AIM: To observe the effect of acupuncture on adenosine A1 receptor (A1R) in the caudate putamen (CPu) of complete Freund's adjuvant (CFA) rats, and to explore the potential mechanism of acupuncture in treatment of inflammatory pain. METHODS: Sixty-four 6~8-week-old male Wistar rats were randomly divided into saline group, model group (CFA group), CFA+manual acupuncture (MA) group, CFA+solvent dimethyl sulfoxide (DMSO) group, CFA+A1R agonist 2-chloro-N6-cyclopentyladenosine (CCPA) group, CFA+A1R antagonist 8-cyclopentyl-1, 3-dipropylxanthine( DPCPX) group, CFA+MA+DMSO group and CFA+MA+DPCPX group. In MA groups, on the 2nd day after modeling, the rats were needled at Zusanli points on both sides, 30 min at a time, once per day, for 7 d. Pain threshold of plantar thermal radiation was used to observe the pain response of the rats. The content of cyclic adenosine monophosphate (cAMP) in the CPu was detected by ELISA. The protein expression and phosphorylation levels of protein kinase A (PKA) and cAMP response element-binding protein (CREB) were detected by Western blot. The expression of A1R in the CPu was detected by immunofluorescence staining. RESULTS: Compared with saline group, CFA modeling significantly lowered the thermal pain threshold of the rats (P<0. 01). Compared with CFA group, the thermal pain threshold of the rats in CFA+MA group and CFA+CCPA group was significantly increased (P<0. 05 or P<0. 01). Compared with CFA+ MA+DMSO group, the thermal pain threshold of the rats in CFA+MA+DPCPX group was decreased (P<0. 05). Compared with CFA group, A1R protein relative expression level and positive cells in the CPu of the rats in CFA+MA group were increased (P<0. 05 or P<0. 01). Compared with saline group, cAMP content and p-CREB protein level in the CPu of the rats in CFA+MA group were decreased (P<0. 05). Compared with CFA+DMSO group, cAMP content and p-CREB protein level in CFA+MA+DMSO and CFA+CCPA groups were significantly decreased (P<0. 01). Compared with CFA+MA+ DMSO group, the levels of cAMP, p-PKA and p-CREB in CFA+MA+DPCPX group were significantly increased (P<0. 05 or P<0. 01). CONCLUSION: Acupuncture on bilateral Zusanli can relieve inflammatory pain in CFA rats, and its mechanism may be related to A1R/cAMP/p-CREB signaling pathway. [ABSTRACT FROM AUTHOR]