Antinociceptive Role of β-alanine in Hot Plate-induced Pain in Mice

Pain is a distressing sensation that arises as a consequence of damage to bodily tissues, whereas β-alanine is an amino acid that is both nonessential and non-proteinogenic, functioning as an inhibitory neurotransmitter. Hence, the purpose of this investigation was to ascertain the analgesic role of β-alanine in the context of pain induced by exposure to a hot plate in mice.

A total of 85 male NMRI mice were employed in five separate experiments. In the initial experiment, the mice were administered saline, β-alanine at doses of 15 mg/kg, 30 mg/kg, and 45 mg/kg, as well as morphine at a dose of 5 mg/kg. In the second experiment, the mice were given saline, β-alanine at a dose of 30 mg/kg once daily for a duration of 7 days, naloxone at a dose of 2 mg/kg, and naloxone in combination with β-alanine at a dose of 30 mg/kg. For experiments 3-5, the mice were subjected to flumazenil (5 mg/kg), L-NAME (10 mg/kg), and 6-hydroxydopamine (100 mg/kg) instead of naloxone. Importantly, the mice received β-alanine once daily for a period of 7 days, whereas all the antagonists were administered 30 minutes prior to the respective tests. Subsequently, the hot plate test was employed to measure pain responses, both prior to and at 10, 15, 20, 25, and 30 minutes following the injections, by recording the response latency time. At the end of the experiments, blood samples were obtained and used to determine the levels of serum malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant status (TAS), and nitric oxide (NO).

The findings revealed that morphine led to a significant increase in the latency time (P<0.05), similarly, β-alanine resulted in a notable increase in the latency time (P<0.05). Interestingly, pretreatment with β-alanine followed by naloxone resulted in a decrease in the latency time (P<0.05). Similarly, pretreatment with β-alanine followed by flumazenil significantly reduced the latency time on the hot plate (P<0.05). Furthermore, pretreatment with β-alanine followed by L-NAME led to an increase in the latency time (P<0.05). Administration of β-alanine resulted in a decrease in serum NO and MDA levels, and an increase in SOD, GPx, and TAS levels (P<0.05).

Collectively, these findings suggest that the antinociceptive activity of β-alanine is mediated through GABAergic mechanisms and NO production, and possibly through its antioxidant properties, in the context of pain induced by exposure to a hot plate in mice.