Comparison of paclitaxel and cisplatin effects on the slowly adapting type I mechanoreceptor

Cisplatin and paclitaxel are two of the most widely used chemotherapy drugs for the treatment of several forms of cancer. Both agents produce significant levels of peripheral neuropathy that can result in changes of treatment regimen. Although there have been recent efforts to understand the effects of these agents on nociceptor populations, little study has been made on their effects on large afferent populations. Here we report acute and chronic effects of paclitaxel and cisplatin administration on the type I mechanoreceptor using a skin-nerve preparation in rat and a standardized mechanical stimulus to compare mechanoreceptor response before and after treatment. In a control preparation, suppression of type I mechanoreceptor response during 2-min, arterial infusion of paclitaxel or cisplatin was significant for paclitaxel (28%, 1 microM; 33%, 10 microM; p<0.025), but not cisplatin (9%, 500 microM; 19%, 5 mM; p>0.05). Response returned to baseline within a 2-min washout period. Following pretreatment with paclitaxel or cisplatin, baseline response was significantly reduced from control animals. In addition, unlike the control preparation, a subsequent infusion of paclitaxel induced prolonged response suppression. Nerve fascicles innervating the preparation showed significant reduction in conduction velocity relative to control (cisplatin pretreatment: Abeta, 22%, p<0.01; C-fiber, 33%, p<0.01. paclitaxel pretreatment: Abeta, 17%, p<0.05; C-fiber, 23%, p<0.05). It was concluded that chronic paclitaxel or cisplatin treatment not only significantly alters the type I mechanotransduction process, but also increases susceptibility of the type I ending to further paclitaxel exposure.