%0 Journal Article %A Alejandro Redondo %A Pablo Anibal Ferreira Chamorro %A Gabriela Riego %A Sergi Leanez %A Olga Pol %T Treatment with sulforaphane produces antinociception and improves morphine effects during inflammatory pain in mice %D 2017 %R 10.1124/jpet.117.244376 %J Journal of Pharmacology and Experimental Therapeutics %P jpet.117.244376 %X The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) exerts potent anti-oxidative and anti-inflammatory effects, however its participation in the modulation of chronic inflammatory pain and on the antinociceptive effects of μ opioid receptor (MOR) agonists has not been evaluated. We investigated whether the induction of Nrf2 could alleviate chronic inflammatory pain, augments the analgesic effects of morphine and mechanisms implicated. In male C57BL/6 mice with inflammatory pain induced by complete Freund's adjuvant (CFA) subplantarly administered, we assessed: 1) antinociceptive actions of the administration of 5 and 10 mg/kg of a Nrf2 activator, sulforaphane (SFN); 2) effects of SFN on the antinociceptive actions of morphine and on protein levels of Nrf2, heme oxygenase 1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) enzymes, microglial activation and inducible nitric oxide synthase (NOS2) over-expression, as well as on mitogen-activated protein kinase (MAPK) and MOR expression in the spinal cord and paw of animals with inflammatory pain. Results showed that treatment with SFN inhibited allodynia and hyperalgesia induced by CFA and increased the local antinociceptive actions of morphine. This treatment also augmented the expression of Nrf2, HO-1, NQO1 and MOR, inhibited NOS2 and CD11b/c overexpression, and MAPK phosphorylation induced by inflammation. Thus, this study shows that the induction of Nrf2 might inhibit inflammatory pain and enhances the analgesic effects of morphine by inhibiting oxidative stress and inflammatory responses induced by peripheral inflammation. This study suggests the administration of SFN alone and in combination with morphine as new ways of treating chronic inflammatory pain. %U https://jpet.aspetjournals.org/content/jpet/early/2017/09/25/jpet.117.244376.full.pdf