Involvement of increased expression of transient receptor potential melastatin 8 in oxaliplatin-induced cold allodynia in mice

Abstract

Oxaliplatin is a chemotherapy drug and induces peripheral neuropathy which is aggravated by exposure to cold, the mechanism of which is unclear. In the present study, we investigated in mice whether transient receptor potential melastatin 8 (TRPM8), which is activated by cooling temperature, would be involved in cold allodynia induced by oxaliplatin. Mice were given an intraperitoneal injection of oxaliplatin. Acetone was applied to hind paw for cooling stimulation, and the time spent for licking to the hind paw was measured. The expression of TRPM8 mRNA in dorsal root ganglion was determined by the RT-PCR method. An injection of oxaliplatin induced cold allodynia, which peaked on day 3 after injection and did not disappear even on day 25. Peak cold allodynia was inhibited by capsazepine, a blocker of both TRPM8 and heat-activated TRPV1, but not by 5′-iodoresiniferatoxin, a TRPV1 blocker. Oxaliplatin increased wet-dog shake and jumping behaviors evoked by the TRPM8 agonist icilin. An injection of oxaliplatin increased the expression level of TRPM8 mRNA at day 3 after injection and the expression was decreased to the near-normal level on days 10 and 25. These results suggest that cold allodynia induced by oxaliplatin is at least partly due to the increased expression of TRPM8 in the primary afferents.