Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1590/S0034-70942011000200009
Brazilian Journal of Anesthesiology
Scientific Article

Antagonistas serotoninérgico e noradrenérgico por via subaracnoidea aumentam a resposta álgica em ratos

Subarachnoid serotonergic and noradrenergic antagonists increase the pain response in rats

Oscar César Pires; Hazem Adel Ashmawi; Elton Constantino; Naira Correa Cusma Pelogia; Irimar de Paula Posso

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Resumo

JUSTIFICATIVA E OBJETIVOS: Há evidências de que a passagem de informações nociceptivas pelo corno posterior da medula espinhal (CPME) seguindo para níveis rostrais do sistema nervoso central sofre profundas influências excitatórias e inibitórias. A presente pesquisa teve como objetivo comparar os efeitos da metissergida, da fentolamina e da fentolamina associada à metissergida, administrados por via subaracnoidea, sobre as fases I, intermediária e II do teste da formalina modificado em ratos. MÉTODO: Foram utilizados 28 ratos Wistar machos, distribuídos aleatoriamente em quatro grupos (n = 7) para receber solução salina (GC), fentolamina (GF), metissergida (GM) ou fentolamina associada à metissergida (GFM) por via subaracnoidea. A dor foi induzida pela administração de formalina na região dorsal da pata posterior direita. O teste foi dividido em três fases; fase I, intermediária e fase II. A análise estatística dos resultados foi realizada utilizando o programa SPSS (Statistical Package for Social Sciences), adotando o nível de significância de 5%. RESULTADOS: Na fase intermediária, o número de elevações da pata foi significativamente maior nos grupos GF, GM e GFM quando comparados com o grupo GC. CONCLUSÕES: Os resultados sugerem a existência de efeito noradrenérgico e serotoninérgico no sistema inibitório descendente da dor aguda, com a possibilidade de emprego de agonistas serotoninérgicos e α1-adrenérgicos para controle da dor aguda.

Palavras-chave

ANATOMIA, Espaço subaracnoideo, ANIMAL, Rato, DOR, DOR, DROGAS, Vasodilatadores, DROGAS, Vasodilatadores

Abstract

BACKGROUND AND OBJECTIVES: There is evidence that the passage of nociceptive information through the posterior horn of the spinal cord (PHSC) on its way to rostral levels of the central nervous system undergoes profound excitatory and inhibitory influences. The objective of the present study was to compare the effects of the subarachnoid administration of methysergide, phentolamine, and phentolamine associated with methysergide on phases I, intermediate, and II of the modified phormaline test in rats. METHODS: Twenty-eight male Wistar rats distributed randomly in four groups (n = 7) to received subarachnoid saline solution (GC), phentolamine (GF), methysergide (GM), or phentolamine associated with methysergide (GFM). Pain was induced by the administration of phormaline in the dorsal region of the right hind paw. The test was divided in three phases: phase I, intermediate, and phase II. Statistical analysis of the results was performed using the software SPSS (Statistical Package for Social Sciences), adopting a level of significance of 5%. RESULTS: In the intermediate phase the number of paw elevations was significantly higher in GF, GM, and GFM groups when compared to the GC group. CONCLUSIONS: The results suggest the existence of a noradrenergic and serotonergic effect in the inhibitory descending system of acute pain, with the possibility of using serotonergic and α1-adrenergic antagonists to control acute pain.

Keywords

Pain measurement, Subarachnoid Space, Phentolamine, Methysergide, Rats

Referencias

D'Mello R, Dickenson AH. Spinal cord mechanisms of pain. Br J Anaesth. 2008;101:8-16.

Vanegas H, Schaible HG. Descendent control of persistent pain: inhibitory or facilitatory?. Brain Res Rev. 2004:295-309.

Mason P. Deconstructing endogenous pain modulation. J Neurophysiol. 2005;94:1659-1663.

Liu RJ, Zhang RX, Qiao JT. Interrelations of opioids with monoamines in descending inhibition of nociceptive transmission at the spinal level: an immunocytochemical study. Brain Res. 1999;830:183-190.

Mochizucki D. Serotonin and noradrenaline reuptake inhibitors in animal models of pain. Hum Psychopharmacol. 2004;19:S15-S19.

Calajesan AA, Chang HC, Zhuo M. Spinal serotonergic receptors mediate of a nociceptive reflex by subcutaneous formalin injection into hindpaw in rats. Brain Res. 1998;798:46-54.

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.

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

Franklin KBJ, Abbott FV. Pentobarbital, diazepam end ethanol abolish the interphase diminution of pain in the formalin test: evidence for pain modulation by GABA A receptors. Pharmacol Biochem Behav. 1993;46:661-66.

Tjolsen A, Beerge O, Hunskaar S. The formalin test: an evaluation of the method. Pain. 1992;51:5-17.

Wheller-Aceto H, Porreca F, Cowan A. The rat paw formalin test: comparison of noxious agents. Pain. 1990;40:229-238.

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

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

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

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, Palmeira CCA. The effects of pyrilamine and cimetidine on mRNA c-Fos expression and nociceptive flinching behavior in rats. Anesth Analg. 2003;97:541-546.

Sousa A, Franco PAB, Ashamawi HA. Efeito analgésico local do tramadol em modelo de dor provocada por formalina em ratos. Rev Bras Anestesiol. 2008:371-379.

Danzebrink RM, Gebhart GF. Evidence that spinal 5-HT1, 5-HT2 and 5-HT3 receptor subtypes modulate responses to noxious colorectal distension in the rat. Brain Res. 1991;538:64-75.

Obata H, Saito S, Sasaki M. Antiallodynic effect of inthathecally administered 5-HT2 agonists in rats with nerve ligation. Pain. 2000;90:173-79.

Henry JL, Yashpal K, Pitcher GM. Physiological evidence that the "interphase" in the formalin test is due to active inhibition. Pain. 1999;82:57-63.

Basbaum AI. Descending control of pain transmission: possible serotoninergic- enkephalinergic interactions. Adv Exp Med Biol. 1981;133:177-189.

Sasaki M, Obata H, Saito S. Antinociception with intratecal α-methyl-5-hydroxytryptamine, a 5-hydroxytryptamine2A/2C receptor agonist, in two rat models of sustained pain. Anesth Analg. 2003;96:1072-1078.

Ki-Myung C, Seong-Soo C, Ki-Jung H. Antinociceptive effects of methysergide in various pain models. Pharmacology. 2003;101:69-93.

Gebhart GF, Ossipov MH. Characterization of inhibition of the spinal nociceptive Tail-Flick Reflex in the rat from the medullary lateral reticular nucleus. Neuroscience. 1986;6:701-713.

Shanon HE, Lutz EA. Yoimbine produces antinociception in the formalin test in rats: involvement to serotonin1A receptors. Psycopharmacology. 2000;149:93-97.

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