Objective:To investigate the effect of protocatechuic acid on chronic neuropathic pain (NP) and its mechanism in rats.Methods:NP models were established in 32 SD rats by sciatic nerve ligation, and they were randomly divided into model group, low- and high-dose protocatechuic acid groups, and ibuprofen group ( n=8); on the 3 rd d of modeling, rats in the latter 3 groups were given 10 or 20 mg/kg protocatechuic acid solution via jugular vein injection or 20 mg/kg ibuprofen tablets by gavage, once a d for consecutive 21 d. A sham-operated group ( n=8) was set up; the sciatic nerve was dissociated but not ligated. The behavioral performance of rats in each group was continuously observed; on the 7 th, 14 th and 21 st d of administration, the mechanical pain threshold of both hind limbs of rats was measured by von-Frey filament stimulation and the thermal pain threshold was measured by BME-410A thermal pain stimulator. Then, rats were sacrificed. The serum levels of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) were detected by ELISA. Cell apoptosis in the spinal cord tissues was observed by TUNEL. Western blotting was used to detect the expressions of nuclear factor-κB (NF-κB)/NOD-like receptor pyrin domain-related protein 3 (NLRP3) signaling pathway related proteins in the spinal cord tissues. Results:On the 7 th, 14 th, and 21 st d of administration, the thermal pain threshold and mechanical pain threshold in the model group were significantly decreased as compared with those in the sham-operated group ( P<0.05); as compared with those in the model group, those in the low- and high-dose protocatechuic acid groups and ibuprofen group were significantly increased ( P<0.05); as compared with those in the low-dose protocatechuic acid group, those in the high-dose protocatechuic acid group and ibuprofen group were significantly increased ( P<0.05); those in the ibuprofen group were significantly increased as compared with those in the high-dose protocatechuic acid group ( P<0.05). (2) On the 21 st d of administration, as compared with those in sham-operated group, the serum levels of TNF-α and IL-1β and number of apoptotic cells in the spinal cord tissues of the model group were significantly increased ( P<0.05); as compared with those in the model group, those in the low- and high-dose protocatechuic acid groups and ibuprofen group were significantly decreased ( P<0.05); as compared with those in the low-dose protocatechuic acid group, those in the high-dose protocatechuic acid group and ibuprofen group were significantly decreased ( P<0.05); those in the ibuprofen group were significantly decreased as compared with those in the high-dose protocatechuic acid group ( P<0.05). (3) On the 21 st d of administration, the protein expressions of phosphorylated (p)-NF-κb-65 (0.77±0.05), NLRP3 (1.03±0.08), apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1 and IL-1β in the spinal cord of rats in the model group were significantly increased as compared with those in the sham-operated group ( P<0.05); as compared with those in the model group, those in the low- and high-dose protocatechuic acid groups were significantly decreased (p-NF-κB-65: 0.49±0.03, 0.25±0.02; NLRP3: 0.81±0.06, 0.69±0.04; P<0.05); as compared with those in the low-dose protocatechuic acid group, those in the high-dose protocatechuic acid group were significantly decreased ( P<0.05). Conclusion:Protocatechuic acid may alleviate pain in chronic NP rats by downregulating NF-κB/NLRP3 signaling pathway transduction.