Zinc protoporphyrin IX, an inhibitor of the enzyme that produces carbon monoxide, blocks spinal nociceptive transmission evoked by formalin injection in the rat.

Carbon monoxide (CO) is now thought to act as a neural messenger, but the role of CO is poorly understood. In the present study, we investigated the role of CO in both the spinal thermal nociceptive transmission and spinal nociceptive transmission during peripheral inflammation using zinc protoporphyrin-IX (Zn-P), a potent inhibitor of hemoxygenase inhibitor (HO). Peripheral inflammation was induced by the paw formalin injection (formalin test). It is thought that CO acts as a second messenger for metabotropic glutamate receptor. We also investigated the effect of metabotropic glutamate receptor antagonists, L-2-amino-3-phosphonopropionic acid (L(+)AP3) and (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG), on the formalin test. Drugs were administered intrathecally 5 min before (pre-treatment) or 7 min after (post-treatment) the formalin injection. In both the pre-treatment and the post-treatment study, Zn-P inhibited the formalin induced flinching behavior in a dose-dependent manner. Both L(+)AP3 and MCPG had no effect on the formalin induced flinching behavior in the pre-treatment study. Zn-P had no effect on the thermal nociceptive test. These data suggest that CO plays an important role in spinal nociceptive transmission during the formalin test, but not during the thermal nociceptive test, and that, during the formalin test, CO may not act as a second messenger for metabotropic glutamate receptor in the spinal cord.