_1713419697 20240418102457000 Rovedar Daryoushbabazadeh@gmail.com Rovedar Journal of Lab Animal Research J Lab Anim. Res 2980-9703 02 25 2024 3 1 Seyed Mohammad Nabavi https://orcid.org/0000-0001-6247-7048 Mohammadreza Rahimnejad https://orcid.org/0009-0002-5905-5754 Ahmad Asadi Ardebili https://orcid.org/0009-0003-5910-2108 Ramin Hajikhani https://orcid.org/0000-0001-6302-1560 Introduction: Visceral pain, originating from internal organs, represents a challenging aspect of pain management due to its intricate mechanisms and often debilitating nature. Understanding the underlying pathways involved in visceral pain perception is crucial for developing effective therapeutic strategies. The current study aimed to delve into recent advancements in the understanding of cannabinergic modulation of visceral pain perception, focusing on findings from interventional studies utilizing animal models, particularly rats. Materials and methods: A total of 30 male rats aged 3 months, with an average weight of 220 g were randomly divided into 3 groups. The groups contained the control group which received an intraperitoneal injection of normal saline, the second group received an intraperitoneal injection of anandamide (2 mg/kg), and the third group received an intraperitoneal injection of tramadol (20 mg/kg). The pain in all groups was assessed by an acetic acid test. Results: The data obtained from the intraperitoneal injection of anandamide to the rats of the experimental group showed a significant decrease in the amount of perceived visceral pain compared to the control group. In addition, the results showed that tramadol injection significantly decreased visceral pain in experimental group 2 compared to the control group. A comparison of the mean experimental groups 1 and 2 showed tramadol as an opioid agonist reduced visceral pain perception to a greater extent than anandamide. Conclusion: The current study provides evidence for the involvement of cannabinoid receptors in the modulation of visceral pain sensation in rats. 02 25 2024 1 5 https://creativecommons.org/licenses/by/4.0 10.58803/jlar.v3i1.38 https://jlar.rovedar.com/index.php/JLAR/article/view/38 https://jlar.rovedar.com/index.php/JLAR/article/download/38/84 https://jlar.rovedar.com/index.php/JLAR/article/download/38/84 Świeboda P, Filip R, Prystupa A, Drozd M. Assessment of pain: types, mechanism and treatment. Pain. 2013; 2(7): 2-7. Available at: https://pubmed.ncbi.nlm.nih.gov/25000833/ Pak DJ, Yong RJ, Kaye AD, Urman RD. Chronification of pain: mechanisms, current understanding, and clinical implications. Curr Pain Headache Rep. 2018; 22:1-6. DOI: 10.1007/s11916-018-0666-8 Yam MF, Loh YC, Tan CS, Khadijah Adam S, Abdul Manan N, Basir R. General pathways of pain sensation and the major neurotransmitters involved in pain regulation. Int J Mol Sci. 2018; 19(8):2164. DOI:10.3390/ijms19082164 Lowe H, Toyang N, Steele B, Bryant J, Ngwa W. The endocannabinoid system: a potential target for the treatment of various diseases. Int J Mol Sci. 2021 1; 22(17): 9472. DOI: 10.3390/ijms22179472 Donvito G, Nass SR, Wilkerson JL, Curry ZA, Schurman LD, Kinsey SG, Lichtman AH. The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain. Neuropsychopharmacology. 2018;43(1):52-79. DOI:10.1038/npp.2017.204 Pascual D, Sánchez-Robles EM, García MM, Goicoechea C. Chronic pain and cannabinoids. Great expectations or a christmas carol. Biochem Pharmacol. 2018; 157:33-42. DOI:10.1016/j.bcp.2018.07.033 Farmer MA. Pathophysiology of Pain: Peripheral and Central. In: Goldstein AT, Pukall CF, Goldstein I, editors. Female Sexual Pain Disorders: Evaluation and Management. 1st ed. Cham: Springer International Publishing; 2020. 15-30. DOI:10.1007/978-1-119-48259-8_3 Giamberardino MA, editor. Visceral pain: clinical, pathophysiological and therapeutic aspects. Oxford University Press; 2009. DOI: 10.1093/med/9780199235193.001.0001 Vergnolle N. Modulation of visceral pain and inflammation by protease‐activated receptors. Br J Pharmacol. 2004;141(8):1264-1274. DOI: 10.1038/sj.bjp.0705750 Zieglgänsberger W, Berthele A, Tölle TR. Understanding neuropathic pain. CNS Spectr. 2005;10(4): 298-308. DOI: 10.1017/S1092852900022628 Lowe H, Toyang N, Steele B, Bryant J, Ngwa W. The endocannabinoid system: a potential target for the treatment of various diseases. Int J Mol Sci. 2021; 22(17): 9472. DOI: 10.3390/ijms22179472 Karimi SA, Zahra FT, Martin LJ. IUPHAR review: Navigating the role of preclinical models in pain research. Pharmacol Res. 2024:107073. DOI: 10.1016/j.phrs.2024.107073 Cervero F, Laird JM. Understanding the signaling and transmission of visceral nociceptive events. J Neurobiol. 2004; 61(1): 45-54. DOI: 10.1002/neu.20084 Lamont LA, Tranquilli WJ, Grimm KA. Physiology of pain. Vet Clin Small Anim Pract. 2000 Jul 1;30(4):703-728. DOI: 10.1016/S0195-5616(08)70003-2 Mallipeddi S, Janero DR, Zvonok N, Makriyannis A. Functional selectivity at G-protein coupled receptors: Advancing cannabinoid receptors as drug targets. Biochem Pharmacol. 2017; 128:1-1. DOI: 10.1016/j.bcp.2016.11.014 Voicu V, Brehar FM, Toader C, Covache-Busuioc RA, Corlatescu AD, Bordeianu A, Costin HP, Bratu BG, Glavan LA, Ciurea AV. Cannabinoids in medicine: a multifaceted exploration of types, therapeutic applications, and emerging opportunities in neurodegenerative diseases and cancer therapy. Biomolecules. 2023; 13(9): 1388. DOI:10.3390/biom13091388 Abdel-Salam OME, Sleem AA, Sayed MAEM, Youness ER, Shaffie N. Neuroprotective Effects of Low Dose Anandamide in Pentylenetetrazole-Induced Kindling in Rats. Biomed Pharmacol J. 2019;12(1): 25-40 DOI:10.13005/bpj/1610 Taylor BF, Ramirez HE, Battles AH, Andrutis KA, Neubert JK. Analgesic Activity of Tramadol and Buprenorphine after Voluntary Ingestion by Rats (Rattus norvegicus). J Am Assoc Lab Anim Sci. 2016 Jan;55(1):74-82. Available at: https://pubmed.ncbi.nlm.nih.gov/26817983/ Collier H, Dinneen LC, Johnson CA, Schneider C. The abdominal constriction response and its suppression by analgesic drugs in the mouse. Br J Pharmacol Chemother. 1968; 32(2): 295-310. DOI:10.1111/j.1476-5381.1968.tb00973.x Wahdan SA, Elsherbiny DA, Azab SS, El‐Demerdash E. Piceatannol ameliorates behavioural, biochemical and histological aspects in cisplatin‐induced peripheral neuropathy in rats. Basic & Clinical Pharmacology & Toxicology. 2021;129(6):486-495. DOI:10.1111/bcpt.13643 Henshaw FR, Dewsbury LS, Lim CK, Steiner GZ. The effects of cannabinoids on pro-and anti-inflammatory cytokines: a systematic review of in vivo studies. Cannabis Cannabinoid Res. 2021 Jun 1;6(3):177-195. DOI:10.1089/can.2020.0105 Conti S, Costa B, Colleoni M, Parolaro D, Giagnoni G. Antiinflammatory action of endocannabinoid palmitoylethanolamide and the synthetic cannabinoid nabilone in a model of acute inflammation in the rat. Br J Pharmacol. 2002; 135(1): 181-187. DOI: 10.1038/sj.bjp.0704466 Lie DC, Song HS, Colamarino A, Ming GL, Gage FH. Neurogenesis in the adult brain: new strategies for central nervous system diseases. Annu Rev Pharmacol Toxicol. 2004; 44: 399-421. DOI:10.1146/annurev.pharmtox.44.101802.121631 Howlett AC, Breivogel CS, Childers SR, Deadwyler SA, Hampson RE, Porrino LJ. Cannabinoid physiology and pharmacology: 30 years of progress. Neuropharmacology. 2004; 47: 345-358. DOI: 10.1016/j.neuropharm.2004.07.030 Nakatomi H, Kuriu T, Okabe S, Yamamoto S, Hatano O, Kawahara N, Tamura A, Kirino T, Nakafuku M. Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors. Cell. 2002; 110: 429-441. DOI:10.1016/S0092-8674(02)00862-0 Jin K, Xie L, Kim SH, Parmentier-Batteur S, Sun Y, Mao XO, Childs J, Greenberg DA. Defective adult neurogenesis in CB1 cannabinoid receptor knockout mice. Mol Pharmacol. 2004; 66: 204-208. DOI:10.1124/mol.66.2.204 Cravatt BF, Demarest K, Patricelli MP, Bracey MH, Giang DK, Martin BR, Lichtman AH. Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. Proc Natl Acad Sci USA. 2001; 98: 9371-9376. DOI:10.1073/pnas.161191698 Stella N, Schweitzer P, Piomelli D. A second endogenous cannabinoid that modulates long-term potentiation. Nature. 1997; 388: 773-738. DOI:10.1038/42015 Mechoulam R, Ben Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, Gopher A, Almog S, Martin BR, Compton DR, et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol. 1995; 50: 83-90. DOI: 10.1016/0006-2952(95)00109-D Manzanares J, Julian MD, Carrascosa A. Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes. Curr Neuropharmacol. 2006 Jul 1;4(3):239-257. DOI:10.2174/157015906778019527 Woodhams SG, Chapman V, Finn DP, Hohmann AG, Neugebauer V. The cannabinoid system and pain. Neuropharmacology. 2017; 124: 105-120. DOI:10.1016/j.neuropharm.2017.06.015 Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 1992; 258: 1946-1949. DOI: 10.1126/science.1470919 Quirion B, Bergeron F, Blais V, Gendron L. The delta-opioid receptor; a target for the treatment of pain. Front Mol Neurosci. 2020; 13:52. DOI: 10.3389/fnmol.2020.00052 Asadi Ardebili, A. (). The Effect of Systemic Administration of Monoterpenes on Visceral Pain in an Animal Model. JLAR, 2023; 2(6), 100–103. DOI:10.58803/jlar.v2i6.35 Bán EG, Brassai A, Vizi ES. The role of the endogenous neurotransmitters associated with neuropathic pain and in the opioid crisis: The innate pain-relieving system. Brain Res Bull. 2020; 155:129-136. DOI:10.1016/j.brainresbull.2019.12.001