The Transition of Pain into Anesthesia—The Effect of Various Doses of Macrovipera lebetina obtusa Venom

Abstract

Blunt-nosed viper venom in high doses causes severe pain, while in low doses an analgesic effect is observed. The opposite effects of different doses of venom are associated with the development of certain metabolic processes and the impact on receptors and channels of nociceptive afferent neurons. The response of the nociceptive system in the periphery and CNS depends on the dose-evoked neurochemical changes in neuronal activity. We studied the effect of various doses of MLO venom in order to understand the mechanisms of the transition of the pain effect of MLO venom into an analgesic one. Pain behavior was studied on outbred white mice at various doses of MLO venom, starting from LD₅₀ for intraplantar and in serial dilutions for intraperitoneal (1.0 and 1/5, 1/10, 1/20 and 1/30 of LD₅₀) administration during the formalin and the hot plate tests. At a dose of 1.0 LD50, experimental mice develop a strong sense of pain, which was examined in the hind paw biting/licking test. The maximum analgesic effect was expressed at 1/20 LD₅₀. To study the degree of participation of the venom’s phospholipase A2 (PLA2) enzymatic activity on pain processes, a venom with the inhibited enzymatic activity of PLA2 was tested. It was obtained, that both in the development of pain and in the analgesic effect, the enzymatic activity of PLA2 plays a significant role. It is proposed that in case of high doses the antinociceptive action of venom is masked.