Pharmacological Synergism: A Multimodal Analgesia Approach to Treat Dental Pain / Sinergismo Farmacológico: Un enfoque de analgesia multimodal para el manejo de dolor dental

Abstract Dental pain is usually managed by clinical interventions and pharmacological coadjuvants such as NSAIDs. However, its perception and modulation is mediated by different nociceptive mechanisms and these strategies can be insufficient. The multimodal analgesia refers to the use of 2 or more analgesic drugs that attenuate or blockade different mechanisms of pain, obtaining a greater clinical effect. Within this concept, pharmacological synergism plays a leading role, combining different molecules in lower doses to diminish also side effects. Since there are no standard prescriptions to be use in all the patients, multimodal approaches allow the clinician to make responsible effective combinations, individualizing analgesia as the pathway to success.

Resumen El dolor dental generalmente se trata con intervenciones clínicas y coadyuvantes farmacológicos como los AINEs. Sin embargo, su percepción y modulación está mediada por diferentes mecanismos nociceptivos y estas estrategias pueden ser insuficientes. La analgesia multimodal se refiere al uso de 2 o más fármacos analgésicos que atenúan o bloquean diferentes mecanismos de dolor, obteniendo un mayor efecto clínico. Dentro de este concepto, el sinergismo farmacológico juega un papel importante, combinando diferentes moléculas en dosis más bajas para disminuir también los efectos secundarios. Dado que no hay prescripciones estándar para ser usadas en todos los pacientes, los enfoques multimodales permiten al clínico realizar combinaciones responsables y eficaces, individualizando la analgesia como el camino hacia el éxito.

Atividade anti-Candida tropicalis dos enantiômeros (R)-(+) ­ & (S)-(-) ­ citronelal em associação com cetoconazol / Anti-Candida tropicalis activity of (R)-(+) ­ & (S)-(-) ­ citronellal enantiomers in combination with ketoconazole

Introdução: aproximadamente 75% das mulheres saudáveis experimentam pelo menos um episódio sintomático de candidíase vulvovaginal (CVV) durante sua vida. Objetivo: avaliar a atividade antifúngica contra cepas de C. tropicalis dos enantiômeros (R)-(+) ­ e (S)-(-)-citronelal [(R)-(+) ­ e (S)-(-)-CT] em associação com cetoconazol. Metodologia: o efeito antifúngico de ambos os enantiômeros foram quantificados e classificados como fungicida ou fungistático a partir dos resultados obtidos da microdiluição em meio líquido RPMI1640 para a obtenção da concentração inibitória mínima (CIM) e da concentração fungicida mínima (CFM). Foram realizados ensaios de associação do antifúngico padrão, cetoconazol com os fitoconstituintes por difusão em Agar e os resultados foram classificados como sinérgicos, antagônicos e indiferentes. Resultados: a CIM50 e a CFM50 dos compostos (R)-(+) ­ e (S)-(-)-citronelal foram respectivamente 16 e 64µg/mL e 2×CIM. Houve sinergismo para todas as cepas testadas com ambos os compostos, porém com maior efeito do enantiômero (S)-(-)-CT sobre as cepas LM 665 e LM 255 em relação ao enantiômero (R)-(+)-CT. Conclusão: os compostos naturais deste estudo mostraram efeito fungicida sobre as cepas testadas, bem como efeito sinérgico significativo quando associado ao cetoconazol

Association of terpinolene and diclofenac presents antinociceptive and anti-inflammatory synergistic effects in a model of chronic inflammation

Pharmacological treatment of inflammatory pain is usually done by administration of non-steroidal anti-inflammatory drugs (NSAIDs). These drugs present high efficacy, although side effects are common, especially gastrointestinal lesions. One of the pharmacological strategies to minimize such effects is the combination of drugs and natural products with synergistic analgesic effect. The monoterpene terpinolene (TPL) is a chemical constituent of essential oils present in many plant species, which have pharmacological activities, such as analgesic and anti-inflammatory. The association of ineffective doses of TPL and diclofenac (DCF) (3.125 and 1.25 mg/kg po, respectively) presented antinociceptive and anti-inflammatory effects in the acute (0, 1, 2, 3, 4, 5 and 6 h, after treatment) and chronic (10 days) inflammatory hyperalgesia induced by Freund's complete adjuvant (CFA) in the right hind paw of female Wistar rats (170-230 g, n=6-8). The mechanical hyperalgesia was assessed by the Randall Selitto paw pressure test, which determines the paw withdrawal thresholds. The development of edema was quantified by measuring the volume of the hind paw by plethismography. The TPL/DCF association reduced neutrophils, macrophages and lymphocytes in the histological analysis of the paw, following a standard staining protocol with hematoxylin and eosin and the counts were performed with the aid of optical microscopy after chronic oral administration of these drugs. Moreover, the TPL/DCF association did not induce macroscopic gastric lesions. A possible mechanism of action of the analgesic effect is the involvement of 5-HT2A serotonin receptors, because ketanserin completely reversed the antinociceptive effect of the TPL/DCF association. These results suggest that the TPL/DCF association had a synergistic anti-inflammatory and analgesic effect without causing apparent gastric injury, and that the serotonergic system may be involved in the antinociceptive effect of this association.