Pruritus is the most common complication of intrathecal
morphine; however, its exact molecular mechanism is unclear, and treatment is challenging. The
analgesic effect of
N-methyl-D-aspartate (
NMDA) receptor antagonists and the
morphine-associated increase in
NMDA receptor activation suggest potential role of
NMDA receptor in the spinal itch sensation. Male C57BL/6 mice were given intrathecal
morphine to induce scratching behavior. The effects of
NMDA,
ketamine,
ifenprodil and
U0126 on
morphine-induced
pruritus and
analgesia were evaluated also. The number of scratching responses was counted for 30 min post-injection to evaluate
pruritus. A warm-water tail immersion assay was conducted before and until 120 min post-injection at 30-min intervals. Percent of maximal possible effect (%MPE) and area under curve (AUC) were calculated based on tail-flick latency to evaluate
analgesic efficacy. Compared with control treatment, intrathecal
morphine elicited an obvious scratching response and
analgesic effect in a dose dependent manner.
Ketamine (1 μg),
ifenprodil (0.1 μg) and
U0126 (0.1 μg and 1.0 μg) all significantly attenuated
morphine induced scratches.
Ifenprodil (0.1 μg) injection significantly prolonged the
analgesic effect of intrathecal
morphine. The ERK1/2 phosphorylation induced by intrathecal
morphine was inhibited by
ketamine,
ifenprodil and
U0126 as well.
U0126 inhibited
morphine-induced
pruritus with no effect on its
analgesia. Therefore, intrathecal coadministration of
morphine with
NMDA receptor antagonists
ketamine and
ifenprodil alleviated
morphine-induced scratching. Intrathecal
morphine increased ERK phosphorylation in the lumbar spinal dorsal horn, which may be related with
morphine-induced
pruritus, and was counteracted by
NMDA receptor antagonists.