![]() ![]() However, all of these studies were conducted using acute rather than chronic models. Animal investigations also demonstrated that GJG suppresses oxaliplatin-induced cold hyperalgesia 10, 24. ![]() Recently, the preventive effect of GJG against oxaliplatin-induced peripheral neurotoxicity in a placebo-controlled double-blind randomized phase II study (the GONE Study) was reported 23. Goshajinkigan (GJG), a traditional Japanese herbal medicine, has been widely used to treat disease-associated neuropathy (i.e., diabetic neuropathy) 20, 21, 22. In addition, several studies have suggested that increased production of reactive oxygen species (ROS) due to treatment with oxaliplatin can lead to the onset of neurotoxicity 11, 19. A previous report observed that peripheral blood flow was also altered in oxaliplatin-treated animals, which might correlate with neurotoxicity 18. Therefore, perception of heat may be a useful method to evaluate abnormal sensations resulting from oxaliplatin-induced chronic neuropathy. Some studies showed hypoesthesia to heat stimulation in animal models with diabetic neuropathy 16, 17. However, there are no reports of reproduction of the abnormal sensations (especially hypoesthesia) in an animal model. Chronic peripheral neuropathy is the most common dose-limiting factor, so prevention and amelioration of these symptoms is very important for continuous oxaliplatin chemotherapy.Īnimal studies have confirmed that treatment with oxaliplatin for a short period of time often results in hyperesthesia to cold stimulation 10, 11, 12, 13, 14, 15. Chronic peripheral neuropathy is characterized by hypoesthesia and dysesthesia as characteristic chronic oxaliplatin-induced neuropathic symptoms 8, 9 and worsens the QOL over the long term. Acute peripheral neuropathy is characterized by hyperesthesia to cold stimulation and temporarily reduces the patient’s quality of life (QOL) 6, 7. Peripheral neuropathy is a well known frequent adverse effect of oxaliplatin treatment 1, 2, 3, 4, 5. The present study provides a useful animal model for oxaliplatin-induced neurotoxicity as well as a promising prophylactic agent. GJG and some of its components attenuated the generation of oxaliplatin-induced reactive oxygen species, which is a possible mechanism of oxaliplatin-induced neurotoxicity. A pharmacokinetic study revealed numerous neuroprotective components of GJG that are rapidly absorbed into the blood. Co-administration of GJG ameliorated both abnormal sensations as well as histological damage to the sciatic nerve. ![]() Microscopy studies revealed atrophy of axons of myelinated sciatic nerve fibers in oxaliplatin-treated rats at 8 wks. The maximum level of cold hyperesthesia was observed at 4 wks with heat hypoesthesia developing later. In this study, neuropathy was induced by injection of oxaliplatin twice weekly for 8 wks. We have developed a rat model expressing both phases and used the model to investigate the action of goshajinkigan (GJG), a traditional Japanese herbal medicine, which was reported to ameliorate oxaliplatin-induced neuropathy in a placebo-controlled double-blind randomized phase II study. The latter is a serious dose-limiting side effect that can often lead to withdrawal of treatment. Oxaliplatin, a widely used chemotherapeutic agent, induces peripheral neuropathy that manifests itself as two distinct phases: acute cold hyperesthesia and chronic peripheral hypoesthesia/dysesthesia.
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