RESUMO
Various animal models, especially rodents, are used to study pain, due to the difficulty of studying it in humans. Many drugs that produce analgesia have been studied and there is evidence among which NSAIDs deserve to be highlighted. Dexketoprofen (DEX) provides a broad antinociceptive profile in different types of pain; therefore, this study was designed to evaluate the profile of antinociceptive potency in mice. Analgesic activity was evaluated using the acetic acid abdominal constriction test (writhing test), a chemical model of visceral pain. Dose-response curves for i.p. DEX administration (1, 3, 10, 30 and 100 mg/kg), using at least six mice in each of at least five doses, was obtained before and 30 min after pre-treatment with different pharmacological agents. Pretreatment of the mice with opioid receptor antagonists was not effective; however, the serotonin receptor antagonist and nitric oxide synthase inhibitor produce a significant increase in DEX-induced antinociception. The data from the present study shows that DEX produces antinociception in the chemical twisting test of mice, which is explained with difficulty by the simple inhibition of COX. This effect appears to be mediated by other mechanisms in which the contribution of the NO and 5-HT pathways has an important effect on DEXinduced antinociception.
Assuntos
Cetoprofeno/análogos & derivados , Receptores Opioides/genética , Receptores de Serotonina/genética , Trometamina/farmacologia , Dor Visceral/tratamento farmacológico , Ácido Acético/farmacologia , Analgesia/métodos , Analgésicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Relação Dose-Resposta a Droga , Humanos , Cetoprofeno/farmacologia , Camundongos , Antagonistas de Entorpecentes/farmacologia , Óxido Nítrico/genética , Serotonina/genética , Antagonistas da Serotonina/farmacologia , Dor Visceral/genética , Dor Visceral/patologiaRESUMO
Neuropathic pain is a complication of cancer and diabetes mellitus and the most commonly used drugs in the treatment of the diabetic neuropathic pain have only limited efficacy. The aim of this study was to evaluate the role of the biomarker interleukin-1beta (IL-1ß) in the pharmacological interaction of gabapentin with tramadol in a model of diabetic neuropathic pain. CF-1 male mice, pretreated with 200 mg/kg i.p. of streptozocin (STZ), were used and at day 3 and 7 were evaluated by the hot plate test and the spinal cord level of IL-1ß was determined. Antinociceptive interaction of the coadministration i.p. of gabapentin with tramadol, in basic of the fixed the ratio 1:1 of their ED50 values alone, was ascertained by isobolographic analysis. Tramadol was 1.13 times more potent than gabapentin in saline control mice, 1.40 times in STZ mice at 3 days and 1.28 times in STZ at 7 days. The interaction between gabapentin and tramadol was synergic, with an interaction index of 0.30 and 0.22 for mice pretreated with STZ at 3 and 7 days. The combination of gabapentin with tramadol reversed the increased concentration of IL-1ß induced by STZ in diabetic neuropathic mice. These findings could help clarify the mechanism of diabetic neuropathy.
Assuntos
Neuropatias Diabéticas/complicações , Gabapentina/farmacologia , Interleucina-1beta/metabolismo , Neuralgia/tratamento farmacológico , Neuralgia/genética , Tramadol/farmacologia , Analgésicos/farmacologia , Animais , Neuropatias Diabéticas/metabolismo , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Masculino , Camundongos , Neuralgia/metabolismo , Medição da Dor/métodos , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Estreptozocina/farmacologiaRESUMO
OBJECTIVE: Diabetic neuropathy (DN) is the most common complication of diabetes and pain is one of the main symptoms of diabetic neuropathy, however, currently available drugs are often ineffective and complicated by adverse events. The purpose of this research was to evaluate the antinociceptive interaction between gabapentin and minocycline in a mice experimental model of DN by streptozocin (STZ). METHODS: The interaction of gabapentin with minocycline was evaluated by the writhing and hot plate tests at 3 and 7 days after STZ injection or vehicle in male CF1 mice. RESULTS: STZ (150 mg/kg, i.p.) produced a marked increase in plasma glucose levels on day 7 (397.46 ± 29.65 mg/dL) than on day 3 (341.12 ± 35.50 mg/dL) and also developed neuropathic pain measured by algesiometric assays. Gabapentin produced similar antinociceptive activity in both writhing and hot plate tests in mice pretreated with STZ. However, minocycline was more potent in the writhing than in the hot plate test in the same type of mice. The combination of gabapentin with minocycline produced synergistic interaction in both test. CONCLUSION: The combination of gabapentin with minocycline in a 1:1 proportion fulfills all the criteria of multimodal analgesia and this finding suggests that the combination provide a therapeutic alternative that could be used for human neuropathic pain management.
Assuntos
Aminas/administração & dosagem , Analgésicos/administração & dosagem , Ácidos Cicloexanocarboxílicos/administração & dosagem , Neuropatias Diabéticas/tratamento farmacológico , Minociclina/administração & dosagem , Medição da Dor/efeitos dos fármacos , Ácido gama-Aminobutírico/administração & dosagem , Aminas/metabolismo , Analgésicos/metabolismo , Animais , Ácidos Cicloexanocarboxílicos/metabolismo , Neuropatias Diabéticas/metabolismo , Relação Dose-Resposta a Droga , Interações Medicamentosas/fisiologia , Quimioterapia Combinada , Gabapentina , Masculino , Camundongos , Minociclina/metabolismo , Medição da Dor/métodos , Ácido gama-Aminobutírico/metabolismoRESUMO
Atorvastatin is a statin that inhibits the 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase. Several landmark clinical trials have demonstrated the beneficial effects of statin therapy for primary and secondary prevention of cardiovascular disease. It is assumed that the beneficial effects of statin therapy are entirely due to cholesterol reduction. Statins have an additional activity (pleiotropic effect) that has been associated to their anti-inflammatory effects. The aim of the present study was to assess the antinociceptive activity of atorvastatin in five animal pain models. The daily administration of 3-100mg/kg of atorvastatin by oral gavage induced a significant dose-dependent antinociception in the writhing, tail-flick, orofacial formalin and formalin hind paw tests. However, this antinociceptive activity of atorvastatin was detectable only at high concentrations in the hot plate assay. The data obtained in the present study demonstrates the effect of atorvastatin to reduce nociception and inflammation in different animal pain models.
Assuntos
Modelos Animais de Doenças , Ácidos Heptanoicos/farmacologia , Ácidos Heptanoicos/uso terapêutico , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Dor/tratamento farmacológico , Pirróis/farmacologia , Pirróis/uso terapêutico , Animais , Atorvastatina , Relação Dose-Resposta a Droga , Temperatura Alta/efeitos adversos , Masculino , Camundongos , Dor/fisiopatologiaRESUMO
Animal models are used to research the mechanisms of pain and to mimic human pain. The purpose of this study was to determine the degree of interaction between dexketoprofen and dexibuprofen, by isobolographic analysis using the formalin orofacial assay in mice. This assay presents two-phase time course: an early short-lasting, phase I, starting immediately after the formalin injection producing a tonic acute pain, leaving a 15 min quiescent period, followed by a prolonged, phase II, after the formalin and representing inflammatory pain. Administration of dexketoprofen or dexibuprofen produced a dose-dependent antinociception, with different potency, either during phases I or II. The co-administration of dexketoprofen and dexibuprofen produced synergism in phase I and II. In conclusion, both dexketoprofen and dexibuprofen are able to induce antinociception in the orofacial formalin assay. Their co-administration produced a synergism, which could be related to the different degree of COX inhibition and other mechanisms of analgesics.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Ibuprofeno/farmacologia , Cetoprofeno/farmacologia , Animais , Comportamento Animal , Interações Medicamentosas , Face , Masculino , Camundongos , Boca , Medição da Dor , EstereoisomerismoRESUMO
OBJECTIVE AND DESIGN: The antinociception induced by the intraperitoneal coadministration in mice of combinations of metamizol and paracetamol was evaluated in the tail flick test and orofacial formalin test. METHODS: The antinociception of each drugs alone and the interaction of the combinations was evaluated by isobolographic analysis in the tail-flick and in the formalin orofacial assay of mice. RESULTS: Mice pretreated with the drugs demonstrated that the antinociception of metamizol and paracetamol is dose-dependent. The potency range on the antinocifensive responses for metamizol or paracetamol was as follows: orofacial (Phase II) > orofacial (Phase I) > tail flick. In addition, the coadministration of metamizol with paracetamol induced a strong synergistic antinociception in the algesiometer assays. Both drugs showed effectiveness in inflammatory pain. CONCLUSION: These actions can be related to the differential selectivity of the drugs for inhibition of COX isoforms and also to the several additional antinociception mechanisms and pathways initiated by the analgesic drugs on pain transmission. Since the efficacy of the combination of metamizol with paracetamol has been demonstrated in the present study, this association could have a potential beneficial effect on the pharmacological treatment of clinical pain.
Assuntos
Inibidores de Ciclo-Oxigenase/farmacologia , Inibidores de Ciclo-Oxigenase/uso terapêutico , Dor/prevenção & controle , Prostaglandina-Endoperóxido Sintases/metabolismo , Acetaminofen/uso terapêutico , Animais , Dipirona/uso terapêutico , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada , Formaldeído/farmacologia , Temperatura Alta , Masculino , Camundongos , Camundongos Endogâmicos , Dor/induzido quimicamente , Medição da Dor/métodosRESUMO
OBJECTIVE: Several authors have suggested that patients adjust more poorly to breast cancer if they are heavily invested in body image as a source of their sense of self-worth. This prospective study examined this possibility, looking at two aspects of concern about body image as predictors of several indices of adjustment over the first postoperative year. METHODS: At diagnosis (and again a year later) 66 women with early stage breast cancer reported how much they valued a) a sense of body integrity (or intactness) and b) a good physical appearance. The day before surgery, a week afterward, and at 3-month, 6-month, and 12-month follow ups, they reported on their mood. At presurgery and at follow ups they also rated their attractiveness and sexual desirability and reported on frequency of sexual interaction. At follow-ups they also indicated how much their illness and treatment were interfering with social and recreational activities. RESULTS: Initial investment in appearance was related to distress across the postsurgical year. In contrast, investment in appearance made women more resilient against deterioration in their perceptions of attractiveness. Concern about body integrity did not strongly predict emotional distress, but it related to adverse impact on social and recreational activities in the follow-up period, to deterioration in feelings of sexual desirability, and to feelings of alienation from the self (feeling "not like yourself anymore"). CONCLUSIONS: Body image is often thought of in terms of physical appearance, but there is also a body image pertaining to integrity, wholeness, and normal functioning. People who are greatly concerned about either aspect of their body image are vulnerable to poorer psychosocial adjustment when confronting treatment for breast cancer. The poorer adjustment takes a different form, however, depending on the nature of the patient's body-image concern.
Assuntos
Adaptação Psicológica , Imagem Corporal , Neoplasias da Mama/psicologia , Ajustamento Social , Adulto , Idoso , Atitude Frente a Saúde , Neoplasias da Mama/terapia , Efeitos Psicossociais da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Análise de Regressão , AutoimagemRESUMO
BACKGROUND: Recent studies indicate that breast cancer patients do not usually experience the devastating psychological consequences once viewed as inevitable. However, some adjust to the disease more poorly than others. This study examined the personality trait of optimism versus pessimism as a predictor of adjustment over the first year, postsurgery. METHODS: Seventy women with early stage breast cancer reported on their general optimism-pessimism at diagnosis. One day before surgery, and at 3-month, 6-month, and 12-month follow-ups, they reported their subjective well-being (mood scales and a measure of satisfaction with life). At follow-ups, they also rated their sex lives, indicated how much physical discomfort was interfering with their daily activities, and reported on thought intrusion. RESULTS: Pessimism displayed poorer adjustment at each time point by all measures except interference from pain. Even controlling for previous well-being, pessimism predicted poorer subsequent well-being, suggesting that pessimism represents a vulnerability to a negative change in adjustment. In contrast, effects of pessimism on quality of sex life and thought intrusion were not incremental over time. Additional analyses indicated that effects of the optimism-pessimism measure were captured relatively well by a single item from the scale. CONCLUSIONS: A sense of pessimism about one's life enhances a woman's risk for adverse psychological reactions to the diagnosis of, and treatment for, breast cancer. This finding suggests the potential desirability of assessing this quality informally in patients, to serve as a warning sign regarding the patient's well-being during the period surrounding and following surgery.
Assuntos
Adaptação Psicológica , Neoplasias da Mama/psicologia , Personalidade , Adulto , Idoso , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Coleta de Dados , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
At diagnosis, 59 breast cancer patients reported on their overall optimism about life; 1 day presurgery, 10 days postsurgery, and at 3-, 6-, and 12-month follow-ups, they reported their recent coping responses and distress levels. Optimism related inversely to distress at each point, even controlling for prior distress. Acceptance, positive reframing, and use of religion were the most common coping reactions; denial and behavioral disengagement were the least common reactions. Acceptance and the use of humor prospectively predicted lower distress; denial and disengagement predicted more distress. Path analyses suggested that several coping reactions played mediating roles in the effect of optimism on distress. Discussion centers on the role of various coping reactions in the process of adjustment, the mechanisms by which dispositional optimism versus pessimism appears to operate, third variable issues, and applied implications.
Assuntos
Adaptação Psicológica , Neoplasias da Mama/psicologia , Moral , Estresse Psicológico/psicologia , Adulto , Idoso , Atitude , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
PURPOSE: Procedure (mastectomy v lumpectomy) and choice of procedure were examined as predictors of adjustment to breast cancer in a prospective study of the experiences of the first year after surgery. PATIENTS AND METHODS: Breast cancer patients were interviewed the day before surgery, 10 days after surgery, and at the 3-month, 6-month, and 12-month follow-ups. Patients included 24 women who received mastectomy on strong recommendation, 24 who chose mastectomy for other reasons, and 15 who chose lumpectomy. Subjective well-being was assessed in terms of mood disturbance, perceived quality of life, life satisfaction, marital satisfaction, perceptions of social support, and self-rated adjustment. RESULTS: Surgical groups differed in well-being in only one respect: lumpectomy patients reported a higher-quality sex life at 6 and 12 months postsurgery than mastectomy patients. Choice of surgical procedure predicted higher levels of life satisfaction at 3 months. CONCLUSION: The lack of difference between surgical groups in areas other than sexual adjustment replicates previous findings, but extends them by (1) using a fully prospective design, (2) providing data on the period surrounding the surgery (as well as later periods), and (3) examining a broader range of indices of well-being than usual.