Upregulations of P2X3 and ASIC3 involve in hyperalgesia induced by cisplatin administration in rats

The role of ion channels expressed in sensory neurons on mechanical and thermal hyperalgesia was examined in a rat model of cisplatin-induced peripheral neuropathy. The rats were injected with 3 mg/kg of cisplatin intraperitoneally once per week for five consecutive weeks. The von Frey test, pin-prick test and plantar test were performed to examine any noxious sensitivity of the skin. The Randall–Selitto test of the gastrocnemius muscle (GM) and the measurement of grip forces were performed to quantify muscle hyperalgesia. Coordination/motor was assessed by Rota-rod testing. Expressions of the ion channels TRPV1, TRPV2, P2X₃ and ASIC3 were examined in dorsal root ganglion (DRG) neurons and the muscle afferent neurons innervating GM. Effects of antagonists against either P2X₃ or ASICs on behavioral responses were evaluated. Mechanical hyperalgesia and allodynia of both skin and muscle were observed in cisplatin-treated animals. Expressions of TRPV2, P2X₃, and ASIC3 increased in all DRG neurons. In addition, expressions of P2X₃ and ASIC3 also increased in muscle afferent neurons in DRGs. Antagonists against P2X_3,2/3 and ASICs showed a suppressive effect on both skin and muscle hyperalgesia induced by cisplatin administration. Upregulation of TRPV2, P2X₃, and ASIC3 may play important roles in the mechanical hyperalgesia induced by cisplatin. Furthermore, cisplatin treatment also induced muscle hyperalgesia in muscle afferent neurons in connection with the upregulation of P2X₃ and ASIC3.