Screening of cetirizine for analgesic activity in mice
Keywords:
Pain, Reaction time, Antihistamine, Cetirizine, AnalgesicAbstract
Background: Pain is the most common symptom for which patients approach doctors. We have multitude of drugs for pain relief, but they have serious side effects ranging from peptic ulcer (e.g. NSAIDs) to renal failure. The other group, opioids have well known side effects ranging from sedation to drug dependence. So a search for a drug for analgesia with high therapeutic effect and fewer side effects will be a boon for the patients. The objective of this study was to find whether cetirizine, a second generation antihistaminic drug, has got any analgesic activity in mice.
Methods: Ten adult albino mice weighing 20-30 grams of either sex were randomized to two groups (n=5). Group I: control group (Treated with solvent 0.1 ml/kg), Group II: Test group (Cetirizine 1mg/kg). All drugs were given orally. The analgesic activity was evaluated by using tail flick, tail immersion and tail clip methods. Reaction time of animals to pain sensation before and after Cetirizine administration were noted at 0, 15, 30, 60 and 90 minutes time intervals respectively on Day 1, 3, 5, 7, 10.
Results: Mean reaction time was expressed as Mean±SEM, and one way ANOVA was used to assess statistical significance. Cetirizine was found to have statistically significant analgesic effect in mice and time dependent increase in analgesic effect were observed in all three pain models and maximum analgesic activity was observed at 60 minutes (p<0.001) after drug administration.
Conclusions: Through this study, Cetirizine, a second generation antihistamine, is found to have significant analgesic activity in mice. This effect has to be studied further elaborately in animals as well as in humans.
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References
Merskey H, Bogduk N. Classifications of chronic pain: Description of chronic pain syndromes and definition of pain terms. Report by the International Association for the Study of Pain Task Force on Taxonomy. In: Merskey H, Bogduk N, editors. Seattle: IASP Press; 1994:209-14.
Bennett PN, Brown MJ. Nervous System: Pain and analgesics. In: Clinical Pharmacology. 10th ed. Edinburgh, Scotland: Churchill Livingstone; 2008:293-6.
Kumar V, Abbas AK, Fausto N. Histamine as mediator of pain and inflammation. In: Robbins and Cotran Pathologic Basis of Disease, edited by Kumar V, Abbas AK, Fausto N, editors. Philadelphia, PA: Elsevier Saunders, 2010:48-85.
Ghosh MN. Evaluation techniques for analgesic activity. In: Fundamental of Experimental Pharmacology. Calcutta India: Scientific Book Agency; 3rd ed., 2007:175-9.
Gerhard Vogel H, Chapter H. Central analgesic activity. In: Vogel Drug discovery and evaluation, 2nd edition, Springer-Verlag: Berlin, New York, I2002:692-8.
Mobarakeh JI, Sakurada S, Katsuyama S, Kutsuwa M, Kuramasu A, Lin ZY, et al. Role of histamine H(1) receptor in pain perception: a study of the receptor gene knockout mice. Eur J Pharmacol 2000;391:81-9.
Malmberg-Aiello P, Lamberti C, Ghelardini C, Giotti A, Bartolini A. Role of histamine in rodent antinociception. Br J Pharmacol 1994;111:1269-79.
Malmberg-Aiello P, Lamberti C, Ipponi A, Bartolini A, Schunack W. Evidence for hypernociception induction following histamine H1 receptor activation in rodents. Life Sci 1998;63:463-76.
Watson JJ, Allen SJ, Dawbarn D. Targeting nerve growth factor in pain: what is the therapeutic potential? BioDrugs 2008;22:349-59.
Kanda N, Watanabe S. Histamine enhances the production of nerve growth factor in human keratinocytes. J Invest Dermatol 2003;121:570-7.
Lipnik-Stanglj M, Carman-Krzan M. The effects of histamine and interleukin-6 on NGF release from cortical astrocytes in primary culture. Pflugers Arch 2000;440(5 Suppl):R99-100.
Lipnik-Stangelj M, Carman-Krzan M. Histamine-stimulated nerve growth factor secretion from cultured astrocyctes is blocked by protein kinase C inhibitors. Inflamm Res 2004;53 Suppl 1:S57-8.
Stempelj M, Ferjan I. Signaling pathway in nerve growth factor induced histamine release from rat mast cells. Inflamm Res 2005;54:344-9.
Babe KS, Serafin WE. Histamine, bradykinin, and their antagonists. In: Brunton LL, Chabner BA, Knollmann BC, editors. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw-Hill; 2011:920-6.
Rang HP, Dale MM, Ritter JM, Flower RJ, Henderson G. Neural mechanism of pain. In: Rang and Dale's Pharmacology. 7th edn. Edinburgh: Elsevier; 2012:505-6.
Rueff A, Mendell LM. Nerve Growth Factor and Inflammatory Pain. Technical Corner from IASP Newsletter, January/February 1996. Available at http://www.iasp-pain.org/AM/Template.cfm?Section=Technical_Corner&Template=/CM/ContentDisplay.cfm&ContentID=2204.
Petty BG, Cornblath DR, Adornato BT, Chaudhry V, Flexner C, Wachsman M, et al. The effect of systemically administered recombinant human nerve growth factor in healthy human subjects. Ann Neurol 1994;36:244-6.
Julius D, Basbaum AI. Molecular mechanisms of nociception. Nature 2001;413:2013-10.
Lewin GR, Mendell LM. Nerve growth factor and nociception. Trends Neurosci 1993;16:353-9.
Ji RR, Kohno T, Moore KA, Woolf CJ. Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci 2003;26:696-705.
Furst DE, Ulrich RW, Varkey-Altamirano C. Nonsteroidal anti-inflammatory drugs, disease modifying antirheumatic drugs, nonopiod analgesics & drugs used in gout. In: Katzung BG, Masters SB, Trevor AJ, editors. Basic and Clinical Pharmacology. 11th edition. New York, NY, USA: McGraw Hill; 2009:624.
