The acute antinociceptive effect of HBO₂ is mediated by a NO-cyclic GMP-PKG-KATP channel pathway in mice

Abstract

Previous research has found that hyperbaric oxygen (HBO(2)) produces an acute antinociceptive effect that is dependent on nitric oxide (NO). The present study was undertaken to determine whether HBO(2)-induced acute antinociception might involve a NO-cyclic GMP-protein kinase G-ATP-sensitive potassium (K(ATP)) channel pathway. Male NIH Swiss mice were subjected to a 5-min HBO(2) treatment (100% oxygen at 3.5 absolute atmospheres) and antinociception was assessed over the next 6 min still under HBO(2) using the acetic acid abdominal constriction test. Pretreatment with 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3-oxide (carboxy-PTIO, an NO scavenger), 1H-[1,2,4]-oxadiazolo-[4,3-a]quinoxalin-1-one) (a soluble guanylyl cyclase-inhibitor, Rp-8-(4-chlorophenylthio)-guanosine-3',5'-cyclic monophosphorothioate (a protein kinase G-inhibitor) or glibenclamide (an ATP-sensitive potassium channel-inhibitor) all led to antagonism of the HBO(2)-induced acute antinociception in a dose-dependent manner. These findings suggest that HBO(2)-induced acute antinociception might be due to activation of a NO-cyclic GMP-protein kinase G-K(ATP) channel pathway.

Fig. 1

Effect of carboxy-PTIO on the antinociceptive effect of HBO₂ at 3.5 ATA. Each bar represents the mean antinociceptive effect and each vertical line represents the SEM of at least 8 mice per group. Significance of difference: ***, P < 0.001, compared to the vehicle pretreatment group (post-hoc Bonferroni's multiple comparison test).

Fig. 2

Effect of ODQ on the antinociceptive effect of HBO₂ at 3.5 ATA. Each bar represents the mean antinociceptive effect and each vertical line represents the SEM of at least 8 mice per group. Significance of difference: ***, P < 0.001, compared to the vehicle pretreatment group (post-hoc Bonferroni's multiple comparison test).

Fig. 3

Effect of Rp-8-pCPT-cGMPS on the antinociceptive effect of HBO₂ at 3.5 ATA. Each bar represents the mean antinociceptive effect and each vertical line represents the SEM of at least 8 mice per group. Significance of difference: ***, P < 0.001, compared to the vehicle pretreatment group (post-hoc Bonferroni's multiple comparison test).

Fig. 4

Effect of glibenclamide on the antinociceptive effect of HBO₂ at 3.5 ATA. Each bar represents the mean antinociceptive effect and each vertical line represents the SEM of at least 8 mice per group. Significance of difference: ***, P < 0.001, compared to the vehicle pretreatment group (post-hoc Bonferroni's multiple comparison test).