Dissertação
Estudo sobre os mecanismos antinociceptivos periféricos induzidos pelo peróxido de hidrogênio (H2O2)
Fecha
2021-12-14Autor
Walace Cássio Pinto Barra
Institución
Resumen
ABSTRACT
INTRODUCTION: Pain is a vital sensory phenomenon to the protection of tissues
and the survival of the organism. Besides being essential in some cases, pain
must be attenuated when it affects the system's welfare. Data from the literature
describe different molecules with the ability to hyperpolarize the neuronal
membrane potential to cause antinociception. Previously studies have shown that
the administration of hydrogen peroxide (H2O2) can cause hyperpolarization in a
variety of cells through opening the K+ channels, including neuronal
cells. AIM: Thus, this study aimed to evaluate de peripheral antinociceptive effect
of hydrogen peroxide in a prostaglandin E2 model of acute pain, and determine if
the opioidergic and cannabinoidergic systems, as well as the nitric oxide pathway
and potassium channels, are involved in the antinociceptive effect mediated by
H2O2. METHODS: The paw compression test was used to measure the
nociceptive threshold in mice (Swiss, male, 30-40 g, n = 5 / CEUA protocol:
212/2020). Acute pain was induced by PGE2 administration, and the study was
conducted using pharmacological tools. All drugs were administrated intraplantar
in a volume of 20 μl. RESULTS: The administration of PGE2 a 2 μg/paw
efficiently decreased the nociceptive threshold of the animals. H2O2 (0,05; 0,1;
0,2 e 0,3 μg/paw) promotes dose-dependent antinociceptive effect in a PGE2
model of acute pain. This antinociceptive effect was not reversed by Naloxone
(Nx - 50 μg/paw) a non-selective opioid receptor antagonist. The reversion did
not occur by antagonizing the CB1 and CB2 receptors using the selective
antagonists AM 251 (80 μg/paw) and AM 630 (100 μg/paw) respectively. The
non-selective inhibition of nitric oxide synthase enzymes with L-NOarg (6, 12 e
24 μg/paw), dose-dependently reversed the H2O2-mediated antinociception.
Thus, to evaluate which isoforms were responsible for the reversion was
administered L-NIL (24 μg/paw), L-NPA (24 μg/paw) e L-NIO (24 μg/paw).
Seletive inhibitors of iNOS, nNOS and eNOS respectively. The antinociceptive
reversion occurs with the inhibition of the three isoforms, being total for iNOS and
partial to nNOS and eNOS. The antinociception caused by H2O2 demonstrated
to be involved with the potassium channels, given that tetraethylammonium
(TEA), a selective voltage-gated potassium channel blocker (15, 30 e 60 μg/paw)
fully reversed the H2O2 antinociception in a dose-dependent manner. The ATP-
sensitive K+ channels selective blockers glibenclamide (40, 80 e 160 μg/paw),
large and small conductance calcium-activated potassium channels paxiline (10,
20 e 40 μg/paw) and dequalinium (12,5; 25 e 50 μg/paw) respectively reversed
the H2O2-mediated antinociception. Nonetheless, only dequalinium fully reversed
the antinociception, and only paxiline didn't have a dose-dependent
response. CONCLUSION: H2O2 has a peripheral antinociceptive effect on the
acute pain model induced by PGE2 administration. It was demonstrated that the
NO pathway and voltage-gated K+ channel, ATP-sensitive K+ channels, large and
small conductance calcium-activated potassium channels take part in the
antinociceptive mechanisms of H2O2. The role of the opioid and cannabinoid
systems was not evidenced in this study.