Brazilian Journal of Anesthesiology
http://www.rba.periodikos.com.br/article/doi/10.1590/S0034-70942008000400006
Brazilian Journal of Anesthesiology
Scientific Article

Efeito analgésico local do tramadol em modelo de dor provocada por formalina em ratos

http://dx.doi.org/10.1590/S0034-70942008000400006 Braz J Anesthesiol, vol.58, n4, p.371-379, 2008
PDF Português
PDF English
Downloads: 0
Views: 2131
JUSTIFICATIVA E OBJETIVOS: O cloridrato de tramadol é um fármaco analgésico de ação central, utilizado no tratamento de dores moderadas e intensas. Foi demonstrado efeito analgésico local do tramadol, mas seu mecanismo de ação não foi estabelecido. MÉTODO: Estudou-se o efeito da administração local, sistêmica e por bloqueio de nervo periférico do tramadol sobre o comportamento de elevação da pata gerado pela injeção de 50 µL de formalina a 1% na região dorsal da pata de ratos. O número de elevações da pata foi observado pelo período de 60 minutos. RESULTADOS: A administração local de tramadol em concentrações maiores (2,5 e 5 mg) levou ao bloqueio praticamente completo do comportamento de elevação da pata durante todo o teste. A administração sistêmica e por bloqueio de nervo periférico não afetou o comportamento de elevação da pata na fase I e diminuiu parcialmente na fase II. CONCLUSÕES: O tramadol apresentou efeito analgésico local no modelo de comportamento de elevações da pata com formalina, que é diferente de sua ação central. Esse efeito, nesse modelo, não parece ser ligado a efeito anestésico local.
ANALGÉSICOS, ANIMAIS, DOR, Experimental, FARMACOLOGIA, Farmacodinâmica
BACKGROUND AND OBJECTIVES: Tramadol hydrochloride is known as a centrally acting analgesic drug, used for the treatment of moderate to severe pain. A local analgesic effect has been demonstrated, but its mechanism of action remains unclear. METHODS: In this study, we examined the effect of local, systemic and nerve block tramadol on the nociceptive flinching behavior elicited by injection of 50 µL of 1% formalin into the dorsal region of hind paw of rats. Nociceptive flinching behavior was observed for 60 minutes. RESULTS: Local tramadol in higher concentrations (2.5 and 5mg) almost eliminated flinching behavior during the entire test. Systemic and neural block tramadol did not affect flinching behavior in phase I and partially decreased it in phase II. CONCLUSIONS: Tramadol presented a local analgesic effect in formalin nociceptive flinching behavior that is different from its central analgesic effect. This analgesic effect, in this model, seems not to be linked to a local anesthetic like effect.
ANALGESICS, ANIMALS, PAIN, PAIN, PHARMACOLOGY, Pharmacodynamic

Dayer P, Desmeules J, Collart L. Pharmacologie du tramadol. Drugs. 1997;53(^s2):18-24.

Lewis KS, Han NH. Tramadol: a new centrally acting analgesic. Am J Health Syst Pharm. 1997;54:643-652.

Raffa RB, Friderichs E. The basic science aspect of tramadol hydrochloride. Pain Rev. 1996;3:249-271.

Scott LJ, Perry CM. Tramadol: a review of its use in perioperative pain. Drugs. 2000;60:139-176.

Gillen C, Haurand M, Kobelt DJ. Affinity, potency and efficacy of tramadol and its metabolites at the cloned human mu-opioid receptor. Naunyn Schmiedeberg´s Arch Pharmacol. 2000;362:116-121.

Driessen B, Reimann W, Giertz H. Effects of the central analgesic tramadol on the uptake and release of noradrenaline and dopamine in vitro. Br J Pharmacol. 1993;108:806-811.

Lee CR, Mctavish D, Sorkin EM. Tramadol: A preliminary review of its pharmacodynamic and phamacokinetic properties, and therapeutic potential in acute and chronic pain states. Drugs. 1993;46:313-340.

Lehmann KA. Le tramadol dans les doulers aigues. Drugs. 1997;53(^s2):25-33.

Pang WW, Mok MS, Chang DP. Local anesthetic effect of tramadol, metoclopramide, and lidocaine following intradermal injection. Reg Anesth Pain Med. 1998;23:580-583.

Sindrup SH, Andersen G, Madsen C. Tramadol relieves pain and allodynia in polyneuropathy: a radomized, double-blind, controlled trial. Pain. 1999;83:85-90.

Kapral S, Gollmann G, Waltl B. Tramadol added to mepivacaine prolongs the duration of an axillary brachial plexus blockade. Anesth Analg. 1999;88:853-856.

Acalovschi I, Cristea T, Margarit S. Tramadol added to lidocaine for intravenous regional anesthesia. Anesth Analg. 2001;92:209-214.

Pang WW, Mok MS, Chang DP. The peripheral analgesic effect of tramadol in reducing propofol injection pain: a comparison with lidocaine. Reg Anesth Pain Med. 1999;24:246-249.

Buttner J, Ott B, Klose R. Effects of adding clonidine to mevacaine: axillary brachial plexus blockade. Anaesthesist. 1992;41:548-554.

Bianchi M, Panerai AE. Anti-hyperalgesic effects of tramadol in rat. Brain Res. 1998;797:163-166.

Bianchi M, Rossoni G, Sacerdote P. Effects of tramadol on experimental inflammation. Fundam Clin Pharmacol. 1999;13:220-225.

Buccellati C, Sala A, Ballerio R. Tramadol anti-inflammatory activity is not related to a direct inhibitory action on prostaglandin endoperoxidases synthases. Eur J Pain. 2000;4:413-415.

Tsai YC, Chang PJ, Jou IM. Direct tramadol application on sciatic nerve inhibits spinal somatosensory evoked potentials in rats. Anesth Analg. 2001;92:1547-1551.

Dubuisson D, Dennis SG. The formalin test: A quantitative study of analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain. 1977;4:161-174.

Tj_xFF;lsen A, Berge OG, Hunskaar S. The formalin test: an evaluation of the method. Pain. 1992;51:5-18.

Abbott FV, Franklin KBJ, Westbrook RF. The formalin test: scoring properties of first and second phases of pain response in rats. Pain. 1995;60:91-102.

Taylor BK, Peterson MA, Basbaum AI. Persistent cardiovascular and behavioural nociceptive responses to subcutaneous formalin require peripheral nerve input. J Neurosci. 1995;15:7575-7584.

Shibata M, Ohkubo T, Takahashi H. Modified formalin test: characteristic bifasic pain response. Pain. 1989;38:347-352.

Wheeler-Aceto H, Cowan A. Standardization of the rat paw formalin test for the evaluation of analgesics. Psychopharmacology (Berl). 1991;104:35-44.

Teng CJ, Abbott FV. The formalin test: a dose-response analysis at three developmental stages. Pain. 1998;76:337-347.

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

Puig S, Sorkin LS. Formalin-evoked activity in identified primary afferent fibers systemic lidocaine suppresses phase-2 activity. Pain. 1996;64:345-355.

Coderre TJ, Vacarino AL, Melzack R. Central nervous system plasticity in the tonic pain response to subcutaneous formalin injection. Brain Res. 1990;535:155-158.

Zimmermann M. Ethical guidelines for investigation of experimental pain in conscious animals. Pain. 1983;16:109-110.

Doak GJ, Sawynok J. Formalin induced nociceptive behavior and oedema: involvement of multiple peripheral 5-hydroxitryptamine receptor subtypes. Neuroscience. 1997;80:939-949.

Granados-Soto V, Rufino MO, Lopes LDG. Evidence for the involvement of the nitric oxide: cGMP pathway in the antinociception of morphine in the formalin test. Eur J Pharmacol. 1997;340:177-180.

Parada CA, Tambeli CH, Cunha FQ. The major role of peripheral release of histamine and 5-hydroxytryptamine in formalin induced nociception. Neuroscience. 2001;102:937-944.

Ashmawi HA, Chambergo FS, Araujo Palmeira CA. The effects of pyrilamine and cimetidine on mRNA C-fos expression and nociceptive flinching behavior in rats. Anesth Analg. 2003;97:541-546.

Mert P, Gunes Y, Ozcengiz Gunay I. Comparative effects of lidocaine and tramadol on injured peripheral nerves. Eur J Pharmacol. 2006;543:54-62.

Oliva P, Aurilio C, Massimo F. The antinociceptive of tramadol in the formalin test is mediated by the serotonergic component. Eur J Pharmacol. 2002;445:179-185.

5dd6abeb0e8825e04813f287 rba Articles
Links & Downloads
2352-2291 (Electronic) 0104-0014 (Printed)
Braz J Anesthesiol ©2025 All rights reserved.

Braz J Anesthesiol

Share this page
Page Sections