Chronic inflammatory pain, often accompanied by anxiety and depression, poses a significant health challenge. Current treatments are insufficiently effective and have side effects. This study investigated the analgesic and mood-modulating effects of novel heme oxygenase-1 (HO-1) inducers (1m, 1a, 1b) and dimethyl fumarate (DMF) in a mice model of complete Freund's adjuvant (CFA)-induced inflammatory pain. Results showed that these compounds effectively inhibited inflammatory pain, reversed grip strength deficits, and alleviated anxiety- and depressive-like behaviors, with 1m being the most potent. These effects were linked to the suppression of NLRP3 inflammasome and activation of the Nrf2 antioxidant pathway, indicated by changes in the expression of Nrf2, HO-1, and SOD-1 in the paw and amygdala.

Montse Pérez-Fernández, Irene Suárez-Rojas, Xue Bai, Ignacio Martínez-Martel, Valeria Ciaffaglione, Valeria Pittalà, Loredana Salerno, Olga Pol