Assessing the Local Anesthetic Effect of Five Essential Oil Constituents

 

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Abstract

We studied the effects of five monoterpenoids, viz. 1,8-cineole, fenchone, linalool, p-cymene and α-pinene, on the sciatic nerve fibers of the frog Rana ridibunda (Pallas, 1771) and compared them to that of lidocaine, a standard local anesthetic. The isolated sciatic nerve, with its perineurium intact, was placed in a three-chambered recording bath, which allowed us to monitor the compound action potentials (CAP), stable in amplitude, for over 2 days. The half-vitality time (IT₅₀), which is the time required for the amplitude of the CAP to decrease to 50 % of its control value, was 53.5 ± 0.9 h for a nerve incubated in normal saline at 26.0 °C. The IT₅₀ values for nerves incubated in saline with p-cymene, 1,8-cineole, or α-pinene, at 30.0 mM, were 19.9 ± 0.4, 32.9 ± 0.5, and 31.0 ± 0.3 hours, respectively. As the IT₅₀ value for 30.0 mM lidocaine, a standard local anesthetic, was 1.6 ± 0.3 min under the same conditions, these three compounds cannot be considered as having a local anesthetic effect. The IT₅₀ values for 30.0 mM linalool and fenchone were 5.7 ± 0.6 and 15.4 ± 1.1 min, respectively; they were significantly, but not markedly different from the respective value for lidocaine. These results combined with the fast inhibition of the CAP and its fast recovery after the removal of either linalool or fenchone indicate a local anesthetic activity of the two compounds. Linalool retained this activity even at lower concentrations of 15.0 and 7.5 mM. The local anesthetic effects of lidocaine and linalool were concentration-dependent; this was not the case for fenchone, which had a relatively strong local anesthetic activity at 30.0 mM, but was entirely inactive at 25.0 mM. On the basis of the effects of the five monoterpenoids on the electrophysiological properties of the sciatic nerve fibers of the frog, we conclude that, whereas 1,8-cineole, p-cymene and α-pinene cause only minor effects, linalool and fenchone exhibit acute local anesthetic activity.

References

• 1 Vokou D. Allelochemicals, allelopathy and essential oils: a field in search of definitions and structure.  Allelopathy J. 2007;  19 119-134
  PubMedGoogle Scholar
• 2 Vokou D, Douvli P, Blionis G J, Halley J M. Effects of monoterpenoids, acting alone or in pairs, on seed germination and subsequent seedling growth.  J Chem Ecol. 2003;  29 2281-2301
  CrossrefPubMedGoogle Scholar
• 3 Lis-Balchin M. Essential oils and 'aromatherapy': their modern role in healing.  R Soc Health J. 1997;  117 324-329
  CrossrefPubMedGoogle Scholar
• 4 Umezu T, Nagano K, Ito H, Kosakai K, Sakaniwa M, Morita M. Anticonflict effects of lavender oil and identification of its active constituents.  Pharmacol Biochem Behav. 2006;  85 713-721
  CrossrefPubMedGoogle Scholar
• 5 Buchbauer G, Jirovetz L, Jager W, Dietrich H, Plank C. Aromatherapy: evidence for sedative effects of the essential oil of lavender after inhalation.  Z Naturforsch. 1991;  46 1067-1072
  PubMedGoogle Scholar
• 6 Sugawara Y, Hara C, Tamura K, Fujii T, Nakamura K, Masujima T, Aoki T. Sedative effect on humans of inhalation of essential oil of linalool: sensory evaluation and physiological measurements using optically active linalools.  Anal Chim Acta. 1998;  365 293-299
  CrossrefPubMedGoogle Scholar
• 7 Peana A T, De Montis M G, Nieddu E, Spano M T, D'Aquila P S, Pippia P. Profile of spinal and supra-spinal antinociception of (−)-linalool.  Eur J Pharmacol. 2004;  485 165-174
  CrossrefPubMedGoogle Scholar
• 8 Narusuye K, Kawai F, Matsuzaki K, Miyachi E. Linalool suppresses voltage-gated currents in sensory neurons and cerebellar Purkinje cells.  J Neural Transm. 2005;  112 193-203
  CrossrefPubMedGoogle Scholar
• 9 Ritchie J M. A pharmacological approach to the structure of sodium channels in myelinated axons.  Annu Rev Neurosci. 1979;  2 341-362
  CrossrefPubMedGoogle Scholar
• 10 Butterworth J F, Strichartz G R. Molecular mechanisms of local anesthesia: a review.  Anesthesiology. 1990;  72 711-734
  CrossrefPubMedGoogle Scholar
• 11 Leal-Cardoso J H, Matos-Brito B G, Lopes-Junior J E G, Viana-Cardoso K V, Sampaio-Freitas A B, Brasil R O, Coelho-de-Souza A N, Albuquerque A A C. Effects of estragole on the compound action potential of the rat sciatic nerve.  Braz J Med Biol Res. 2004;  37 1193-1198
  CrossrefPubMedGoogle Scholar
• 12 Brodin P, Roed A. Effects of eugenol on rat phrenic-nerve diaphragm preparations.  Arch Oral Biol. 1984;  8 611-615
  PubMedGoogle Scholar
• 13 Dallmeier K, Carlini E A. Anesthetic, hypothermic, myorelaxant and anticonvulsant effects of synthetic eugenol derivates and natural analogues.  Pharmacology. 1981;  22 113-127
  CrossrefPubMedGoogle Scholar
• 14 Ghelardini C, Galeotti N, Salvatore G, Mazzanti G. Local anesthetic activity of the essential oil of Lavandula angustifolia.  Planta Med. 1999;  65 700-703
  Article in Thieme ConnectPubMedGoogle Scholar
• 15 Lima-Accioly P M, Lavor-Porto P R, Cavalcante F S, Magalhães P J C, Lahlou S, Morais S M, Leal-Cardoso J H. Essential oil of Croton nepetaefolius and its main constituent, 1,8-cineole, block excitability of rat sciatic nerve in vitro.  Clin Exp Pharmacol Physiol. 2006;  33 1158-1163
  CrossrefPubMedGoogle Scholar
• 16 Ferreira-da-Silva F W, Barbosa R, Moreira-Júnior L, dos Santos-Nascimento T, de Oliveira-Martins M D, Coelho-de-Souza A N, Cavalcante F S A, Ceccatto V M, de Lemos T L G, Magalhães P J C, Lahlou S, Leal-Cardoso J H. Effects of 1,8-cineole on electrophysiological parameters of neurons of the rat superior cervical ganglion.  Clin Exp Pharmacol Physiol. 2009;  36 1068-1073
  CrossrefPubMedGoogle Scholar
• 17 Geronikaki A, Vicini P, Theophilidis G, Lagunin A, Poroikov V, Dearden J C. Study of local anesthetic activity of some derivatives of 3-amino-benzo-[d]-isothiazole.  SAR QSAR Environ Res. 2003;  14 485-495
  CrossrefPubMedGoogle Scholar
• 18 Geronikaki A, Vicini P, Dabarakis N, Lagunin A, Poroikov V, Dearden J, Modaresi H, Hewitt M, Theophilidis G. Evaluation of the local anesthetic activity of 3-aminobenzo[d]isothiazole derivatives using the rat sciatic nerve model.  Eur J Med Chem. 2009;  44 473-481
  CrossrefPubMedGoogle Scholar
• 19 Andreou A, Dabarakis N, Kagiava A, Kosmidis E K, Geronikaki A, Theophilidis G. Assessing the effects of three dental impression materials on the isolated sciatic nerve of rat and frog.  Toxicol In Vitro. 2007;  21 103-108
  CrossrefPubMedGoogle Scholar
• 20 Sazler J L, Brophy P J, Peles E. Molecular domains of myelinated axons in the peripheral nervous system.  Glia. 2008;  56 1532-1540
  CrossrefPubMedGoogle Scholar
• 21 Devaux J, Gola M, Jacquet G, Crest M. Effects of K⁺ channel blockers on developing rat myelinated CNS axons: identification of four types of K⁺ channels.  J Neurophysiol. 2002;  87 1376-1385
  PubMedGoogle Scholar
• 22 Poliak S, Peles E. The local differentiation of myelinated axons at nodes of Ranvier.  Nat Rev Neurosci. 2003;  4 968-980
  CrossrefPubMedGoogle Scholar
• 23 Mert T. Roles of axonal voltage-dependent ion channels in damaged peripheral nerves.  Eur J Pharmacol. 2007;  568 25-30
  CrossrefPubMedGoogle Scholar
• 24 Nau C, Wang G K. Interactions of local anesthetics with voltage-gated Na⁺ channels.  J Membr Biol. 2004;  201 1-8
  CrossrefPubMedGoogle Scholar
• 25 Heimburg T, Jackson A D. The thermodynamics of general anesthesia.  Biophys J. 2007;  92 3159-3165
  CrossrefPubMedGoogle Scholar
• 26 Andersen S S L, Jackson A D, Heimburg T. Towards a thermodynamic theory of nerve pulse propagation.  Prog Neurobiol. 2009;  88 104-113
  CrossrefPubMedGoogle Scholar
• 27 Moreira M R, Cruz G M P, Lopes M S, Albuquerque A A C, Leal-Cardoso J H. Effects of terpineol on the compound action potential of the rat sciatic nerve.  Braz J Med Biol Res. 2001;  34 1337-1340
  CrossrefPubMedGoogle Scholar
• 28 Todd B A, Inman C, Sedgwick E M, Abbott N J. Ionic permeability of the frog sciatic nerve perineurium: parallel studies of potassium and lanthanum penetration using electrophysiological and electron microscopic techniques.  J Neurocytol. 2000;  29 551-567
  CrossrefPubMedGoogle Scholar

1 Equal contribution.

Dr. George Theophilidis

Department of Zoology
School of Biology
Aristotle University

University Campus

Thessaloniki 54124

Greece (Hellas)

Phone: + 30 23 10 99 82 61 and 99 82 75

Fax: + 30 23 10 99 82 69

Email: theophil@bio.auth.gr