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Published in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie 7/2010

01-07-2010 | Reports of Original Investigations

Effects of local tramadol administration on peripheral glutamate-induced nociceptive behaviour in mice

Authors: Jimmy T. C. Wang, MSc, Cheryl C. W. Chung, MSc, Ryan A. Whitehead, BSc, Stephan K. W. Schwarz, MD, PhD, Craig R. Ries, MD, PhD, Bernard A. MacLeod, MD

Published in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie | Issue 7/2010

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Abstract

Purpose

The use of peripheral tramadol to block pain has been advocated. However, since its actions in the periphery have not been elucidated fully, we tested the hypothesis that peripheral tramadol blocks peripheral glutamate-induced nociceptive behaviour in mice.

Methods

First, we compared the duration of paw licking after intraplantar (ipl.) glutamate administration, with and without tramadol, using a randomized blinded controlled design. Next, we established the half maximal effective concentrations (EC50s) for local tramadol and reference compound lidocaine in the hot water tail-flick latency test and the glutamate-induced paw allodynia assay.

Results

Tramadol reduced glutamate-induced paw licking from 33 ± 12 sec to 4 ± 4 sec (mean ± SD; t test, P < 0.05; n = 6 per group). The tramadol and lidocaine EC50 nerve conduction blocks in the tail did not differ significantly (84 ± 24 mM vs 69 ± 5 mM, respectively). Although tramadol reduced glutamate-induced allodynia (EC50, 46 ± 13 mM), lidocaine was more potent (EC50, 13 ± 5 mM; Dixon’s up-and-down method; P < 0.05). Tramadol was 2.5 times as effective at blocking nerve conduction in the tail compared with allodynia in the paw.

Conclusions

Local tramadol administration blocked nociceptive behaviour in mice induced by peripheral glutamate. Compared with lidocaine, the relative potency of tramadol was lower for blocking glutamate-induced allodynia than for sensory nerve conduction blockade, suggesting the activation of a pronociceptive receptor system in the periphery.
Literature
1.
go back to reference Kargi E, Babuccu O, Altunkaya H, et al. Tramadol as a local anaesthetic in tendon repair surgery of the hand. J Int Med Res 2008; 36: 971-8.PubMed Kargi E, Babuccu O, Altunkaya H, et al. Tramadol as a local anaesthetic in tendon repair surgery of the hand. J Int Med Res 2008; 36: 971-8.PubMed
2.
go back to reference Haeseler G, Foadi N, Ahrens J, Dengler R, Hecker H, Leuwer M. Tramadol, fentanyl and sufentanil but not morphine block voltage-operated sodium channels. Pain 2006; 126: 234-44.CrossRefPubMed Haeseler G, Foadi N, Ahrens J, Dengler R, Hecker H, Leuwer M. Tramadol, fentanyl and sufentanil but not morphine block voltage-operated sodium channels. Pain 2006; 126: 234-44.CrossRefPubMed
3.
go back to reference Marincsak R, Toth B, Czifra G, Szabo T, Kovacs L, Biro T. The analgesic drug, tramadol, acts as an agonist of the transient receptor potential vanilloid-1. Anesth Analg 2008; 106: 1890-6.CrossRefPubMed Marincsak R, Toth B, Czifra G, Szabo T, Kovacs L, Biro T. The analgesic drug, tramadol, acts as an agonist of the transient receptor potential vanilloid-1. Anesth Analg 2008; 106: 1890-6.CrossRefPubMed
4.
go back to reference Beyzadeoglu T, Yilmaz C, Bekler H, Gokce A, Sayin M. Intraarticular tramadol plus pericapsular incisional bupivacaine provides better analgesia than intraarticular plus pericapsular incisional bupivacaine after outpatient arthroscopic partial meniscectomy. Knee Surg Sports Traumatol Arthrosc 2007; 15: 564-8.CrossRefPubMed Beyzadeoglu T, Yilmaz C, Bekler H, Gokce A, Sayin M. Intraarticular tramadol plus pericapsular incisional bupivacaine provides better analgesia than intraarticular plus pericapsular incisional bupivacaine after outpatient arthroscopic partial meniscectomy. Knee Surg Sports Traumatol Arthrosc 2007; 15: 564-8.CrossRefPubMed
5.
go back to reference Zeidan A,Kassem R,Nahleh N,Maaliki H,El-Khatib M,Struys MM,Baraka A. Intraarticular tramadol-bupivacaine combination prolongs the duration of postoperative analgesia after outpatient arthroscopic knee surgery. Anesth Analg 2008; 107: 292-9.CrossRefPubMed Zeidan A,Kassem R,Nahleh N,Maaliki H,El-Khatib M,Struys MM,Baraka A. Intraarticular tramadol-bupivacaine combination prolongs the duration of postoperative analgesia after outpatient arthroscopic knee surgery. Anesth Analg 2008; 107: 292-9.CrossRefPubMed
6.
go back to reference Zeidan A, Struys MM. Intraarticular Tramadol or “Hot Chili Peppers”? (Reply). Anesth Analg 2008; 107: 2093.CrossRef Zeidan A, Struys MM. Intraarticular Tramadol or “Hot Chili Peppers”? (Reply). Anesth Analg 2008; 107: 2093.CrossRef
7.
go back to reference Hara K, Sata T. The effects of the local anesthetics lidocaine and procaine on glycine and gamma-aminobutyric acid receptors expressed in xenopus oocytes. Anesth Analg 2007; 104: 1434-9.CrossRefPubMed Hara K, Sata T. The effects of the local anesthetics lidocaine and procaine on glycine and gamma-aminobutyric acid receptors expressed in xenopus oocytes. Anesth Analg 2007; 104: 1434-9.CrossRefPubMed
8.
go back to reference Manocha A, Sharma KK, Mediratta PK. On the mechanism of anticonvulsant effect of tramadol in mice. Pharmacol Biochem Behav 2005; 82: 74-81.CrossRefPubMed Manocha A, Sharma KK, Mediratta PK. On the mechanism of anticonvulsant effect of tramadol in mice. Pharmacol Biochem Behav 2005; 82: 74-81.CrossRefPubMed
9.
go back to reference Beirith A, Santos AR, Calixto JB. Mechanisms underlying the nociception and paw oedema caused by injection of glutamate into the mouse paw. Brain Res 2002; 924: 219-28.CrossRefPubMed Beirith A, Santos AR, Calixto JB. Mechanisms underlying the nociception and paw oedema caused by injection of glutamate into the mouse paw. Brain Res 2002; 924: 219-28.CrossRefPubMed
10.
go back to reference Mert T, Gunes Y, Gunay I. Local analgesic efficacy of tramadol following intraplantar injection. Eur J Pharmacol 2007; 558: 68-72.CrossRefPubMed Mert T, Gunes Y, Gunay I. Local analgesic efficacy of tramadol following intraplantar injection. Eur J Pharmacol 2007; 558: 68-72.CrossRefPubMed
11.
go back to reference Omote K, Kawamata T, Kawamata M, Namiki A. Formalin-induced release of excitatory amino acids in the skin of the rat hindpaw. Brain Res 1998; 787: 161-4.CrossRefPubMed Omote K, Kawamata T, Kawamata M, Namiki A. Formalin-induced release of excitatory amino acids in the skin of the rat hindpaw. Brain Res 1998; 787: 161-4.CrossRefPubMed
12.
go back to reference Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL. Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an ‘atypical’ opioid analgesic. J Pharmacol Exp Ther 1992; 260: 275-85.PubMed Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL. Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an ‘atypical’ opioid analgesic. J Pharmacol Exp Ther 1992; 260: 275-85.PubMed
13.
go back to reference Zhang Y, Laster MJ, Eger EI II, Sharma M, Sonner JM. Lidocaine, MK-801, and MAC. Anesth Analg 2007; 104: 1098-102.CrossRefPubMed Zhang Y, Laster MJ, Eger EI II, Sharma M, Sonner JM. Lidocaine, MK-801, and MAC. Anesth Analg 2007; 104: 1098-102.CrossRefPubMed
14.
go back to reference Zhou S, Bonasera L, Carlton SM. Peripheral administration of NMDA, AMPA or KA results in pain behaviors in rats. Neuroreport 1996; 7: 895-900.CrossRefPubMed Zhou S, Bonasera L, Carlton SM. Peripheral administration of NMDA, AMPA or KA results in pain behaviors in rats. Neuroreport 1996; 7: 895-900.CrossRefPubMed
15.
go back to reference Dixon WJ. Quantal response variable experimentation: the up and down method. In: McArthur C (Ed.). Statistics in Endocrinology. Cambridge: MIT Press; 1970: 251-67. Dixon WJ. Quantal response variable experimentation: the up and down method. In: McArthur C (Ed.). Statistics in Endocrinology. Cambridge: MIT Press; 1970: 251-67.
17.
go back to reference Grant GJ, Zakowski MI, Vermeulen K, Langerman L, Ramanathan S, Turndorf H. Assessing local anesthetic effect using the mouse tail flick test. J Pharmacol Toxicol Methods 1993; 29: 223-6.CrossRefPubMed Grant GJ, Zakowski MI, Vermeulen K, Langerman L, Ramanathan S, Turndorf H. Assessing local anesthetic effect using the mouse tail flick test. J Pharmacol Toxicol Methods 1993; 29: 223-6.CrossRefPubMed
18.
go back to reference Lichtman AH. The up-and-down method substantially reduces the number of animals required to determine antinociceptive ED50 values. J Pharmacol Toxicol Methods 1998; 40: 81-5.CrossRefPubMed Lichtman AH. The up-and-down method substantially reduces the number of animals required to determine antinociceptive ED50 values. J Pharmacol Toxicol Methods 1998; 40: 81-5.CrossRefPubMed
19.
go back to reference Hara K, Minami K, Sata T. The effects of tramadol and its metabolite on glycine, gamma-aminobutyric acidA, and N-methyl-D-aspartate receptors expressed in xenopus oocytes. Anesth Analg 2005; 100: 1400-5.CrossRefPubMed Hara K, Minami K, Sata T. The effects of tramadol and its metabolite on glycine, gamma-aminobutyric acidA, and N-methyl-D-aspartate receptors expressed in xenopus oocytes. Anesth Analg 2005; 100: 1400-5.CrossRefPubMed
20.
go back to reference Pozos-Guillen AJ, Aguirre-Banuelos P, Arellano-Guerrero A, Castaneda-Hernandez G, Hoyo-Vadillo C, Perez-Urizar J. Isobolographic analysis of the dual-site synergism in the antinociceptive response of tramadol in the formalin test in rats. Life Sci 2006; 79: 2275-82.CrossRefPubMed Pozos-Guillen AJ, Aguirre-Banuelos P, Arellano-Guerrero A, Castaneda-Hernandez G, Hoyo-Vadillo C, Perez-Urizar J. Isobolographic analysis of the dual-site synergism in the antinociceptive response of tramadol in the formalin test in rats. Life Sci 2006; 79: 2275-82.CrossRefPubMed
Metadata
Title
Effects of local tramadol administration on peripheral glutamate-induced nociceptive behaviour in mice
Authors
Jimmy T. C. Wang, MSc
Cheryl C. W. Chung, MSc
Ryan A. Whitehead, BSc
Stephan K. W. Schwarz, MD, PhD
Craig R. Ries, MD, PhD
Bernard A. MacLeod, MD
Publication date
01-07-2010
Publisher
Springer-Verlag
Published in
Canadian Journal of Anesthesia/Journal canadien d'anesthésie / Issue 7/2010
Print ISSN: 0832-610X
Electronic ISSN: 1496-8975
DOI
https://doi.org/10.1007/s12630-010-9301-9

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