Ilex paraguariensis Promotes Orofacial Pain Relief After Formalin Injection: Involvement of Noradrenergic Pathway.
BACKGROUND
Drinking mate or chimarrão, a hot infusion of Ilex paraguariensis (ILEX) leaves, is a common habit in Southern South America that has a social and almost ritualistic role. It has been used as a stimulant beverage in South America and analgesic in regions of Argentina for treatment of headache and others painful inflammatory conditions such as arthritis and rheumatism.


OBJECTIVE
The aim of this study was to evaluate the pharmacological activity of I. paraguariensis infusion (ILEX) on orofacial nociception model induced by formalin, and study its mechanism of action.


METHODS
The analgesic effect of ILEX was assessed through writhing test, paw formalin test, paw edema induced by carrageenan, and orofacial pain induced by formalin. To study the action mechanism of ILEX, opioidergic, dopaminergic, nitrergic, and adrenergic pathways were investigated.


RESULTS
The high-performance liquid chromatography analysis of ILEX infusion revealed caffeine and theobromine. The treatment with ILEX reduced the number of writhing. However, it was effective neither in the formalin paw test nor in the paw edema induced by carrageenan. Different from formalin paw test, ILEX was able to reduce the orofacial reactivity to formalin in 31.8% (70.4 ± 2.5 s; first phase), and 20% (127.3 ± 18.9 s; second phase). The analgesic effect of ILEX results from the modulation of noradrenergic pathways since prazosin (α1-adrenoceptor antagonist, 0.15 mg/kg; intraperitoneal) reversed the analgesic effect of ILEX.


CONCLUSIONS
The present report demonstrates that analgesic effect of ILEX in orofacial formalin test is due mainly to modulation of noradrenergic pathways.


CONCLUSIONS
Ilex paraguariensis (ILEX) has been used as a stimulant beverage in South America and analgesic in regions of Argentina for the treatment of headache and others painful inflammatory conditions such arthritis and rheumatism.The aim of this study was to evaluate the pharmacological activity of ILEX on orofacial nociception model induced by formalin, and study its mechanism of action.ILEX reduced the number of writhing and orofacial reactivity to formalin in mice. However, it was effective neither in the formalin paw test nor in the paw edema induced by carrageenan.The analgesic effect of ILEX results from the modulation of noradrenergic pathways. Abbreviation Used: ILEX: Infusion of Ilex paraguariensis, NSAIDs: Nonsteroidal anti-inflammatory drugs, L-NOARG: L-NG-nitro-arginine, UV: Ultraviolet, i.p.: Intraperitoneal, NOS: Nitric Oxide Synthase,
Analysis of variance, S.E.M.: Standard error of mean, HPLC: High-performance liquid chromatography, NO: Nitric Oxide, v.o.: Oral route, DCQ: dicaffeoylquinic acid, BMS: Burning mouth syndrome, PBS: Phosphate-buffered saline.
Laboratory of Pharmacology, Area of Biological and Health Science, University of the West of Santa Catarina, Joaçaba, Brazil.
Eudislaine Fonseca
EF
de Carvalho
Department of Plant Science, Plant Morphogenesis and Biochemistry Laboratory, Federal University of Santa Catarina, Florianópolis, SC, Brazil.
Simone Kobe
SK
de Oliveira
Laboratory of Pharmacology, Area of Biological and Health Science, University of the West of Santa Catarina, Joaçaba, Brazil.
Viviane Koepp
VK
Nardi
Laboratory of Pharmacology, Area of Biological and Health Science, University of the West of Santa Catarina, Joaçaba, Brazil.
Tathiana Carla
TC
Gelinski
Department of Oral Medicine, State University of Ponta Grossa, Ponta Grossa, PR, Brazil.
Marcelo Carlos
MC
Bortoluzzi
Department of Plant Science, Plant Morphogenesis and Biochemistry Laboratory, Federal University of Santa Catarina, Florianópolis, SC, Brazil.
Marcelo
M
Maraschin
Laboratory of Pharmacology, Area of Biological and Health Science, University of the West of Santa Catarina, Joaçaba, Brazil.
Geisson Marcos
GM
Nardi
Caffeine; Ilex paraguariensis; mate; noradrenergic pathways; orofacial pain