Ziconotide (SNX-111), a selective blocker of neuronal N-type voltage-sensitive 
calcium channels, is antinociceptive when it is administered intrathecally. It 
is currently under clinical investigation for the treatment of malignant and 
non-malignant pain syndromes. The present study was undertaken to compare and 
contrast antinociceptive properties of ziconotide, morphine and clonidine in a 
rat model of post-operative pain. Post-operative pain was produced by making a 
longitudinal incision through the skin, fascia, and muscle of the plantar aspect 
of the left hindpaw. This procedure produced immediate (0.5 h after surgery) and 
long-lasting (4-7 days post-surgery) heat hyperalgesia and mechanical allodynia 
in the injured hindpaw. Pain thresholds in the contralateral hindpaw were 
unaffected. Administered one day after incisional surgery, intrathecal 
ziconotide blocked established heat hyperalgesia in the injured hindpaw in a 
dose-dependent manner yielding an ED(50)4 h) but reversible (<24 h) blockade of 
established mechanical allodynia. Administered one day after surgery, 
intrathecal bolus injection of morphine dose-dependently blocked heat 
hyperalgesia in the injured hindpaw with an ED(50) of 1.6 microg (2.1 nmol) and 
heat nociceptive responses in the normal hindpaw with an ED(50) of 2.7 microg 
(3.6 nmol). The effects were immediate and short-lasting (</=1 h). Intravenous 
bolus injection of 3 mg/kg (1.1 micromol/kg) ziconotide, administered either 
before or after incisional surgery, had no effect on thermal pain thresholds 
measured in either the injured or normal hindpaw. In contrast, intraperitoneal 
injections of 2 mg/kg (2.6 micromol/kg) morphine and 2.5 mg/kg (9.4 micromol/kg) 
clonidine blocked heat hyperalgesia in the injured hindpaw; morphine, but not 
clonidine, also elevated thermal (heat) nociceptive response thresholds in the 
normal hindpaw. The results of this study show that intrathecal ziconotide is 
antinociceptive in a rat incisional model of post-operative pain and is more 
potent, longer acting, and more specific in its actions than intrathecal 
morphine.