*** 0.001 compared with sham group, # 0.05, ## 0.01, ### 0.001 compared with SNI+IgG group. Reduction of SIRT1 Is Involved in the Mechanical Allodynia Induced by SNI SIRT1 plays an important role in synaptic plasticity and chronic pain. and IL-1 by IL-33 remain unclear. In the present study, we found that the dorsal root ganglion (DRG) IL-33 and ST2 were upregulated in a rat model of spared nerve injury (SNI) and intrathecal injection of either IL-33 or ST2 antibodies alleviated mechanical allodynia and downregulated TNF- and IL-1 induced by SNI. In addition, activation of SIRT1 decreased enhanced DRG IL-33/ST2 signaling in SNI rats. Artificial inactivation of SIRT1 intrathecal injection of an SIRT1 antagonist could induce mechanical allodynia and upregulate IL-33 and ST2. These results exhibited that reduction in SIRT1 could induce upregulation of DRG IL-33 and ST2 and contribute to mechanical allodynia induced by SNI in rats. binding to its receptor ST2 (Xu et al., 2019). It has been exhibited that IL-33 plays a vital role in many inflammatory conditions, including septic shock (Ding et al., 2019), atherosclerosis (Buckley et al., 2019) and rheumatoid arthritis (Pinto et al., 2019). Furthermore, other studies have suggested that IL-33 modulates cutaneous hyper-nociception in inflammatory pain in mice (Verri et al., 2008) and has been implicated in activating astrocytes in the spinal cord in mouse models of bone pain (Zhao et al., 2013). However, the role of IL-33 in the dorsal root ganglion (DRG) in neuropathic pain remains unclear. The silent information regulator 1 (SIRT1) is an NAD+-dependent deacetylase belonging to the SIRT family (Hattori and Ihara, 2016). Among SIRT family, SIRT1 has been validated to be most related in this family and function as deacetylating and regulating histones (Ling et al., 2018) as well as a wide range PF429242 dihydrochloride of non-histone substrates, such as NF-B PF429242 dihydrochloride (Kauppinen et al., 2013), p53 (Nakamura et al., 2017), FOXO (Brunet et al., 2004), ERK (Han et al., 2017), peroxisome proliferator-activated receptor (PPAR) as well as others (Kauppinen et al., 2013). With regulating this protein, SIRT1 plays a central role in regulating cellular processes, including apoptosis (Ling et al., 2017), cellular proliferation (Jablonska et al., 2016), and inflammation (Zhang et al., 2017). In the nervous system, SIRT1 suppress the neurodegenerative diseases such as Alzheimers disease and Parkinsons disease anti-apoptosis, anti-inflammation (Singh et al., 2017; Gomes et al., 2018). Recently, several studies have reported that this activation of SIRT1 in the spinal cord alleviates neuropathic pain induced by chronic constriction PF429242 dihydrochloride injury (CCI) surgery in rats and mice inhibition of the inflammatory cascade (Shao et al., 2014; Lv et al., 2015). In addition, SIRT1 in the spinal cord epigenetically upregulates inflammasome NALP1 expression and contributes to the chronic pain induced by the chemotherapeutic drug bortezomib (Chen et al., 2018). However, whether SIRT1 modulates the inflammatory cytokine IL-33 remains unclear. In the present study, we performed spared nerve injury (SNI) surgery in TPOR rats to establish a neuropathic pain model and hypothesized that downregulation of SIRT1 in the DRG induced by SNI enhances IL-33/ST2 signaling and triggers a downstream inflammatory cascade leading to mechanical allodynia. Materials and Methods Animals Male Sprague-Dawley rats, weighing 200C250 g, were obtained from the Institute of Experimental Animals of Southern Medical University or college (Guangzhou, China; Approval number: SCXK 2016-0041). The animals were housed in standard cages in a temperature-controlled (24 1C) colony room under a 12 h light/dark routine regimen, with usage of food and water. The experimental protocols were approved by the Southern Medical College or university Animal Use and Treatment.