蜂毒镇痛作用的昼夜变化及对外周血P物质β-内啡肽和IL-1β水平的影响

doi:10.3969/j.issn.1006-6233.2024.03.08

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Abstract Objective: To investigate the circadian rhythm of pain threshold in mouse models and the circadian difference in the analgesic effects of bee venom for injection (BVI) and its mechanisms. Methods: Mouse pain models were established using the hot plate test and radiant heat tail-flick test. Pain thresholds were measured at six zeitgeber time (ZT) points (ZT2, ZT6, ZT10, ZT14, ZT18, ZT22) to analyze their circadian rhythms. Qualified Kunming mice were randomly divided into Bee Venom for Injection high dose (BVI-H), Bee Venom for Injection medium dose (BVI-M), Bee Venom for Injection low dose (BVI-L), Morphine (MOR), and Model (MOD) groups. Each group was further divided into two subgroups based on the circadian rhythm of pain thresholds, and drugs were administered at two time points corresponding to the peak and trough of pain thresholds. The dynamic changes in the behavioral effects on pain models in mice were observed using the hot plate test, radiant heat tail-flick test, and writhing test. The levels of serum Substances P (SP), Beta-endorphin (β-EP), and interleukin-1β (IL-1β) were measured by ELISA. Results: The pain thresholds of the mouse pain model exhibited circadian rhythms with a peak in the mid-light phase (ZT6) and a trough in the late dark phase (ZT22). The three BVI dose groups and the MOR group all showed significant analgesic effects, and the analgesic effect of BVI in the hot plate and writhing models was dose-dependent. In the hot plate test and radiant heat test models, BVI administration at ZT22 showed stronger analgesic effects than at ZT6. Bee venom did not upregulate serum β-EP levels in pain model mice but significantly reduced serum SP levels, with a circadian variation (lower at ZT22 than at ZT6, P<0.05). The serum IL-1β levels were significantly downregulated in the writhing test and radiant heat test (ZT22 administration group only) pain model mice, while they were significantly increased in the hot plate test. Conclusion: The pain threshold in mice exhibits a circadian rhythm with a peak in the middle-late light phase and a trough value in the late dark phase. BVI has analgesic effect on various pain models in mice, and there is a diurnal difference. The analgesic effect of BVI and its diurnal variation may be related to the regulation of endogenous pain mediators.

Key words： Bee venom Pain Circadian rhythm Chronotherapy P substance β-endorphins Interleukin-1β

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2024.03.08 OR http://www.hbyxzzs.cn/EN/Y2024/V30/I3/393

[1] Raja SN,Carr DB,Cohen M,et al.The revised International association for the study of pain definition of pain:concepts,challenges,and compromises[J].Pain,2020,161(9):1976-1982.
[2] Zheng Y,Zhang T,Yang X,et al.A survey of chronic pain in China[J].Libyan Med,2020,15(1):1730550.
[3] Allada R,Bass J.Circadian mechanisms in medicine[J].New England Journal of Medicine,2021,384(6):550-561.
[4] 董泓,李振彬,王志强等.注射用蜂毒对热痛模型小鼠的痛阈和外周血P物质、β-内啡肽水平的影响[J].风湿病与关节炎,2023,12(6):1-5,12.
[5] Bumgarner JR,Mc crey EW,Nelson RJ.The disruptive relationship among circadian rhythms,pain,and opioids[J].Front Neurosci,2023(17):1109480.
[6] Martinez-gmez M,Cruz Y,Salas M,et al.Assessing pain threshold in the rat:changes with estrus and time of day[J].Physiol Behav,1994,55(4):651-657.
[7] 刘晓平,宋建国.小鼠对疼痛反应的昼夜节律[J].皖南医学院学报.2002,21(1):18-19.
[8] Yoshida M,Ohdo S,Takane H,et al.Chronopharmacology of analgesic effect and its tolerance induced by morphine in mice[J].Journal of Pharmacology & Experimental Therapeutics,2003,305(3):1200-1205.
[9] Kusunose N,Koyanagi S,Hamamura K,et al.Molecular basis for the dosing time-dependency of anti-allodynic effects of gabapentin in a mouse model of neuropathic pain[J].Mol Pain,2010(6):83.
[10] Sowa GA,Perera S,Bechara B,et al.Associations between serum biomarkers and pain and pain-related function in older adults with low back pain:a pilot study[J].Am Geriatr Soc,2014,62(11):2047-2055.
[11] 程施瑞,李政杰,周俊等.针刺对膝骨性关节炎患者临床症状及血清β-内啡肽水平的影响[J].世界科学技术-中医药现代化,2021,23(1):217-224.
[12] Sung SH,Lee G.Bee venom acupuncture effects on pain and its mechanisms:an updated review[J].Toxins (Basel),2021,13(9):608.
[13] Raghuraman H,Chattopadhyay A.Melittin:a membrane-active peptide with diverse functions[J].Biosci Rep,2007,27(4-5):189-223.