Evaluation of central and peripheral analgesic activity of amitriptyline in mice


  • Ishteyaque Ahmad Department of Pharmacology, Al Falah School of Health Sciences and Research, Al Falah University, Dhauj, Faridabad, Haryana, India
  • Md. Nazer Hasan Department of Pharmacology, School of Medical Sciences and Research, Sharda University, 32-34, Knowledge Park-III, Greater Noida, Uttar Pradesh, India
  • Ajitesh Kumar Mishra Department of Pharmacology, Government Medical College Ambikapur, Kanyaparisar Road, Gangapur, Ambikapur, Surguja, Chhattisgarh, India




Amitriptyline, Analgesic activity, Central and peripheral pain mechanism


Background: Pain is one of the most frequent reasons for visiting a doctor. Large-scale studies in Western countries have shown that a fifth of the adult population suffer from chronic pain. Treatment of pain, still a major problem in clinical practice. Despite several available analgesics, unrelieved pain remains a major health care issue. Amitriptyline is a tricyclic antidepressant drug, which is regarded as adjuvant analgesic. There is a common consensus among the researchers on analgesic effect of amitriptyline which is mediated by central pathway but for the peripheral mechanism no conclusive evidence exists till now.

Methods: To establish the analgesic mechanism of amitriptyline we tried to evaluate the analgesic activity on different mice models for central (Radiant heat tail flick test and Haffner’s tail clip method) and peripheral analgesia (Writhing test). We also compare the effects of amitriptyline with standard drugs for central and peripheral analgesia.

Results: Both in Radiant heat tail flick test and Haffner’s tail clip method we found that the amitriptyline showed significant (p<0.05 to p<0.001) activity as compared to control and diclofenac group. But in comparison to pentazocin group amitriptyline didn’t show significant difference in the reaction time. In acetic acid induced writhing test amitriptyline group mice showed 41.09% reduction in number of writhes as compared to control group. While the standard control (Diclofenac) showed reduction of 65.17% as compared to control. So, amitriptyline showed comparable efficacy towards reduction in number of writhes with that of diclofenac.

Conclusions: The results revealed that amitriptyline has significant analgesic activity which is mediated by modulation of both the central and peripheral pathways.


Kumar KH, Elavarasi P. Definition of pain and classification of pain disorders. J Adv Clin Res Insights. 2016;3(3):87-90.

Gallup survey conducted by the Gallup Organization from May 21 to June 9, 1999. Supported by the Arthritis Foundation and Merck & Company, Inc. Available at: http://chronicpainaware.org/pain-101/pain-survey-results.

Fox CD, Berger D, Fine PG. Pain assessment and treatment in the managed care environment. a position statement from the American Pain Society. Glenview, IL: American Pain Society. 2000;11(5):50-3.

Oertel BG, Lötsch J. Clinical pharmacology of analgesics assessed with human experimental pain models: bridging basic and clinical research. Br J Pharmacol. 2013;168(3):534-53.

Goldberg DS, McGee SJ. Pain as a global public health priority. BMC Public Health. 2011;11(1):770.

Świeboda P, Filip R, Prystupa A, Drozd A. Assessment of pain: types, mechanism and treatment. Ann Agric Environ Med. 2013;1:2-7.

Mojtabai R, Olfson M. Proportion of antidepressants prescribed without a psychiatric diagnosis is growing. Health Aff (Millwood). 2011;30(8):1434-42.

Mercier A, Aubin AI, Lebeau JP, Schuers M, Boulet P, et al. Evidence of prescription of antidepressants for non-psychiatric conditions in primary care: an analysis of guidelines and systematic reviews. BMC Fam Pract 2013;14(1):55.

Dharmshaktu P, Tayal V, Kalra BS. Efficacy of antidepressants as analgesics: a review. J Clin Pharmacol. 2012;52:6-17.

Smitherman TA, Walters AB, Maizels M, Penzien DB. The use of antidepressants for headache prophylaxis. CNS Neurosci Ther. 2011;17:462-69.

Galer BS. Neuropathic pain of peripheral origin: advances in pharmacologic treatment. Neuro. 1995;45:S17-25.

Shukla AK, Srivastav AK. Comparative study of tramadol and diclofenac as analgesic for postoperative pain. Int J Med Res Rev. 2015;3(11):1311-6.

Satoskar RS, Rege NN, Bhandarkar SD. Pharmacology and Pharmacotherapeutics 24th edition. New Delhi: Reed Elsevier India Pvt. Ltd.; 2015.

Gupta AK, Parasar D, Sagar A, Choudhary V, Chopra BS, Garg R, et al. Analgesic and anti-inflammatory properties of gelsolin in acetic acid induced writhing, tail immersion and carrageenan induced paw edema in mice. PLoS ONE. 2015;10:e0135558.

Shu H, Hayashida M, Arita H, Huang W, Zhang H, An K et al. Pentazocine-induced antinociception is mediated mainly by μ-opioid receptors and compromised by κ-opioid receptors in mice. J Pharmacol Exp Ther. 2011;338(2):579-87.

Paudel KR, Das BP, Rauniar GP, Sangraula H, Deo S, Bhattacharya SK. Antinociceptive effect of amitriptyline in mice of acute pain models. Indian J Exp Biol. 2007;45(6):529-31.

Vogel HG, Vogel WH, Scholkens BA, Sandow J, Muller G, Vogel WF. Drug discovery and evaluation 2nd edition. Berlin Heidelberg: Springer-Verlag; 2002.

Amour DFE, Smith DL. A method for determining loss of pain sensation. J Pharmacol Exp Ther. 1941;72(1):74-9.

Saha A, Masud MA, Bachar SC, Kundu JK, Datta BK, Nahar L et al. The analgesic and anti-inflammatory activities of the extracts of Phyllanthus reticulatus in Mice Model, Phar Bio. 2007;45(5):355-9.

RezaeeAsl M, Sabour M, Nikoui V, Ostadhadi S, Bakhtiarian A. The study of analgesic effects of Leonurus cardiaca L. in mice by formalin, tail flick and hot plate tests. Int Sch Res Notices. 2014 Sep 1;2014:687697.

Ghosh MN. Fundamentals of experimental pharmacology. 5th ed. Kolkata: Hilton and company; 2008:151-152.

Bianchi C, Franceschini J. Experimental observations on Haffner’s method for testing analgesic drugs. Br J Pharmacol. 1954;9(3):280-4.

Ghaisas MM, Dandawate PR, Zawar SA, Ahire YS, Gandhi SP. Antioxidant, antinociceptive and anti-inflammatory activities of atorvastatin and rosuvastatin in various experimental models. Inflammopharmacol. 2010;18(4):169-77.

Ardid D1, Marty H, Fialip J, Privat AM, Eschalier A, Lavarenne J. Comparative effects of different uptake inhibitor antidepressants in two pain tests in mice. Fundam Clin Pharmacol. 1992;6(2):75-82.

Paudel KR, Das BP, Rauniar GP, Sangraula H, Deo S, Bhattacharya SK. Antinociceptive effect of amitriptyline in mice of acute pain models. Indian J Exp Biol. 2007;45(6):529-31.

Jagla G, Mika J, Makuch W, Obara I, Wordliczek J, Przewlocka B. Analgesic effects of antidepressants alone and after their local co-administration with morphine in a rat model of neuropathic pain. Pharmacol Rep. 2014;66(3):459-65.

Valverde O, Micó JA, Maldonado R, Mellado M, Gibert-Rahola J. Participation of opioid and monoaminergic mechanisms on the antinociceptive effect induced by tricyclic antidepressants in two behavioural pain tests in mice. Prog Neuropsychopharmacol Biol Psychiatry. 1994;18(6):1073-92.

Dubner R, Hargreaves KM. The neurobiology of pain and its modulation, Clin J Pain. 1989;5(2):S1-4.

Millan MJ. Descending control of pain. Prog Neurobiol. 2002;66(6):355-474.

Jasmin L, Tien D, Janni G, Ohara PT. Is noradrenaline a significant factor in the analgesic effect of antidepressants?. Pain. 2003;106(1):3-8.

Galeotti N, Ghelardini C, Bartolini A. Involvement of potassium channels in amitriptyline and clomipramine analgesia. Neuropharmaco. 2001;40(1):75-84.

Fattahian E, Hajhashemi V, Rabbani M, Minaiyan M, Mahzouni P. Anti-inflammatory effect of amitriptyline on ulcerative colitis in normal and reserpine-induced depressed rats. Iran J Pharm Res. 2016;15(Suppl):125-37.

Rafiee L, Hajhashemi V, Javanmard SH. In vitro and in vivo modulation of LPS and carrageenan-induced expression of inflammatory genes by amitriptyline. J Pharm Pharmacogn Res. 2017;5(3):144-55.

Manning J, Kulbida R, Rai P, Jensen L, Bouma J, Singh SP et al. Amitriptyline is efficacious in ameliorating muscle inflammation and depressive symptoms in the mdx mouse model of Duchenne muscular dystrophy. Exp Physiol. 2014;99(10):1370-86.

Hajhashemi V, Sadeghi H, Minaiyan M, Movahedian A, Talebi A. The role of central mechanisms in the anti-inflammatory effect of amitriptyline on carrageenan-induced paw edema in rats. Clinics. 2010;65(11):1183-7.




How to Cite

Ahmad, I., Hasan, M. N., & Mishra, A. K. (2019). Evaluation of central and peripheral analgesic activity of amitriptyline in mice. International Journal of Basic & Clinical Pharmacology, 8(7), 1622–1627. https://doi.org/10.18203/2319-2003.ijbcp20192661



Original Research Articles