Hydroalcoholic extracts of three Artemisia species attenuate dental pulp pain and pain-related abnormal feeding behavior of rats

Document Type : Research Article


1 Endodontology Research Center, Kerman University of Medical Sciences, Kerman, Iran.

2 Department of Physiology and Pharmacology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.

3 Physiology Department, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.

4 Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran.

5 Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran

6 Department of biology, Faculty of Science, Lorestan University, Khorramabad, Iran.

7 epartment of Orofacial Pain and Dysfunction, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, Netherlands.


This study considered the therapeutic efficacy of three different Artemisia species extracts on capsaicin-induced dental pulp pain and pain-associated changes in feeding behaviors in adult male Wistar rats. The animals were alienated into five groups (n=6), comprising: sham, capsaicin, and capsaicin groups pre-treated with hydroalcoholic extracts of A. sieberi, A.persica, and A.biennis. Pulpitis was evoked by intradental administration of capsaicin (100 µg). The plant extracts (200 mg/kg/ i.p.) were administered 10 min before capsaicin. Pain scores were recorded for forty min. Afterward, feeding behavior was evaluated within 6 hours. All extracts could suppress capsaicin-related dental pulp pain. Furthermore, capsaicin decreased the number of visits to the food and water ports of the feeding behavior evaluation device that led to a reduced amount and duration of meals consumed. These harmful effects of capsaicin on meal duration, and frequency were attenuated by A.persica. Moreover, capsaicin inhibitory effect on food intake and water consumption was suppressed by all the extracts. Taken together, the present study showed that Artemisia species extracts are useful in supressing capsaicin-induced pulpal pain and pain-induced feeding abnormalities.


1.    Mohammed A, Ofuonye I. Dentine Hypersensitivity: Review of a Common Oral Health Problem. J Dent  Craniofac Res. 2017;2(2):16.
2.    Abd-Elmeguid A, Yu DC. Dental pulp neurophysiology: part 1. Clinical and diagnostic implications. J  Can  Dent  Ass. 2009;75(1).
3.    Rahbar I, Abbasnejad M, Haghani J, Raoof M, Kooshki R, Esmaeili‐Mahani S. The effect of central administration of alpha‐pinene on capsaicin‐induced dental pulp nociception. Int Endod J. 2019;52(3):307-17.
4.    Byers M, Narhi M. Dental injury models: experimental tools for understanding neuroinflammatory interactions and polymodal nociceptor functions. Crit Rev  Oral Biol Med. 1999;10(1):4-39.
5.    Gibbs JL, Urban R, Basbaum AI. Paradoxical surrogate markers of dental injury-induced pain in the mouse. PAIN®. 2013;154(8):1358-67.
6.    Kooshki R, Abbasnejad M, Esmaeili-Mahani S, Raoof M. The role of trigeminal nucleus caudalis orexin 1 receptors in orofacial pain transmission and in orofacial pain-induced learning and memory impairment in rats. Phys  Behav. 2016;157:20-7.
7.    Beaudette JR, Fritz PC, Sullivan PJ, Ward WE. Oral health, nutritional choices, and dental fear and anxiety. Dent  J. 2017;5(1):8.
8.    de la Puente B, Romero-Alejo E, Vela JM, Merlos M, Zamanillo D, Portillo-Salido E. Changes in saccharin preference behavior as a primary outcome to evaluate pain and analgesia in acetic acid-induced visceral pain in mice. J Pain Res. 2015;8:663.
9.    Becker S, Gandhi W, Schweinhardt P. Cerebral interactions of pain and reward and their relevance for chronic pain. Neurosci  Lett. 2012;520(2):182-7.
10.    Tamaddonfard E, Khalilzadeh E, Hamzeh-Gooshchi N, Seiednejhad-Yamchi S. Central effect of histamine in a rat model of acute trigeminal pain. Pharmacol  Rep. 2008;60(2):219.
11.    Kawabata A. Prostaglandin E2 and pain—an update. Biological and Pharmaceutical Bulletin. 2011;34(8):1170-3.
12.    Benemei S, Nicoletti P, Capone JG, Geppetti P. CGRP receptors in the control of pain and inflammation. Curr Opin  Pharmacol. 2009;9(1):9-14.
13.    Hökfelt T, Brumovsky P, Shi T, Pedrazzini T, Villar M. NPY and pain as seen from the histochemical side. Peptides. 2007;28(2):365-72.
14.    Kerins C, Carlson D, Hinton R, Hutchins B, Grogan D, Marr K, et al. Specificity of meal pattern analysis as an animal model of determining temporomandibular joint inflammation/pain. Int J oral Maxillofacial Surg. 2005;34(4):425-31.
15.    Thut PD, Hermanstyne TO, Flake NM, Gold MS. An operant conditioning model to assess changes in feeding behavior associated with temporomandibular joint inflammation in the rat. J Orofacial Pain. 2007;21(1).
16.    Terhune CE. Dietary correlates of temporomandibular joint morphology in the great apes. Am  J  Phys  Anthropol. 2013;150(2):260-72.
17.    Schuh CM, Benso B, Aguayo S. Novel strategies for the treatment of dental pulp-derived pain: pharmacological approaches and beyond. Front  Pharmacol. 2019;10:1068.
18.    Yu C, Abbott PV. An overview of the dental pulp: its functions and responses to injury. Aust  Dent  J. 2007;52:S4-S6.
19.    Magni G, Marinelli A, Riccio D, Lecca D, Tonelli C, Abbracchio MP, et al. Purple corn extract as anti-allodynic treatment for trigeminal pain: role of microglia. Front Cell Neurosci. 2018;12:378.
20.    Cruz Martinez C, Diaz Gómez M, Oh MS. Use of traditional herbal medicine as an alternative in dental treatment in Mexican dentistry: a review. Pharmaceut  Biol. 2017;55(1):1992-8.
21.    Mahboubi M, Farzin N. Antimicrobial activity of Artemisia sieberi essential oil from central Iran. 2009.
22.    Darabian A, Mosavi Z, Asgarpanah J, Bakhtiarian A. In vivo analgesic and anti-inflammatory effects of the essential oil from Artemisia sieberi fruit. Res J Pharmacogn. 2017;4(4):7-15.
23.    Karimi H, Monajemi R, Amjad L. Analgesic and anti-inflammatory effects of artemisia deserti krasch (Extract in rats). Int J Basic Sci  Appl Res. 2014;3(1):1-6.
24.    Dashti M, Morshedi A, Dehghan M, Bagherinasab M. The effect of Artemisia sieberi Besser on inflammatory and neurogenic pain in mice. 2011.
25.    Hadi A, Hossein N, Shirin P, Najmeh N, Abolfazl M. Anti-inflammatory and analgesic activities of Artemisia absinthium and chemical composition of its essential oil. Int J Pharm Sci Rev Res. 2014;38:237-44.
26.    Baek HK, Shim H, Lim H, Shim M, Kim C-K, Park S-K, et al. Anti-adipogenic effect of Artemisia annua in diet-induced-obesity mice model. J Vet  Sci. 2015;16(4):389-96.
27.    Lim DW, Kim YT, Jang Y-J, Kim Y-E, Han D. Anti-obesity effect of Artemisia capillaris extracts in high-fat diet-induced obese rats. Molecules. 2013;18(8):9241-52.
28.    Taraghdari SB, Nematy M, Mazidi M, Kamgar M, Soukhtanloo M, Hosseini M, et al. The effect of hydro-alcoholic extract of Artemisia absinthium on appetite in male rats. Av J Phytomed. 2015;5(2):78.
29.    Wang M, Park C, Wu Q, Simon JE. Analysis of artemisinin in Artemisia annua L. by LC-MS with selected ion monitoring. J  Agric  Food Chem. 2005;53(18):7010-3.
30.    Nikbakht M, Sharifi S, Emami S, Khodaie L. Chemical composition and antiprolifrative activity of Artemisia persica Boiss. and Artemisia turcomanica Gand. essential oils. Res Pharmaceut  Sci. 2014;9(2):155.
31.    Shadi A, Saharkhiz MJ. Changes in essential oil contents and chemical compositions of Artemisia sieberi at different phenological growth stages. Ana  Chem  Lett. 2016;6(3):249-56.
32.    Mirjalili BF, Meybody MHH, Ardakani MM, Rustaiyan A, Ameri N, Masoudi S, et al. Chemical composition of the essential oil from aerial parts, leaves, flowers and roots of Artemisia persica Boiss. from Iran. J Ess  Oil Res. 2006;18(5):544-7.
33.    Nematollahi F, Rustaiyan A, Larijani K, Nadimi M, Masoudi S. Essential oil composition of Artemisia biennisz Willd. and Pulicaria undulata (L.) CA Mey., two compositae herbs growing wild in Iran. J Ess  Oil Res. 2006;18(3):339-41.
34. Ebrahimi T, Setorki M, Dastanpour N. Antinociceptive effects of Artemisia persica boiss essential oil in male mice using formalin and tail immersion tests. Qom Uni Med Sci J. 2019;12(11):23-31.
35.    Raoof M, Soofiabadi S, Abbasnejad M, Kooshki R, Esmaeili‐Mahani S, Mansoori M. Activation of orexin‐1 receptors in the ventrolateral periaqueductal grey matter (vlPAG) modulates pulpal nociception and the induction of substance P in vlPAG and trigeminal nucleus caudalis. Int  Endod J. 2019;52(3):318-28.
36.    Raoof R, Esmaeili-Mahani S, Abbasnejad M, Raoof M, Sheibani V, Kooshki R, et al. Changes in hippocampal orexin 1 receptor expression involved in tooth pain-induced learning and memory impairment in rats. Neuropeptides. 2015;50:9-16.
37. Abad MJ, Bedoya LM, Apaza L, Bermejo P. The Artemisia L. genus: a review of bioactive essential oils. Molecules. 2012;17(3):2542-66.
38. Vengerfeldt V, Mändar R, Saag M, Piir A, Kullisaar T. Oxidative stress in patients with endodontic pathologies. J Pain Res. 2017;10:2031.
39. Alagöz LG, Karadağlıoğlu Öİ, Ulusoy N. Antioxidants used in Restorative Dentistry. 2019.
40.    De Paula E, Kossatz S, Fernandes D, Loguercio A, Reis A. Administration of ascorbic acid to prevent bleaching-induced tooth sensitivity: a randomized triple-blind clinical trial. Operative dentistry. 2014;39(2):128-35.
41.    Takanche J, Lee YH, Kim JS, Kim JE, Han SH, Lee SW, et al. Anti‐inflammatory and antioxidant properties of Schisandrin C promote mitochondrial biogenesis in human dental pulp cells. Int Endod  J. 2018;51(4):438-47.
42. Mojarrab M, Nasseri S, Hosseinzadeh L, Farahani F. Evaluation of antioxidant and cytoprotective activities of Artemisia ciniformis extracts on PC12 cells. Ira J Basic Med Sci. 2016;19(4):430.
43.    Kim MH, Seo JY, Liu KH, Kim J-S. Protective effect of Artemisia annua L. extract against galactose-induced oxidative stress in mice. PloS one. 2014;9(7).
44.    Temraz A, El-Tantawy WH. Characterization of antioxidant activity of extract from Artemisia vulgaris. Pak J Pharm Sci. 2008;21(4):321-6.
45. Kerins C, Carlson D, McIntosh J, Bellinger L. Meal pattern changes associated with temporomandibular joint inflammation/pain in rats; analgesic effects. Pharmacol Biochem Behav. 2003;75(1):181-9.
46. Martin TJ, Kahn WR, Eisenach JC. Abdominal Surgery Decreases Food-reinforced Operant Responding in RatsRelevance of Incisional Pain. Anesthesiology: J Am  Soc Anesthesiol. 2005;103(3):629-37.
47. Schou WS, Ashina S, Amin FM, Goadsby PJ, Ashina M. Calcitonin gene-related peptide and pain: a systematic review. J  Headache Pain. 2017;18(1):34.
48. Smeets PA, Charbonnier L, van Meer F, van der Laan LN, Spetter MS. Food-induced brain responses and eating behaviour. Proc  Nut Soc. 2012;71(4):511-20.
49. Hollis JH, Lemus M, Evetts MJ, Oldfield BJ. Central interleukin-10 attenuates lipopolysaccharide-induced changes in food intake, energy expenditure and hypothalamic Fos expression. Neuropharmacology. 2010;58(4-5):730-8.
50.    Laviano A, Gleason JR, Meguid MM, Yang Z-J, Cangiano C, Rossi FF. Effects of intra-VMN mianserin and IL-1ra on meal number in anorectic tumor-bearing rats. Journal of investigative medicine: the official publication of the Am  Federation Clin  Res. 2000;48(1):40-8.
51.    Sanford D, Luong L, Gabalski A, Oh S, Vu JP, Pisegna JR, et al. An intraperitoneal treatment with calcitonin gene-related peptide (CGRP) regulates appetite, energy intake/expenditure, and metabolism. J Mol  Neurosci. 2019;67(1):28-37.
Volume 14, Issue 2 - Serial Number 27
This issue XML file is being prepared.
June 2022
Pages 29-37
  • Receive Date: 13 September 2021
  • Revise Date: 12 May 2022
  • Accept Date: 18 May 2022
  • First Publish Date: 01 June 2022