed.	NI
Baliki et al. (2014)	PLoS One	United State of America	Case-control	Medical	KOA group (n = 14, 42,9% female), age = 58.29 (42–77) years; control group (n = 36, 66,7% female), age = 41.36 (21–70) years	MRI and rs-fMRI	In KOA compared to control group, decreased connectivity (via the average spatial representation of the DMN) of left SMG region was observed.	p < 0.001
Barroso et al. (2020)	Pain	Portugal	Case-control	Clinical classification of the American College of Reumatology and Kellgren-Lawrence classification	KOA group (n = 91, 79.1% female), age = 65.5 ± 6.5; control group (n = 36, 55.5% female), age 59.2 ± 8 years	MRI and rs-fMRI	Total neocortical GM volume and GM volume in the right and left ACC and paracingulate gyri were not significantly different between the KOA and control group; In KOA compared to control group, decresead volumen in left primary motor cortex (precentral cortex), left temporal pole, and GM volumen in the precuneus cortex was observed; and a increased GM volume in the medial frontal gyrus was observed.	p < 0.001
Barroso et al. (2020)	Human Brain Mapping	Portugal	Case-control	Clinical classification of the American College of Reumatology and Kellgren-Lawrence classification	KOA group (n = 46, 65.2% female), age = 65.3 ± 7.41 years; control group (n = 35, 57.1% female), age = 59.5 ± 7.91 years	MRI and rs-fMRI	Global measures of network topology (e.g., clustering coefficient, global efficiency, betweenness centrality) were no significantly different between KOA and control groups.	NI
Cheng et al. (2022)	Frontiers in Neurology	China	Case-control	Clinical classification of the American College of Reumatology- Kellgren-Lawrence classification	KOA group (n = 166, 76.8% female), age = 52.87 ± 5.23 years; control group (n = 88, 63.3% female), age 53.76 ± 4.82 years	MRI	In KOA compared to control group, increased fractional anisotropy and decreased axial diffusivity, radial diffusivity, and mean diffusivity* in the corpus callosum, corona radiata, longitudinal fasciculus, cingulum, and thalamic radiation were observed.	p < 0.05
Cottam et al. (2016)	NeuroImage: Clinical	United kingdom	Case-control	Radiological	KOA group (n = 26, 53.8% female), age = 67.0 (45–84) years; control group (n = 27, 66.7% female), age 64.5 (43–80) years	rs-fMRI	Global GM cerebral blood flow was not significantly different between KOA and control group.	p > 0.05
Cottam et al. (2018)	Pain	United kingdom	Case-control	Radiological	KOA group (n = 25, 52% female), age = 65.0 (48–84) years; control group (n = 19, 57.9% female), age 65.5 (51–80) years	MRI and rs-fMRI	In KOA compared to control group, increased in the right anterior insula functional connectivity within the cuneus and decreased in right anterior insula functional connectivity in areas associated with the DMN including the posterior cingulate cortex, bilateral parietal areas, and the superior frontal gyrus were observed; In KOA compared to control group, reduced CEN functional connectivity in a single cluster that extended superiorly from the right temporal pole into the inferior frontal gyrus was observed; posterior cingulate cortex functional connectivity displayed a similar extent of the DMN between KOA and control group.	p < 0.05
Gao et al. (2022)	Frontiers in Neurology	China	Pre-experimental	Chinese Guideline for Diagnosis and Treatment of Osteoarthritis (2021 edition)	KOA group (n = 15, 53.3% female), age = 59.13 ± 10.27 years; control group (n = 15, 73.3% female), age = 58.53 ± 8.15 years	rs-fMRI	Periaqueductal gray and raphe nuclei were not significantly different between KOA and control groups at pre-acupuncture.	NI
Guo et al. (2021)	Frontiers in Human Neuroscience	China	Case-control	Radiological	KOA group (n = 13, 100% female), age = 55.5 ± 5.5 years; control group (n = 13, 100% female), age = 53.9 ± 5.6 years	MRI and rs-fMRI	In KOA compared to control group, reduced GM volume in the bilateral insula and bilateral hippocampus was observed; In KOA compared to control group, reduced fractional ALFF in the left cerebellum, left precentral gyrus, and right superior occipital gyrus increased was observed; and increased fractional ALFF in the left insula and bilateral hippocampus was observed.	p < 0.001
Kang et al. (2021b)	Brain and behavior	China	Case-control	Kellgren-Lawrence classification	KOA group (n = 37, 91.9% female), age = 71.6 ± 5.6; control group (n = 37, 81.1% female), age = 69.5 ± 5.1	MRI and rs-fMRI	In KOA compared to control group, decreased GM volume in the left middle TG and left inferior TG was observed; In KOA compared to control group, decreased resting state-functional connectivity in the left middle TG to the superior FG, left middle FG, and left medial superior FG was observed.	p < 0.05
Lan et al. (2020)	Frontiers in Neurology	China	Pre-experimental	Medical and radiological	KOA group (n = 23, 65.2% female), age = 71.2 ± 4.2 years; control group (n = 23, 60.9% female), age = 71.4 ± 4.1 years	rs-fMRI	In KOA compared to control group, decreased ALFF in the bilateral angular, precuneus, and medial superior frontal gyrus was observed; In KOA compared to control group, increased ALFF in the bilateral amygdaloid nucleus and cerebellum posterior lobe was observed.	p < 0.001
Lewis et al. (2018)	Pain Medicine	New Zealand	Pre-experimental	NI	KOA group (n = 29, 51.7% female), age = 68.0 ± 10.0 years; control group (n = 18, 38.9% female), age = 71.0 ± 8.0 years	MRI	In KOA compared to control group, an increase in the GM volume bilaterally in the nucleus accumbens (NAc) and amygdala, and in the ipsilateral primary somatosensory cortex (S1) was observed.	p < 0.01
Liao et al. (2018)	Medicine	China	Case-control	Clinical classification of the American College of Reumatology	KOA group (n = 30, 86.7% female), age = 56.5 ± 6.8 years; control group (n = 30, 86.7% female), age = 55.2 ± 5.7 years	MRI	In KOA compared to control group, a decrease in GM volumne in several cortical structures including the bilateral orbital frontal cortex, the right lateral prefrontal cortex, the precentral and part of postcentral cortex was observed.	p < 0.05
Mao et al. (2016)	Frontiers in Aging Neuroscience	China	Case-control	Clinical classification of the American College of Reumatology	KOA group (n = 26, 84.6% female), age = 55.5 ± 9.1; control group (n = 31, 83.9% female), age = 53.1 ± 6.4 years	MRI	In KOA compared to control group, smaller volumes of caudate nucleus and hippocampus were observed.	P = 0.004
Ushio et al. (2020)	Journal of Pain Research	Japan	Case-control	Kellgren-Lawrence classification	KOA group (n = 19, 100% female), age = 73.2 ± 5.1 years; control group (n = 15, 100% female), age = 74.9 ± 4.6 years	rs-fMRI	In female volunteers with chronic severe KOA compared to control group, the left anterior insular cortex showed stronger resting state-functional connectivity with the right orbitofrontal cortex and the subcallosal area, and the right anterior insulate cortex showed stronger resting state-functional connectivity with the right orbitofrontal cortex, subcallosal area, and the bilateral frontal pole.	p < 0.005

Notes.

Abbreviations

KOA

Knee Osteoarthritis

MRI

Magnetic Resonance Imaging

ACC

Anterior Cingulate Cortex

NI

no informed

DMN

Default Mode Network

SMG

Supramarginal Gyrus

rs-fMRI

Rest State-Functional MRI

GM

Gray Matter

CEN

Central Executive Network

ALFF

Amplitude of Low-Frequency Fluctuation

TG

Temporal Gyrus

FG

Frontal Gyrus

NAc

Nucleus Accumbens