PT - JOURNAL ARTICLE AU - Mireia Carcolé AU - Sílvia Castany AU - Sergi Leánez AU - Olga Pol TI - Treatment with a Heme Oxygenase 1 Inducer Enhances the Antinociceptive Effects of <em>µ</em>-Opioid, <em>δ</em>-Opioid, and Cannabinoid 2 Receptors during Inflammatory Pain AID - 10.1124/jpet.114.215681 DP - 2014 Oct 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 224--232 VI - 351 IP - 1 4099 - http://jpet.aspetjournals.org/content/351/1/224.short 4100 - http://jpet.aspetjournals.org/content/351/1/224.full SO - J Pharmacol Exp Ther2014 Oct 01; 351 AB - The administration of µ-opioid receptor (MOR), δ-opioid receptor (DOR), and cannabinoid 2 receptor (CB2R) agonists attenuates inflammatory pain. We investigated whether treatment with the heme oxygenase 1 (HO-1) inducer, cobalt protoporphyrin IX (CoPP), could modulate the local effects and expression of MOR, DOR, or CB2R during chronic inflammatory pain. In mice with inflammatory pain induced by the subplantar administration of complete Freund’s adjuvant, we evaluated the effects of the intraperitoneal administration of 10 mg/kg CoPP on the antiallodynic and antihyperalgesic actions of locally administered MOR (morphine), DOR (DPDPE {[d-Pen(2),d-Pen(5)]-enkephalin}), or CB2R [JWH-015 {(2-methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone}] agonists and its reversion with the HO-1 inhibitor, tin protoporphyrin IX (SnPP). The effect of CoPP treatment on the dorsal root ganglia expression of HO-1, MOR, DOR, and CB2R was also assessed. The results show that treatment with CoPP increased the local antinociceptive effects produced by morphine, DPDPE, or JWH-015 during chronic inflammatory pain, and these effects were blocked by the subplantar administration of SnPP, indicating the participation of HO-1 in the antinociceptive actions. CoPP treatment, apart from inducing the expression of HO-1, also enhanced the expression of MOR, did not alter CB2R, and avoided the decreased expression of DOR induced by inflammatory pain. This study shows that the HO-1 inducer (CoPP) increased the local antinociceptive effects of MOR, DOR, and CB2R agonists during inflammatory pain by altering the peripheral expression of MOR and DOR. Therefore, the coadministration of CoPP with local morphine, DPDPE, or JWH-015 may be a good strategy for the management of chronic inflammatory pain.