Brazilian Journal of Anesthesiology
https://app.periodikos.com.br/journal/rba/article/doi/10.1016/j.bjane.2013.10.020
Brazilian Journal of Anesthesiology
Scientific Article

Subarachnoid meloxicam does not inhibit the mechanical hypernociception on carrageenan test in rats

Meloxicam subaracnoide não inibe a hipernocicepção mecânica no teste da carragenina em ratos

Lanucha Fidelis da Luz Moura; Silvana Bellini Vidor; Anelise Bonilla Trindade; Priscilla Domingues Mörschbächer; Nilson Oleskovicz; Emerson Antonio Contesini

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Abstract

BACKGROUND AND OBJECTIVE: Evaluate the antinociceptive effects of subarachnoid meloxicam on the mechanical hypernociception induced by carrageenan in rats. METHODS: Randomized controlled trial. Eighteen adult male Wistar rats underwent a cannula implantation into the subarachnoid space and were randomly divided into two groups: Group I received saline solution 5 µL, while Group II received meloxicam 30 mg. The mechanical hypernociception was induced by intraplantar injection of carrageenan and evaluated using a digital analgesy meter every 30 min during a 4-h period. The results were recorded as the Δ withdrawal threshold (in g), calculated by subtracting the measurement value after treatment from baseline. RESULTS: The Δ withdrawal threshold mean values were lower in the group of patients treated with meloxicam over all time points between 45 and 165 min, however, there was no statistical significance (p = 0.835) for this difference. CONCLUSION: Subarachnoid meloxicam at a dose of 30 µg animal-1 did not suppress the mechanical hypernociception in a model of inflammatory pain induced by intraplantar administration of carrageenan in rats. The data suggest that other dosages should be investigated the drug effect is discarded.

Keywords

NSAIDs, Carrageenan, Pain, Spinal cord

Resumo

JUSTIFICATIVA E OBJETIVO: Avaliar os efeitos antinociceptivos do meloxicam subaracnóideo sobre a hipernocicepção mecânica induzida pela carragenina em ratos. MÉTODOS: Estudo randômico e controlado. Dezoito ratos Wistar, machos adultos, foram submetidos à implantação de uma cânula subaracnóidea, e aleatoriamente distribuídos em dois grupos: o Grupo I (GI) recebeu 5 µL de solução salina, enquanto que ao Grupo II (GII) foram administrados 30 µg de meloxicam, ambos pela via subaracnóidea. A hipernocicepção mecânica foi induzida pela injeção intraplantar de carragenina e avaliada com o emprego de um analgesímetro digital a cada 30 minutos durante um período de 4 horas. Os resultados foram registrados como o Δ do limiar de retirada (g), calculado subtraindo-se o valor das mensurações após os tratamentos, do valor basal. RESULTADOS: Os valores médios do Δ do limiar de retirada foram menores no grupo tratado com meloxicam ao longo de todos os momentos de avaliação entre 45 e 165 minutos, contudo não foi demonstrada significância estatística (p = 0,835) para essa diferença. CONCLUSÃO: A administração subaracnóidea do meloxicam na dose de 30 µg.animal-1 não foi capaz de suprimir a hipernocicepção mecânica em um modelo de dor inflamatória induzida pela administração intraplantar de carragenina em ratos. Os dados sugerem que outras doses sejam pesquisadas antes que o efeito do fármaco seja descartado.

Palavras-chave

AINE, Carragenina, Dor, Medula espinhal

References

Vinegar R, Truax JF, Selph JL. Pathway to carrageenaninduced inflammation in the hind limb of the rat. Fed Proc.. 1987;46:118-26.

Malmberg AB, Yaksh TL. Antinociceptive actions of spinal nonsteroidal anti-inflammatory agents on the formalin test in the rat. J Pharmacol Exp Ther.. 1992;263:136-46.

Malmberg AB, Yaksh TL. Hyperalgesia mediated by spinal glutamate or substance P receptor blocked by spinal cyclooxygenase inhibition. Science.. 1992;257:1276-9.

Breder CD, Dewitt D, Kraig RP. Characterization of inducible cyclooxygenase in rat brain. J Comp Neurol.. 1995;355:296-315.

Burian M, Geisslinger G. COX-dependent mechanisms involved in the antinociceptive action of NSAIDs at central and peripheral sites. Pharmacol Ther.. 2005;107:139-54.

Beiche F, Scheuerer S, Brune K. Up-regulation of cyclooxygenase-2 mRNA in the rat spinal cord following peripheral inflammation. FEBS Lett.. 1996;390:165-9.

Bianchi M, Panerai AE. The dose-related effects of paracetamol on hyperalgesia and nociception in the rat. Br J Pharmacol.. 1996;117:130-2.

Bustamante D, Paeile C, Willer JC. Effects of intrathecal or intracerebroventricular administration of nonsteroidal antiinflammatory drugs on a C-fiber reflex in rats. J Pharmacol Exp Ther.. 1997;281:1381-91.

Herrero JF, Parrado A, Cervero F. Central and peripheral actions of the NSAID ketoprofen on spinal cord nociceptive reflexes. Neuropharmacology.. 1997;36:1425-31.

McCormack K. Non-steroidal anti-inflammatory drugs and spinal nociceptive processing. Pain.. 1994;59:9-43.

Willingale HL, Gardiner NJ, McLymont N. Prostanoids synthesized by cyclo-oxygenase isoforms in rat spinal cord and their contribution to the development of neuronal hyperexcitability. Br J Pharmacol.. 1997;122:1593-604.

Leal LB, Silva MCT, Bedor DCG. Desenvolvimento de teste de dissolução para o meloxicam utilizando o planejamento fatorial: estudo comparativo de produtos industrializados x produtos magistrais. Rev Bras Farm.. 2008;89:160-3.

Turner PV, Chen HC, Taylor WM. Pharmacokinetics of meloxicam in rabbits after single and repeat oral dosing. Comp Med.. 2006;56:63-7.

Pinardi G, Sierralta F, Miranda HF. Atropine reverses the antinociception of nonsteroidal anti-inflammatory drugs in the tail-flick test of mice. Pharmacol Biochem Behav.. 2003;74:603-8.

Pinardi G, Prieto GC, Miranda HF. Analgesic synergism between intrathecal morphine and cyclooxygenase-2 inhibitors in mice. Pharmacol Biochem Behav.. 2005;82:120-4.

Takeda K, Sawamura S, Tamai H. Role for cyclooxygenase 2 in the development and maintenance of neuropathic pain and spinal glial activation. Anesthesiology.. 2005;103:837-44.

Kimura S, Kontani H. Demonstration of antiallodynic effects of the cyclooxygenase-2 inhibitor meloxicam on established diabetic neuropathic pain in mice. J Pharmacol Sci.. 2009;110:213-7.

Yaksh TL, Rudy T. Chronic catheterization of the spinal subarachnoid space. Physiol Behav.. 1976;17:1031-6.

Vivancos GG, Verri WA Jr, Cunha TM. An electronic pressure-meter nociception paw test for rats. Braz J Med Biol Res.. 2004;37:401-7.

Francischi JN, Chaves CT, Moura AC. Selective inhibitors of cyclo-oxygenase-2 (COX-2) induce hypoalgesia in a rat paw model of inflammation. Br J Pharmacol.. 2002;137:837-44.

Zhang Y, Shaffer A, Portanova J. Inhibition of cyclooxygenase-2 rapidly reverses inflammatory hyperalgesia and prostaglandin E2 production. J Pharmacol Exp Ther.. 1997;283:1069-75.

Riendeau D, Percival MD, Brideau C. Etoricoxib (MK0663): preclinical profile and comparison with other agents that selectively inhibit cyclooxygenase-2. J Pharmacol Exp Ther.. 2001;296:558-66.

Kelly DJ, Ahmad M, Brull SJ. Preemptive analgesia I: physiological pathways and pharmacological modalities. Can J Anaesth.. 2001;48:1000-10.

Nantel F, Denis D, Gordon R. Distribution and regulation of cycloocygenase-2 in carrageenan-induced inflammation. Br J Pharmacol.. 1999;128:853-9.

Martin F, Fletcher D, Chauvin M. Constitutive cyclooxygenase-2 is involved in central nociceptive processes in humans. Anesthesiology.. 2007;106:1013-8.

Vanegas H, Schaible HG. Prostaglandins and cyclooxygenases in the spinal cord. Prog Neurobiol.. 2001;64:327-63.

Wang BC, Hiller JM, Simon EJ. Analgesia following subarachnoid sodium ibuprofen in rats. Anesthesiology.. 1992;79:856.

Wang BC, Li D, Hiller JM. The antinociceptive effect of S-(+)-ibuprofen in rabbits: epidural versus intravenous administration. Anesth Analg.. 1995;80:92-6.

Parris WC, Janicki PK, Johnson B Jr. Intrathecal ketorolac tromethamine produces analgesia after chronic constriction injury of sciatic nerve in rat. Can J Anesth.. 1996;43:867-70.

Massue T, Dohi S, Asano T. Spinal antinociceptive effect of epidural nonsteroidal antiinflammatory drugs on nitric oxide induced hyperalgesia in rats. Anesthesiology.. 1999;91:198-206.

Miranda HF, Pinardi G. Lack of effect of naltrexone on the spinal synergism between morphine and non steroidal antiinflammatory drugs. Pharmacol Rep.. 2009;61:266-74.

Eisenach JC, Curry R, Tong C. Effects of intrathecal ketorolac on human experimental pain. Anesthesiology.. 2010;112:1216-24.

Lopeza-Garcia JA, Laird JM. Central antinociceptive effects of meloxicam on rat spinal cord in vitro. Neuroreport.. 1998;9:647-51.

Santos AR, Vedana EM, De Freitas GA. Antinociceptive effect of meloxicam, in neurogenic and inflammatory nociceptive models in mice. Inflamm Res.. 1998;47:302-7.

Di Rosa M, Sorrentino L. Some pharmacodynamic properties of carrageenin in the rat. Br J Pharmacol.. 1970;38:214-20.

Hilário MO, Terreri MT, Len CA. Nonsteroidal anti-inflammatory drugs: cyclooxygenase 2 inhibitors. J Pediatr.. 2006;82:S206-12.

Dirig DM, Isakson PC, Yaksh TL. Effect of COX-1 and COX-2 inhibition on induction and maintenance of carrageenanevoked thermal hyperalgesia in rats. J Pharmacol Exp Ther.. 1998;285:1031-8.

Yamamoto T, Nozaki-Taguchi N. Role of spinal cyclooxygenase (COX)-2 on thermal hyperalgesia evoked by carageenan injection in the rat. Neuroreport.. 1997;8:2179-82.

Le Bars D, Gozariu M, Cadden SW. Animal models of nociception. Pharmacol Rev.. 2001;53:597-652.

Kraychete DC, Gozzani JL, Kraychete AC. Dor neuropática --aspectos neuroquímicos. Rev Bras Anestesiol.. 2008;58:492-505.

Millan MJ. The induction of pain: an integrative review. Prog Neurobiol.. 1999;66:1-164.

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