Skip to main content
Log in

The analgesic effects and mechanisms of orally administered eugenol

  • Research Articles
  • Drug Actions
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

In the present study, the antinociceptive profiles of eugenol were examined in ICR mice. Eugenol administered orally (from 1 to 10 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. Duration of antinociceptive action of eugenol maintained at least for 30 min. Moreover, the cumulative response time of nociceptive behaviors induced by an intraplantar formalin injection was reduced by eugenol treatment during the 2nd phases. Furthermore, the cumulative nociceptive response time for intrathecal injection of substance P (0.7 μg) or glutamate (20 μg) was diminished by eugenol. Intraperitoneal pretreatment with yohimbine (α2-adrenergic receptor antagonist) or naloxone (opioid receptor antagonist) attenuated antinociceptive effect induced by eugenol in the writhing test. However, methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by eugenol in the writhing test. Our results suggest that eugenol shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of eugenol may be mediated by α2-adrenergic and opioidergic receptors, but not serotonergic receptor.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Cervero, F. and Laird, J. M. A., Visceral pain. Lancet, 353, 2145–2148 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Choi, S. S., Lee, J. K., and Suh, H. W., Antinociceptive profiles of aspirin and acetaminophen in formalin, substance P and glutamate pain models. Brain Res., 921, 233–239 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Choi, S. S., Han, K. J., Lee, J. K., Lee, H. K., Han, E. J., Kim, D. H., and Suh, H. W., Antinociceptive mechanisms of orally administered decursinol in the mouse. Life Sci., V 73, 471–485 (2003).

    Article  Google Scholar 

  • Chung, K. M., Lee, K. C., Choi, S. S., and Suh, H. W., Differential roles of spinal cholera toxin- and pertussis toxin sensitive G proteins in nociceptive responses caused by formalin, capsaicin and substance P in mice. Brain Res. Bull., 54, 537–542 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Cumberbatch, M. J., Herrero, J. H., and Headley, P. M., Exposure of rat spinal neurons to NMDA, AMPA and kainate produces only short-term enhancements of responses to noxious and non-noxious stimuli. Neurosci. Lett., 181, 98–102 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Hirafuji, M., Inhibition of prostaglandin I2 biosynthesis in rat dental pulp by phenolic dental medicaments. Jpn. J. Pharmacol., 36, 544–546 (1984).

    Article  PubMed  CAS  Google Scholar 

  • Hunskaar, S., Fasmer, O. B., and Hole, K., Formalin test in mice, a useful technique for evaluating mild analgesics. J. Neurosci. Methods, 14, 69–76 (1985).

    Article  PubMed  CAS  Google Scholar 

  • Hunskaar, S. and Hole, K., The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain, 30, 103–114 (1987).

    Article  PubMed  CAS  Google Scholar 

  • Hylden, J. L. and Wilcox, G. L., Intrathecal morphine in mice: a new technique. Eur. J. Pharmacol., 67, 313–316 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Hylden, J. L. and Wilcox, G. L., Intrathecal substance P elicits a caudally-directed biting and scratching behavior in mice. Brain Res., 217, 212–215 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Irie, Y. and Keung, W. M., Rhizoma acori graminei and its active principles protect PC-12 cells from the toxic effect of amyloid-β peptide. Brain Res., 963, 282–289 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Jensen, T. S. and Yaksh, T. L., Spinal monoamine and opiate systems partly mediate the antinociceptive effects produced by glutamate at brainstem sites. Brain Res., 321, 287–297 (1984).

    Article  PubMed  CAS  Google Scholar 

  • Kim, S. S., Oh, O. J., Min, H. Y., Park, E. J., Kim, Y., Park, H. J., Han, Y. N., and Lee, S. K., Eugenol suppresses cyclooxygenase-2 expression in lipopolysaccharide-stimulated mouse macrophage RAW264.7 cells. Life Sci., 73, 337–348 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Koster, R., Anderson, M., and Beer, E. J., Acetic acid for analgesic screening. Federal Proceeding, 18, 412 (1959).

    Google Scholar 

  • Kozam, G., The effect of eugenol on nerve transmission. Oral Surg. Oral Med. Oral Pathol., 44, 799–805 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Kumar, S. S., Priyadarsini, K. I., and Sainis, K. B., Inhibition of peroxynitrite-mediated reactions by vanillin. J. Agric. Food Chem., 52, 139–145 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Kurihara, T., Nonaka, T., and Tanabe, T., Acetic aicd conditioning stimulus induces long-lasting antinociception of somatic inflammatory pain. Pharmacol. Biochem. Behav., 74, 841–849 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Li, W., Tsubouchi, R., Qiao, S., Haneda, M., Murakami, K., and Yoshino, M., Inhibitory action of eugenol compounds on the production of nitric oxide in RAW264.7 macrophages. Biomed. Res., 27, 69–74 (2006).

    Article  PubMed  Google Scholar 

  • Müller, M., Pape, H. C., Speckmann, E. J., and Gorji, A., Effect of eugenol on spreading depression and epileptiform discharges in rat neocortical and hippocampal tissues. Neuroscience, 140, 743–751 (2006).

    Article  PubMed  Google Scholar 

  • Nangle, M. R., Gibson, T. M., Cotter, M. A., and Cameron, N. E., Effects of eugenol on nerve and vascular dysfunction in streptozotocin-diabetic rats. Planta Med., 72, 494–500 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Ohkubo, T. and Shibata, M., The selective capsaicin antagonist capsazepine abolishes the antinociceptive action of eugenol and guaiacol. J. Dent. Res., 76, 848–851 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Ozeki, M., The effects of eugenol on the nerve and muscle in crayfish. Comp. Biochem. Physiol. C, 50, 183–191 (1975).

    PubMed  CAS  Google Scholar 

  • Park, S. H., Sim, Y. B., Choi, S. M., Seo, Y. J., Kwon, M. S., Lee, J. K., and Suh, H. W., Antinociceptive Profiles and Mechanisms of Orally Administered Vanillin in the Mice. Arch. Pharm. Res., 32, 1643–1649 (2009).

    Article  PubMed  CAS  Google Scholar 

  • Patacchini, R., Maggi, C. A., and Meli, A., Capsaicin-like activity of some natural pungent substances on peripheral endings of visceral primary afferents. Naunyn Schmiedebergs Arch. Pharmacol., 342, 72–77 (1990).

    Article  PubMed  CAS  Google Scholar 

  • Puig, S. and Sorkin, L. S., Formalin-evoked activity in identified primary afferent fibers: systemic lidocaine suppresses phase-2 activity. Pain, 64, 345–355 (1989).

    Article  Google Scholar 

  • Satyanarayana, P. S. V., Jain, N. K., Singh, A., and Kulkarni, S. K., Isobolographic analysis of interaction between cyclooxigenase inhibitors and tramadol in acetic acid-induced writhing in mice. Prog. Neuropsychopharmacol. Biol. Psychiatry, 28, 641–649 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Sawa, T., Nakao, M., Akaike, T., Ono, K., and Maeda, H., Alkylperoxyl radical-scavenging activity of various flavonoids and other phenolic compounds: implications for the anti-tumour promoter effect of vegetables. J. Agric. Food Chem., 47, 397–402 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Schmauss, C. and Yaksh, T. L., In vivo studies on spinal opiate receptor systems mediating antinociception. II. Pharmacological profiles suggesting a differential association of mu, delta and kappa receptors with visceral chemical and cutaneous thermal stimuli in the rat. J. Pharmacol. Exp. Ther., 228, 1–12 (1984).

    PubMed  CAS  Google Scholar 

  • Shibata, M., Ohkubo, T., Takahashi, H., and Inoki, R., Modified formalin test: characteristic biphasic pain response. Pain, 38, 347–352 (1989).

    Article  PubMed  CAS  Google Scholar 

  • Sneddon, I. B. and Glew, R. C., Contact dermatitis due to propanidid in an anaesthetist. Practitioner, 211, 321–323 (1973).

    PubMed  CAS  Google Scholar 

  • Suh, H. W., Song, D. K., Son, K. H., Wie, M. B., Lee, K. H., Jung, K. Y., Do, J. C., and Kim, Y. H., Antinociceptive mechanisms of dipsacus saponin C administered intracerebroventricularly in the mouse. Gen. Pharmacol., 27, 1167–1172 (1996).

    PubMed  CAS  Google Scholar 

  • Suh, H. W., Song, D. K., and Kim, Y. H., Differntial effects of adenosine receptor antagonist injected intrathecally on antinociception induced by morphine and beta-endorphin administered intracerebroventricularly in the mouse. Neuropeptides, 31, 339–344 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Suh, H. W., Chung, K. M., Kim, Y. H., Huh, S. O., and Song, D. K., Effect of histamine receptor antagonists injected intrathecally on antinociception induced by opioids administered intracerebroventricularly in the mouse. Neuropeptides, 33, 121–129 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Takashi, M., Matsuyama, M., Furuhashi, K., Kodama, Y., Shinzato, M., Shamoto, M., and Nakashima, N., Composite tumor of mucinous cystadenoma and somatostatinoma of the kidney. Int. J. Urol., 10, 603–606 (2003).

    Article  PubMed  Google Scholar 

  • Trowbridge, H., Edwall, L., and Panopoulos, P., Effect of zinc oxide-eugenol and calcium hydroxide on intradental nerve activity. J. Endod., 8, 403–406 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Ulugol, A., Ozyigit, F., Yesilyurt, O., and Dogrul, A., The additive antinociceptive interaction between WIN 55,212-2, a cannabinoid agonist, and ketorolac. Anesth. Analg., 102, 443–447 (2006).

    Article  PubMed  Google Scholar 

  • Vyklicky, L., The techniques for the study of pain in animals. In Bonica, J. J., Liebeskind, J. C., and Albe-Fessard, D. G. (Eds.). Advances in Pain Research and Theraphy, Vol. 3. Raven Press, New York, pp. 727–745, (1979).

    Google Scholar 

  • Wie, M. B., Won, M. H., Lee, K. H., Shin, J. H., Lee, J. C., Suh, H. W., Song, D. K., and Kim, Y. H., Eugenol protects neuronal cells from excitotoxic and oxidative injury in primary cortical cultures. Neurosci. Lett., 225, 93–96 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Wigdor, S. and Wilcox, G. L., Central and systemic morphine-induced antinociception in mice: contribution of descending serotonergic and noradrenergic pathways. J. Pharmacol. Exp. Ther., 242, 90–95 (1987).

    PubMed  CAS  Google Scholar 

  • Won, M. H., Lee, J. C., Kim, Y. H., Song, D. K., Suh, H. W., Oh, Y. S., Kim, J. H., Shin, T. K., Lee, Y. J., and Wie, M. B., Postischemic hypothermia induced by eugenol protects hippocampal neurons from global ischemia in gerbils. Neurosci. Lett., 254, 101–104 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Yaksh, T. L., Opiate receptors for behavioral analgesia resemble those related to the depression of spinal nociceptive neurons. Science, 199, 1231–1233 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Yaksh, T. L., Direct evidence that spinal serotonin and noradrenaline terminals mediate the spinal antinpciceptive effects of morphine in the periaqueductal gray. Brain Res., 160, 180–185 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Yaksh, T. L., Multiple opioid receptor systems in brain and spinal cord: Part I. Eur. J. Anaesthesiol., 1, 171–199 (1984).

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hong-Won Suh.

Additional information

These authors contributed equally to this work

Rights and permissions

Reprints and permissions

About this article

Cite this article

Park, SH., Sim, YB., Lee, JK. et al. The analgesic effects and mechanisms of orally administered eugenol. Arch. Pharm. Res. 34, 501–507 (2011). https://doi.org/10.1007/s12272-011-0320-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-011-0320-z

Key words

Navigation