Antinociceptive Effect of Cinnamaldehyde in Male Mice: Investigation of the Mechanisms of Action Through In Silico and In Vivo Approaches.

Cinnamaldehyde (CA), a major component of Cinnamomum spp. essential oils, has recognized bioactivity, including possible analgesic effects. However, its acute antinociceptive mechanisms remain unclear. This study assessed the influence of CA (15, 30, and 60 mg/kg, p.o.) on locomotor and exploratory behaviors via rotarod and open field tests in male Swiss mice. Antinociceptive activity was evaluated using chemical and thermal nociception models. Mechanistic investigations were performed in the opioid and adrenergic systems, as well as in silico molecular docking in nociceptive targets. A significance level of p = 0.01 was adopted. CA significantly reduced nociceptive behaviors in all models without impairing motor coordination. In the formalin test, it inhibited neurogenic and inflammatory phases. In glutamate and capsaicin tests, CA markedly reduced nociceptive responses. In the hot plate test, it increased latency at 30 mg/kg. Naloxone reversed the antinociceptive effect of CA in the formalin test, supporting the hypothesis of opioid receptor involvement, while yohimbine partially blocked the response, suggesting α