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Individuals with KOA knee pain were divided randomly into groups of verum acupuncture (VA), sham acupuncture (SA), celecoxib (SC), placebo (PB), and waiting list (WT), with 36 patients in each group. VA and SA groups included ten sessions of puncturing acupoints or puncturing non\u2010acupoints acupuncture treatment for two successive weeks. Celecoxib capsules were continuously given orally to patients in the SC group at a dosage of 200\u2009mg daily for 2\u2009weeks. In the PB group, patients received a placebo capsule once a day for 2\u2009weeks at the same dosage as celecoxib capsules. In the WL group, patients did not receive any treatment. Patients underwent a resting\u2010state BOLD\u2010fMRI scan pre\u2010 and post\u2010receiving the therapy, whereas HCs only underwent a baseline scan. Seed (ventrolateral periaqueductal gray, vlPAG, a key node in DPMS) based resting\u2010state functional connectivity (rs\u2010FC) was applied in the data analysis.<\/jats:p><\/jats:sec>Results<\/jats:title>All groups demonstrated improved knee pain scores relative to the initial state. There was no statistical difference between the VA and SA groups in all clinical outcomes, and vlPAG rs\u2010FC alterations. KOA knee pain individuals reported higher vlPAG rs\u2010FC in the bilateral thalamus than HCs. KOA knee pain patients in the acupuncture group (verum\u2009+\u2009sham, AG) exhibited increased vlPAG rs\u2010FC with the right dorsolateral prefrontal cortex (DLPFC) and the right angular, which is associated with knee pain improvement. In contrast with the SC and PB group, the AG exhibited significantly increased vlPAG rs\u2010FC with the right DLPFC and angular. Contrary to the WT group, the AG showed greater vlPAG rs\u2010FC with the right DLPFC and precuneus.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Acupuncture treatment, celecoxib, and placebo medication have different modulation effects on vlPAG DPMS in KOA knee pain patients. Acupuncture could modulate vlPAG rs\u2010FC with brain regions associated with cognitive control, attention, and reappraisal for knee pain relief in KOA patients, compared with celecoxib and placebo medication.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14153","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T05:08:05Z","timestamp":1678338485000},"page":"1965-1980","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Modulation effects of different treatments on periaqueductal gray resting state functional connectivity in knee osteoarthritis knee pain patients"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9288-6299","authenticated-orcid":false,"given":"Jun","family":"Zhou","sequence":"first","affiliation":[{"name":"Chengdu University of Traditional Chinese Medicine Chengdu 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