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1.
Drug Dev Res ; 78(5): 173-183, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28593649

RESUMO

Preclinical Research The presence of pain as part of the cancer process is variable. Glioblastoma multiform (GBM) can produce bone metastasis, a condition that involves other pathological phenotypes including neuropathic and inflammatory pain. Tramadol and gabapentin are drugs used in the treatment of neuropathic pain. However, there are no studies evaluating their analgesic effects in bone metastasis. We produced a pain model induced by the inoculation of glioma cells (105 ) into the rat femur, by perforating the intercodiloid fossa. Painful behavior was evaluated by measuring mechanical allodynia using the Von Frey test while thermal hyperalgesia was assessed in the plantar test. Histopathological features were evaluated and antinociceptive responses were compared using tramadol and gabapentin. The inoculation of cells inside the right femur produced nociceptive behaviors. Tramadol and gabapentin produced an anti-allodynic effect in this condition, but tramadol did not produce an anti-hyperalgesic response. The development of this model will allow us to perform tests to elucidate the pathology of bone metastasis, cancer pain, and in particular the pain produced by glioma. Drug Dev Res 78 : 173-183, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Aminas/administração & dosagem , Analgésicos/administração & dosagem , Neoplasias Ósseas/secundário , Dor do Câncer/tratamento farmacológico , Ácidos Cicloexanocarboxílicos/administração & dosagem , Fêmur/patologia , Tramadol/administração & dosagem , Ácido gama-Aminobutírico/administração & dosagem , Aminas/farmacologia , Analgésicos/farmacologia , Animais , Neoplasias Ósseas/complicações , Neoplasias Ósseas/patologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ácidos Cicloexanocarboxílicos/farmacologia , Gabapentina , Glioblastoma/patologia , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Transplante de Neoplasias , Medição da Dor , Ratos , Tramadol/farmacologia , Resultado do Tratamento , Ácido gama-Aminobutírico/farmacologia
2.
Drug Dev Res ; 77(5): 258-66, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27449485

RESUMO

Preclinical Research Obesity is a risk factor associated with alterations in pain perception. The aim of this study was to analyse a time-course of nociceptive responses (plantar test) in hypoestrogenic rats after the induction of obesity. Animals (hypoestrogenic and naïve) received either a hypercaloric or regular diet for 24 weeks. Thermal nociception and body weight were measured during this period. At the 4th and 17th weeks after treatment, oral glucose tolerance, blood insulin levels, abdominal fat weight, and uric acid levels were measured. The hypoestrogenic rats on a high sucrose diet had higher body weight and abdominal fat weight than control rats. A biphasic response was observed in the ovariectomized group fed with sucrose with thermal latency being decreased in the fourth week. During weeks 12-18, thermal latency increased compared to that of the hypoestrogenic control. There were no differences in basal blood glucose levels at the 4th and 17th weeks; however, oral glucose tolerance, insulin, and uric acid levels were altered. This indicated that increased body weight and fat as well as alteration sin glucose tolerance, hyperinsulinemia and hyperuricemia, may be associated with the biphasic nociceptive response. Drug Dev Res 77 : 258-266, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Estrogênios/deficiência , Obesidade/complicações , Percepção da Dor/fisiologia , Dor/fisiopatologia , Animais , Glicemia/metabolismo , Peso Corporal/fisiologia , Sacarose Alimentar/efeitos adversos , Feminino , Teste de Tolerância a Glucose , Insulina/sangue , Ratos , Ratos Wistar , Fatores de Risco , Fatores de Tempo , Ácido Úrico/sangue
3.
Drug Dev Res ; 77(3): 134-42, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27041220

RESUMO

Preclinical Research Neuropathic pain is particularly difficult to treat because of its diverse etiologies and underlying pathophysiological mechanisms. Drug combinations have been proposed to effectively treat some neuropathies. In the present study the interaction of five combinations of meloxicam and gabapentin, were studied to assess the possible synergistic antinociceptive response in neuropathic pain using the von Frey and acetone tests in rat models. Coadministration of meloxicam and gabapentin increased the antihyperalgesic or antiallodynic effects as compared with the compounds administered alone. The area under the curve (AUC) of the antihyperalgesic effects produced by the combination of the two drugs was generally similar to the theoretical sum of effects produced by each drug alone. However, the AUC of the antiallodynic effect produced by one combination (meloxicam 1.0 mg/kg + gabapentin 10 mg/kg) was greater than the theoretical sum of the effects produced by each drug alone. The type of final interaction on the drug combinations can be additive or cause potentiation of antinociceptive effects and depends on the proportion of each compound used in dosing. Drug Dev Res 77 : 134-142, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Aminas/administração & dosagem , Analgésicos/administração & dosagem , Ácidos Cicloexanocarboxílicos/administração & dosagem , Neuralgia/tratamento farmacológico , Tiazinas/administração & dosagem , Tiazóis/administração & dosagem , Ácido gama-Aminobutírico/administração & dosagem , Aminas/uso terapêutico , Analgésicos/uso terapêutico , Animais , Área Sob a Curva , Ácidos Cicloexanocarboxílicos/uso terapêutico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada , Gabapentina , Masculino , Meloxicam , Ratos , Tiazinas/uso terapêutico , Tiazóis/uso terapêutico , Resultado do Tratamento , Ácido gama-Aminobutírico/uso terapêutico
4.
Drug Dev Res ; 77(5): 217-26, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27300150

RESUMO

Preclinical Research The current work evaluates the interaction between two commonly used drugs, tramadol (Tra) and gabapentin (Gbp). Dose-response curves (DRC) and isobolographic analysis were used to confirm their synergistic antihyperalgesic and anti-allodynic responses in a rat neuropathic pain model involving chronic constriction injury of the sciatic nerve and in von Frey and acetone tests. Tra and Gbp produced dose-dependent antihyperalgesic and anti-allodynic effects. Dose-response studies of combinations of Tra and Gbp in combination showed the DRC was leftward-shifted compared to the DRCs for each compound alone. One combination demonstrated both antihyperalgesic and anti-allodynic effects greater than those observed after individual administration. The remaining combinations demonstrated an additive effect. The Tra+Gbp combination demonstrated a potentiative effect with smaller doses of Tra. Additionally, it was determined lethal dose 50 (LD50 ) of Tra alone and tramadol + Gbp 10 using mice to 48 h post administration. The DRC (death) were similar for Tra alone and in Tra in combination, despite the improved effectiveness of Tra in the presence of GBP, 10 mg/kg. A combination of these drugs could be effective in neuropathic pain therapy because they can produce potentiative (at a low dose) or additive effects. Drug Dev Res 77 : 217-226, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Aminas/farmacologia , Analgésicos/farmacologia , Ácidos Cicloexanocarboxílicos/farmacologia , Neuralgia/tratamento farmacológico , Tramadol/farmacologia , Ácido gama-Aminobutírico/farmacologia , Aminas/administração & dosagem , Analgésicos/administração & dosagem , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/farmacologia , Animais , Ácidos Cicloexanocarboxílicos/administração & dosagem , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada , Gabapentina , Dose Letal Mediana , Masculino , Camundongos , Neuralgia/patologia , Ratos , Ratos Wistar , Tramadol/administração & dosagem , Ácido gama-Aminobutírico/administração & dosagem
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