Pharmacological evidence for the involvement of adenosine triphosphate sensitive potassium channels in chloroquine-induced itch in mice.

BACKGROUND

Chloroquine (CQ) evokes itch in human and scratching behavior in rodents through a histamine-independent pathway. Chloroquine directly excites peripheral sensory neurons which convey itch signals to the central nervous system. It has been revealed that ATP-sensitive potassium channels (K channels) are important in regulating neuronal excitability. Thus, we aimed to investigate the involvement of K channels in CQ-induced itch which may also reveal a linkage between metabolic state of cells and itch.

METHODS

Intradermal (id) injection of CQ at dose of 400μg/site induces the scratching behavior. K channel openers, diazoxide (DZX) and minoxidil (MIN), and a K channel blocker, glibenclamide (GLI), were administered intraperitoneally (ip) before CQ. Then the behavior was recorded for 30min, in an unmanned condition, and the scratching bouts were counted by an expert observer who was blinded to the experiments. Furthermore, quantitative reverse transcription-PCR (qRT-PCR) was used to investigate the possible changes in dermal expression of Kcnj8 and Kcnj11, the genes encoding the K channels.

RESULTS

Our results show that either DZX (10mg/kg, ip) or MIN (10mg/kg, ip) significantly attenuated CQ-induced scratching behavior in mice. Moreover, pretreatment with GLI (3mg/kg, ip) significantly reversed the anti-pruritic effects of DZX and MIN. Our finding of qRT-PCR analysis also show that the expression of Kcnj8 is decreased after CQ injection.

CONCLUSIONS

We suggest that K channels are possibly involved in CQ-induced itch. While, further studies will be significant to better elucidate the association of metabolic state of cells and itch.