RESUMO
BACKGROUND: Chemotherapy-induced neuropathic pain (CINP) is a serious side effect of chemotherapy. Korean Red Ginseng (KRG) is a popular herbal medicine in Asian countries. We examined the therapeutic potential of intrathecally administered KRG for CINP and clarified the mechanisms of action with regard to 5-hydroxytryptamine (5-HT)7 receptor at the spinal level. METHODS: CINP was evoked by intraperitoneal injection of cisplatin in male Sprague-Dawley rats. After examining the effects of intrathecally administered KRG on CINP, 5-HT receptor antagonist (dihydroergocristine [DHE]) was pretreated to determine the involvement of 5-HT receptor. In addition, intrathecal 5-HT7 receptor antagonist (SB269970) was administered to define the role of 5-HT7 receptor on the effect of KRG. 5-HT7 receptor mRNA expression levels and 5-HT concentrations were examined in the spinal cord. RESULTS: Intrathecally administered KRG produced a limited, but a dose-dependent, antiallodynic effect. Intrathecally administered DHE antagonized the antiallodynia caused by KRG. Furthermore, intrathecal SB269970 also reversed the effect of KRG. No changes in 5-HT7 receptor mRNA expression were seen in the dorsal horn of the spinal cord after cisplatin injection. After injecting cisplatin, 5-HT levels were decreased in the spinal cord, whereas those of 5-HT were increased by intrathecal KRG. CONCLUSIONS: Intrathecally administered KRG decreased CINP. In addition, spinal 5-HT7 receptors contributed to the antiallodynic effect of KRG.
Assuntos
Cisplatino/toxicidade , Neuralgia/prevenção & controle , Panax/química , Extratos Vegetais/farmacologia , Animais , Antineoplásicos/toxicidade , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Hiperalgesia/induzido quimicamente , Hiperalgesia/prevenção & controle , Injeções Espinhais , Masculino , Neuralgia/induzido quimicamente , Extratos Vegetais/administração & dosagem , Ratos , Ratos Sprague-Dawley , Receptores de Serotonina/metabolismo , Serotonina/metabolismo , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismoRESUMO
BACKGROUND: Bone cancer pain has a disruptive effect on the cancer patient's quality of life. Although ginsenosides have been used as traditional medicine in Eastern Medicine, the effect on bone cancer pain has not been thoroughly studied. The aim of this study was to determine whether ginsenosides may alter the bone cancer pain at the spinal level. METHODS: NCTC 2472 tumor cells (2.5 × 10(5)) were injected into the femur of adult male C3H/HeJ mice to evoke bone tumor and bone cancer pain. To develop bone tumor, radiologic pictures were obtained. To assess pain, the withdrawal threshold was measured by applying a von Frey filament to the tumor cells inoculation site. The effect of intrathecal ginsenosides was investigated. Effect of ginsenosides (150, 500, 1,000 µg) was examined at 15, 30, 60, 90, 120 min after intrathecal delivery. RESULTS: The intrafemoral injection of NCTC 2472 tumor cells induced a radiological bone tumor. The withdrawal threshold with tumor development was significantly decreased compared to the sham animals. Intrathecal ginsenosides effectively increased the withdrawal threshold in the bone cancer site. CONCLUSIONS: NCTC 2472 tumor cells injection into the mice femur caused bone tumor and bone cancer pain. Intrathecal ginsenosides attenuated the bone cancer-related pain behavior. Therefore, spinal ginsenosides may be an alternative analgesic for treating bone cancer pain.