The Effect of Systemic Administration of Monoterpenes on Visceral Pain in an Animal Model

Main Article Content

Ahmad Asadi Ardebili


Introduction: Pain is one of the primary and fundamental issues associated with various diseases that every individual will encounter throughout their lifetime. Non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are commonly used for pain control, but they have significant side effects. The current study aimed to evaluate the effect of systemic administration of monoterpenes on visceral pain in an animal model.

Materials and methods: In this experimental study, 30 male albino rats weighing approximately 21 to 25 grams were used. The rats were randomly divided into three groups of 10. The control group did not receive any drug, while the first treatment group received d-limonene orally at a dose of 10 milligrams per kilogram, known as a monoterpene compound. The second treatment group received tramadol orally at a dose of 20 milligrams per kilogram. To assess the effects of monoterpenes on colonic pain, intraperitoneal injection of 6% acetic acid (4 mg/kg) was used, and the number of reflex contractions, which could be easily distinguishable and lasted for several seconds, was observed and counted for 90 minutes. Data were collected and averaged every 5 minutes and then subjected to initial statistical analysis.

Results: A significant difference in terms of visceral pain was observed between these two groups. The rats in the first treatment group that received limonene perceived significantly less visceral pain than those in the control group. The findings indicated a significant difference between treatment groups 1 and 2, meaning that tramadol creates a greater analgesic effect.

Conclusion: This finding suggests that monoterpenes cannot produce the same level of analgesic effects on visceral pain as opioids.

Article Details

How to Cite
Asadi Ardebili, A. (2023). The Effect of Systemic Administration of Monoterpenes on Visceral Pain in an Animal Model. Journal of Lab Animal Research, 2(6), 100–103.
Short Communication


Fitzcharles M-A, Cohen SP, Clauw DJ, Littlejohn G, Usui C, Häuser W. Nociplastic pain: towards an understanding of prevalent pain conditions. Lancet. 2021; 397(10289): 2098-2110. DOI: 10.1016/S0140-6736(21)00392-5

Dydyk A, Sizemore D, Trachsel L, Dulebohn S, Porter B. Tennessee controlled substance prescribing for acute and chronic pain. StatPearls. 2023. Available at:

Bach-Rojecky L, Vađunec D, Žunić K, Kurija J, Šipicki S, Gregg R, et al. Continuing war on pain: a personalized approach to the therapy with non-steroidal anti-inflammatory drugs and opioids. Personalized Med. 2019; 16(2): 171-184. DOI: 10.2217/pme-2018-0116

Bindu S, Mazumder S, Bandyopadhyay U. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochem Pharmacol. 2020; 180: 114147. DOI: 10.1016/j.bcp.2020.114147

Mercadante S. Opioid analgesics adverse effects: the other side of the coin. Curr Pharm Des. 2019;25(30):3197-3202. DOI: 10.2174/1381612825666190717152226

Doneddu PE, Pensato U, Iorfida A, Alberti C, Nobile-Orazio E, Fabbri A, et al. Neuropathic Pain in the Emergency Setting: Diagnosis

and Management. J Clin Med. 2023; 12(18): 6028. DOI: 10.3390/jcm12186028

Cohen SP, Vase L, Hooten WM. Chronic pain: an update on burden, best practices, and new advances. Lancet. 2021; 397(10289): 2082-2097. DOI: 10.1016/S0140-6736(21)00393-7

Mills SE, Nicolson KP, Smith BH. Chronic pain: a review of its epidemiology and associated factors in population-based studies. Br J Anaesth. 2019; 123(2): 273-283. DOI: 10.1016/j.bja.2019.03.023

Sadler KE, Mogil JS, Stucky CL. Innovations and advances in modelling and measuring pain in animals. Nat Rev Neurosci. 2022; 23(2): 70-85. DOI: 10.1038/s41583-021-00536-7

Puschmann A-K, Drießlein D, Beck H, Arampatzis A, Moreno Catalá M, Schiltenwolf M, et al. Stress and self-efficacy as long-term predictors for chronic low back pain: A prospective longitudinal study. J Pain Res. 2020: 613-621. DOI: 10.2147/JPR.S223893

Turnaturi R, Piana S, Spoto S, Costanzo G, Reina L, Pasquinucci L, et al. From Plant to Chemistry: Sources of Active Opioid Antinociceptive Principles for Medicinal Chemistry and Drug Design. Molecules. 2023; 28(20): 7089. DOI: 10.3390/molecules28207089

Saeed M, Sadr S, Gharib A, Lotfalizadeh N, Hajjafari A, Simab PA, et al. Phytosomes: A Promising Nanocarrier for Enhanced Delivery of Herbal Compounds in Cancer Therapy. J Lab Anim Res. 2022; 1(1): 26-32. DOI: 10.58803/jlar.v1i1.8

Riaz U, Iqbal S, Sohail M, Samreen T, Ashraf M, Akmal F, et al. A comprehensive review on emerging importance and economical potential of medicinal and aromatic plants (MAPs) in current scenario. Pak J Agric Res. 2021; 34(2): 381-392. DOI: 10.17582/journal.pjar/2021/34.2.381.392

Sharmeen JB, Mahomoodally FM, Zengin G, Maggi F. Essential oils as natural sources of fragrance compounds for cosmetics

and cosmeceuticals. Molecules. 2021; 26(3): 666. DOI: 10.3390/molecules26030666

Astutik S, Pretzsch J, Ndzifon Kimengsi J. Asian medicinal plants’ production and utilization potentials: A review. Sustainability. 2019; 11(19): 5483. DOI: 10.3390/su11195483

Qadir SU, Raja V. Herbal medicine: Old practice and modern perspectives. Phytomedicine. 2021; 149-180. DOI: 10.1016/B978-0-12-824109-7.00001-7

Saggar S, Mir PA, Kumar N, Chawla A, Uppal J, Kaur A. Traditional and herbal medicines: Opportunities and challenges. Pharmacognosy Res. 2022; 14(2): 107-114. DOI: 10.5530/pres.14.2.15

Jadhav CA, Vikhe DN, Jadhav R. Global and domestic market of herbal medicines: A review. Res J Sci Technol. 2020; 12(4): 327-330. DOI: 10.5958/2349-2988.2020.00049.2

Yousofvand N, Moloodi B. An overview of the effect of medicinal herbs on pain. Phytother Res. 2023;37(3):1057-1081. DOI: 10.1002/ptr.7697

Zielinska-Blajet M, Feder-Kubis J. Monoterpenes and their derivatives-Recent development in biological and medical applications. Int J Mol Sci. 2020; 21(19): 7078. DOI: 10.3390/ijms21197078

Huang C, Bian C, Wang L, Zhou W, Li Y, Li B. Development and validation of a method for determining d-limonene and its oxidation products in vegetables and soil using GC-MS. Microchem J. 2022; 179: 107470. DOI: 10.1016/j.microc.2022.107470

Santana HS, de Carvalho FO, Silva ER, Santos NG, Shanmugam S, Santos DN, et al. Anti-inflammatory activity of limonene in the prevention and control of injuries in the respiratory system: A systematic review. Curr Pharm Des. 2020; 26(18): 2182-2191. DOI: 10.2174/1381612826666200320130443

Sousa C, Leitão AJ, Neves BM, Judas F, Cavaleiro C, Mendes AF. Standardised comparison of limonene-derived monoterpenes identifies structural determinants of anti-inflammatory activity. Sci Rep. 2020; 10(1): 7199. DOI: 10.1038/s41598-020-64032-1

Anandakumar P, Kamaraj S, Vanitha MK. D‐limonene: A multifunctional compound with potent therapeutic effects. J Food Biochem. 2021; 45(1): e13566. DOI: 10.1111/jfbc.13566

Soulimani R, Bouayed J, Joshi RK. Limonene: natural monoterpene volatile compounds of potential therapeutic interest. Am J Essent Oils Nat Prod. 2019; 7(4): 1-10. Available at: https://www.essencejournal. com/pdf/2019/vol7issue4/PartA/7-4-2-526.pdf

Hoffmann T, Klemm F, I Kichko T, Sauer SK, Kistner K, Riedl B, et al. The formalin test does not probe inflammatory pain but excitotoxicity in rodent skin. Physiol Rep. 2022; 10(6): e15194. DOI: 10.14814/phy2.15194

Liu Q, Liu Y, Bian J, Li Q, Zhang Y. The preemptive analgesia of pre-electroacupuncture in rats with formalin-induced acute inflammatory pain. Mol Pain. 2019; 15: 1744806919866529. DOI: 10.1177/1744806919866529

Zanandrea R, Bonan CD, Campos MM. Zebrafish as a model for inflammation and drug discovery. Drug Discov Today. 2020; 25(12): 2201-2211. DOI: 10.1016/j.drudis.2020.09.036

Oktavia SN, Ifora I. Anti-inflammatory, Analgesic, and Antipyretic Potential of Azadirachta indica: A Review. J Drug Deliv Ther. 2022; 12(3): 245-254. DOI: 10.22270/jddt.v12i3-S.5502

Amaral MPdMd, Silva Junior MPd, Lima FdCA, Gutierrez SJC, Arcanjo DDR, Oliveira RdCM. Anxiolytic/Sedative Effect of Monoterpene (-)-Borneol in Mice and In Silico Molecular Interaction with GABAA Receptor. Future Pharmacol. 2023; 3(1): 132-141. DOI: 10.3390/futurepharmacol3010009

Most read articles by the same author(s)