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

Abstract

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^-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.

Results: 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.

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

Keywords: Heme oxygenase-1; IL-1β; Inflammation; TNF-α.; Temporomandibular joint.