Here, we demonstrated the downregulation of LXRβ not LXRα in ACC of chronic inflammatory pain (CIP) mice, and knockdown of LXRβ by short hairpin RNA (shRNA) led to thermal hyperalgesia, while activation of LXRβ by GW exerted analgesic effects through both anti-inflammation and correction in synaptic transmission in ACC. Here, NR1H2 is linked to hereditary sensory and autonomic neuropathy.