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

OBJECTIVE AND DESIGN

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

MATERIALS AND METHODS

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), DMDC (0.025, 0.25, or 2.5 µmol kg), biliverdin (1, 3, or 10 mg kg), or ZnPP-IX (1, 3 or 9 mg kg) were injected (s.c.) 60 min before zymosan. ODQ (12.5 µmol kg; s.c.) or glibenclamide (10 mg kg; i.p.) was administered 1 h and 30 min prior to DMDC (2.5 µmol kg; s.c), respectively.

RESULTS

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

CONCLUSIONS

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