McNair Research Journal - University of St. Thomas

More documents

Recommendations

Info

Science strain the hotplate was set at 50-510C, for ND4 mice it was set at 52-530C. This sensitivity to pain was also evident when comparing the significant time points after injection of 48/80: C57BL/6 mice showed significant hypernociceptive responses 15min post-injection, whereas the earliest significant time point for ND4 mice was 30min post-injection of 48/80. This difference may be due to difference between strains, or simply differences in learned action, but only further research on the topic will elucidate the factors. II. Mechanical hypernociceptive responses and measurement are not definitively reliable. In addition, the issue of using mechanical hypernociception must still be broached. It is without a doubt that mechanical hypernociception present a more reliable and familiar method of quantifying hypernociceptive responses, as most recent papers use this method over the thermal method. Furthermore, even from our basic and preliminary results it can be seen that the mechanical method of measurement offers a means to measure hypernociception not only in each paw independently, but also without the worry that repeated exposure to stimulus will eventually either slowly impair the nociceptive ability in the foot pad, nor will it over sensitize the animal with repeated stimulus. Nevertheless, there are still some issues that arise when using this method, namely the methodology itself. The exact amount of time it takes for mice to acclimate to both the cages and the sensation of the von Frey tip or hair can be generalized, but it still largely depends on the individual animals itself. Moreover, as there was a clear difference observed between the temperament and socialization of the two mouse strains used in our study, ND4 and C57Bl/6, it may be the case that this method simply isn’t suited to ND4 mice. Nevertheless, the problems seen during observations, namely acclimation time differences and receptiveness to the sensation of the von Frey tool, tended to be issues in both strains. Furthermore, both of these problems may only be spurred on by the eventual injections of c48/80 into the foot pads. These problems, however, can only be examined in the case of our model with further experimentation and research. III. c48/80 significantly lowers thermal latency measurements in ND4 and C57BL/6 mice. In addition, our proposed model uses heat as the stimulus rather than pressure, and it has been documented in research that the hotplate model used to study hypernociception and hyperalgesia is slightly flawed in nature. This is because it employs repeated exposure to heat on the hotplate to create pain, although the repeated exposure could also result in paw sensitivity, which would produce part of the hyperalgesia observed in the observed mouse responses. In our experiment this critique held true and particularly evident at the 24h time point where neither the ip saline-ipl c48/80 group nor the ip SCG-ipl c48/80 group were significantly different from each other, or from the control groups. We believe this could be caused through two mechanisms: 1) again, the repeated exposure to heat sensitized mice towards later time points and produced the outcome of hyperalgesia and/or 2) that c48/80-induction of inflammatory hypernociception recedes within 24h. It is this same unknown factor, namely the duration of the effects of c48/80 that lead us to examine the effects of a 15 minutes time point in our observations. In light of the results, it appears that c48/80’s effects on at least a localized level may be rather short, lasting no longer than one day. While this factor, and the issue of overexposure-induced hyperalgesia, might both be presumed from our data, further research must also be accomplished in order to obtain definitive results. IV. SCG can only partially prevent c48/80-induced hypernociception. Another important finding was that sodium cromolyn could block, although not always completely, the hypernociceptive responses induced by c48/80 in both strains of mice. The significance of this finding could be two fold, the first importance being that the proposed c48/80-inflamatrory pathway does not only work through mast cells. This is very likely considering the previously pathways that c48/80 has been known to activate or modify. The second meaning could be that the dosage of SCG Paul L. Maitland-McKinley Inflammatory Hypernociception was not large enough to produce the level of mast cell stabilization that was estimated, and only a fraction of the local mast cells were prevented from degranulating. The backing for this second claim, however, could only be given by future histological data that could quantify the percentage of degranulation in each hind paw. V. Future prospects and applications. In the scope of possibly future projects involving characterizing cytokine and mediator cascades, it will be important to develop a working model of inflammatory hypernociception using not just thermal means, but mechanical means as well. Furthermore, the creation of a reliable model for inflammatory hypernociception has important therapeutic applications. It’s creation would mean the possibility of identifying specific molecules as the source of key hypernociceptive actions. Preventing their dispersal or cellular uptake may serve to reduce the pain associated with inflammation in a variety of human medical conditions including, but not limited to: asthma, a variety of cancers, anaphylaxis, rheumatoid arthritis, and multiple sclerosis (21). As these are chronic diseases that millions worldwide are afflicted with, any attempt at bettering, or possibly curing, their symptoms should be looked at as a valuable activity. Particularly because medications for the aforementioned illnesses still leave much to be desired, growth in this field of knowledge will only grow more important as the numbers of those afflicted grow simultaneously. The potential for medical treatment based on a model of inflammatory hypernociception and its chemical pathways is vast. As such, our studies into inflammatory hypernociception will undoubtedly have important therapeutic applications. Again, if a source can be identified as a source of key hypernociceptive mediators, or if mediators can be implicated specifically, either will aid in reducing pain associated with inflammation in a variety of human (and animal) medical conditions. While our studies will open many potential questions in multiple fields of the sciences, it will primarily have an effect particularly on the fields of immunology, molecular cell biology and biomedical research. Finally, at the end of this research, experimentation around this subject will have surpassed one year. The amounts of valuable data and techniques collected by our team over this amount time will allow for future classes and individuals to continue our work. 5. Acknowledgements. We would like to thank Lin Aanonsen for the training that she provided, along with Catie Bonesho, Camilla Engblom, Zac Schwager and Laura Miller who were a significant part of the data collection process during the spring semester and summer. 32 University of St. Thomas McNair Research Journal
Science 6. References. Paul L. Maitland-McKinley Inflammatory Hypernociception Aanonsen, L.M., J.D. Richardson, R. Nakkash, J. Knoll, K.M. Hargreaves, R. Whitehead. “Characterization of carrageenan-induced inflammation in the mouse.” Society for Neuroscience. Abstract 22 (1996): 880. Cunha, T.M., W.A. Verri, J.S. Silva, S. Poole, F.Q. Cunha, S.H. Ferreira. “A cascade of cytokines mediates mechanical inflammatory hypernociception in mice.” Proceedings of the National Academy of Sciences 102 (2005): 1755-1760. Buzzi M.G., Dimitriadou V., Theoharides T.C., M.A. Moskowitz. 5-Hydroxytriptamine receptor agonists for the abortive treatment of vascular headaches block mast cell, endothelial and platelet activation within the rat dura mater after trigeminal stimulation. Brain Research 583 (1992): 137-149. Verri Jr., W.A., Cunha T.M., Poole S., Ferreira S.H., Cunha F.Q. Cytokine inhibitors and pain control. Revista Brasileira de Reumatologia 47 (2007): 341-53. Hucho T. and D. Levine. Signaling pathways in sensitization: toward a nociceptor cell biology. Neuron 55 (2007): 365-376 Busse W.W. and R.F. Lemanske Jr. Asthma. New England Journal of Medicine 344 (2001): 350-362. Galli S.J., Kalesnikoff J., Grimbaldeston M.A., Piliponsky A.M., William C.M., M. Tsai. Mast cells as “tunable” effector and immunoregulatory cells: recent advances. Annual Reviews of Immunology 23 (2005): 749-786. Cunha, T.M., Verri Jr., W.A., Schivo, I.R., Napimoga, N.H., Parada, C.A., Poole, S., Teixeira, M.M., Ferreira, S.H. and F.Q. Cunha. Crucial role of neutrophils in the development of mechanical inflammatory hypernociception. Journal of Leukocyte Biology 83 (2008): 824-832. Cunha, T.M., Verri, W.A., Silva, J.S., Poole, S., Cunha, F.Q. and S.H. Ferreira. A cascade of cytokines mediates mechanical inflammatory hypernociception in mice. Proceedings of the National Academy of Sciences 102 (2006): 1755-1760. Verri, W.A., T.M. Cunha, C.A. Parada, X. Wei, S.H. Ferreira, F.Y. Liew, F.Q. Cunha. “IL-15 mediates immune inflammatory hypernociception by triggering a sequential release of IFN-gamma, endothelin, and prostaglandin.” Proceedings of the National Academy of Sciences 103 (2006): 9721-9725. Piovezan A.P., ‘Orleans-Juste P.D., Frighetto M., Souza G.E.P., Henriques M.O., G.A. Rae. Endothelins contribute towards nociception induced by antigen in ovalbuminsensitized mice. British Journal of Pharmacology 141 (2004): 755-763. Cunha, T.M., Verri Jr. , W.A., Vivancos, G.G., Moreira, I.F., Reis, S., Parada, C.A., Cunha, F.Q. S.H. Ferreira. An electronic pressure-meter nociception paw test for mice. Brazilian Journal of Medical and Biological Research 37 (2004) 401-407. Levy, D., R. Burstein, V. Kainz, M. Jakubowski, A.M.Strassman. “Mast cell degranulation activates a pain pathway underlying migraine headache.” Pain 130 (2007): 166-176. Liu, T., Z.T. Bai, X.Y. Pang, Z.F. Chai, F. Jiang, Y.H. Ji. “Degranulation of mast cells and histamine release involved in rat pain-related behaviors and edema induced by scorpion Buthus Martensis Karch venom.” European Journal of Pharmacology 575 (2007): 46-56. Alves, E.W. and L. de Meis. Effect of compound 48/80 and ruthenium red on the Ca2+ -ATPase of sarcoplasmic reticulum. Journal of Biology and Chemistry 261 (1986): 16854-16859. Bronner, C., Wiggins, C., Monté, D., Märki, F., Capron, A., Landry, Y. and R.C. Franson. Compound 48/80 is a potent inhibitor of phospholipase C and a dual modulator of phospholipase A2 from human platelet. Biochimica et Biophysica Acta 920 (1987):301-305. Fuller, R.W., Dixon, C.M., Cuss, F.M., and P.J. Barnes. Bradykinin-induced bronchoconstriction in humans: Mode of action. The American Review of Respiratory Disease 135 (1987): 176-180. Dixon C.M. and P.J. Barnes. Bradykinin-induced bronchoconstriction: inhibition by nedocromil sodium and sodium cromoglycate. British Journal of Clinical Pharmacology 27 (1989): 831–836. Lee P.Y. and F.L. Pearce. Histamine secretion from mast cells stimulated with bradykinin. Inflammation Research 30 (1990): 67-69. Rocha, A.C.C., E.S. Fernandes, N. L. M. Quintão, M.M. Campos, J.B. Calixto. Relevance of tumour necrosis factor- for the inflammatory and nociceptive responses evoked by carrageenan in the mouse paw. British Journal of Pharmacology 148 no. 5 (2006): 688–695. Klimscha, W., G. Horvath, M. Szikszay, I. Dobos, G. Benedek. Antinociceptive effect of the S(+)-enantiomer of ketamine on carrageenan hyperalgesia after intrathecal administration in rats. Anesthesia & Analgesia 86 (1998): 561-565. University of St. Thomas McNair Research Journal 7. Figures and Tables. 33
Page 1 and 2: Office of Institutional Diversity M
Page 3 and 4: The University of St. Thomas McNair
Page 5 and 6: Our McNair participants are encoura
Page 7 and 8: Humanities & Social Sciences How Ea
Page 9 and 10: Humanities & Social Sciences rearin
Page 11 and 12: Humanities & Social Sciences Univer
Page 13 and 14: Humanities & Social Sciences Resear
Page 15 and 16: Humanities and Social Sciences The
Page 17 and 18: Humanities and Social Sciences Work
Page 19 and 20: Professions pronouns, or subject in
Page 21 and 22: Professions beating. We are in the
Page 23 and 24: Professions integration of multicul
Page 25 and 26: Humanities & Social Sciences school
Page 27 and 28: Humanities & Social Sciences that w
Page 29 and 30: Science Abstract This study compile
Page 31 and 32: Science findings which can be disti
Page 33 and 34: Science and runoff, far lower water
Page 35 and 36: Science (OVA) model, which will be
Page 37: Science cance was only apparent bet
Page 41 and 42: Science University of St. Thomas Mc
Page 43 and 44: Professions situations perceived as
Page 45 and 46: Professions University of St. Thoma
Page 47 and 48: Professions University of St. Thoma
Page 49 and 50: Humanities & Social Sciences Bridgi
Page 51 and 52: Humanities & Social Sciences Youth
Page 53 and 54: Humanities & Social Sciences A Stud
Page 55 and 56: Humanities & Social Sciences Schaff
Page 57 and 58: Humanities & Social Sciences Refere
Page 59 and 60: Humanities & Social Sciences higher
Page 61 and 62: Humanities & Social Sciences childh
Page 63 and 64: Humanities & Social Sciences being
Page 65 and 66: Humanities & Social Sciences Mai Ch
Page 67 and 68: Humanities & Social Sciences Propin
Page 69 and 70: Humanities & Social Sciences Refere
Page 71 and 72: The University of St. Thomas McNair

McNair Research Journal - University of St. Thomas

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?