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

IF 0.5 4区医学 Q4 NEUROSCIENCES Neurochemical Journal Pub Date : 2024-01-30 DOI:10.1134/s1819712423040098

A. A. Darbinyan, L. M. Parseghyan, A. V. Moghrovyan, M. A. Babajanyan, A. V. Voskanyan

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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.

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从疼痛到麻醉的转变--不同剂量的钝头巨蝮蛇毒的影响

摘要钝鼻蝰蛇毒在高剂量时会引起剧烈疼痛，而在低剂量时则会产生镇痛效果。不同剂量毒液的相反效果与某些代谢过程的发展以及对痛觉传入神经元受体和通道的影响有关。外周和中枢神经系统的痛觉系统的反应取决于剂量引起的神经元活动的神经化学变化。我们研究了不同剂量 MLO 毒液的影响，以了解 MLO 毒液的疼痛效应转变为镇痛效应的机制。在福尔马林试验和热板试验中，我们以不同剂量的 MLO 毒液（从 LD50 开始椎管内给药，连续稀释腹腔给药（1.0 和 LD50 的 1/5、1/10、1/20 和 1/30））对近交系白鼠的疼痛行为进行了研究。剂量为 1.0 LD50 时，实验小鼠会产生强烈的疼痛感，这在后爪咬/舔试验中得到了检验。1/20 LD50 时镇痛效果最强。为了研究毒液的磷脂酶 A2（PLA2）酶活性对疼痛过程的参与程度，对一种具有抑制 PLA2 酶活性的毒液进行了测试。结果表明，无论是在疼痛的发展过程中还是在镇痛效果中，PLA2 的酶活性都起着重要作用。据推测，在高剂量的情况下，毒液的镇痛作用会被掩盖。

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来源期刊

Neurochemical Journal 医学-神经科学

自引率

20.00%

发文量

审稿时长

>12 weeks

期刊介绍： Neurochemical Journal (Neirokhimiya) provides a source for the communication of the latest findings in all areas of contemporary neurochemistry and other fields of relevance (including molecular biology, biochemistry, physiology, neuroimmunology, pharmacology) in an afford to expand our understanding of the functions of the nervous system. The journal presents papers on functional neurochemistry, nervous system receptors, neurotransmitters, myelin, chromaffin granules and other components of the nervous system, as well as neurophysiological and clinical aspects, behavioral reactions, etc. Relevant topics include structure and function of the nervous system proteins, neuropeptides, nucleic acids, nucleotides, lipids, and other biologically active components. The journal is devoted to the rapid publication of regular papers containing the results of original research, reviews highlighting major developments in neurochemistry, short communications, new experimental studies that use neurochemical methodology, descriptions of new methods of value for neurochemistry, theoretical material suggesting novel principles and approaches to neurochemical problems, presentations of new hypotheses and significant findings, discussions, chronicles of congresses, meetings, and conferences with short presentations of the most sensational and timely reports, information on the activity of the Russian and International Neurochemical Societies, as well as advertisements of reagents and equipment.