Pruritus, including neuropathic and psychogenic
pruritus, is an unpleasant feeling that causes a desire to scratch, which negatively impacts physical and psychological aspects of daily life. Nonetheless, little is known about the neural mechanisms involved in
pruritus.
Glutamate is a predominant excitatory
neurotransmitter in the mammalian central nervous system and exerts its effects by binding to various
glutamate receptors, including
kainate (KA) receptors; however, the precise involvement of each
glutamate receptor in pruriceptive processing remains unclear, particularly that of KA receptors. Therefore, the roles of KA receptors in
histamine-dependent and -independent itch were investigated using
CNQX, an
AMPA/KA receptors antagonist,
UBP310 and
UBP302, antagonists of KA receptors, and small interfering (si)RNAs against KA receptor subunits in mice with acute and chronic
pruritus. The effects of KA receptor antagonists on
histamine-induced c-Fos expression in the spinal cord were also examined. The intrathecal administration of
CNQX reduced the number of scratching events induced by
histamine and
chloroquine. On the other hand,
UBP310 or
UBP302 and the siRNAs of KA receptor subunits 1-3 significantly inhibited the induction of scratching events in mice treated with
histamine, while no significant change was observed in the induction of spontaneous scratching events in mice with chronic
pruritus. In addition, antagonists of KA receptors attenuated c-Fos expression in the superficial layers of the dorsal horn induced by
histamine. These results indicate that KA receptors are involved in acute pruriceptive processing in the spinal cord induced by
histamine, but not
chloroquine or chronic itch.