Most studies believe that the analgesic effect of metformin is mainly depends on the activation of AMP-activated protein kinase (AMPK), which can alleviate the nociceptive behavior of animals in a variety of pain models, such as those caused by nerve injury, surgical incision, diabetes neuropathy and chemotherapy (Melemedjian et al., 2011; Tillu et al., 2012; Mao-Ying et al., 2014; Ma et al., 2015; Maixner et al., 2015; Wang et al., 2018; Inyang et al., 2019). This evidence concerns the gene PRKAA1 and diabetic neuropathy.