Influence of MLC901 Alone and with Moderate Exercise on Pain Response Concurrent Due to Stress of Male Mice
DOI:
https://doi.org/10.31661/gmj.v8i.1253Keywords:
Exercise, Stress, MLC901, Pain, MiceAbstract
Background: Physical exercise is known to have a positive effect on pain responses induced by stress, while chronic stress causes a negative effect on cognitive abilities. Depending on the type, duration, and intensity of the stressor, it can induce analgesia or hyperalgesia. Furthermore, the beneficial effects of traditional Chinese medicine MLC901 on stress processes have been reported. Here, the effects of MLC901 and moderate physical activity on pain response in restraint-stressed mice was investigated. Materials and Methods: Male NMRI mice were used in this study and were restrained in plexiglass mesh restrainers for induction of chronic restraint stress. Treadmill exercise was carried out for moderated exercise, 5 days/week for 4 weeks. MLC901 was intraperitoneally administered in the experimental groups. The pain response of the adult NMRI mice was detected via the hot-plate test. Results: It was showed that intraperitoneal administration of MLC901 dose (0.4 but not 0.1 and 0.2 mg/kg; once/2 days; for 25 days) resulted in the decreased percentage of time in the hot plate, indicating hyperalgesia. Moreover, restraint stress for 3 but not 6 and 9 hours/day elicit hyperalgesia in mice. The data showed that subthreshold dose of MLC901 (0.1 mg/kg) reduced hyperalgesia in 3-day stressed mice. Moderate treadmill running (10 meters/min for 30 min/day, 5 days/week) potentiated the effect of 6 and 9 days on pain (induced hyperalgesia) that was blocked by MLC901 (0.1 mg/kg). Conclusion: Our findings indicated that subthreshold dose of MLC901 alone or when it associated with moderate exercise decreased hyperalgesia induced by stress, indicating the protective effect of MLC901. [GMJ.2019;8:e1253]
References
Parikh D, Hamid A, Friedman TC, Nguyen K, Tseng A, Marquez P, et al. Stress-induced analgesia and endogenous opioid peptides: the importance of stress duration. Eur J Pharmacol. 2011;650(2-3):563-7. https://doi.org/10.1016/j.ejphar.2010.10.050PMid:21044625 PMCid:PMC3033575 Yilmaz P, Diers M, Diener S, Rance M, Wessa M, Flor H. Brain correlates of stress-induced analgesia. Pain. 2010;151(2):522-9. https://doi.org/10.1016/j.pain.2010.08.016PMid:20817354 Rocchi A, Orsucci D, Tognoni G, Ceravolo R, Siciliano G. The role of vascular factors in late-onset sporadic Alzheimer's disease. Genetic and molecular aspects. Curr Alzheimer Res. 2009;6(3):224-37. https://doi.org/10.2174/156720509788486644PMid:19519304 Sandi C, Pinelo-Nava MT. Stress and memory: behavioral effects and neurobiological mechanisms. Neural plasticity. 2007;2007:78970. https://doi.org/10.1155/2007/78970PMid:18060012 PMCid:PMC1950232 Krishnan V, Nestler EJ. The molecular neurobiology of depression. Nature. 2008;455(7215):894-902. https://doi.org/10.1038/nature07455PMid:18923511 PMCid:PMC2721780 Watanabe Y, Gould E, McEwen BS. Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons. Brain Res. 1992;588(2):341-5. https://doi.org/10.1016/0006-8993(92)91597-8 Taylor AH, Dorn L. Stress, fatigue, health, and risk of road traffic accidents among professional drivers: the contribution of physical inactivity. Annu Rev Public Health. 2006;27:371-91. https://doi.org/10.1146/annurev.publhealth.27.021405.102117PMid:16533122 Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, et al. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A. 2011;108(7):3017-22. https://doi.org/10.1073/pnas.1015950108PMid:21282661 PMCid:PMC3041121 van Dongen EV, Kersten IH, Wagner IC, Morris RG, Fernandez G. Physical Exercise Performed Four Hours after Learning Improves Memory Retention and Increases Hippocampal Pattern Similarity during Retrieval. Curr Biol : CB. 2016;26(13):1722-7. https://doi.org/10.1016/j.cub.2016.04.071PMid:27321998 Berchtold NC, Castello N, Cotman CW. Exercise and time-dependent benefits to learning and memory. Neuroscience. 2010;167(3):588-97. https://doi.org/10.1016/j.neuroscience.2010.02.050PMid:20219647 PMCid:PMC2857396 Chen K, Zhang L, Tan M, Lai CS, Li A, Ren C, et al. Treadmill exercise suppressed stress-induced dendritic spine elimination in mouse barrel cortex and improved working memory via BDNF/TrkB pathway. Transl Psychiatry. 2017;7(3):e1069. https://doi.org/10.1038/tp.2017.41PMid:28323283 PMCid:PMC5416682 Shulman LM, Katzel LI, Ivey FM, Sorkin JD, Favors K, Anderson KE et al. Randomized clinical trial of 3 types of physical exercise for patients with Parkinson disease. JAMA neurology. 2013;70(2):183-90. https://doi.org/10.1001/jamaneurol.2013.646PMid:23128427 PMCid:PMC4574905 Brown BM, Peiffer JJ, Martins RN. Multiple effects of physical activity on molecular and cognitive signs of brain aging: can exercise slow neurodegeneration and delay Alzheimer's disease?. Mol Psychiatry. 2013;18(8):864-74. https://doi.org/10.1038/mp.2012.162PMid:23164816 van Praag H, Christie BR, Sejnowski TJ, Gage FH. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci U S A. 1999;96(23):13427-31. https://doi.org/10.1073/pnas.96.23.13427PMid:10557337 PMCid:PMC23964 Yau SY, Lau BW, Tong JB, Wong R, Ching YP, Qiu G, et al. Hippocampal neurogenesis and dendritic plasticity support running-improved spatial learning and depression-like behaviour in stressed rats. PloS one. 2011;6(9):e24263. https://doi.org/10.1371/journal.pone.0024263PMid:21935393 PMCid:PMC3174166 Radahmadi M, Alaei H, Sharifi MR, Hosseini N. Preventive and therapeutic effect of treadmill running on chronic stress-induced memory deficit in rats. J Bodyw Mov Ther. 2015;19(2):238-45. https://doi.org/10.1016/j.jbmt.2014.04.007PMid:25892378 Kim TW, Lim BV, Kim K, Seo JH, Kim CJ. Treadmill exercise alleviates stress-induced impairment of social interaction through 5-hydroxytryptamine 1A receptor activation in rats. J Exerc Rehabil. 2015;11(4):192-7. https://doi.org/10.12965/jer.150225PMid:26331133 PMCid:PMC4548675 Kim DM, Leem YH. Chronic stress-induced memory deficits are reversed by regular exercise via AMPK-mediated BDNF induction. Neuroscience. 2016;324:271-85. https://doi.org/10.1016/j.neuroscience.2016.03.019PMid:26975895 Quintard H, Lorivel T, Gandin C, Lazdunski M, Heurteaux C. MLC901, a Traditional Chinese Medicine induces neuroprotective and neuroregenerative benefits after traumatic brain injury in rats. Neuroscience. 2014;277:72-86. https://doi.org/10.1016/j.neuroscience.2014.06.047PMid:24993477 Moha Ou Maati H, Borsotto M, Chatelain F, Widmann C, Lazdunski M, Heurteaux C. Activation of ATP-sensitive potassium channels as an element of the neuroprotective effects of the Traditional Chinese Medicine MLC901 against oxygen glucose deprivation. Neuropharmacology. 2012;63(4):692-700. https://doi.org/10.1016/j.neuropharm.2012.05.035PMid:22659084 Quintard H, Borsotto M, Veyssiere J, Gandin C, Labbal F, Widmann C, et al. MLC901, a traditional Chinese medicine protects the brain against global ischemia. Neuropharmacology. 2011;61(4):622-31. https://doi.org/10.1016/j.neuropharm.2011.05.003PMid:21605573 Liss B, Roeper J. Molecular physiology of neuronal K-ATP channels (review). Mol Cell Neurosci. 2001;18(2):117-27. https://doi.org/10.1080/09687680110047373PMid:11463204 Heurteaux C, Gandin C, Borsotto M, Widmann C, Brau F, Lhuillier M, et al. Neuroprotective and neuroproliferative activities of NeuroAid (MLC601, MLC901), a Chinese medicine, in vitro and in vivo. Neuropharmacology. 2010;58(7):987-1001. https://doi.org/10.1016/j.neuropharm.2010.01.001PMid:20064536 Lorivel T, Gandin C, Veyssiere J, Lazdunski M, Heurteaux C. Positive effects of the traditional Chinese medicine MLC901 in cognitive tasks. J Neurosci Res. 2015;93(11):1648-63. https://doi.org/10.1002/jnr.23591PMid:25821139 Eddy NB, Leimbach D. Synthetic analgesics. II. Dithienylbutenyl- and dithienylbutylamines. J Pharmacol Exp Ther. 1953;107(3):385-93. Butkevich IP, Mikhailenko VA, Vershinina EA, Aloisi AM. Effects of neonatal pain, stress and their interrelation on pain sensitivity in later life in male rats. Chin J Physiol. 2016;59(4):225-31. https://doi.org/10.4077/CJP.2016.BAE412PMid:27426261 Spradley JM, Davoodi A, Carstens MI, Carstens E. Effects of acute stressors on itch- and pain-related behaviors in rats. Pain. 2012;153(9):1890-7. https://doi.org/10.1016/j.pain.2012.05.032PMid:22770638 PMCid:PMC3413756 Amit Z, Galina ZH. Stress-induced analgesia: adaptive pain suppression. Physiol Rev. 1986;66(4):1091-120. https://doi.org/10.1152/physrev.1986.66.4.1091PMid:2876446 Ford GK, Finn DP. Clinical correlates of stress-induced analgesia: evidence from pharmacological studies. Pain. 2008;140(1):3-7. https://doi.org/10.1016/j.pain.2008.09.023PMid:18930350 Dai S, Ma Z. BDNF-trkB-KCC2-GABA pathway may be related to chronic stress-induced hyperalgesia at both the spinal and supraspinal level. Med Hypotheses. 2014;83(6):772-4. https://doi.org/10.1016/j.mehy.2014.10.008PMid:25454160 Holschneider DP, Guo Y, Mayer EA, Wang Z. Early life stress elicits visceral hyperalgesia and functional reorganization of pain circuits in adult rats. Neurobiol Stress. 2016;3:8-22. https://doi.org/10.1016/j.ynstr.2015.12.003PMid:26751119 PMCid:PMC4700548 Huang P, Li C, Fu T, Zhao D, Yi Z, Lu Q et al. Flupirtine attenuates chronic restraint stress-induced cognitive deficits and hippocampal apoptosis in male mice. Behav Brain Res. 2015;288:1-10. https://doi.org/10.1016/j.bbr.2015.04.004PMid:25869780 Heurteaux C, Widmann C, Moha ou Maati H, Quintard H, Gandin C, Borsotto M, et al. NeuroAiD: properties for neuroprotection and neurorepair. Cerebrovasc Dis. 2013;35 Suppl 1:1-7. https://doi.org/10.1159/000346228PMid:23548913 Yanagita S, Amemiya S, Suzuki S, Kita I. Effects of spontaneous and forced running on activation of hypothalamic corticotropin-releasing hormone neurons in rats. Life Sci. 2007;80(4):356-63. https://doi.org/10.1016/j.lfs.2006.09.027PMid:17067638
