Caffeine attenuates seizure and brain mitochondrial disruption induced by Tramadol: the role of adenosinergic pathway

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Tramadol (TR) is an analgesic effective for moderate-to-severe pain but can induce seizures, even at therapeutic doses.
• The precise mechanism of Tramadol-induced seizures is unclear, with proposed pathways including serotonin, GABA, and nitrous oxide (NOS) inhibition.
• The adenosinergic system is critical for seizure modulation, and seizures often lead to oxidative damage.

Purpose of the Study:

• To investigate the role of the adenosinergic system in Tramadol-induced seizures and oxidative stress.
• To evaluate the effects of an adenosine receptor antagonist on seizure threshold and oxidative stress biomarkers.

Main Methods:

• Albino mice were used to assess Tramadol-induced clonic seizures and seizure threshold.
• Caffeine (CAF), a nonselective adenosine receptor antagonist, was administered intraperitoneally (8 mg/kg) one hour before seizure induction.
• Oxidative stress biomarkers (reactive oxygen species, protein carbonyl content, lipid peroxidation, glutathione) were measured in brain mitochondria.

Main Results:

• Caffeine administration significantly increased the seizure threshold compared to the Tramadol-only group (p < 0.001).
• In caffeine-treated mice, oxidative stress biomarkers (reactive oxygen species, protein carbonyl, lipid peroxidation) were significantly decreased in brain mitochondria.
• Glutathione content was significantly increased in the brain mitochondria of caffeine-treated mice compared to the Tramadol group.

Conclusions:

• The adenosinergic system is implicated in Tramadol-induced seizures.
• Inhibiting adenosine receptors with caffeine can elevate the seizure threshold induced by Tramadol.
• Adenosine receptor antagonism mitigates Tramadol-induced oxidative damage in brain mitochondria.