The pharmacological interaction between tramadol and meloxicam on the level of peripheral and visceral analgesia in mice

Main Article Content

Khalid Shaban
https://orcid.org/0000-0002-5368-6558
Yarub Jafaar Mousa
https://orcid.org/0000-0003-0004-097X

Abstract

The combined effect of tramadol and meloxicam on peripheral and visceral analgesia were the main focus of this study evaluation of the pharmacological interaction between the two drugs in mice. Using the up-and-down approach, the median effective analgesic doses (ED50) were found to be 17.2 mg/kg for intraperitoneal tramadol and 3.26 mg/kg for intramuscular meloxicam. When the medications were mixed at a 1:1 ratio of their ED50 values, isobolographic analysis showed a synergistic effect (Y = 0.92), with tramadol and meloxicam doses being reduced by 56.3% and 51.8%, respectively. The combination outperformed the effects of either medication alone (tramadol: 65%; meloxicam: 55%) in the acetic acid-induced writhing test, producing full analgesia (100% writhing inhibition) when compared to the control group. These results show that tramadol and meloxicam work together to improve antinociception, supporting their combined use for multimodal pain management.

Downloads

Download data is not yet available.

Article Details

How to Cite
Shaban, K., & Mousa, Y. J. (2026). The pharmacological interaction between tramadol and meloxicam on the level of peripheral and visceral analgesia in mice. Veterinarski Glasnik, 80(1). https://doi.org/10.2298/VETGL250427001S
Section
Full research article

References

Baldo, B.A., Rose, M.A. 2020. The anaesthetist, opioid analgesic drugs, and serotonin toxicity: a mechanistic and clinical review. British Journal of Anaesthesia 124(1):44-62.

https://doi.org/10.1016/j.bja.2019.08.010

Bashar, Q.M., Albadrany, Y.M. 2022a. Evaluation of the antipyretic, analgesic, and anti-inflammatory effects of pregabalin in chicks. Egyptian Journal of Veterinary Sciences 53(3):323-328.https://doi.org/10.21608/ejvs.2022.131986.1336

Bashar, Q.M., Albadrany, Y.M. 2022b. Pregabalin potentiates the analgesic effect of tramadol, diclofenac, and paracetamol in chicks: isobolographic analysis. Iraqi Journal of Veterinary Science 36(4), 931-937.https://doi.org/10.33899/ijvs.2022.132586.2108

Bianchi, M., Panerai, A.E. 1998. Anti-hyperalgesic effects of tramadol in the rat. Brain Research 797(1):163-166.https://doi.org/10.1016/S0006-8993(98)00388-6

Chevalier, P., Smulders, M., Chavoshi, S., Sostek, M., LoCasale, R. 2014. A description of clinical characteristics and treatment patterns observed within prescribed opioid users in Germany and the UK. Pain Management 4(4):267-276.https://doi.org/10.2217/pmt.14.26

Dixon, W.J. 1980. Efficient analysis of experimental observations. Annual Review of Pharmacology and Toxicology 20(1):441-462.https://doi.org/10.1146/annurev.pa.20.040180.002301

Engelhardt, G., Homma, D., Schlegel, K., Utzmann, R., Schnitzler, C. 1995. Anti-inflammatory, analgesic, antipyretic and related properties of meloxicam, a new non-steroidal anti-inflammatory agent with favourable gastrointestinal tolerance. Inflammation Research 44:423-433.https://doi.org/10.1007/BF01757699

Engelhardt, G. 1996. Pharmacology of meloxicam, a new non-steroidal anti-inflammatory drug with an improved safety profile through preferential inhibition of COX-2. Rheumatology 35(suppl_1):4-12.https://doi.org/10.1093/rheumatology/35.suppl_1.4

Gawade, S. 2012. Acetic acid induced painful endogenous infliction in writhing test on mice. Journal of Pharmacology and Pharmacotherapeutics 3(4):348.https://doi.org/10.4103/0976-500X.103699

Gonzalez, C., Zegpi, C., Noriega, V., Prieto, J. C., Miranda, H. F. 2011. Synergism between dexketoprofen and meloxicam in an orofacial formalin test was not modified by opioid antagonists. Pharmacological Reports 63(2):433-440.

https://doi.org/10.1016/S1734-1140(11)70509-6

Hijazi, M. A., El-Mallah, A., Aboul-Ela, M., Ellakany, A. 2017. Evaluation of analgesic activity of Papaver libanoticum extract in mice: involvement of opioids receptors. Evidence-Based Complementary and Alternative Medicine 2017(1):8935085.https://doi.org/10.1155/2017/8935085

Jain, V., Singh, R. 2010. Dicyclomine-loaded Eudragit®-based microsponge with potential for colonic delivery: preparation and characterization. Tropical Journal of Pharmaceutical Research 9(1).https://doi.org/10.4314/tjpr.v9i1.52039

Jendi, S.K., Talathi, A. 2019. Tramadol hydrochloride: an alternative to conventional local anaesthetics for intraoral procedures—a preliminary study. Journal of Oral Biology and Craniofacial Research 9(1):111-114.https://doi.org/10.1016/j.jobcr.2018.11.002

Karrouf, G. 2016. Potential effect of meloxicam and tramadol on neuropathic wound healing in rats. Journal of Veterinary Science and Animal Welfare 1(1):1-5.

Mousa, Y.J. and Mahmood, M.B. 2022. Effect of meloxicam coadministration on the anaesthetic potency of thiopental sodium in a chick model. Veterinarska Stanica, 53 (2): 155-163.https://doi.org/10.46419/vs.53.2.5

Naser, A.S., Albadrany, Y., Shaaban, K.A. 2021. Methods of pain assessment in chicks as a model. Egyptian Journal of Veterinary Sciences 52(2):241-249.https://doi.org/10.21608/ejvs.2021.64605.1219

Naser, A.S., Albadrany, Y., Shaaban, K.A. 2020. Isobolographic analysis of analgesic interactions of silymarin with ketamine in mice. Journal of the Hellenic Veterinary Medical Society 71(2):2171-2178.https://doi.org/10.12681/jhvms.23653

Naser, A.S., Amin, Y.M. 2019. Analgesic effect of silymarin in chicks. Iraqi Journal of Veterinary Sciences 33(2):273-276.https://doi.org/10.33899/ijvs.2019.162906

Raffa, R.B. 2001. Pharmacology of oral combination analgesics: rational therapy for pain. Journal of Clinical Pharmacy and Therapeutics 26(4):257-264.

https://doi.org/10.1046/j.1365-2710.2001.00355.x

Shouip, H.A. 2015. Tramadol synthesis and mechanism of action. Sinai University

Sweetman, S.C., Martindale, C. 2009. The Complete Drug Reference. Pharmaceutical Press, London.

Del Tacca, M., Colucci, R., Fornai, M., Blandizzi, C. 2002. Efficacy and tolerability of meloxicam, a COX-2 preferential nonsteroidal anti-inflammatory drug: A review. Clinical Drug Investigation 22:799-818.

https://doi.org/10.2165/00044011-200222120-00001

Taqa, G.A. 2012. Synergism of the analgesic activities of tramadol with α2 adrenoreceptor agonist xylazine in mice. Iraqi Journal of Veterinary Sciences 26(2):109-13

https://doi.org/10.33899/ijvs.2012.67485

Thurmon, J.C., Tranquilli, W.J., Grimm, K.A. 2007. Lumb and Jones’ Veterinary Anesthesia and Analgesia. Blackwell.

Tsai, Y.C., Chang, P.J., Jou, I.M. 2001. Direct tramadol application on sciatic nerve inhibits spinal somatosensory evoked potentials in rats. Anesthesia & Analgesia 92(6):1547-1551.

https://doi.org/10.1097/00000539-200106000-00040