Heme oxygenase-1/biliverdin/carbon monoxide pathway downregulates hypernociception in rats by a mechanism dependent on cGMP/ATP-sensitive K⁺ channels

To investigate the role of heme oxygenase-1 (HO-1), carbon monoxide (CO), and biliverdin (BVD) in the zymosan-induced TMJ arthritis in rats.

Mechanical threshold was assessed before and 4 h after TMJ arthritis induction in rats. Cell influx, myeloperoxidase activity, and histological changes were measured in the TMJ lavages and tissues. Trigeminal ganglion and periarticular tissues were used for HO-1, TNF-α, and IL-1β mRNA time course expression and immunohistochemical analyses. Hemin (0.1, 0.3, or 1 mg kg⁻¹), DMDC (0.025, 0.25, or 2.5 µmol kg⁻¹), biliverdin (1, 3, or 10 mg kg⁻¹), or ZnPP-IX (1, 3 or 9 mg kg⁻¹) were injected (s.c.) 60 min before zymosan. ODQ (12.5 µmol kg⁻¹; s.c.) or glibenclamide (10 mg kg⁻¹; i.p.) was administered 1 h and 30 min prior to DMDC (2.5 µmol kg⁻¹; s.c), respectively.

Hemin (1 mg kg⁻¹), DMDC (2.5 µmol kg⁻¹), and BVD (10 mg kg⁻¹) reduced hypernociception and leukocyte migration, which ZnPP (3 mg kg⁻¹) enhanced. The effects of DMDC were counteracted by ODQ and glibenclamide. The HO-1, TNF-α, and IL-1β mRNA expression and immunolabelling increased.

HO-1/BVD/CO pathway activation provides anti-nociceptive and anti-inflammatory effects on the zymosan-induced TMJ hypernociception in rats.