Bezirci Kadir, Borisova Boryana, Papadakis Konstantinos, Danalev Dancho, Nocheva Hristina
Department of Physiology and Pathophysiology, Medical University-Sofia, 1 Sv. Georgi Sofiyski Blvd, 1431 Sofia, Bulgaria.
Biotechnology Department, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd, 1797 Sofia, Bulgaria.
Int J Mol Sci. 2025 Apr 19;26(8):3883. doi: 10.3390/ijms26083883.
The adaptation of the body when exposed to a lower-than-usual temperature is a challenge that involves neuro-endocrine-immune mechanisms and affects the pharmacokinetics and/or pharmacodynamics of drugs taken before or after cold exposure. The experiments presented in this study clearly show differences in the analgesic effect of an exogenously introduced model substance (C-terminal fragment of calcium-binding protein, spermatid-specific 1) before and after cold exposure compared to its effect at an ambient temperature. The model substance used for the experiments is an octapeptide, TDIFELLK, which was synthesized via standard solid-phase peptide synthesis. Preliminary studies proved TDIFELLK's analgesic activity. The ANOVA analysis performed showed statistically significant differences in the pain thresholds, measured by a paw pressure test, in 109 rats distributed among 14 groups and subjected to cold exposure according to different set-ups. Cold exposure immediately after TDIFELLK administration appears to enhance its analgesic effect, while cold exposure before administration reduces the effect. In some of the set-ups, antagonists of the most significant for analgesia receptors, i.e., opioid, cannabinoid, and serotonergic, were also introduced. The results showed that cold exposure had a modulating influence on the effect of the exogenously administered substances. The modulating effect was manifested differently depending on whether the intake occurred before or after cold exposure. The results also showed that the interaction with individual mediator systems was also subjected to differences depending on intake occurring before and after cold exposure.
身体在暴露于低于正常温度时的适应过程是一项挑战，涉及神经 - 内分泌 - 免疫机制，并会影响在冷暴露之前或之后服用的药物的药代动力学和/或药效学。本研究中呈现的实验清楚地表明，与在环境温度下的效果相比，外源性引入的模型物质（钙结合蛋白C末端片段，精子细胞特异性1）在冷暴露前后的镇痛效果存在差异。用于实验的模型物质是一种八肽，TDIFELLK，它是通过标准固相肽合成法合成的。初步研究证实了TDIFELLK的镇痛活性。所进行的方差分析表明，在根据不同设置进行冷暴露的14组共109只大鼠中，通过爪压力测试测量的疼痛阈值存在统计学上的显著差异。在给予TDIFELLK后立即进行冷暴露似乎会增强其镇痛效果，而在给药前进行冷暴露则会降低该效果。在一些设置中，还引入了对镇痛最具意义的受体（即阿片类、大麻素类和血清素能受体）的拮抗剂。结果表明，冷暴露对外源性给药物质的效果具有调节作用。调节作用根据摄入发生在冷暴露之前还是之后而表现不同。结果还表明，与各个介质系统的相互作用也因冷暴露前后的摄入情况而存在差异。
