Effects of intra-fourth ventricle injection of crocin on capsaicin-induced orofacial pain in rats

Document Type : Original Research Article


1 Division of Physiology, Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, I.R. Iran

2 Faculty of Veterinary Medicine, Urmia Azad University, Urmia, I.R. Iran


Objectives: Crocin, a constituent of saffron and yellow gardenia, possesses anti-nociceptive effects. In the present study, we investigated the effects of intra-fourth ventricle injection of crocin in a rat model of orofacial pain. The contribution of opioid system was assessed using intra-fourth ventricle injection of naloxone, an opioid receptor antagonist.
Materials and Methods: A guide cannula was implanted into the fourth ventricle of brain in anesthetized rats. Orofacial pain was induced by subcutaneous (s.c.) injection of capsaicin (1.5 µg/20 µl) into the right vibrissa pad. The time spent face rubbing/grooming was recorded for a period of 20 min. Locomotor activity was measured using an open-field test.
Results: Intra-fourth ventricle injection of crocin (10 and 40 µg/rat) and morphine (10 and 40 µg/rat) and their co-administration (2.5 and 10 µg/rat of each) suppressed capsaicin-induced orofacial pain. The analgesic effect induced by 10 µg/rat of morphine, but not crocin (10 µg/rat), was prevented by 20 µg/rat of naloxone pretreatment. The above-mentioned chemical compounds did not affect locomotor activity.
Conclusion: The results of this study showed that the injection of crocin into the cerebral fourth ventricle attenuates capsaicin-induced orofacial pain in rats. The anti-nociceptive effect of crocin was not attributed to the central opioid receptors.


Main Subjects

Alavizadeh SH, Hosseinzadeh H. 2014. Bioactivity assessment and toxicity of crocin: a comprehensive review. Food ChemToxicol, 64: 65-80.
Arendt-Nielsen L, Svenson P, Sessle BJ, Cairns BE, Wang K. 2008. Interactions between glutamate and capsaicin in inducing muscle pain and sensitization in humans. Eur J Pain, 12: 661-670.
Asri-Rezaei S, Tamaddonfard E, Ghasemsoltani-Momtaz B, Erfanparast A, Gholamalipour S. 2015. Effects of crocin and zinc chloride on blood levels of zinc and metabolic and oxidative parameters in streptozotocin-induced diabetic rats. Avicenna J Phytomed, 5: Article in Press.
Aung HH, Wang CZ, Ni M, Fishbain A, Mehendale SR, Xie JT, Shoyama CY, Yuan CS. 2007. Crocin from Crocus sativus possesses significant anti-proliferation effects on human colorectal cancer cells. Exp Oncol, 29: 175-180.
Bourne S. Machada AG, Nagel SJ. 2014. Basic anatomy and physiology of pain pathways. Neurosurg Clin N Am, 25: 629-638.
Carter GT, Duong V, Ho S, Ngo KC, Greer CL, Weeks DL. 2014. Side effects of commomnly prescribed analgesic medications. Phys Med RahabilClin N Am, 25: 457-470.
De Rossi SS. 2013. Orofacial pain: a primer. Dent Clin N Am, 57: 383-392.
Duale C, Luccarini P, Cadet R, Woda A. 1996. Effects of morphine microinjections into the trigeminal sensory complex on the formalin test in rats. Exp Neurol, 142: 331-339.
Eisenberg E, Vos BP, Strassman AM. 1996. The peripheral antinociceptive effect of morphine in a rat model of facial pain. Neuroscience, 72: 519-525.
Erfanparast A, Tamaddonfard E, Taati M, Dabbaghi M. 2015. Effects of crocin and safranal, saffron constituents, on the formalin-induced orofacial pain in rats. Avicenna J Phytomed, 5: Article in Press.
Hamurtekin E, Bagdas D, Gurun MS. 2007. Possible involvement of supraspinal opioid and GABA receptors in CPD-choline-induced antinociception in acute pain models in rats. Neurosc Lett, 420: 116-121.
Hamzeh-Gooshchi N, Tamaddonfard E, Farshid AA. 2015. Effects of microinjection of histamine into the anterior cingulate cortex on pain-related behaviors induced by formalin in rats. Pharmacol Rep, 67: 593-599.
Helm S, Trescot A, colson J, Sehgal N, Silverman S. 2008. Opioid antagonists, partial agonists, and agonists/antagonists: the role of office-based detoxification. Pain Physician, 11: S225-S235.
Holanda Pinto SA, Pinto LM, Guedes MA, Cunha GM, Chaves MH, Santos FA, Rao VS. 2008. Antinociceptive effect of triterpenoid alpha, beta-amyrin in rats on orofacial pain induced by formalin and capsaicin. Phytomedicine, 15: 630-634.
Honda K, Shinoda M, Furukawa A, Kita K, Noma N, Iwata K. 2014. TRPA1 contributes to capsaicin-induced facial cold hyperalgesia in rats. Eur J Oral Sci, 122: 391-396.
Kahveci N, Gulec G, Ozluk K. 2006. Effects of intracerebroventricularly-injected morphine on anxiety, memory retrieval and locomotor activity in rats: involvement of vasopressinergic system and nitric oxide pathway. Pharmacol Biochem Behav, 85: 859-867.
Karami M, Bathaie SZ, Tiraihi T, Habbibi-Rezaei M, Arabkheradmand J, Faghihzadeh S. 2013. Crocin improved locomotor function and mechanical behavior in a rat model of contused spinal cord injury through decreasing calcitonic gene related peptide (CGRP). Phytomedicine, 21: 62-67.
Lee DJ, Gurkoff GG, Goodarzi A, Muizelaar JD, Boggan JE, Shahlaie K. 2014. Intracerebroventricular opiate infusion for refractory head and face pain. World J Clin Cases, 16: 851-856.
Lee IA, Lee JH, Baek NI, Kim DH. 2005. Antihyperlipidemic effect of crocin isolated from the fructus of Gardenia jasminoides and its metabolite crocetin. Biol Pharm Bull, 28: 2106-2110.
National Research Council (NRC) Committee for the update of the Guide for Care and Use of Laboratory Animals. (2011). Guide for the Care and Use of Laboratory Animals. 8th edition, Washington (DC): National Academies Press (US).
Ossipov MH, Dussor GO, Porreca F. 2010. Central modulation of pain. J Clin Invest, 120: 3779-3787.
Paxinos G, Watson C. 1997. The rat brain in stereotaxic coordinates.Compact Third Edition, Academic Press, San Diego, USA.
Pelissier T, Pajot J, Dallel R. 2002. The orofacial capsaicin test: effects of different capsaicin concentrations and morphine. Pain 96: 81-87.
Quintans-Junior LJ, Melo MS, De Sausa DP, Araujo AA, Onofre AC, Gelain DP, Goncalves JC, Araujo DA, Almeida JR, Bonjardim LR. 2010. Antinociceptive effect of citronellal in formalin-, capsaicin-, and glutamate-induced orofacial nociception in rodents and its action on nerve excitability. J Orofac Pain, 24: 305-312.
Takeda M, Matsumoto S, Sessle BJ, Shinoda M, Iwata K. 2011. Peripheral and central mechanisms of trigeminal neuropathic and inflammatory pain. J Oral Biosci, 53: 318-329.
Takemura M, Sugiyo S, Moritani M, Kobayashi M, Yonehara N. 2006. Mechanisms of orofacial pain control in the central nervous system. Arch Histol Cytol, 69: 79-100.
Tamaddonfard E, Erfanparast A, Farshid AA, Khalilzadeh E. 2011. Interaction between histamine and morphine at the level of the hippocampus in the formalin-induced orofacial pain in rats. Pharmacol Rep, 63: 423-432.
Tamaddonfard E, Erfanparast A, Taati M, Dabbaghi M. 2014. Role of opioid system in verapamil-induced antinociception in a rat model of orofacial pain. Res Vet Forum, 5: 49-54.
Tamaddonfard E, Farshid AA, Ahmadian E, Hamidhoseyni A. 2013a. Crocin enhanced functional recovery after sciatic nerve crush injury in rats. Iran J Basic Med Sci, 16: 83-90.
Tamaddonfard E, Farshid AA, Eghdami K, Samadi F, Erfanparast A. 2013b. Comparison of the effects of crocin, safranal and diclofenac on local inflammation and inflammatory pain responses induced by carrageenan in rats. Pharmacol Rep, 65: 1272-1280.
Tamaddonfard E, Hamzeh-Gooshchi N. 2010a. Effect of crocin on the morphine-induced antinociception in the formalin test in rats. Phytother Res, 24: 410-413.
Tamaddonfard E, Hamzeh-Gooshchi N. 2010b. Effect of intraperitoneal and intracerebroventricular injection of crocin on acute corneal pain in rats. Phytother Res, 24: 1463-1467.
Tamaddonfard E, Hamzeh-Gooshchi N, Seiednejad-Yamchi S. 2012.Central effect of crocin on penicillin-induced epileptiform activity in rats.Pharmacol Rep, 64: 94-101.
Tang ML, haas DA, Hu JW. 2004. Capsaicin-induced joint inflammation is not blocked by anesthesia. Anesth Prog, 51: 2-9.
Trescot AM, Datta S, Lee M, Hansen H. 2008. Opioid pharmacology. Pain Physician, 11: 133-153.
Vanegas H, Schaible HG. 2004. Descending control of persistent pain: inhibitory or facilitatory. Brain Res Rev, 46: 295-309.