Agmatine is a polycationic
amine synthesized from
L-arginine by
arginine decarboxylase in brain and several tissues. It binds to
N-methyl-D-aspartate (
NMDA) subtype of glutamatergic, alpha(2)-adrenergic and
imidazoline (I) receptors. The present study was designed to investigate effect of
agmatine on acute and mononeuropathic
pain after chronic constriction injury (CCI). CCI was created by four loose
ligations around the right sciatic nerve. The
analgesic threshold in rats was evaluated by using
thermal hyperalgesia/
allodynia (THA) at 4 degrees C. The evaluations were made preoperatively, on postoperative day 15, and after
drug administration.
Agmatine (10, 20, 40, 80, and 100 mg/kg) was administered intraperitoneally for 5 days beginning on postoperative day 15.
Agmatine significantly reduced the
hyperalgesia in all doses applied. When
agmatine was injected intraperitoneally (10, 20, 40, 80, and 100 mg/kg), it increased the nociceptive threshold in the tail-immersion test in a dose-dependent manner, but it had no effect in the hot-plate test. This effect of
agmatine in the tail-immersion test was blocked by both
yohimbine (1 mg/kg) and
idazoxan (0.5 mg/kg). When
agmatine was administered intracerebroventricularly (25-200 microg/10 microL), it increased the nociceptive threshold in the hot-plate but not in the tail-immersion test. We conclude that
agmatine, an endogenous substance derived from
arginine, can modulate both acute and
chronic pain.